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pmc-6594277-1 | A 37-year-old woman, gravida 2, para 0, with a suspicious tumor at the liver hilum at 21 weeks 5 days of gestation was admitted to the department of obstetrics and gynecology of our hospital. Physical examination revealed a very sick and suffering patient. The patient presented with dyspnoea, jaundice, epigastric pain, ascites, and abdominal tenderness. Orange urine and white stool were reported. There was no previous or family history of any cancer. No regular medication was reported. The patient was a former light smoker; she did not smoke during pregnancy. Magnetic resonance imaging (MRI) had been performed eight days before the patient's admission; it revealed an enlarged liver with a centrally located tumor at the liver hilum and disseminated hepatic and abdominal lymph node metastases. MRI also displayed mechanical cholestasis with dilated biliary ducts and ascites ().
On obstetrical ultrasonography at the time of admission, the estimated fetal weight was 470 g (59th percentile), a Doppler measurement of blood flow through the uterine arteries was performed, and the median PI (pulsatile index) was below 1.5. Fetal movements, fetal anatomy, placenta, amniotic-fluid volume, and the length of the cervix (40.0 mm) were normal.
At the time of the patient's initial presentation, laboratory results showed severe normocytic normochromic anemia with haemoglobin level 6.7 g/dl and hematocrit 20.2%, leukocytosis with a white blood cell count of 14.47 G/l, and a normal platelet count. Liver function parameters were elevated as follows: total bilirubin 16.64 mg/dl, glutamate oxaloacetate transaminase (GOT) 70 U/l, glutamate pyruvate transaminase (GPT) 42 U/l, and gamma-glutamyl transferase (GGT) 90 U/l. Cholinesterase was <1 kU/l; both alkaline phosphatase (843 U/l) and lactate dehydrogenase (LDH) (635 U/l) were elevated. Total protein and albumin levels were reduced (52.5 g/l, 28.0 g/l, respectively). Blood coagulation analysis resulted in a prothrombin time of 34%; an activated partial thromboplastin time (APTT) was 45.1 s. Fibrinogen (279 mg/dl) was normal. A high level of C-reactive protein (CRP) (8.23 mg/dl) was detected. Common kidney function parameters and serum electrolytes were normal. These laboratory findings are shown in . Tests for viral hepatitis B and hepatitis C and HIV were all negative.
Acute hepatic failure was diagnosed. According to the findings, the patient underwent a percutaneous transhepatic biliary drainage (PTBD) (). Pathological examination of the liver-biopsy specimens, obtained at PTBD, revealed a poorly differentiated, diffusely infiltrating SRCC, grade 3 (). By immunohistochemistry, the tumor was positive for cytokeratin (CK) 7 (). Tumor cells were negative for CK20, caudal-type homeobox transcription factor 2 (CDX2), estrogen receptor (ER), progesterone receptor (PR), PAX8, and human epidermal growth factor receptor 2 (HER2). Positive expression of programmed death-ligand 1 (PD-L1) was found in 30% of the tumor cells. Immunohistochemistry of phosphatase and tensin homolog (PTEN) was weak and not conclusive. In conclusion, histomorphology and immunohistochemical findings argued for a primary tumor of the upper gastrointestinal tract. DNA repair proteins like MLH1, MSH2, MSH6, and PMS2 were positively expressed. Thus, these findings argued against microsatellite instability. Next generation sequencing-based analysis of common targetable cancer mutations was ordered. The Ion AmpliSeq™ Cancer Hotspot Panel v2 (Ion Torrent™) and the Ion AmpliSeq™ BRCA1 and BRCA2 Panel (Thermo Fisher Scientific Inc., Waltham, MA, USA) were used for mutational analyses.
The following day, recurrence of ascites was observed. Therefore ultrasound-guided paracentesis was performed.
Two days after admission, regular labour started spontaneously at 6 am; therefore the patient was transferred to the delivery room. Immediately, the patient had rupture of membranes and delivered a female infant in pelvic presentation, by spontaneous vaginal delivery, at full 22 weeks of gestation. The baby weighed 427 g; the Apgar scores at 1, 5, and 10 minutes were all 1. The placenta seemed cleft; thus ultrasonography of the uterine cavum was performed, and no placental residues were detected. In general, loss of blood and involution of uterus were normal.
Afterwards, an abdominal CT (computed tomography) scan detected metastatic disease, a large mass located at the liver hilum (6 cm at maximum) next to the gastric cardia, hepatic metastasis, cholangiectasis, and enlarged locoregional lymph nodes, and bone metastases in the whole axial skeletal system. Additionally, the CT showed signs of a paralytic ileus; therefore a stomach tube has been inserted. A chest CT scan demonstrated a large right upper lobe mass (5 cm in diameter), appearing malignant, and bilateral pleural effusions ().
In conjecture, histopathologic and imaging findings were most consistent with a primary signet cell carcinoma of gastric origin.
Despite antibiotic coverage with ampicillin after PTBD, the patient developed clinical signs of sepsis including tachycardia, fever, dyspnoea, and low blood pressure, along with significantly elevated procalcitonin (PCT) levels (5.12 ng/ml). PCT is used as a biomarker for the diagnosis of sepsis, and PCT is used to guide antibiotic therapy []. Initially, no specific focus of sepsis was found. Accordingly, antibiotic therapy was changed by replacing ampicillin with piperacillin/tazobactam.
Blood cultures later grew Candida albicans and streptococci. Teicoplanin and fluconazole were thus added to the piperacillin/tazobactam regimen. Moreover, polymerase chain reaction (PCR) for DNA quantification of CMV revealed 1.63 x 102 c/ml. Thus, valganciclovir was administered.
Seven days after admission, an ultrasound examination of the liver demonstrated minimal intrahepatic cholangiectasis and gallbladder wall thickening. Decompression effect and clinical improvement were observed, but there was no improvement in laboratory parameters of cholestasis with bilirubin levels plateauing at 26.87 mg/dl.
Antitumor therapy was discussed: Because of her poor performance status (ECOG 3) and cholestasis, the patient was not a candidate for chemotherapy, and beyond PD-L1, no drugable targets were discovered in immunohistochemical analyses. After careful discussion with the patient and her family and after obtaining informed consent experimental therapy with pembrolizumab (200 mg as intravenous infusion) was initiated and well tolerated. Pembrolizumab represents a monoclonal antibody which binds to PD-1, blocking the interaction between PD-1 and its ligands (e. g. PD-L1) [, ]. In tumor tissues, binding of PD-1 on T-cells to PD-L1 expressed by tumor cells inhibits the antitumor immune response of T-cells, thus enabling immune escape of tumor cells and neoplastic growth [, , ].
A few days later, the results from sequencing analyses were available: Sequencing results revealed a deletion in exon 19 of the epidermal growth factor receptor (EGFR) [p.(E746_A750del)], which represents a prototypical mutation characterizing as subset of adenocarcinomas of the lung. In addition, mutations of RB1 (exon 22) and TP53 (exon4) were detected. The patient did not have a BRCA1/2 mutation. Additional immunohistochemical stains ordered based on sequencing results revealed that the tumor cells were highly positive for thyroid transcription factor-1 (TTF1), which represents a useful marker in the diagnosis of tumors of thyroid or lung origin () [, ].
Based on the mutational profile, treatment with afatinib was recommended. Afatinib shuts down the signalling activity of receptor tyrosine kinases of the ErbB family by binding to three members of the family, namely, EGFR, HER2 and HER4, and by inhibiting the transphorylation of a fourth member, HER3 []. Owing to her rapidly deteriorating health status, the patient was not able to commence afatinib. Despite supportive measures the patient died on the 14th day of admission.
Taken together, this pregnant woman was diagnosed with signet ring cell carcinoma which was primary assumed to originate from the upper gastrointestinal tract. In addition, liver and bone metastasis and a malignant-appearing lung lesion were observed. According to the histopathological (CK7 positive, CK20 negative, TTF1 positive) and genetic findings (mutation of EGFR, exon 19), primary SRCC of the lung was the final diagnosis. |
pmc-6594278-1 | A 26-year-old female with a medical history of neurofibromatosis type-1 and 28-week gestational age complicated by preeclampsia was referred to the cardiovascular center for evaluation of an expanding, pulsatile, tender mass on the right neck. On admission, her vital signs reflected a hypertensive emergency with systolic blood pressures of 200s mmHg, tachycardia of 112 beats per minute, tachypnea of 20 breaths per minute with oxygen saturation of 98% on room air. On physical examination, there were several features consistent with her preexisting diagnosis of NF-1, which included multiple “café-au-lait” macules and neurofibromas throughout her chest and abdomen, with both axillary and inguinal freckling [].
Routine blood investigations were normal, 12-lead electrocardiography indicated a sinus tachycardia with left ventricular hypertrophy which was also visualized on an inpatient transthoracic echocardiogram. A computerized tomography scan revealed a dissected pseudoaneurysm of the right external carotid artery (ECA). In the interim, she was treated with an intravenous nitroglycerin infusion and hydralazine to achieve near-normotensive pressures over the ensuing 12 hours (see ). Subsequently, on the second day of hospitalization, selective carotid angiography demonstrated a dissected pseudoaneurysm of the right ECA measuring 2.7 cm, arising in association with the occipital branch with contrast extravasation (see ). Ad-hoc successful coil embolization was achieved with 0.018” and 0.035” Tornado® embolization coils (Cook Medical LLC, Bloomington, IN, USA) (see ). At the conclusion of the procedure, cineangiography revealed complete occlusion of the vessel distal to the superior thyroid branch with no further opacification of the aneurysm (see ). |
pmc-6594284-1 | A 70-year-old man was evaluated for a long history of symptomatic varicose veins (pain and perimalleolar edema formation) on his left leg. Except for a dyslipidemia and arterial hypertension treated, respectively, with simvastatin and lisinopril, no other comorbidities were known. Personal and family history for prior venous thromboembolic events or neoplasia were negative. The physical examination revealed varicose veins in the area of the knee and lower leg mediodorsally, with perimalleolar edema on the left side. No varicose veins or local signs of inflammation were present in the groin. On the duplex ultrasound examination, an insufficient left GSV was disclosed, showing a long-lasting reflux (>2sec.) from the SFJ down to the ankle. The maximum diameter of the vein was 10mm in the thigh. Unexpectedly, a 10x10x8 mm isoechogenic mass with an hyperechogenic component could be detected in the region of the SFJ, in an eccentric dilated segment of the GSV adherent both to the terminal valve and to the vein wall. This mass was only partially obstructing the GSF (). No color Doppler signals could be detected within the structure. The deep venous system of the left leg was patent and sufficient, without postthrombotic sequelae. Several characteristics, such as the location in a dilated segment of the vein, the echogenicity, and the absence of a Doppler signal within the mass, favored a diagnosis of focal thrombosis.
We started a thromboembolic prophylaxis with Rivaroxaban 10mg once daily. In addition, we discussed with the patient an accelerated EVLA of the GSV with the aim to treat the varicose veins, excluding at the same time the thrombotic mass. The outpatient-based intervention took place 7 days later. At that time, the thrombotic mass was still present and unchanged. A 1470nm wavelength radial fiber with a diameter of 600μm (ELVeS Biolitec Radial Laser) was inserted via a 21G introducer under echographic guidance from the mid third of the lower leg and pushed up to the SFJ. The thrombotic mass was passed under echographic guidance by maneuvering the tip laterally to the thrombotic mass () without dislodging the thrombus () by gently steering the fiber, applying distal external manual pressure onto the laser fiber. The laser fiber was eventually placed at the confluence of the GSV with the common femoral vein without a safety distance in order to exclude the thrombotic mass. After tumescence anesthesia with diluted prilocaine and epinephrine, EVLA was performed (10W/100J proximally and 8W/80J distally, for a total energy of 6614 Joules and a treated length of 66cm). Subsequently, the tributaries were treated by miniphlebectomy. At the end of the procedure, an extrinsic compression with gauzes and elastic compression stocking (23-32 mmHg) were applied. Prophylactic anticoagulation with Rivaroxaban 10mg daily was continued for 5 days, according to our internal protocol after standard EVLA. Wound healing occurred without relevant complications, and the patient was asymptomatic during the follow-up.
Duplex ultrasound visits on day 1 and day 13, at 6 weeks, and one year after the intervention showed a permanent occlusion of the treated GSV up to the confluence without evidence of any thrombus propagation into the deep vein system (). Particularly, no residual mass could be detected at the level of the SFJ. |
pmc-6594285-1 | The patient is a 15-year-old Caucasian female who was diagnosed with CRMO in 2007 at 5 years in the context of right thigh pain. provides a timeline of the patient's symptoms and course of disease. Magnetic resonance imaging (MRI) showed multifocal abnormal bone marrow signal in the right femur, the left femoral neck, and the proximal epiphysis and metaphysis of the right tibia, which was associated with osteolysis and callus formation (). Radio-nucleotide bone scan found increased uptake involving the left sacrum, left proximal femur, and femoral neck region as well as the midshaft of the right femur and the proximal right tibia. Bone biopsy of the lytic lesion involving the midshaft of the right femur was not consistent with malignancy and showed red blood cells and scattered neutrophils and lymphocytes. Over the next several years (2007–2015), she was followed by orthopedic surgery and was treated only with intermittent ibuprofen as needed for pain. She was noted to have a leg length discrepancy at the age of 7 years, and in 2014, at the age of 12 years, she had surgery to fuse the growth plate to prevent right leg growth (right leg was 4.5 cm longer than her left leg at that time).
She established Rheumatologic care in March 2015 at age 13, and right quadriceps muscle atrophy and failure to thrive with a weight and height under the third percentile were noted at this time. Bone scan revealed increased uptake in the right femur and asymmetry of activity in the growth plates of the knees and ankles with decreased activity in the right side compared to left. She was treated with naproxen 250 mg twice daily (8.7 mg/kg BID) and prednisone 20 mg per day (0.7 mg/kg), tapered by 5 mg weekly. Two months later, prednisone was discontinued, and she continued to have good control of her leg pain on NSAID monotherapy. After a few months, she developed new diarrhea with vomiting and weight loss. Her blood pressure was elevated, and a renal ultrasound and electrocardiogram were unremarkable.
She was referred for Gastroenterology evaluation and was found to have positive stool occult blood along with a perirectal skin tag. Laboratory studies revealed anemia with a hemoglobin of 7.1 g/dL (nl 12–16 g/dL), thrombocytosis with platelets of 744 k (nl 150–450 k), erythrocyte sedimentation rate (ESR) of 69 mm/hr (nl 0–10 mm/hr), and C-reactive protein (CRP) of 129 mg/L (nl 0–3 mg/L). There was no family history of autoimmune disease, and tuberculin testing was negative. Colonoscopy revealed pancolitis with crypt inflammation and crypt abscesses with no granuloma consistent with ulcerative colitis (). NSAID therapy was discontinued, and treatment for UC with prednisone 1 mg/kg/day (40 mg) tapering by 5 mg weekly along with sulfasalazine was initiated. Infliximab 3 mg/kg infusions were added the following month.
At the visit for her second infliximab infusion, she presented with tachycardia, a blood pressure of 230/190, and headache and was admitted to the pediatric intensive care unit for hypertensive emergency requiring nicardipine infusion. Her examination was notable for right-sided Horner's syndrome, decreased right leg pulse pressure, and an abdominal bruit. Echocardiogram showed a small pericardial effusion with reduced left ventricular ejection fraction. Laboratory studies revealed negative ANA and ANCA screens, normal C3 and C4, and normal von Willebrand factor antigen. CT angiogram (CTA) of the abdomen and pelvis showed narrowing of the mid-aorta, proximal renal arteries, celiac artery, and superior mesenteric artery (Figures –). CTA of the chest showed marked descending thoracic and abdominal aortic wall thickening with progressive luminal narrowing and wall thickening of the visualized portion of the right common carotid artery and celiac trunk, enlarged left atrium, left ventricular hypertrophy, and a small pericardial effusion (). MRI/MRA brain showed anterior and posterior circulations of the brain were without occlusion or aneurysm with the patent carotid and vertebral arteries of the neck (Figures and ). Given these findings, she was diagnosed with TA complicated by middle aortic syndrome. She was started on metoprolol 50 mg daily (1.5 mg/kg daily), amlodipine 5 mg daily, famotidine 20 mg twice daily, aspirin 81 mg daily, and increased dose and frequency of infliximab from 3 mg/kg every 8 weeks to 5 mg/kg IV every 4 weeks along with prednisone 20 mg daily (0.6 mg/kg daily) and mesalamine 1 g BID. The patient continued infliximab every 8 weeks rather than every 4 weeks as recommended.
Magnetic resonance (MR) angiography of the chest, abdomen, and pelvis and Cardiac MR three months later showed luminal narrowing of the distal thoracic and upper abdominal aorta similar to previous CT studies, stenosis of origin of celiac axis, stenosis of proximal superior mesenteric artery (SMA), and moderate stenosis of bilateral proximal renal arteries. Echocardiogram noted concentric LVH with mildly reduced function, measuring 45%, and normal coronary arteries.
At this point, the patient transferred her care to our rheumatology clinic, and despite treatment with infliximab 5 mg/kg every 8 weeks, she continued to report right thigh pain and developed new inflammatory arthritis of the left ankle and increased inflammatory markers with an ESR of 55 mm/hr (nl 0–20 mm/hr) and an elevated CRP of 73 mg/L (nl < 3 mg/L). Additionally, interval imaging found new wall thickening around the right common carotid artery. This was concerning for uncontrolled TA and CRMO activity. There was an unfortunate delay in treatment escalation due to social circumstances. Two months later, she started treatment with parenteral methylprednisolone 1 gram weekly for 8 weeks, and her dose of infliximab was increased from 5 mg/kg to 10 mg/kg every 4 weeks. Based on adult data demonstrating a positive response to higher doses of infliximab, the decision was made to increase the dose of infliximab instead of trying another TNF inhibitor.
Multidisciplinary evaluation at Boston Children's Hospital, Center for Middle Aortic Syndrome by neurosurgery, nephrology, and rheumatology, led to recommendations of a prednisone dose increase and the addition of methotrexate 15 mg/m2 weekly to infliximab 10 mg/kg every 4 weeks. At this time, her echocardiogram revealed moderate left ventricle dilation and mildly depressed left ventricular systolic function. One month later, repeat head and neck CTA showed progression of her right carotid artery stenosis to 80%. Her ESR had normalized, and CRP decreased to 7.8 mg/L at this time. Given her worsening carotid artery stenosis, infliximab was increased from 10 to 15 mg/kg every 4 weeks. On a combination of moderate dose prednisone, weekly methotrexate, and infliximab, she denied joint pain, swelling, abdominal pain, diarrhea, or blood in stool. Follow-up brain MRI/MRA three months later was normal. Repeat chest and abdomen MRA showed all of the areas of stenosis appeared to be stable and inflammatory markers had normalized.
Currently, her clinical course is stable without further anatomic progression, and she has normal inflammatory markers. Thus, she has continued on her current regimen with infliximab 15 mg/kg every 4 weeks and methotrexate 15 mg/m2 once weekly. Prednisone decreased gradually and discontinued. She has not developed any infectious sequelae on this regimen. Her blood pressure is stable on carvedilol alone. We continue to assess blood work monthly. Given her use of prednisone, vitamin D level was followed and found to be low, and she has started on a vitamin D supplement. Dilated ophthalmologic exam was normal. Repeat MRI of the lower extremities and bone scan show that her CRMO lesions are inactive. Repeat MRI/MRA of the brain, chest, abdomen, and pelvis in June of 2018 show stable changes without the need for stenting. Given the predisposition for autoinflammatory conditions in this patient, the authors are considering genetic testing in search of a monogenic cause that may support a unifying diagnosis. |
pmc-6594292-1 | A 64-year-old female with past medical history of hypertension, obesity, and gastroesophageal reflux disease presented to tertiary hospital with complaints of eight days of abdominal pain in the right upper quadrant accompanied by nausea, vomiting, fevers, and diarrhea. On admission, vital signs were notable for BP 130/90, HR 133, RR 18, and temperature of 102.7 F. Physical exam revealed jaundice but did not appreciate abdominal tenderness or guarding. Laboratory investigations showed leukocytosis of 20.2 x 109 cells per liter, total bilirubin 2.4 mg/dL, alkaline phosphatase 114 units per liter (U/L), AST 62 U/L, ALT 59 U/L, and albumin 2.6 g/dL. An abdominal computed tomographic (CT) scan was performed and showed a 6.9 cm heterogeneously enhancing abscess collection within the left hepatic lobe (Figures and ).
On admission, interventional radiology performed CT-guided percutaneous drainage and placed biliary drain. Abscess cultures returned with alpha hemolytic streptococcus. Due to persistent leukocytosis, a repeat abdominal CT was performed and showed a 2.1 cm fish bone as radiopaque foreign body at the level of the falciform fissure with inflammation tracking to the abscess cavity. Subsequent upper endoscopy failed to visualize a fistulous opening by foreign body in the gastric antrum. The case was discussed in multidisciplinary hepatobiliary conference. Due to rapid clinical improvement with minimal biliary drain output, drains were removed and patient was treated with extended intravenous antibiotics. Patient was seen in clinic 6 weeks later, with no complaints. Repeat CT imaging indicated resolution of hepatic abscess to a size of 1.7x1.3 cm without any further migration of foreign body (Figures and ). |
pmc-6594293-1 | A 3-year-old girl who had previously received hepatocyte-based LCT (see [] for details) was then treated with ADHLSC-based LCT.
At the time of the ADHLSC infusions, the child was weighing 14.9 kg. She first received two infusions of 262 and 230 million cryopreserved/thawed ADHLSCs and received a third infusion of 430 million fresh ADHLSCs two weeks later. The immunosuppression regimen based on tacrolimus remained identical to reach trough levels 6-8 ng/ml []. Needle biopsies of the liver were taken before ADHLSC infusion and at 3.5 months postinfusion. The child received a liver transplant 10 months post ADHLSC-based LCT, and the liver was recovered and cryopreserved as slices taken from the left to the right lobe. The samples were stored frozen at -80°C. |
pmc-6594294-1 | A 31-year-old male presented to the emergency department secondary to bilateral lower extremity edema for the last two days. He denied shortness of breath, chest pain, fever, and chills. The patient's past medical history was unremarkable except for a recent dental procedure to drain abscess. His social history was significant for recent alcohol abuse and denied intravenous drug use.
Physical exam showed a temperature of 102.8 F, heart rate of 154 beats per minute, respiratory rate of 20 breaths per minute, and an oxygen saturation of 94% on room air. The cardiovascular exam revealed a normal rhythm with tachycardia but no murmurs, rubs, or gallops. He also had rales present to the mid lungs bilaterally without wheezes or rhonchi. Extremity examination revealed +1 pitting edema of the bilateral lower extremities and clubbing of the fingernails bilaterally without lesions or rashes on the palms or soles of the feet.
While in the emergency department, labs revealed a white blood cell count of 10.7 K/uL (4.8–10.8 K/uL), hemoglobin of 7.6 g/dL (13.1–17.1 g/dL), hematocrit of 23.6% (42.0–52.0%), platelet of 315 K/uL (150–450 K/uL), lactate of 1.5 mmol/L (0.7–2.0 mmol/L), procalcitonin of 3.11 ng/mL (0.05–1.90 ng/mL), pro-BNP of 1720 pg/mL (0–125 pg/mL), and a troponin of 0.131 ng/mL (0.000–0.034 ng/mL). The chest radiograph showed no signs of infection or pulmonary edema. Computed tomography of the chest, abdomen, and pelvis with intravenous contrast showed an atypical inflammatory pattern in the lungs with mild cardiomegaly, hepatomegaly, and splenomegaly with a hypodensity suggestive of an infarct.
The patient was started on empiric antibiotics of piperacillin/tazobactam and vancomycin, normal saline bolus of 30 cc/kg, and two units of packed red blood cells and admitted to the transitional care unit for further management of sepsis due to an unclear etiology. While on the floor, the patient became hypoxic and required noninvasive ventilation and was transitioned to intensive care unit. The following morning, a transthoracic echocardiogram revealed a medium-sized mobile vegetation on the body of the anterior leaflet of the mitral valve and severe mitral valve regurgitation. Both blood cultures were positive for S. gordonii, and antibiotics were deescalated to ceftriaxone and vancomycin based upon sensitivity analysis. The patient was transferred to a tertiary care center where he underwent a mechanical mitral valve replacement and was placed on ceftriaxone for six weeks. |
pmc-6594297-1 | An eight-year-old boy was referred to our department (Clinica Odontologica de la Universidad Europea de Valencia) for an orthodontic consultation. The patient had a Class I canine occlusion on both sides, increased overjet, and moderate crowding in the anterior segments in both the upper jaw and the lower jaw. The lower-left first molar (4.6) appeared tipped forward in the space of the second deciduous molar (8.5).
Severe caries were affecting the second deciduous molars in the upper jaw (5.5 and 6.5), and ectopic eruption of the first permanent molars (1.6 and 2.6) could be diagnosed from a clinical examination ().
A radiographic examination was carried out to check the eruption process and the maturation stage. From the orthopantomogram (OPG), the second deciduous molar on the right side (8.5) appeared to be totally submerged ().
On the basis of the clinical and radiologic assessments, the extraction of the 8.5 was planned in order to prevent impaction of the permanent successor. An appropriate space regaining strategy had to be carried out to gain access to the infraoccluded tooth and facilitate its extraction. Due to the high risk of caries of the patient and not wanting to rely on his collaboration, we designed minimally invasive mechanics to carry on the space regaining procedure.
A band with a double buccal tube was fitted on the permanent molar, and a .014-inch round NiTi wire (Highland Metals Inc., Franklin, IN) was compressed in between the first permanent molar and the first deciduous molar using the described procedure.
The following are the steps of the clinical procedure ():
A piece of .014 NiTi wire is cut and bonded with flowable composite to the buccal surface of the first permanent molar. It is very important to bond the wire perpendicular to the main tooth axis. (In this case, a band was used to improve stability, and the buccal tube was perpendicular to the main tooth axis) (Figures and ) The arch wire is then bonded to the surface of the mesial tooth, and also in this case, it is very important to bond the wire perpendicular to the main tooth axis to improve the uprighting moment of the mechanics. To avoid the bond between the flowable composite and the archwire, the latter is isolated with liquid Vaseline () The wire is then compressed by pulling it down and distally, and then, a loop is formed between the mesial tooth and distal tooth (Figures and ) The wire extending from the mesial tooth is then cut flush and sealed with some flowable composite to prevent it from coming out from the mesial end (Figures and ) The compressed wire gently recovers the original straight shape delivering a reciprocal sagittal force and two uprighting moments on the mesial and distal units of the system (Figures and )
The mechanics did not need reactivation, and after three months, the space was recovered and the extraction of the second deciduous molar was performed ().
At this stage, a stiffer .018 Green Australian archwire (A.J. Wilcock Scientific and Engineering Company, Whittlesea, Victoria, Australia) was bonded instead of the NiTi one in order to maintain the space for the eruption of the second premolar (Figures and ).
One year later, the second premolar erupted. The final OPG shows the eruption of the second premolar, the uprighting of the first permanent molar (with no side effects on the eruption of the first premolars), and the canine on the same side (). |
pmc-6594310-1 | A previously healthy 52-year-old Samoan woman initially presented to her primary care provider with complaints of otalgia and swelling in the left side of her face for three weeks. She reported no facial weakness, trismus, dysphagia, odynophagia, dental pain, fevers, chills, weight loss, and fatigue. On initial physical exam, a 6 cm nontender, subcutaneous, cystic mass was palpated in the left parotid. The oral cavity showed no deformities or evidence of abnormalities. There was no lymphadenopathy of the anterior or posterior cervical chain, supraclavicular, or axillary lymph nodes. At that time, she was prescribed with antibiotics for presumed sialadenitis with no effect on her symptoms. On the next follow-up visit, she was referred to otolaryngology for further evaluation.
A neck and chest computer topography (CT) scan demonstrated two necrotic left parotid masses measuring 2.5 × 2.8 cm and 2.7 × 2.8 cm, respectively, multiple ipsilateral lymph nodes measuring up to 1.9 cm in diameter, and an asymmetrically enhancing left nasopharynx. A fine needle aspiration (FNA) of an involved local lymph node revealed a nonkeratinizing, undifferentiated carcinoma composed of pleomorphic cells positive for Epstein-Barr virus (EBV). The differential diagnosis based on FNA findings includes primary parotid carcinoma, lymphoepithelial carcinoma, or metastatic nasopharyngeal carcinoma. Blind biopsies of the nasopharynx were negative. PET/CT revealed hypermetabolic activity in the left parotid gland and several local nodes, highly suggestive of a primary parotid neoplasm. Excisional biopsy revealed a nonkeratinizing, undifferentiated carcinoma composed of pleomorphic cells, positive for Epstein-Barr virus (EBV). The results of subsequent excisional biopsy of the parotid gland masses were consistent with previous FNA findings.
The patient was staged as Stage IVa (cT3N2bM0) per AJCC 7th ed. Due to the extension of the parotid disease toward the main trunk of cranial nerve (CN) VII, there was a concern for postoperative CN VII palsy with surgical management. Surgery was therefore deferred, and definitive cisplatin-based concurrent/chemoradiation treatment was initiated. On first surveillance PET/CT, at 12 weeks postconcurrent chemoradiation treatment, she was found to have PET-avid hepatic and bone lesions (). A CT-guided portacaval lymph node biopsy confirmed a metastatic disease (). IHC staining of the portal cava lymph node demonstrated 100% PD-L1 expression. Next Generation Sequencing was negative for additional mutations. Pembrolizumab monotherapy resulted in a near complete resolution of her hepatic metastasis and complete metabolic resolution of the left parotid mass, cervical adenopathy, and skeletal lesions on PET/CT following four cycles (). Follow-up PET/CT scan found a progression of disease per RECIST v1.1 criteria after seven months of treatment. |
pmc-6594314-1 | A 45-year-old obese postmenopausal female with a history of coronary artery disease (CAD), hypertension, hyperlipidemia, diabetes, and chronic angina was brought to the Emergency Department midsummer after a motor vehicle accident (MVA) in which she was the restrained driver. While stationary, she was struck by another vehicle from behind at a high rate of speed with immediate airbag deployment. Though the patient did not lose consciousness at the scene and had self-extricated prior to EMS arrival, she requested hospital transport for further evaluation of chest, neck, and back pain. On initial evaluation, the patient complained of chest pain primarily across her left chest and shoulder in a seatbelt-type distribution, though she did also endorse some bilateral chest wall pain, diffuse midline neck pain, and low back pain.
In addition to her cardiac risk factors, her medical history was significant for anxiety, gastroesophageal reflux disease (GERD), migraines, and fibromyalgia. Her home medications included escitalopram, buspirone, pantoprazole, ranitidine, aspirin, clopidogrel, evolocumab, and isosorbide mononitrate. She had an extensive surgical history including a total abdominal hysterectomy, bilateral salpingo-oophorectomy, coronary artery bypass grafting (CABG), and placement of coronary stents. She denied current use of tobacco, alcohol, or illicit drugs. She had just been admitted to the hospital for unstable angina a few months prior, at which time cardiac catheterization was performed, demonstrating three patent bypass grafts: right internal mammary artery (RIMA) to left anterior descending artery (LAD), left internal mammary artery (LIMA) to obtuse marginal artery, and a saphenous vein graft from the proximal aorta to the proximal right coronary artery (RCA). One saphenous vein graft from the posterior descending artery (PDA) to the posterolateral ventricular artery segment was occluded, though this was not a new finding as it was first discovered to be occluded several years ago. Both previously placed drug-eluding stents in the second marginal and left circumflex arteries were widely patent. The catheterization also demonstrated severely diseased and diffusely calcified coronary arteries, with 95% occlusion in the proximal LAD and 100% occlusion in both the first marginal artery and the mid to distal RCA. Of note, her stenosis had worsened since her last catheterization one year earlier, which showed 70% occlusion in the mid-LAD, 90% occlusion in the distal LAD, and 90% occlusion in the mid to distal RCA. No intervention was performed during either catheterization procedure.
Physical exam revealed that the patient was in notable distress and had diffuse midline spinal and paraspinal tenderness, as well as chest wall tenderness. Her pulse was 100/minute, temperature 37.6°C, blood pressure 157/119 mmHg, respiratory rate 16 breaths/min, and SpO2 99% on room air. Chest radiographs and head computed tomography (CT) scans were unremarkable, and the aorta had a normal course and caliber on thorax CT scan. Electrocardiogram (EKG) was also unremarkable, without any ST depression or elevation, T wave inversions, or QTc prolongation noted. Laboratory workup revealed an elevated troponin-T level at 0.564 [normal <0.010]. The patient was not hyponatremic. Three hours later, her troponin-T level decreased to 0.459. BNP, CK, and lactate levels were not obtained.
Cardiac contusion secondary to blunt chest trauma from the MVA was suspected as the initial diagnosis. The patient was admitted to the acute cardiology service and underwent a transthoracic echocardiogram the following morning, which demonstrated reduced systolic function with an ejection fraction of 35%, diffuse areas of mid to apical hypokinesis, and hyperkinesis in the anterior and inferior basal segments (). Previous echocardiograms completed three months and one year prior to this episode did not show these abnormalities; those studies lacked wall motion abnormalities and demonstrated normal systolic function with ejection fractions of 60% and 65%, respectively. Thus, these new wall motion abnormalities and reduced systolic function in conjunction with elevated cardiac enzymes, a normal electrocardiogram, and the patient's clinical presentation were consistent with a diagnosis of stress-induced cardiomyopathy.
She was started on a beta blocker and discharged the next day. A follow-up echocardiogram four months later demonstrated return of systolic function with an improved ejection fraction of 55% and normal wall motion, indicating complete resolution. |
pmc-6594316-1 | An 89-year-old male with no history of cutaneous malignancies was referred to General Surgery for evaluation of a persistent nodule on the skin of the right perianal region that he had noticed for more than a year. Past medical history was significant for gastric lymphoma (non-Hodgkins follicular type, with spontaneous remission).
He palpated the perianal lesion while cleaning the skin in this region. The lesion was not associated with bleeding, oozing, pain, or itching. He denied any concomitant skin lesion or rashes. He also denied fever, chills, or abdominal symptoms. On physical exam, a single small 0.5 cm cutaneous nodule with central dimpling and no discoloration was visualized in the perianal region. No concerning lesions were palpated on digital rectal exam. An excisional biopsy of the nodule was performed for histopathological examination.
Microscopic exam confirmed the diagnosis of perianal BCC, nodular type (). Histopathology revealed a lesion strongly and diffusely positive for immunohistochemical staining of smooth muscle actin (SMA) () and negative for carcinoembryonic antigen (CEA) and pancytokeratin (AE1/AE3), supporting the diagnosis. Staining for epithelial membrane antigen (EMA) was negative in the tumor cells while monoclonal antibody BER-Ep4 displayed strong and diffuse positivity, further supporting the diagnosis (). The patient responded well to excision of the lesion and no further treatment was required. |
pmc-6594322-1 | A 74-year-old Caucasian male was referred to the Periodontics Clinic of the Dental College of Georgia, Augusta University, Augusta, Georgia, in May of 2015, with a chief complaint of “something has poked through my gum.” The patient had been on a routine three-month maintenance cycle and reported no previous incidence of the condition, which had been present approximately six months. The medical history review was remarkable for hypertension, hyperlipidemia, and implanted artificial pacemaker and noncontributory social history (no use of gutka products). Current medications included metoprolol, amlodipine, losartan, ezetimibe/simvastatin, and aspirin daily. Clinical examination revealed a 3 × 5 mm fenestration through the facial gingiva at tooth #11 (). Patient reported daily brushing and flossing using an extra soft toothbrush that was routinely changed at each hygiene appointment. Oral hygiene instructions were reinforced and reviewed at each appointment, and through demonstration, the patient exhibited proper brushing and flossing technique. All gingival probings were ≤3 mm with no mobility, no suppuration or swelling present, and no decay detected, but there was a sharp, pointy edge of what appeared to be the coronal border of a NCCL (abfraction). Evidence of previous occlusal trauma to #11 was visible with blunted cusp tip and craze line; similarly, tooth #10 displayed a wear facet. The patient does not present with cuspid-protected occlusion. The tooth tested vital, and the lesion was asymptomatic, except for the noticeable perforation of the gingiva. A radiograph taken showed only mild interproximal horizontal bone loss ().
Various treatment options were discussed with the patient including no treatment, gingivectomy and direct restoration, gingival flap and odontoplasty, or connective tissue grafting (CTG) with odontoplasty, along with limited occlusal adjustment. The patient was thoroughly informed of all aspects of the treatment for this unique association between NCCL and GF. CTG was preferred to improve upon the patient's thin phenotype in order to address the patient's chief complaint. He was counseled and consented to surgical treatment to correct the soft tissue defect and odontoplasty of the root surface irregularity.
Occlusal adjustment was made on #11 cuspid until light occlusal contacts evenly distributed bilaterally. Under local anesthesia with 2% lidocaine and 1 : 100,00 epinephrine, a facial sulcular-modified papilla preservation incision was made from #10 to #12, and a mucoperiosteal flap reflected revealing a NCCL with prominent sharp edges at #11 (). The root prominence of the NCCL was reduced with high speed rotary instrumentation (), and the site prepared for soft tissue grafting. A connective tissue graft was taken from the left maxillary tuberosity region, and closure was obtained with 5-0 PTFE monofilament sutures after copious irrigation of the surgical site ().
The surgical site healed without complication. shows healing at 2 months with correction of the gingival perforation evident. An 18-month follow-up () reveals mature healing of the defect, and the patient has had no complaints. Noticeable from the 2-month to the 18-month postop is approximately 1 mm coronal gingival migration by “creeping attachment,” a phenomenon described by Goldman and Cohen []. |
pmc-6594337-1 | A 45-year-old man presented mobility of a metal-ceramic fixed bridge in the second quadrant after ten years of function (). After the exploration, the bridge and the pillar teeth were considered nonrestorable, and in the Cone Beam Computed Tomography (CBCT), a severe loss of the alveolar bone of the second quadrant is evidenced (). Extraction of the teeth, regeneration of the lost bone, and following rehabilitation with dental implants were the agreed treatment.
After the teeth extraction, we decided to wait a month to make sure the healing and stabilization of the soft tissues (). In a second surgery stage, we performed a regenerative surgery. A heterologous cortical lamina (OsteoBiol Lamina® from Tecnoss®) was decided to be used instead of other barrier techniques, such as a titanium mesh, because of its resorbable condition. The surgical procedure was as follows: (i) mucoperiosteal flap with vertical discharges (Figures , , and ); (ii) periosteoplasty techniques; (iii) decorticalization and bone collection with a bone scraper (); (iv) palatal fixation of the cortical lamina with two microscrews—no previously hydration is needed—(); (v) filling of the defect with mixture of autologous bone and heterologous bone (OsteoBiol Apatos® from Tecnoss®) (Figures and ); (vi) vestibular fixation with two microscrews; (vii) mesial sealing with heterologous collagen membrane and resorbable polyglycolic acid suture (Serapid® from Serag-Wiessner®) (); (viii) hydration with physiological serum prior to suture; and (ix) closure by first intention, without tensions, using monofilament suture, with simple and mattress stiches that relieve stress when inflamed (). Immediately after the surgery, a control orthopantomography was taken ().
The treatment was performed under antibiotic coverage with amoxicillin 750 mg (1 comp/8 h) 24 h before and 7 days later. 11.4 mg of postoperative intramuscular (gluteus) betamethasone was administered right after the surgery and dexketoprofen 25 mg (1 comp/8 h) was prescribed for 5 days. An antiseptic topical gel based on 0.2% chlorhexidine (one application every 8 hours) for 10 days was given to the patient. After 10 days, the suture was removed. During the bone healing period, the patient was told not to use any removable prostheses.
Six months after the surgery, a new CBCT was performed () for implant planning and three internal conical connection implants (Galimplant® Sarria, Lugo, Spain) were placed in positions 22, 24, and 25 (3.5 × 12 mm, 4 × 12 mm, and 4.5 × 8 mm, respectively), with an insertion torque of 30 N/cm (Figures and ). During this surgery, the microscrews that blocked the implant placement were removed.
After four months, prosthetic rehabilitation was made by another clinician in another dental office, and thus, the follow-up was not possible. |
pmc-6594495-1 | The patient, a 30-year-old Tibetan man, was treated in the Lhasa Hospital for right tibiofibular fracture December 2012 (Fig. ). After the swelling subsided, he underwent right tibia fracture intramedullary internal fixation. Two weeks after the operation, the patient was able to walk with double crutches without load, and was able to walk without crutches and with some load 3 months after the operation. However, the patient complained of pain in his right lower extremity, especially when moving downhill or down stairs, and experienced a limping gait and obvious tenderness at the fracture end. Three years after originally presenting at Lhasa Hospital, the patient was experiencing persistent pain in the right lower extremity, and his daily activities were severely affected. Thus, he was re-diagnosed with nonunion of the right tibial fracture after internal fixation (Fig. ). The main causes of the nonunion of the fracture were considered to be the excessively thin intramedullary nails and unstable fixation of the fracture. The operation was repeated with replacement of the crude intramedullary nails and grafting of iliac bone (Fig. ). Three months after the operation, the tibial fracture had failed to heal, and further surgical treatment was performed. The proximal locking screw of the intramedullary nail was removed with an expectation to eliminate the stress shielding effect and to promote fracture healing by increasing the microdynamic force while retaining the static interlocking nail. Five months after the operation, the patient abandoned the crutches and was able to walk with a heavy load. Nevertheless, 2 years after the operation, active pain of the right leg persisted with some tenderness around the fracture, especially when moving downhill or down stairs. August 2018 the patient was admitted to our hospital. Physical examination revealed that two old incision healing scars, approximately 2 cm in length, were present at the proximal and distal ends of the right tibia. The middle section showed a scar from an approximately 10-cm incision; pigmentation was found around the incision and tenderness was experienced around the fracture. Imaging results revealed a nonunion of the right tibial fracture, and the admission diagnosis was nonunion of the right tibial fracture after surgery (Fig. ).
Two days after admission, “right tibial locking intramedullary nail removal, open reduction and porous tantalum metal plate fixation” was performed. After removal of intramedullary nails during the operation, nonunion of the tibial fracture was corrected and osteoporosis of the fracture end. Osteosclerosis of the fracture was observed, and the sclerotic bones as well as part of the hyperplastic epiphysis were removed; the marrow was reamed at the fracture to keep the medullary cavity open. The resected osteophytes were implanted into the fracture, followed by fixation with a porous tantalum plate.
After the operation, the affected limbs were fixed with plaster. Ankle joint activity training was initiated on the first day after the operation, and knee joint activity training began 2 weeks after the operation. The patient was able to walk with double crutches without load 4 weeks after the operation and could perform normal activities 12 weeks after the operation without pain in the right limb. However, slight tenderness was still experienced around the fracture. Five months after the surgery, the right tibial fracture had healed, based on imaging examination, and the tenderness around the fracture had disappeared; the patient was able to work normally (Fig. ). |
pmc-6595020-1 | A 67-year-old female with Sjögren’s syndrome was found to have multiple pulmonary nodules in both lungs on chest computed tomography (CT) (Fig. a–c), because she was found with multiple pulmonary nodules on chest x-ray. She had a history of hypertension and osteoporosis. No increase was observed in the levels of tumor markers, such as carcinoembryonic antigen and squamous cell carcinoma antigen. Pulmonary functions were within normal limits. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed FDG accumulation in all pulmonary nodules (Fig. d). A transbronchial biopsy results in alveolar tissue showing interstitial fibrous thickening and lymphoid cells infiltrations. Since it did not result in a definitive diagnosis, the patient was admitted to our department for a surgical biopsy. Because a substantial amount of tissue is essential for the diagnosis, CT-guided lung biopsy was not performed. Wedge resection was performed for pulmonary nodule located beneath the pleura of left lower lobe. The nodule was gray, elastic, and hard. Intraoperative frozen-section analysis was performed that suspected amyloid nodule with lymphoma. In a permanent pathological section, eosinophilic deposition with lymphoplasmacytic infiltration was noted (Fig. a). Because the eosinophilic deposition stained positive with Congo red (Fig. b), a diagnosis of amyloidosis was established. In addition, immunostaining for AE1/AE3 and CD20 revealed extensive infiltration of B cells to the bronchial epithelial cells (lymphoepithelial lesion) (Fig. c). B cells with monoclonal proliferation predominantly had a κ chain by in situ hybridization (κ chain: λ chain ratio, 20:1) (Fig. d, e). The findings of immunohistochemical staining were as follows: CD3 (+), CD20 (+), CD138 (+), bcl-2 (+), CD5 (−), CD10 (−), CD23 (−), CD56 (−), and cyclin D1 (−). This nodule was diagnosed as mucosa-associated lymphoid tissue (MALT) lymphoma. The postoperative course was uneventful. She was discharged on the fourth day after surgery and received chemotherapy for MALT lymphoma at another hospital. |
pmc-6595100-1 | We report a case of a 66-year-old male with minimal co-morbidities who presents with lower trunk flat back deformity, severe iatrogenic kyphosis and sagittal imbalance following 9 months postoperative lumbar decompression and fusion (L2-L5) with postero-lateral grafting, without inter-body implants from a different institute. He experienced significant pain due to L4 and L5 motor / sensory radiculopathy. Reflexes were absent in both lower limbs with a bilateral foot drop. Oswestry Disability Index was 74%, with Visual Analog Scale pain score of 10 in the standing position, 8 on lying flat.
Computed tomography (CT) scan revealed loosening and non-union of the inferior aspect of the fusion construct. There is pull-out of the inferior screws (Fig. A) with haloing around the body and distal aspect of the pedicle screws. (Fig. ). Standing EOS scan reveals gross sagittal imbalance. The kyphotic angle due to the construct failure at L3/4 level was approximately 45°. A flat back deformity can be seen along the vertebral levels above the level of screw pull-out. Bone mineral density was normal for his age. Figure A shows the pre-operative presentation, with significant sagittal plane deformity and bent-knees in order to maintain a gaze along the horizon while requiring a walking aid for ambulatory.
The haloing effect demonstrated by the pedicle screws is consistent with hardware failure, and also seen in the “PEEK-Halo” effect when PolyEther-Ether-Ketone (PEEK) is being used as an intervertebral implant which results in poor osseointegration. However, in this case, the poor osseointegration was a result of repetitive screw cranial-caudal micromotions and toggling which prevent consistent screw – bone contact but not due to hardware material.
A revision procedure utilizing both anterior and posterior approach was carried out (Fig. ). Lordosis was restored utilizing 2 anterior lumbar interbody fusion (ALIF) cages (L3/4 and L4/5 levels) and Posterior Smith-Peterson osteotomy at L3/4. Focal lordosis of approximately 22o was corrected resulting in a total correction of over 65 degrees at L3/4. The patient was able to stand up-right which enabled him to maintain his view on horizon when his spine was in a neutral position. Figure B shows patient post-op with a corrected posture requiring no walking aids to ambulate. |
pmc-6595109-1 | The patient was a 73-year-old Chinese woman with osteoarthritis in both knees. In the recent half year, she had been suffering from intractable right knee pain with failed conservative treatment and prepared for right side TKA. She had a 27-year history of hypertension and her blood pressure was controlled well by medication. She had no other medical history, including smoking history. Her BMI was 24. The physical examination showed a limited range of motion (ROM) of 0°–120° without varus or valgus deformity. Preoperative X-ray showed narrow medial knee joint space and osteophyte formation without vascular calcification (Fig. ). The peripheral pulses and capillary refill were normal, although the preoperative Doppler ultrasound showed arteriosclerosis with plaque formation in the arteries in both legs.
The right side TKA with a posterior stabilized design (LPS, NexGen, Zimmer, Warsaw, USA) was performed under general anesthesia. A tourniquet was applied for 70 min at a pressure of 250 mmHg. The whole surgery was completed without any complications and there was normal intraoperative bleeding at the surgical site. The postoperative X-ray showed successful implantation for the right knee (Fig. ).
However, immediately after the surgery, routine peripheral pulse check in the operating room found absent dorsalis pedis artery pulse in the right foot. The patient was closely monitored in the recovery room. After approximately 2 h, there was no improvement in peripheral pulses, capillary refill, and oxygen saturation. In consideration of the high possibility of arterial occlusion, the vascular consultant recommended using 1000 U heparin for anticoagulation and immediate evaluation by arteriography for diagnosis. An emergency arteriography under local anesthesia showed that there was a short segmental occlusion of the popliteal artery (Fig. ). Then the angioplasty was performed with a balloon with a diameter of 5 mm for 3 min. Follow-up imaging showed excellent blood flow although vascular stenosis was still observed in popliteal artery (Fig. ). There was a return of palpable pulses and a normal capillary refill and oxygen saturation.
After the patient returned to the ward, 12 500 U heparin in 50 mL saline was pumped 1 mL/h and activated partial thromboplastin time (APTT) was controlled around 40 s. The peripheral pulses were closely monitored. On postoperative day 2, the patient was allowed to walk with aids. On postoperative day 6, the anticoagulation plan was changed to rivaroxaban 10 mg two times a day and aspirin 100 mg one time a day for 3 weeks orally. The patient was discharged home 2 weeks after surgery without any complaints.
At the most recent follow-up in the orthopaedic clinic (3 months after surgery), there were no orthopaedic or vascular complaints. The patient had an ROM of 0° to 125° with excellent muscle strength and could walk without aids for 1 km. |
pmc-6595352-1 | A 51-year-old white male, with a past medical history of hypertension and hypothyroidism, presented with a 12-day history of shortness of breath, cough, and fever with new onset lower extremity swelling, orthopnea, paroxysmal nocturnal dyspnea, and dyspnea on exertion. He was seen by his primary care physician approximately one week ago and started on azithromycin, but did not improve. He had also been taking 5 mg of motrin and had used 30 tablets of motrin in the past week. His other medications included amlodipine 10 mg once daily and levothyroxine 50 mcg once daily. He was afebrile on initial presentation. Physical exam was pertinent for rales auscultated in the left lower lung base. EKG only pertinent for sinus tachycardia with no ST segment changes. His initial labs were pertinent for findings of new onset acute renal failure with a creatinine (Cr) of 3.4 mg/dL, microscopic hematuria and proteinuria on urinalysis, with urine protein: creatinine ratio of 1.34 g/gCr. He had appreciable leukocytosis with white blood cell count of approximately 20k. CT chest revealed small to moderate sized bilateral pleural effusions and moderate to large sized pericardial effusion. He was admitted to the inpatient service. Over the next 48 hours, he developed worsening shortness of breath, hypoxemia, and pericardial tamponade with echocardiogram (ECHO) revealing a worsening large circumferential pericardial tamponade in comparison to an ECHO done the previous day. ECHO also noted paradoxical septal motion during cardiac cycles with diastolic collapse of the right ventricle and right atrium. Pericardiocentesis was performed and approximately 500 mL of serosanguinous fluid was drained from the pericardial space with noted improvement in the patient's blood pressure and heart rate (see Tables and for pericardial studies).
Further workup revealed positive autoantibodies for c-ANCA (1:160), ANA (1:1280) and PR-3 (>100). Anti-SSA (Sjogren's Syndrome–A), anti-SSB (Sjogren's Syndrome–B), anti-dsDNA (double stranded-DNA), anti-Smith, anti-RNP (ribonucleoproteins), and anti-GBM (glomerular basement membrane) were reported negative (). This prompted a renal biopsy which revealed fibrinoid necrosis, capillary wall rupture, fibrin formation, and cellular crescents consistent with rapidly progressive crescentic glomerulonephritis (). Examination of provided electron microscopy images showed 2 glomeruli which revealed no evidence of immune type electron dense deposits in the glomeruli, tubular basement membranes, or the interstitium ().
Normal findings on electron microscopy were thought to be related to sampling error. Immunofluorescence revealed pauci-immune pattern. Based on the renal biopsy, he was diagnosed with PR3-ANCA related pauci-immune glomerulonephritis with extra renal manifestation of pleuropericardial disease progressing to pericardial tamponade. Patient then received pulse steroids and a dose of rituximab. BUN and Cr were 91 mg/dL and 3.2 mg/dL after getting this treatment. He was then discharged after one week of inpatient stay with plans to slowly taper steroids and to continue with weekly rituximab injections.
However, BUN/Cr worsened over the course of the next week to 176 mg/dL and 8.6 mg/dL, and thus he was concluded as rituximab failure and started on cyclophosphamide and plasmapheresis in the inpatient setting.
An ECHO done on readmission showed a small fibrin filled pericardial effusion which required no clinical intervention. Chest X-ray (CXR) on readmission showed stable opacity consistent with prior pleural effusion. Pericardial effusion remained stable in size and patient remained asymptomatic when ECHO was repeated 10 days after readmission. After 7 sessions of plasmapheresis and treatment with 1200 mg IV cyclophosphamide, his creatinine stabilized at 1.7 mg/dL (). |
pmc-6595384-1 | The patient is a 31-year-old African American pregnant female who presented with polyuria, constipation, myalgia, fatigue, and excessive nausea and vomiting. The transvaginal ultrasonography confirmed the pregnancy at 6 weeks 5 days. The laboratory results on presentation were significant for high calcium at 14.1 mg/dL and high PTH at 622 ng/L. Her neck ultrasound revealed homogenous echotexture of thyroid glands and a complex cystic nodule in the posterior inferior part of right lobe. FNA of that nodule was performed, and the patient was transferred to our facility for better management. The surgical removal of the tumor was done during the 1st trimester at the 7th week. According to the operation note, the tumor was a 5 cm rock hard mass, adherent to the surrounding strap muscles. The PTH level dropped significantly from 807 ng/L to 35 ng/L after parathyroidectomy. The parathyroid specimen was received in a fresh state at the frozen section room. The size of the tumor was 5 × 4 × 3 cm and the weight was 37 grams. It was a relatively circumscribed, reddish brown, soft, and partially cystic tumor. Serial sectioning revealed that the tumor had an irregular thick capsule and it was adherent to the surrounding strap muscles.
The tumor had both solid and cystic areas filled with thin blood-tinged fluid (). Representative sections of the tumor and the whole capsule were submitted for histological examination. Microscopically, the tumor was surrounded by the thick capsule, demonstrated with a blue arrow (). The tumor cells were arranged in nests and cords and were composed of multiple cell types, predominantly chief cells.
Bizarre atypical cells were frequent with nucleomegaly and hyperchromasia (). The tumor demonstrated increased capillary vascular proliferation, but no definitive vascular invasion was noted (). Careful examination of the thick capsule revealed surrounding chronic inflammation, extensive foreign body type reactions with cholesterol clefts, and variable entrapped groups of normal appearing parathyroid cells (). The adherence to the capsule continued up to the surrounding strap muscles, and a possible needle tract from previous FNA procedure was noted (). The tumor cell mitotic activity was low and the immunohistochemistry with Ki-67 showed low proliferation index, <1%. The tumor cells were mostly negative for BCL-1 immunostain. A diagnosis of giant parathyroid adenoma with nuclear atypia was made. The slides were sent to a reference facility for a second opinion, and the consulting pathology experts concurred with our diagnosis. The patient had been followed up regularly with obstetrics, oncology, and endocrinology clinics. She was compliant with her prescriptions of calcium and vitamin supplementations. She had a normal delivery of a healthy infant. Her most recent laboratory work showed normal calcium levels. The patient has been generally doing well, denying any nausea, vomiting, constipation, diarrhea, fever, or pain. |
pmc-6595396-1 | A 13-year-old Hispanic male with a history of ulcerative colitis, diagnosed 2 years previously and marginally controlled on 6-mercaptopurine, presented to the emergency department with 1 week of abdominal pain, vomiting, and worsening hematochezia. He was found to have significant anemia (Hgb of 3.9 g/dL), thrombocytopenia (platelet count of 54 × 109/L), and acute kidney injury (AKI) (serum creatinine of 1.8 mg/dL, BUN of 25 mg/dL) on presentation. His serum C3 level was normal and his serum C4 level was slightly low at 13.0 mg/dL.
The anemia, thrombocytopenia, and AKI were initially attributed to his ongoing gastrointestinal bleeding and acute tubular necrosis, but the hematologic abnormalities were refractory to 9 units of packed red blood cells and 3 units of platelets given during the first 6 days of admission. Stool culture obtained at time of presentation was negative for organisms producing Shiga-like toxin. Further workup revealed an elevated lactic acid dehydrogenase (LDH) (818 units/L), a low haptoglobin (< 6 mg/dL), normal ADAMTS13 activity level (68%), positive direct Coombs test, and presence of platelet autoantibodies. Given the presumed autoimmune etiology of the hematologic abnormalities, the patient was treated with 1 dose of 1 g/kg of intravenous immunoglobulin (IVIg) and then placed on 30 mg twice daily of methylprednisolone for 7 days, followed by an oral prednisone taper. However, his hemoglobin and platelet count continued to remain low with this therapy, and the patient subsequently received 6 treatments of therapeutic plasma exchange (TPE), over the course of which his hemoglobin and platelet count stabilized and slowly recovered to normal ().
However, his kidney function continued to worsen, with serum BUN and creatinine further increasing to 110 mg/dL and 4.5 mg/dL, respectively, by hospital day 11, necessitating the initiation of acute intermittent hemodialysis. A kidney biopsy was performed on hospital day 21 due to the lack of renal recovery. The biopsy revealed fibrin deposition and fragmented red blood cells within capillary loops and acute tubular injury consistent with thrombotic microangiopathy (). Eculizumab therapy was initiated for the diagnosis of aHUS with a standard weight-based induction dosing regimen of 900 mg weekly for 4 weeks, then receiving maintenance dosing with 1,200 mg biweekly. The patient’s urine output gradually increased during his induction dosing with eculizumab, and serum creatinine obtained prior to each hemodialysis treatment decreased steadily, until hemodialysis was discontinued 6 weeks after the initiation of eculizumab. The patient’s estimated glomerular filtration rate was 45 mL/min/1.73m2 at the cessation of dialysis.
Retrospectively, further studies of the complement system were performed on the patient’s serum sample that had been separated and stored at –80°C at the time of his admission, which revealed normal levels of factor H, factor B, and factor I. Testing was also negative for factor H autoantibodies. Sequencing of CFH, CFI, MCP, CFB, C3, and THBD genes as well as multiplex ligation-dependent probe amplification testing (MLPA) of the factor H-related genes CFHR1 and CFHR3 failed to identify any known mutations that have been implicated in the pathogenesis of aHUS. EDTA plasma was not obtained to facilitate testing complement activation fragments such as sC5b-9, Bb, and C3a.
The patient received 23 doses of eculizumab over a total course of 38 weeks. Given his unrevealing genetic assessment and ongoing requirement for intravenous access placement, the patient and his family elected to discontinue treatment. Since discontinuing eculizumab therapy, his hemoglobin and platelets have remained normal, and his renal function has improved, now with stable chronic kidney disease (CKD) stage II. His ulcerative colitis has also remained well-controlled on 6-mercaptopurine without any recurrent disease. |
pmc-6595396-2 | A 12-year-old previously healthy Caucasian male presented to the emergency department with a 1-day history of fever, abdominal pain, and acute onset of cola-colored urine. Laboratory testing revealed anemia (Hgb 11.0 g/dL), thrombocytopenia (platelet count of 25 × 109/L), and AKI (serum creatinine of 1.3 mg/dL, BUN of 41 mg/dL). The patient also had a mild coagulopathy, with an INR of 1.98. He was initially diagnosed with disseminated intravascular coagulation (DIC), thought to be secondary to an infectious etiology. However, infectious workup, including heterophile antibody test for EBV, blood and urine cultures, EBV PCR, CMV PCR, and HHV6 PCR, was negative for any known triggers of the DIC. Serum levels of C3 and C4 were normal. Several hours after admission, he developed respiratory distress, and a chest X-ray revealed diffuse bilateral infiltrates consistent with pulmonary edema. Due to the onset of additional end-organ involvement concerning for a multisystem disease, he was treated with TPE for the presumed diagnosis of thrombotic thrombocytopenic purpura (TTP), although pre-TPE ADAMTS13 activity and vWF multimer analysis were later found to be normal. The patient received 11 consecutive daily TPE treatments with fresh frozen plasma (FFP), followed by 3 additional TPE treatments with FFP on alternate days. The patient experienced an anaphylactic reaction during his 4th TPE treatment, but tolerated subsequent treatments without incident. The patient’s thrombocytopenia (A) and elevated LDH gradually improved and ultimately normalized by the 9th day of his TPE treatment course. Interestingly, his serum creatinine continued to rise after initiation of TPE (A), peaking at 2.7 mg/dL on the 3rd day of TPE treatment, then gradually improved, with renal function normalizing by the 9th day of treatment.
15 months later, the patient presented to the emergency department again with a 3-day history of fever, abdominal pain, vomiting, diarrhea, and dark cola-colored urine. Initial laboratory testing revealed recurrence of anemia (Hgb of 12.5 g/dL), thrombocytopenia (platelet count of 18 × 109/L/μL), and AKI (serum creatinine of 1.9 mg/dL, BUN of 55 mg/dL). ADAMTS13 activity was again obtained, and later found to be normal, but based on the severe thrombocytopenia and mild renal dysfunction, the patient was given a presumptive diagnosis of relapsed TTP. He received 8 consecutive daily treatments with TPE, followed by 3 additional TPE treatments on alternate days, with gradual improvement and ultimately normalization of his thrombocytopenia by the 5th day of his TPE treatment course (B), and his LDH by the 9th day of his course. With this occurrence of his relapsed thrombotic microangiopathy, his renal dysfunction worsened quickly despite initiation of TPE, with creatinine peaking at 3.6 mg/dL (B) and BUN peaking at 82 mg/dL and the development of oliguria on the second day of TPE treatment, necessitating a single hemodialysis treatment, then gradually improved, with renal function normalizing by the 6th day of treatment. As ADAMTS13 activity was normal on both occurrences of disease, complement testing performed later revealed normal serum levels of C3, C4, factor H, and factor I but reduced expression of MCP on peripheral blood mononuclear cells by flow cytometry to 52% of a control sample. Subsequent genetic testing revealed a heterozygous mutation (IVS2+2 T>G) in the gene for membrane cofactor protein (MCP), which is known to be associated with aHUS [].
Approximately 2 years later, the patient developed bloody diarrhea and weight loss. He underwent upper endoscopy and colonoscopy that showed colitis with granulomas consistent with Crohn’s disease. He was initially placed on steroids, with resolution of gastrointestinal symptoms. He remains in remission from aHUS and Crohn’s disease without any further immunosuppressant therapy. |
pmc-6595396-3 | An 11-year-old Caucasian male with a known history of aHUS originally diagnosed at the age of 6 years was treated previously with multiple episodes of plasma therapy and transitioned to eculizumab according to the manufacturer’s recommendations at the time of a disease relapse associated with a blood catheter infection. His platelet count, hemoglobin, and hematocrit normalized within 30 days of starting eculizumab. The patient’s genetic assessment revealed no mutations in the currently identified genes associated with aHUS. The patient carried an additional diagnosis of iron deficiency anemia.
After ~ 1 year of eculizumab therapy, the patient presented again with worsening anemia in the absence of overt hemolytic parameters (negative direct Coombs, high haptoglobin, normal platelet count and LDH) but with elevated inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). Additional workup revealed persistence of iron deficiency and worsening of his microcytosis (MCV 71 fL). Due to the worsening anemia without apparent etiology and a modest increase in C5 function indicating breakthrough of his terminal complement blockade despite standard eculizumab dosing, an eculizumab level was tested and found to be in the therapeutic range. No changes in the patient’s anti-complement therapy were made. One month after initial presentation with microcytic anemia, the patient developed diarrhea, with stools positive for occult blood. Upper endoscopy and colonoscopy revealed terminal ileal disease consistent with Crohn’s disease. The patient was placed on mesalamine and infliximab with clinical improvement.
He remains on a combination of eculizumab, mesalamine, and infliximab, with no evidence of aHUS recurrence. His family history is significant for a brother who also has IBD, but there is no family history of aHUS. |
pmc-6595549-1 | An 11-year old boy came to our attention, presenting with acute onset of simple and complex motor tics, oral tics, obsessions and compulsions (fear of contamination, aggressive behaviour, superstitions, repetitive compulsions, religious compulsions, etc.), irritability and anxiety. A deterioration in writing (micrographia) was also observed.
The boy had been delivered at term after an uneventful pregnancy, and developmental milestones were reached at normal ages. Birth weight was 3.200 g emotional and social development within normal range. At 6 years of age, the parents noticed a subtle beginning of tic disorders, which slowly disappeared.
In regard to family history, the patient’s father suffered from OCD and tics during childhood, while his mother suffered from thyroid cancer, Hashimoto’s thyroiditis and depression.
The boy suffered from recurrent familial streptococcal infection, celiac disease was also diagnosed.
Due to elevated Antistreptococcal (ASO) (650 UI nv 0–200) and antiDNAse titres (950 UI nv 0–300), associated with positive swab test for streptococcal infection during exarcebation together with the abrupt onset of clinical presentation, a diagnosis of PANDAS syndrome was made. The boy underwent treatment with antibiotics (oral amoxicillin), followed by prophylaxis with penicillin (1.200,000 UI every 21 days). From 2016 until 2017, the patient received prophylactic treatment, and an adenotonsillectomy was performed in 2016. The patient’s clinical condition was stable, with slight improvement in accordance with the relapsing-remitting course.
During the period of observation, the boy does not show a complete remission of the symptoms, that worsened during infection sometimes associated with positive swab test for streptococcocal infection; also ASO and antiDNAse titres remain elevated (530 UI and 900 UI respectively).
The boy underwent a full neuropsychological evaluation, including the Child Behavior Checklist (CBCL)(6–18 years), Conners’ Parent Rating Scales Long Version (CPRS-R:L) Yale Global Tic Severity Scale (YGTSS) and Child Yale-Brown Obsession and Compulsion Scale (CY-BOCS).
The results of EEG and MRI scans were normal, with no basal ganglia alterations and a normal cortical structure.
Due to poor response to prophylaxis with penicillin, PMT was performed with the parents and child, followed by individual sets of EMDR.
The work with EDMR was initially focused on acute episodes related to tics. The installation of resources favoured the transition from an external to internal focus, with the creation of new coping strategies that were more adaptive than previous ones.
Before EDMR treatment, the boy was assessed according to the YGTSS and CY-BOCS, and then re-examined with the same scales after a 6-month follow-up period. The scores are presented in Table .
The boy showed great improvement in motor and vocal tics following treatment, in addition to a marked reduction in obsessions and compulsions. At present, after 2 years of follow-up, he has completed EMDR treatment with great clinical improvement. No more tics or obsessive compulsion disorders were noticed. He is not currently receiving prophylactic treatment. In addition, ASO and antiDNAse titres are within normal ranges.
In the present case, treatment with EMDR was proposed, with the aim of reforming the patient’s unfavourable experiences and improving his coping strategies.
The EMDR procedure consists of eight stages. The 8 stages consist of:Phase 1 - History taking: obtain background information, identify suitability for EMDR treatment. and identify processing targets from events in client’s life according to standardized three-pronged protocol; Phase 2 - Preparation: prepare appropriate clients for EMDR processing of targets; Phase 3 - Assessment: access the target for EMDR processing by stimulating primary aspects of the memory; Phase 4 - Desensitization: process experiences toward an adaptive resolution (no distress); Phase 5 - Installation: Increase connections to positive cognitive networks; Phase 6 - Body Scan: Complete processing of any residual disturbance associated with the target; Phase 7 - Closure: Ensure client stability at the completion of an EMDR session and between sessions; Phase 8 - Reassessment: Ensure maintenance of therapeutic outcomes and stability of client. (Shapiro 2014).
After taking the patient’s history, explaining EMDR and identifying the most distressing seizure-related memories (i.e., target selection), the target image(s) are processed consecutively. The therapist asks the patient to keep the disturbing target memory and aspects related to it in mind, while simultaneously performing a distractive task introduced by the therapist. The child is asked to follow the therapist’s finger, making saccadic movements at a rate of about two stimuli per second for approximately 30 s. In the case of problems with eye movements, auditory bilateral stimulation or tactile stimulation is used. The child is then asked to briefly report what comes to mind (associations). The procedure is repeated until the original target is no longer disturbing, and dysfunctional cognitions regarding the trauma have become functional [].
Upon completion of the eight phases, we proceeded with the Installation of the Resources and with the Future Model, where the patient is asked to project themselves into the future problematic situations and imagine using the new resources installed.
Parent management training is a training and information course (training) which is focussed on the parents. In recent years, our clinical knowledge concerning behavioural disorders during development has increased, and interventions have moved toward integrated clinical interventions that involve the parent(s) as an active part of the treatment. Parent training aims to establish an active collaboration of parents through appropriate training and training procedures. It is based on the theory of social learning, and has been implemented for uncooperative, oppositional children with behavioural disorders or attention-deficit hyperactivity disorder []. Currently, PMT is suggested as one of a large number of treatments that can be applied during the child’s development.
Parent training is applicable in all circumstances in which parents have to face an educational task with problematic children. The general objectives of the intervention involve informing parents about the manifestations of the disorder, the symptoms, and the vicious circuits that maintain them, thereby promoting acceptance of the diagnosis and collaboration between parent and child.
Parents are trained through the teaching of educational methods on functional analysis of behaviour in order to increase the educational skills best suited to the child. The aim is to improve the style of family communication, especially between parents and children. |
pmc-6595566-1 | A 48-year-old woman complained of dysphagia for 1 month. In April 2018, she underwent esophagogastroduodenoscopy in our hospital and an esophageal submucosal tumor (SMT) was discovered in the upper-mid esophagus about 22–24 cm from the incisors. Under white light endoscopy, this lesion was broad-based, poorly defined, sessile, and elevated in size of 1.5 cm in diameter. The overlying mucosal surface was pale-whitish gray without ulcer or erosion (Fig. a). The adjacent esophageal mucosa was normal. There was no evidence of simon-red mucosal metaplastic changes. No additional tumor was identified. The stomach and duodenum were normal. Further endoscopic evaluation of this esophageal lesion with endoscopic ultrasonography (EUS) demonstrated a hypoechoic mass with heterogeneous echo and microcystic features; signs for blood flow were absent. The lesion was located primarily in the submucosal space without involvement of the underlying esophageal muscularis propria (Fig. b). This submucosal lesion was considered clinically as a benign lesion that was completely resected by endoscopic submucosal dissection (ESD) for histopathologic diagnosis and to relieve the patient’s symptoms.
The resected lesion measured 1.5 × 1.2 × 1.0 cm in size and exhibited whitish-gray, polypoid gross appearances. After routine formalin fixation, the lesion was serially sectioned to show whitish-gray, soft and vaguely spongy cut surface. No solid tumor or nodule was noted. No necrosis/hemorrhage was identified. Microscopically, the lesion involved both lamina propria and submucosa, but not muscularis propria, and was composed of thin-walled, micro-cystically dilated lymphatic channels in various sizes, which were separated by delicate fibrous stroma (Fig. c). The lymphatic channels were lined by flat endothelial cells with occasional small lymphocytic aggregates present between channels (Fig. d). Within some lymphatic channels was amorphous lymphoid fluid. Hemosiderin deposition and blood vessels invested by smooth-muscle layers were absent. No dysplasia or malignancy was identified in the tumor or the overlying squamous epithelium. By immunohistochemistry with valid controls, the lymphatic channel lining cells exhibited diffuse immunopositivity for D2–40 (Fig. e), but focal positivity for CD34, and negativity for FVIII.
The patient post-ESD hospital course was uneventful. She was well at a 12-month follow-up without complaints. |
pmc-6595583-1 | An 82-year-old Japanese man with a history of RA presented with fever and malaise. His medical history revealed RA for 10 years. He had been undergoing treatment with MTX, prednisolone, and bucillamine for 9 years and 6 months (MTX 12 mg/week, prednisolone 2.5 mg/day, and bucillamine 100 mg/day). The MTX dose was initially 4 mg/week; however, the RA symptoms were not well controlled. Therefore, the dose was gradually increased to MTX 12 mg/week, and the total dosage was 3454 mg. Other medical history included benign prostatic hyperplasia and gout. He smoked cigarettes at 1.5 packs per day for 20 years but did not drink alcohol. His family history was unremarkable.
On presentation, he was alert, and his Glasgow Coma Score was 15. His body mass index was 23.7 kg/m2 with no noticeable body weight changes. He had a fever, but his other vital signs were stable: blood pressure, 128/57 mmHg; pulse, 88/minute; body temperature, 39.2 °C; respiratory rate, 18/minute; and oxygen saturation, 98%. No particular abnormal physical findings were noted other than chronic swelling of his wrists and ulnar deviation of his digits, although he was adequately treated. Furthermore, no enlargement of superficial lymph nodes was observed. Laboratory studies revealed findings of elevation of C-reactive protein (CRP) and soluble interleukin-2 receptor (sIL-2R). Serum hepatobiliary enzymes, rheumatoid factor, and anti-cyclic citrullinated peptide antibody were also elevated (Table ). Three months prior to the admission, his serum hepatobiliary enzymes were within normal range: aspartate aminotransferase, 20 IU/L; alanine aminotransferase, 18 IU/L; lactate dehydrogenase (LDH), 180 IU/L; γ-glutamyl transpeptidase, 26 IU/L; and alkaline phosphatase, 323 IU/L. No lymphoma cells were detected in his peripheral blood. Tests for viral markers revealed: hepatitis B surface antigen negative, hepatitis C antibody negative, and Epstein–Barr virus (EBV) viral capsid antigen antibody immunoglobulin G and EBV anti-Epstein–Barr nuclear antigen titers were elevated (1:320 and 1:20, respectively). Serum carbohydrate antigen 19-9, sialyl Lewis X-I antigen, and neuron-specific enolase were slightly elevated. Abdominal ultrasonography showed several hypoechoic masses in his liver. We performed contrast-enhanced computed tomography (CT) of his chest and abdomen to identify the cause of his fever, which revealed multiple nodular masses without enhancement in his lung, liver, spleen, and para-aortic lesions (Fig. ). He was admitted for further evaluation to make a definitive diagnosis.
Soon after admission, MTX was discontinued considering the possibility of MTX-LPD. The differential diagnoses included hepatic malignant lymphoma, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastatic liver cancers because sIL-2R and some tumor markers were elevated. Upper and lower gastrointestinal endoscopy were performed, but no malignant findings were noted. Although percutaneous liver biopsy was performed, it failed to approach the mass. Subsequently, endoscopic ultrasound-guided fine-needle aspiration biopsy for liver tumors was performed. Histological examinations of the specimens revealed cluster of differentiation 20 (CD 20)-positive B cell lymphocytes with necrotic tissue and no malignant findings (Fig. ). The EBV-encoded small ribonucleic acid by in situ hybridization of liver specimen was negative. The tumor began shrinking after MTX was discontinued, and CT of his lung and abdomen 3 months later revealed the disappearance of most of the tumors spontaneously and dramatically (Fig. ). Serum levels of sIL-2R, LDH, and carbohydrate antigen 19-9 also improved spontaneously (314 U/mL, 120 IU/L, and 74.3 U/mL, respectively), and serum levels of sialyl Lewis X-I antigen and neuron-specific enolase were normalized as well. Serum level of liver enzymes also became within normal range in our case. A definitive diagnosis of MTX-LPD was made based on the clinical course and pathological findings. After withdrawal of MTX, he started abatacept for his RA and experienced no deterioration in his joints. There has been no sign of recurrence for 6 months. |
pmc-6595610-1 | A 44-year-old male was admitted to the emergency department with sudden onset of severe mid-sternal chest pain radiating to the back. He did not report complaints of dysphagia lusoria or hoarseness. The patient was hemodynamically stable and the physical examination was unremarkable. Laboratory results showed no significant deviations. The patient has previously been followed for a bicuspid aortic valve, with yearly cardiac echocardiography. At the time of his current presentation a contrast-enhanced computer tomography (CT) scan revealed a contained rupture of a saccular aneurysm of the base of the left subclavian artery - 7 × 8.5 cm in diameter. The aneurysm extended to the transverse aortic arch with evidence of a large diffuse mediastinal hematoma, small left pleural effusion and bovine aortic arch (Fig. a, b). Cardiac echocardiography demonstrated a bicuspid aortic valve with moderate aortic regurgitation grade 2+: jet width 40% of LV outflow tract, regurgitate fraction 35%, end-systolic dimension 50 mm, end-diastolic dimension 65 mm, end-diastolic volume 150 ml/m2, end-systolic volume 55 ml/m2, LV EF 50%.. After reviewing the radiographic studies, the patient was urgently taken to the operating room.
The right axillary artery, left common carotid artery, left subclavian artery and left common femoral artery were exposed. Right auxiliary artery “chimney graft” was created using 8 mm Terumo (Terumo, Vascutek, Ann Arbor, MI) graft in an end-to-side fashion via right subclavicular incision. Next, left common carotid artery-left subclavian artery bypass was performed using an 8–mm Terumo straight graft with end-to-side (to the carotid artery) and end-to-end anastomosis (to the left subclavian artery). The left subclavian artery was completely divided, and proximal part was oversewn.
A median sternotomy was performed, great vessels were dissected, and the anatomy was confirmed. The area of contained rupture was distal to the origin of KD, originating at the base of the left subclavian artery and measuring 8.5 cm in maximum diameter. Heparin was introduced per weight protocol and the patient was placed on cardiopulmonary bypass with arterial access via the right axillary artery conduit and venous access in the right atrium. Systemic cooling was undertaken to 28 °C. Seldiger’s technique was utilized to gain percutaneous access via the left common femoral artery (CFA). This allowed us to use intravascular ultrasound and interrogate from the aortic root to the left CFA, confirming the distal aortic arch aneurysm and intact bovine aortic arch. The diameter of the ascending aorta was 38 mm and native descending aorta was 24 mm. Due to the lack of adequate “landing zone” proximally, the acuity of the situation and the patient’s age purely endovascular approach was not considered. After clamping at the base of the innominate artery under conditions of moderate hypothermia circulatory arrest (28 C), antegrade cerebral perfusion via the chimney graft was initiated.
After initiating circulatory arrest, the aorta was transected at the proximal level of the bovine arch. The bovine arch was detached from the arch and the stump was over sewn with 4–0 Prolene. This provided us with a reliable ~ 3 cm of landing zone. Over the previously placed “through-and-through” wire (Landerquist wire, Cook Medical, Bloomington, IN) from the left common femoral artery access to the aortic arch, we delivered the first endograft (Medtronic 28x28x150 mm, Minneapolis, MN), starting immediately at our newly created landing zone across the Kommerell diverticulum and into the healthy descending aorta. Next we sutured a 26 mm Terumo graft (with 14 mm side branch) to the proximal aortic arch. The Bovine arch was re-anastomosed to the 14 mm Terumo side branch, using 4–0 Prolene in end-to-end fashion. This was done in a way to provide 5 cm of distance from the debranched Bovine arch to the proximal extent of the first piece of endograft. Using the same “through-and-through” wire, we delivered the second piece endograft (28x28x150 mm, WL Gore Inc., Flagstaff, AZ), starting just distal to the debranched bovine arch, across through the previous arch anastomosis and into the first piece endograft, completing our hydrid arch repair, providing two layers of endograft material at the level of the transverse arch and across the base of the aneurysm.
An overlap of 4 cm between the Gore endograft and the 26 mm Terumo graft was secured. At least 8 cm of overlap was also assured between the two separate endografts. After de-airing, aortic clamp was applied proximal to the debranching 14 mm Terumo graft. Perfusion to the distal body with systemic rewarming was initiated. The ascending aorta was excised at the level of the sinotubular junction and send to pathology. The bicuspid aortic valve was reconstructed using subcommissural annuloplasty technique performed with 4–0 Prolene pledgeted felt sutures. A second piece of 26 mm Terumo graft was used to replace the ascending aorta. The anastomosis at the sinotubular junction was created in end-to-end manner using 4–0 Prolene suture. After adequate tailoring, required because of the cardiac dextrorotation with abnormal position for the aortic root (very deep in the posterior mediastinum), the neo-ascending aorta was anastomosed to the neo arch with 4–0 Prolene suture in a running fashion (Fig. ). After de-airing, the aortic cross clamp was removed. The patient was subsequently weaned off from cardiopulmonary bypass without difficulties. Time of circulatory arrest was 28 min. Cross-Clamp time was 95 min and cardio-pulmonary bypass time was 170 min. For cardioprotection, we utilized Del Nido solution delivered in retrograde fashion through the coronary sinus.
We did not use blood transfusion or pro-coagulants intraoperatively. No aortic insufficiency was revealed on postoperative transesophageal echocardiography. The flow velocity in the both vertebral arteries was normal. Due to apparent osteopenia, longitudinal, rigid sternal fixation was undertaken.
Postoperative course was uneventful and the patient was discharged on postoperative day 5.
Histologic assessment of resected ascending aorta revealed mucoid medial degeneration with fibrosis, and lipid deposition (Fig. ). Three- and eighteen-month CT-scans have shown no evidence of endoleak with normal perfusion of all the arch vessels. On the last CTA, we also observed positive aortic remodeling with distal arch aneurysm which was decreased in size from 7 × 8.5 cm to 3 × 3.5 cm. |
pmc-6595679-1 | Our patient is an 11-year-old girl of double first-cousin parents (first cousins from both maternal and paternal sides), from Muthanna, Southern Iraq. Since the first 2 years of her life, she had a history of food allergy (egg and peanuts), and severe eczematous skin lesion which was resistant to local and systemic steroids. She also had repeated sinopulmonary infections and were often treated in an outpatient setting. Moreover, recurrent infection with molloscum contagiosum and flat warts on the face, neck, behind ears, axillary area and genitalia, were encountered. Notably, she had a history of dental problems related to malocclusion and retention of primary teeth, necessitating dental intervention, in addition to mucocutaneous candidiasis. Vaccinations were given according to schedule in Iraq. At 9-year-old, the patient presented with a slowly growing right jaw mass and toothache, with no history of fever, headache or bone pain. Antibiotics were used, yet the mass continued to increase slowly in size over several months without a change in the overlying skin. Upon examination, she had coarse facies with eczematous scaly itchy skin lesion distributed over her face, scalp, and body as well as genitalia. A non-tender right jaw swelling was evident, with a right submandibular lymph node (2.5 cm), and bilateral cervical and axillary lymphadenopathy (1.5–2 cm). Oral examination showed a fungating mass related to right mandible with a bad odor. Otherwise, no dysmorphic facies, jaundice, fever, café au lait spots, or edema was observed. Scattered crepitation, and a palpable liver were evident by chest and abdominal examination, respectively, whereas, neurological and musculoskeletal examination was normal. Her growth parameters were below 3rd-centile, yet her school performance was good. Although, not genetically determined, her older brother shared with our case similar but milder clinical features of DOCK8 deficiency. On the other hand, her younger brother was phenotypically diagnosed with Crigler–Najjar syndrome.
During the assessment for the jaw swelling, laboratory investigations in Iraq showed a marked eosinophilia and lymphopenia, along with Ig assays of 20, 3.3 and 1.7-fold above maximum normal level for age of IgE, IgA and IgG, respectively, whereas IgM was low (Table ). She also had hypercellular BMA with eosinophilia, iron deficiency anemia, reactive thrombocytosis, and elevated erythrocyte sedimentation rate and lactate dehydrogenase levels, as well as deranged liver function, and a high anti-tissue transglutaminase (anti-tTG) of 10-fold above normal. Meanwhile, two-biopsies were taken from the jaw mass, and NHL was suggested in Iraq. One of the biopsy specimens was re-evaluated in Japan. The immunostaining in Japan revealed that most of the tissue was plasma cells with positive-CD138, along with Ig-kappa and lambda chain expressions, and few small lymphocytes showing the polyclonal pattern (Fig. ). Epstein-Barr virus (EBV) was undetectable by in situ hybridization (ISH) in Japan. Furthermore, no other significant etiological microorganisms including human herpes virus 8, bacteria, or fungi were detected in the tissue after using immunohistochemistry, Gram staining, Grocott staining, and acid-fast staining. Based on the finding that neither light chain deviation in plasma cells was apparent (Figs.e and f), nor PCR clonality in Ig-heavy chain complementarity determining region (CDR)-III was disclosed, the lymphoplasmacytic proliferation in the mass was interpreted as non-neoplastic/reactive process. Thus, the diagnosis of a polyclonal reactive proliferation spectrum of lymphoproliferative disease (LPD) complicating PID was made in Japan. Concurrently, FTA cards were used to transfer a few drops of the patient’s BMA to Japan, where the DNA was extracted from the DBS on FTA filter-paper and was subjected to WES []. A DOCK8 homozygous frameshift deletion (NM_203447:c.3332delT, p.Phe1113Leufs*2) was detected in a region of run of homozygosity in chromosome 9p, suggesting that the mutation became homozygous because of consanguinity [].
Therefore, the patient was diagnosed as DOCK8 deficiency, and the jaw swelling was managed conservatively, through applying strict oral hygiene measures as recommended by the maxillofacial surgeon, who also performed frequent superficial debridement to remove any necrotic tissue, along with extraction of any deciduous tooth that was badly carious. Moreover, antimicrobial agents (amoxiclav and co-trimoxazole, in addition to metronidazole and nystatin oral drops) were used. Concomitantly, a gluten-free diet was firmly introduced for the management of autoimmune enteropathy (Celiac disease) that was diagnosed serologically in accordance with World Gastroenterology Organization guidelines in countries with limited resources [].
Eventually, her jaw mass regressed gradually over several months using neither steroid nor chemotherapy (Fig. ). Considering the difficult socioeconomic status of the family and the unhealthy condition of the 2 brothers, the option of HSCT was excluded (Additional file ). |
pmc-6595694-1 | A 39-year old Chinese male patient transferred to our hospital for sudden onset of blurred vision in both eyes for 1 day. The patient went to sleep after taking the flu medicine (combination of paracetamol 250 mg, caffein 15 mg, atificial cow-bezoar 10 mg and chlorphenamine 1 mg) three times the recommended dose on the previous night. On the next morning, the vision of both eyes decreased significantly. There was no prior history of ocular disease or myopia. Other medical history was insignificant rather than hypertension was diagnosed more than 1 year ago. However, the patient denied taking antihypertensive drugs and any other drugs.
Ocular examination revealed uncorrected vision of 20/400 in both eyes. Vision was corrected to 20/100 OD and 20/60 OS with − 4.50 OD and − 7.00 OS. Intraocular pressure (IOP) was 54 mmHg OD and 55 mmHg OS. Pupillary reactions were sluggish but present. Slit lamp examination revealed mild hyperemia of the bulbar conjunctivas, the cornea of both eyes was still transparent, shallow anterior chambers, the pupils were round, about 3 mm in diameter, and no other obvious abnormalities were found under the small pupil (Fig. ). The central anterior chamber depth measured by Lenstar (Haag-Streit AG) was 1.97 mm in the right eye and 2.05 mm in the left eye. Lens thickness was 4.43 mm OD and 4.40 mm OS. OCT (Optovue, Inc., Freemont, CA) showed no obvious abnormality in macular region. Parapapillary OCT showed normal nerve fiber layer thickness, C/D was 0.33 in the right eye and 0.53 in the left eye. Ultrasonography showed that there were no special findings in vitreous cavity and posterior wall of the ball in both eyes, but the highly reflective band was separated from the wall in the periphery (Fig. ). The axial length of the eye was 22.95 mm in the right eye and 23.09 mm in the left eye measured by Lenstar. Ultrasound biomicroscopy (UBM) (Suoer, CHN) showed bilateral ciliochoroidal effusions, disappearance of the ciliary sulcus, closure of the angle of the anterior chamber, and anterior displacement of the lens-iris diaphragm (Fig. ). Treatment with timolol drops twice daily OU, atropine eye ointment once daily OU, oral methazolamide (50 mg) twice daily, and oral prednisone (30 mg) once daily. Syphilis, HIV and tuberculosis tests were all negative,
A day later, the patient’s uncorrected vision was 20/125 OU and was corrected to 20/50 OD and 20/40 OS with − 5.75D OU. IOP was 36 mmHg OD and 39 mmHg OS, the anterior chamber angles remained closed. On the third day, the patient’s IOP was 14 mmHg OD and 13 mmHg OS. On the fourth day, IOP was 8 mmHg OD and 9 mmHg OS. Treatment with oral and topical aqueous suppressants was terminated. On the fifth day, the uncorrected vision improved to 20/20 OU, and the myopia had disappeared. IOP was 11 mmHg OD and 12 mmHg OS. UBM revealed major resolution of the ciliochoroidal effusions in both eyes, deepening of the anterior chamber, return of the lens-iris diaphragm to a more posterior position. The anterior chamber depth of both eyes were 2.98 mm OD and 2.90 mm OS. The lens thickness was 4.12 mm OD and 4.06 mm OS. Half a year later, the follow-up UBM demonstrated complete resolution of the ciliochoroidal effusion. The anterior chamber depth was 2.79 mm OD and 2.91 mm OS. |
pmc-6597131-1 | A 62-year-old female with a past medical history of tobacco abuse, hypertension, constipation, and chronic headaches managed by ibuprofen, presented to the emergency room with complaints of diffuse abdominal pain and bright red blood per rectum since two days. On physical examination, the patient was afebrile, the abdomen was soft, non-tender, with normal bowel sounds. The rectal exam was unrevealing except for bright red blood on the gloved finger. Laboratory studies showed hemoglobin of 15 g/dl, white blood cell count of 23,700/µl with normal serum lactate, amylase, and lipase levels. Colonoscopy showed discontinuous areas of non-bleeding ulcerated mucosa with no stigmata of recent bleeding in the sigmoid colon and descending colon for a total of 20 cms, consistent with the “single-stripe sign”, characteristic of colonic ischemia (Figure ). Further, microscopic evaluation of the biopsied tissue revealed characteristic features of surface epithelial injury, crypt epithelial atrophy, crypt loss, lamina propria hemorrhage, and lamina propria hyalinization consistent with the colonoscopy findings of colonic ischemia (Figure ).
The patient was discharged on a seven-day course of oral ciprofloxacin and metronidazole, managed for constipation with polyethylene glycol, and was advised to quit smoking and to avoid non-steroidal anti-inflammatory drugs. |
pmc-6597132-1 | A 51-year-old female patient presented to the hospital, reporting shortness of breath of two days’ duration that was associated with a dry cough but not with fever or chills, abdominal pain, nausea or vomiting, or a change in bowel or urine habits. She had a medical history of hypertension, hypothyroidism, diabetes mellitus type 2, and breast cancer for which she had undergone a lumpectomy. Of note, the patient had taken tamoxifen for five years following her lumpectomy, after which she developed postmenopausal bleeding. As tamoxifen therapy increases the risk for endometrial cancer, an endometrial biopsy was done that showed atypical hyperplasia with atypia for which the patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The surgery was complicated by an accidental bladder injury that was repaired at the time of surgery, 15 days prior to her current admission.
On physical examination, the patient’s blood pressure was 114/76 mmHg, heart rate 93 beats per minute, and respiratory rate 20 breaths per minute. Her temperature was 36.1°C and oxygen saturation 94% on room air. She was alert and oriented to person, place, and time. Heart examination showed a regular rate and rhythm with normal S1 and S2 sounds. Lung examination showed decreased breath sounds with dullness on percussion of the right side of the chest. Her abdomen was soft and lax, with no tenderness or organomegaly. There were no other significant physical findings.
Laboratory findings were as follows: leukocytosis with a white blood cell (WBC) count of 14000 /μL; hemoglobin level of 10 g/dL; serum creatinine level of 3.9 mg/dL (baseline 0.6 mg/dl); blood urea nitrogen level of 35 mg/dL; negative test results for antinuclear antibody, rheumatoid factor, and glomerular basement membrane antibody IgG; normal results for complement C3 and C4 levels; erythrocyte sedimentation rate 32 mm/h. The chest X-ray showed a large, right-sided pleural effusion (Figure ). A transthoracic echocardiogram showed a preserved left ventricular ejection fraction with no valvular abnormalities.
The pulmonary team was consulted and the patient underwent thoracentesis that yielded 3 L of yellow fluid. She reported immediate improvement in shortness of breath after the procedure. Pleural fluid analysis (PFA) showed the fluid to be transudative in accordance with Light’s criteria, with the following values: lactate dehydrogenase (LDH) 143 U/L, albumin 1.6 g/dL, total protein 2.8 g/dL, glucose 115 mg/dL, pH 7.5, and triglycerides 45 mg/dL. Cytological examination of the aspirated fluid showed no malignant cells, and the results of fluid culture were negative. The serum LDH level was 290 U/L, total protein 7 g/dL, and albumin 3.9 g/dL. Because of the pleural fluid color and the patient’s recent procedure, pleural creatinine was measured and found to be 6.72 mg/dL, with a pleural fluid creatinine-to-serum creatinine ratio of 1.7, suggesting a diagnosis of urinothorax.
A computed tomography (CT) scan of the abdomen and pelvis with contrast was performed, which revealed a small amount of subdiaphragmatic and perihepatic fluid, as well as fluid in the cul-de-sac. The urology team was consulted and a CT cystogram was performed, showing extravasated contrast material within the pelvis, with a small pocket of contrast noted along the right anterior aspect of the urinary bladder (Figure ), likely at the site of the bladder leak. A renal ultrasound (US) showed no hydronephrosis, mild bilateral renal cortical thinning, and a small cyst in the superior left kidney.
With the source of the urine leak from the genitourinary (GU) tract established, together with a pleural effusion creatinine level of 6.72 mg/dL and a pleural fluid/serum creatinine (PF/S Cr) ratio of >1, we confirmed the diagnosis of urinothorax. A Foley’s catheter was used to seal the bladder leak, and a repeated chest X-ray one month later showed resolution of the right-sided pleural effusion (Figure ), after which the patient reported no further shortness of breath. She was discharged with the Foley’s catheter in place and instructions to follow up with urology in two weeks. Repeated fluoroscopy cystography on follow-up showed no extravasation and the Foley’s catheter was removed. Repeated serum creatinine results showed the resolution of the kidney injury, and the serum creatinine levels returned to normal. |
pmc-6597133-1 | A 54-year-old man with a history of hypertension and smoking presented with nine months of epigastric pain, decreased appetite, and a 30 lb. weight loss. His family history was significant for PDAC in maternal aunt and breast cancer in another aunt. Abdominal computed tomography (CT) performed at an outside facility showed a mass in the pancreas, measuring 4 cm x 3.8 cm x 2.6 cm, encasing the superior mesenteric artery, and he was referred to our institution for further management. His hepatic panel showed an elevated alanine transaminase at 160 IU/L (normal: 7 - 56 IU/L) and an alkaline phosphatase of 256 IU/L (normal: 44 - 147 IU/L). Carbohydrate antigen 19-9 (CA 19-9) was elevated at 177 U/mL (normal: 0-37 U/mL). An esophagogastroduodenoscopy (EGD) demonstrated a nodule at the gastroesophageal junction (Figure ).
An endoscopic ultrasound (EUS) revealed an ill-defined, hypoechogenic, lobular area, measuring 19.6 mm x 24.7 mm, located between the head and body of the pancreas (Figure ).
No lymph nodes were seen. The patient was additionally found to have an approximately 1 cm nodule at the gastroesophageal junction (GEJ), which was limited to the mucosa and submucosa, and removed with endoscopic mucosal resection (EMR). The pathology from the pancreatic mass confirmed adenocarcinoma (positive for CK7, CK20, DPP4, and CDX2) with microsatellite stability (with an intact expression of MLH1, MSH2, MSH6, and PMS2). The pathology of the GEJ nodule proved to be adenocarcinoma with mucinous features (microsatellite stable but with KRAS amplification) with NOTCH1 E905* and TP53 C135Y genomic alterations (Figure ).
The patient was diagnosed with a double primary of the pancreas and the esophagus and started on FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) in consultation with medical oncology. He has received 10 cycles of FOLFIRONOX thus far and was doing well at his six-month follow-up. |
pmc-6597135-1 | A 24-year-old Hispanic woman with a past medical history of post-partum pre-eclampsia presented to the emergency department with a two-week history of abdominal pain, nausea, vomiting, diarrhea, jaundice, and scleral icterus. On a review of systems, she denied recent travel, sick contacts, hepatotoxic medications or supplements, or parenteral exposure risks. She reported a distant history of tattoos placed with clean needles and had undergone a cesarean section three months prior, with the delivery of a healthy baby boy. Aside from obesity, she denied other risk factors for liver disease.
Her physical exam was unremarkable except for obesity, jaundice, and scleral icterus. The patient had no exophthalmos, goiter, or tachycardia. Initial laboratory workup revealed elevated liver function tests, including aspartate transaminase (AST) 1,041 IU/L (8-48 IU/L), alanine transaminase (ALT) 809 IU/L (7-55 IU/L), total bilirubin 11.5 mg/dL (0.1-1.2 mg/dL), direct bilirubin 8.7 mg/dL (<0.3 mg/dL), and prothrombin time 15.1 seconds (9.5-13.8 seconds). Anti-smooth muscle antibody (ASMA) was positive and immunoglobulin G (IgG) was elevated at 2,288 mg/dL (767-1,590 mg/dL). Anti-nuclear/anti-mitochondrial antibodies and hepatitis viral serologies were negative. Iron/copper studies were within normal limits. Thyroid studies were not performed at this time, as she did not exhibit any clinical evidence of thyroid dysfunction.
Subsequently, an ultrasound-guided core needle liver biopsy was performed, which showed interface hepatitis with extensive portal lymphocytic infiltration, mild to moderate (Grade 2-3) periportal and lobular inflammation, portal fibrosis, and early (Stage 1-2) portal-to-portal septa (Figure ), consistent with a diagnosis of autoimmune hepatitis.
The probability of our patient having AIH was calculated using a standardized scoring system. Based on the presence of ASMA, IgG elevation >1.1 times the upper limit of normal, histology compatible with a diagnosis of AIH, and negative viral serologies, the patient’s score was 6 as per the simplified AIH scoring system. This was indicative of a probable diagnosis of AIH [,-]. Human leukocyte antigen (HLA) allele was not tested.
Treatment was started with high-dose prednisone to be tapered from 60 mg to 40 mg after two weeks. Azathioprine 50 mg daily was added after three weeks. Initially, her transaminases and total bilirubin trended downward, but these values sharply increased at the six-week mark (Figure ). She also complained of palpitations, sweating, and heat intolerance, which prompted readmission for further evaluation. Additional workup revealed underlying hyperthyroidism with thyroid-stimulating hormone (TSH) <0.01 µIU/mL (0.4-5.5 µIU/mL), freetriiodothyronine (T3) 11.5 pg/mL (2.8-4.4 pg/mL), and free thyroxine (T4) 39.5 ng/dL (0.9-1.7 ng/dL). Grave's disease was confirmed with a radioactive iodine uptake of 44% (8-25%) and positive thyroid-stimulating immunoglobulin.
Given her hepatic function, the patient was not a candidate for standard therapy with methimazole or propylthiouracil. She was instead started on high-dose hydrocortisone, which provided an added benefit of decreased peripheral conversion of T4 to T3 []. Her hyperthyroid symptoms improved while AST, ALT, and total bilirubin decreased by nearly 75% within one week. This represented the first time in three months that the patient’s transaminases dropped below 200 IU/L. Subsequently, she underwent radioactive thyroid ablation and began levothyroxine supplementation. Her AST, ALT, and total bilirubin also normalized - signifying the biochemical remission of AIH - once she received the ablation. Afterward, the patient remained stable on standard immunosuppressive therapy, with 20 mg prednisone and 150 mg azathioprine daily. |
pmc-6597137-1 | During routine dissection of the thigh, a variant anterior scrotal branch was found in an African-American fresh-frozen male cadaver whose age at death was 79-years-old. The anterior division of the femoral nerve gave rise to two cutaneous nerves, the medial femoral cutaneous nerve of the thigh (MFC) and the intermediate cutaneous nerve of the thigh (ICN). The MFC was traced and found to supply three branches to the skin of the anterior and medial thigh. The MFC then traveled medially and superiorly to join the anterior scrotal branch of the ilioinguinal nerve which coursed superficial to the spermatic cord (Figures , ). The origin of the femoral nerve and ilioinguinal nerves was L2-4 and L1, respectively. There were no variations of the iliohypogastric or genitofemoral nerves. |
pmc-6597479-1 | A 72-year-old man came to our Thoracic Surgery Department in March 2018 for a persistent cough that was resistant to therapy. He underwent chest X-ray and a CT scan with enhancement, which showed a mass of 34 × 32 mm located in the left upper lobe of the lung, infiltrating the left main pulmonary artery and the left bronchus (). No signs of an atherosclerotic plaque or tumor infiltration involving the entire aortic wall were detected. Invasion of a calcified plaque was slight and appeared to involve only the adventitia. A PET/CT with 18F-FDG was positive (Standard Uptake Value, SUV max = 15) for hypermetabolic mass with negative lymph node stations bilaterally. The patient had a smoking history (one pack/50 pack-years), with no other previous malignancies, and 20 years of comorbidities, including diabetes mellitus type 2, hypertension and hypercholesterolemia treated with medical therapy. Pulmonary function tests before surgery showed a forced expiratory volume in the 1st second (FEV1) of 1.7, equal to 80% predicted, and a forced volume vital capacity (FVC) of 2.4, equal to 82% predicted. The endobronchial ultrasound (EBUS) showed no N2 lymph node infiltration, although the percutaneous lung mass biopsy was highly suspect for adenocarcinoma of the lung. After signing the consent, the patient underwent a double-sleeve left upper lobectomy plus en bloc resection of the aortic wall adventitia for 4 × 2 cm2 through a left posterior thoracotomy. At the beginning of the operation, during the mobilization of the mass, a 5-mm aortic rupture occurred in the adventitia due to the presence of an atherosclerotic calcified plaque at this level (C). At first, manual pressure was applied on the bleeding site, then the surgeon tried to place a suture on the bleeding site, but the hardness of the plaque hindered the maneuvering. In the same time, the anesthesiologist maintained low mean arterial pressure (MAP). Patient conditions stayed persistently stable and after 15 min the bleeding was under controlled, however, for the high risk of an another unexpected bleeding, the thoracic wall was closed and the patient intubated was transferred urgently to the interventional operating room where an endovascular stent was placed from the left subclavian artery to the descending aorta using percutaneous retrograde common femoral artery access (D and E). After the vascular procedure, the patient was retransferred to the operative room, the chest was re-opened for inspection and for proceeding with the lung resection.
Intraoperative blood loss was totally 800 ml. Clinical parameters were stable during and after the procedure. The patient tolerated the endovascular stent placement and the subsequent double-sleeve left upper lobectomy within six total hours of operation. The patient was placed in the intensive care unit (ICU) for 48 h after surgery for optimal stabilization of his clinical condition. Chest tubes were removed on the third postoperative day, and the patient was discharged after six days from surgery with no morbidities (A). No stent-related complications were noted. Histology confirmed the diagnosis of adenocarcinoma of the lung, stage pT2 pN1 pM0 (TNM 8th), and an oncologic evaluation was requested for the next treatment options. Chest X-rays at one-month and four-month follow-up from surgery (B–C) revealed no complications. |
pmc-6597482-1 | We report a case of a 51-year-old female who was diagnosed with clear cell renal cell carcinoma (ccRCC) of the right kidney and underwent radical nephrectomy. The patient was in remission for 6 years post-nephrectomy when she presented with a solitary lesion in the head of the pancreas that was discovered upon surveillance (). It was then resected via a Whipple procedure, interestingly, histopathology reported it as a multi-focal lesion of renal cell carcinoma rather than a solitary lesion (). Ten years after the resection of the primary tumor, the patient presented with a thyroid nodule without any history of thyroid dysfunction. Accordingly, imaging was performed, and a 5.16 cm lesion was found. Subsequently, a fine needle aspiration was done, which revealed RCC metastasis, so the patient underwent a total thyroidectomy ( & ). Six months later, the patient presented with a mass on the anteromedial aspect of the forearm, which was biopsied and confirmed to be yet another metastatic lesion of RCC, and thus it was excised with negative margins (). Within the following year, the patient presented with another mass on the forearm, distal to the site of the previous one. Following the discovery of the subcutaneous lesion on the forearm, metastatic workup was promptly performed, and CT scan showed multiple enhanced pancreatic lesions (). The patient underwent a completion pancreatectomy and resection of the second forearm mass. One year later, another metastatic lesion was found in the left kidney, for which the patient underwent left partial nephrectomy with negative margins. The patient is currently alive and in good condition, as per a recent follow-up. |
pmc-6597494-1 | 1: A-39-years-old male referred to our General Hospital with sensation of giving away and unable to extend on the right knee after car accident 1.5 years ago. He had history of close fracture of lateral condyle right femur. The patient complain of irreducible patellar dislocation during flexion and extension of the right knee joint. He underwent 4 times surgery of his right knee by other orthopaedic surgeon. The first surgery result still unreduced fragment fracture, and we done open reduction and internal fixation (ORIF) also PCL reconstruction. The right knee became valgus knee after fracture union and instability sensation on the medial knee joint. On physical examination, the right knee had 18° of valgus deformity, moderate instability to valgus stress, complete lateral dislocation of the patellae during extension and flexion, and tenderness at the lateral joint line (). Range of motion was 0–110°.
During radiographic examination, the standing knee radiograph showed mild arthritic changes on the lateral compartment of the right knee that were not observed on the left knee. The long-leg weight-bearing standing radiograph showed 18° valgus on the right knee and 5° valgus on the left knee with depression of the lateral tibia plateau and a mechanical axis passing outside the lateral compartment, and the weight bearing line locates lateral to Fujisawa point. The anatomical lateral distal femoral angles of the right and left knees were 105° and 82° respectively (normal value is 81° and 62°, respectively); the medial proximal tibial angles were 94° and 93° respectively (normal value is 87° and 63°, respectively). This result confirmed valgus deformities of both knees. A skyline view radiograph showed complete lateral dislocation of the patella () [].
2: A-26-years-old obese female came into outpatient clinic with chief complain of left patellar dislocation. She had history of left knee surgery for dislocation at age 5 years old. Her left knee never felt comfortable and she is frequent fall down. In physical examination, we found left knee valgus alignment, its Q angle was 25°, muscle atrophy and positive J sign. Long-leg radiographs of the left leg showed a mechanical angle of 11° of valgus, and the weight bearing line locates lateral to Fujisawa point (, , ). |
pmc-6597495-1 | The patient is a 33-year-old male with a known case of chronic relapsing ITP diagnosed in 2012. Additionally, he is diagnosed with temporal lobe epilepsy on anti-epileptic medications, Graves’ disease status post radiation of thyroid and on levothyroxine replacement, and valvular heart disease.
The patient presented at the time of diagnosis in April 2012 with severe thrombocytopenia that was complicated by pulmonary hemorrhage which required ICU admission. His investigation at the time showed platelets count of only 1 × 10 9/L (normal range 150–450 × 109/L). The patient was treated with intravenous immunoglobulin (IVIG) and steroids (Prednisone 25 mg/day), responding for 4 months with a rise in platelet count to 62 × 10 9/L. After which he relapsed developing epistaxis, purpura and a platelet count of 2 × 10 9/L. Again, the patient was treated with higher dose of steroid (30 mg/day) and IVIG and a surgical team was consulted for possible splenectomy. A bone marrow aspirate and biopsy was preformed which showed increased megakaryocytes consistent with ITP and was otherwise normal. Laparoscopic splenectomy was done in October 2012, the surgery went well and the patient was discharged in good condition. Three years later in December 2015, he presented again with bleeding and ulcer in the oral cavity and minimal episodes of fresh blood per rectum. He was admitted as a case of chronic relapsing ITP with platelets of 6 × 10 9/L, which increased to 96 × 10 9/L after a short course of steroid (Prednisone 25 mg/day), and IVIG. About 3 months later in March, he relapsed with platelets of 3 × 10 9/L. During hospital course, he underwent CT scan of abdomen and pelvis with contrast which revealed a small-sized mass originating from the medial part of the tail of the pancreas that was suspected to be an accessory spleen (). Thus, a surgical team was consulted and a colloid scan was advised that confirmed accessory spleen originating from the tail of the pancreas (). Repeated bone marrow aspirate and biopsy was done in the same admission to rule out malignancy.
Meanwhile, IVIG and steroid were continued and a laparoscopic accessory splenectomy (LAcS) was performed on the scheduled date in April 2016 as the patient was seen by neurology and cardiology for his conditions and found to be fit for surgery. Platelet count on the day of surgery was 230 × 10 9/L. The intraoperative setting confirmed the radiological data of accessory spleen which was surrounded by a fibrotic capsule that separates it from the adjacent pancreatic parenchyma, consistent with gross examination reported in the literature []. Using three trocars including the scope, the lesser sac was opened and pancreas was localized. Then the inferior border of the pancreas was dissected to find the small splenule in the inferior part which was removed from within the pancreas. The surgical time was 80 min, following which there were no post-operative complications. Pathologic assessment of the excised tissue confirmed the specimen to be accessory spleen. As expected, within a few days, platelets increased up to 754 × 10 9/L and the patient was started on Aspirin 81 mg daily for 3 months.
The patient was followed up regularly in hematology clinic and was continued on prednisone 20 mg daily and Eltrombopag 50 mg daily until both were tapered off in May 2016. His platelets continued to range from 265 × 10 9/L to 363 × 10 9/L since then. Although his platelet count dropped slightly during his last clinic visit on October 2018 (30 months’ post-surgery) where it was 130 × 10 9/L, it was still considered acceptable as it did not reach a threshold level that could cause a significant increased risk of bleeding. |
pmc-6597496-1 | An 86-year-old woman who had been living with her elderly husband was admitted to our hospital with the complaints of nausea, anorexia, and epigastric discomfort. When she was 73 years old, the patient had undergone laparotomy and right hemicolectomy for resection of colon cancer. Five years after hemicolectomy, she had received hernia repair surgery using mesh for an abdominal incisional hernia. There was no history of abdominal or thoracic trauma. Laboratory tests were all within the normal range. Her electrocardiogram showed no ischemic changes. Although chest X-ray revealed an abnormal gas-filled mass in the left thoracic cavity, the patient had no symptom of dyspnea. Contrast-enhanced computed tomography (CT) scan confirmed herniation of the gastric corpus through the left posterior part of the diaphragm (). We diagnosed adult Bochdalek hernia and planned its surgical treatment. As mesh had been placed under the previous upper abdominal midline incision more than 10 years earlier, dense adhesions between the mesh and abdominal tissues were expected. Therefore, we decided to perform diaphragmatic hernia repair by HALS, considering the patient’s safety. After induction of general anesthesia, the patient was placed in the supine position with her legs apart. The previous midline incision was opened carefully to insert a LAP DISC® (Hakko, Nagano, Japan) for a hand port. Dense adhesions, which had to be divided, were found between the mesh used to repair her incisional hernia and loops of the small intestine. The disk for HALS was placed after complete removal of the mesh. Subsequently, a 12 mm trocar was inserted into the inferior umbilical region for the laparoscope. A 5 mm trocar was also inserted into the left upper abdominal region. Herniation of the gastric corpus into the left thoracic cavity through a hernial orifice in the left posterior diaphragm was confirmed. The gastric corpus could not be pulled back into the abdominal cavity because of adhesions around the hernial orifice. After these adhesions were carefully removed by HALS using Harmonic ACE shears (Ethicon, NJ, USA) (a), the stomach was completely freed and could be returned to the abdominal cavity. A 5 × 3 cm hernial defect with sac was observed (b). We decided to perform simple closure of the defect without mesh reinforcement because the rim of the hernial orifice was relatively strong. Accordingly, the defect was repaired with interrupted nonabsorbable sutures (2-0 Nesporen; Alfresa Pharma Corporation, Osaka, Japan) using a 5 mm port on the left upper abdomen and the surgeon’s left hand via the hand port (c). The midline incision for the hand port was closed without mesh reinforcement. A drain tube was placed under the left hemidiaphragm. The operating time was 244 min and there was no significant bleeding. Her postoperative course was uneventful. The patient was discharged on postoperative day 20. There was no evidence of recurrence at 1-year follow-up. |
pmc-6597617-1 | A 76-year-old woman had been transferred to our hospital because the acute pain in the left lower leg. The lower extremity of affected side was cyanotic, while regular pulsation was palpable in the femoral artery (FA) and popliteal artery (PA). The previous medical history of this patient was hypertension and right total knee arthroplasty; however, arrhythmia had not been detected. CT scan revealed a left PSA aneurysm (a), the left PA fed from the PSA and the hypoplastic superficial FA (b). These results indicated “complete-type PSA” [,]. The PA ran more laterally than the normal pattern (a) and the three artery branches of the lower leg were occluded (b). The underlying cause was identified as embolic ischemia from the PSA aneurysm. Surgery was not performed because clinical symptoms rapidly improved with the administration of heparin. Conservative treatments by oral anti-platelet medicines and the dripped intravenous administration of heparin were continued for one week. MRI examination during hospitalization showed the patency of the posterior-tibial artery (PTA) and peroneal artery (). The patient was reluctant to surgical treatment to the PSA and discharged; however, the same symptoms recurred 6 months later and emergent surgical treatments were performed. Under general anesthesia, thrombectomy of PTA was performed and blood flow from distal side was observed. Next, the bypass between FA-PTA with a reversed saphenous vein graft were performed. Additionally, the proximal side of PTA from the anastomosis site was ligated to avoid the recurrence of embolism. One year after surgery, the recurrence of embolism and other complications have not occurred, furthermore the aneurysm is occluded by thrombus (). |
pmc-6598236-1 | A 55-year-old man was on the waiting list for orthotopic liver transplant because of a decompensated HBV-related liver cirrhosis (Child C11, MELD 16) complicated by intractable ascites for which a transjugular intrahepatic portosystemic shunt (TIPS) had been placed 5 months earlier. He was also affected by asymptomatic gallbladder stones and admitted to our unit because of sudden recurrence of abdominal distension. The patient reported a few days before severe epigastric pain that lasted for about 20 min and was spontaneously resolved; he, however, denied hematemesis or melena. At admission, physical examination revealed normal vital signs. Laboratory workup revealed a haemoglobin level of 6.4 g/dl (compared to that of 10.3 g/dl recorded 3 weeks earlier), leucocyte count of 4930/mm3, platelet count of 49/mm3, international normalised ratio of 1.44, bilirubin 3.2 mg/dl, alanine aminotransferase 25 UI/l, aspartate aminotransferase 47 UI/l, alkaline phosphatase 105 UI/l, gamma glutamyl transferase 27 UI/l, albumin 2.0 g/dl, creatinine 0.91 mg/dl and C reactive protein 48 mg/l. The patient was made to undergo urgent blood transfusion. An urgent gastroscopy revealed no varices, gastric ulcer or any other source of bleeding. An ultrasound sonography confirmed the presence of ascites and normal flow within the portal vein and the TIPS. The patient underwent diagnostic paracentesis with leakage of high-pressure blood-like fluid: the cell count analysis confirmed hemoperitoneum (haemoglobin 2.8 g/dl) and showed normal leucocyte count and no malignant cells. The analysis of the ascitic fluid also documented a transudate (total proteins < 2 g/dl, LDH 162 UI/l) with high serum-ascites albumin gradient (1.4 g/dl), bilirubin concentration of 2.9 mg/dl and ascitic culture as negative. A contrast-enhanced abdomen CT-scan showed a scleroatrophic gallbladder bearing only one stone inside and irregularity along the wall, but no frank interruption while numerous radiopaque elements were evident in the pelvis alongside dense ascites (Hounsfield Units 19; uncomplicated ascites normal value 0–15) [], configuring a picture like “starry sky” (Fig. ). No ectopic gallbladder varices have been recorded. Both abdominal CT and ultrasound performed a month before described contracted gallbladder, whose lumen was completely occupied by stones. A perforation of the gallbladder with occult bleeding was therefore diagnosed. Based on absence of fever, signs of peritoneal involvement, stability of haemoglobin levels and expected waitlist time, a conservative therapeutic strategy (antibiotic therapy and control of the coagulation parameters, haemoglobin and renal function) was chosen to avoid high-risk cholecystectomy before liver transplantation. In the following days, clinical and laboratory parameters remained stable and, particularly, no fever or exacerbation of hepatic encephalopathy were observed. The patient was discharged in 15 days, asymptomatic, with a stable level of haemoglobin. Two months later, the patient underwent a successful liver transplantation. During the transplantation, the surgeon visualised the stones that had migrated into the pelvis and decided not to remove them because of an unfavourable risk-benefit ratio. The pathological report documented a scleroatrophic gallbladder with chronic inflammation but did not identify any perforation. |
pmc-6598251-1 | Patient (I) is a 15-year-old male who reported a two-year history of non-painful “crooked” fingers in the absence of trauma. His past medical history was significant for possible Raynaud phenomenon but otherwise noncontributory. On physical examination, his growth parameters were age appropriate. There was radial deviation of the second, third, fourth and fifth terminal phalanges bilaterally. There was asymmetrical involvement of the hands; the third phalanges were most affected and the right-hand digits were more severely affected than the left (Fig. , a1). His total hand length was 18 cm (50–75%) and middle finger length was 8 cm (75%). Other joints including those in the feet were normal on examination. His peripheral neurological examination was unremarkable.
Laboratory investigations (white blood cells, erythrocyte sedimentation rate, C-reactive protein, anti-nuclear antibodies, rheumatoid factor, anti-double stranded DNA antibodies, anti-SM antibodies, anti-RNP antibodies, anti-SS-A (RO) antibodies and anti-SS-B (La) antibody) were normal or negative. |
pmc-6598254-1 | A 38-year-old man was aware of bilateral lower limb weakness 3 days after upper respiratory infection. The next day, he showed disturbance of consciousness and bilateral upper limb weakness. Two days after onset, he showed respiratory failure and needed support by mechanical ventilation. The patient was admitted to our hospital. At admission, he showed bradycardia (heart rate was 40 beats per minute). In neurological examination under no sedation, he showed no response to painful and visual stimuli. Light reflex was bilaterally dull though pupil diameter was 5 mm. No voluntary ocular and facial movements were observed. Oculocephalic, corneal, gag and cough reflexes were absent. He showed complete flaccid tetraplegia with areflexia in all limbs. Babinski reflex was negative. At 13 days after onset, cerebrospinal fluid examination revealed a normal cell count at 4 /μL, but protein levels increased to 98.5 mg/dL. At 21 days after onset, the nerve conduction study showed that compound muscle and sensory nerve action potentials decreased from the distal portion in upper limb nerves, and distal latencies and nerve conduction velocities were normal in all nerves tested. These findings were electrophysiologically consistent with the pattern of axonal damage in peripheral nerves (Table ). Brain MRI showed no intracranial abnormal signals on diffusion-, T1-, T2- and fluid-attenuated inversion recovery-weighted images. Spinal MRI also showed no intramedullary abnormal signals. Auditory brain stem response was normal. Various anti-ganglioside antibodies were detected in laboratory examinations. Anti-GQ1b, GT1a, GT1b, GD1a, GD1b and GD3 IgG antibodies were positive (Fig. ). These data confirmed the diagnosis of GBS. At 4 days after onset, we started to administrate intravenous immunoglobulin (IVIg) at a daily dose of 0.4 g/kg for five days and intravenous methylprednisolone (IVMP) at a daily dose of 1000 mg for three days. At 22 days after onset, we repeated IVIg, followed by IVMP (Fig. ). Disturbance of consciousness, eye symptoms and weakness of the distal upper and lower limbs improved gradually, whereas severe PCB-like weakness of the oropharynx, neck, and proximal upper limbs remained. Anti-GQ1b, GT1b, GD1a, GD1b and GD3 IgG antibodies were turned to be negative, but anti-GT1a IgG antibodies remained positive. We added plasma exchange (PE) three times from 39 days after onset. However, the PCB-like weakness did not improve, muscle atrophy of limbs became apparent, and anti-GT1a IgG antibodies persistently positive. We further performed PE four times from 68 days after onset. Although anti-GT1a IgG antibodies decreased, severe PCB-like weakness did not ameliorate. Consequently, mechanical ventilation and tube feeding was required for 7 and 10 months, respectively. At 18 months after onset, in the nerve conduction study, the decrease in compound muscle action potentials in upper limb nerves was persistently observed (Table ). Two years later, he could walk using assistance, but weakness of the proximal upper limbs remained as sequelae (Fig. ). Additionally, his pulmonary dysfunction failed to improve fully as vital capacity decreased to 71.0%. |
pmc-6598259-1 | A 46-year-old Asian woman was referred to our department for a renal angiogram following 8 months of uncontrolled hypertension despite receiving medications. Initially, the patient presented with severe headache and fatigue. She had no history of smoking or drinking alcohol, was not diabetic, and had no history of diabetes in her family. She had no history of atherosclerosis. Apart from high blood pressure, the result of her physical examination was unremarkable; her general, cardiovascular system, respiratory system, and abdominal examinations were unremarkable. Neurological examination on admission showed that the patient was alert, attentive, and oriented. Her speech was clear and fluent with good repetition, comprehension, and naming. She recalled 3/3 objects at 5 min. All of her cranial nerves were intact. Motor examination revealed no pronator drift of outstretched arms. Her muscle bulk and tone were normal. Her strength was full bilaterally. Her reflexes and sensory were both intact. Her coordination and gait were normal. Laboratory investigations revealed normal complete blood count, serum cholesterol, lipid profile, and renal function (serum creatinine 119 μmol/L). Her left kidney size was normal with measurement of 9.6 cm by 4.8 cm. Renal Doppler ultrasound confirmed renal artery stenosis with renal resistive index of 0.58. The percentage of renal artery stenosis in the two branches of the left renal artery was 70% and 75%, respectively , before the first balloon angioplasty; after the first balloon angioplasty, these percentages remained the same. After the second ballooning and stenting procedure, revascularization was achieved. The patient had been attending a hypertension clinic and receiving antihypertensive drugs for the past 8 months on a regular basis under close observation. Despite this treatment and care, her blood pressure remained high at 175/110 mmHg, which the attending doctor concluded to be uncontrolled blood pressure. Initial imaging indicated left renal artery stenosis, and the patient was referred to our department (Fig. ). Prior to the diagnosis of renal artery stenosis, the patient had been receiving amlodipine 10 mg twice daily, bisoprolol 10 mg twice daily, and indapamide 2.5 mg every morning.
The procedure was performed under the guidance of digital subtraction angiography (floor-mounted Artis zee; Siemens Medical Solutions, Munich, Germany) using the Seldinger technique. With the patient under local anesthesia, the right femoral artery was punctured by a 21-gauge vascular access needle with an angled tip 0.035-inch guidewire, then catheterized with a 5-French introducer sheath (Terumo Interventional Systems, Tokyo, Japan). The first aortogram was obtained using a pigtail catheter (Fig. a), then an 8-French guiding catheter (Cook Medical, Bloomington, IN, USA; Cordis, Hialeah, FL, USA) was used to obtain selective renal angiograms whereby the proximal main flow and the stenosis of both branches and their respective distal flow on the left renal side were revealed. The right renal artery was normal in appearance. The left renal artery angiogram then was used as a reference for further guided interventional procedures in which the individual length and diameter of stenosis were measured. The decision was reached to perform percutaneous transluminal renal angioplasty, and the length and diameter of balloon needed were calibrated. With two balloons of 4 mm × 18 mm (Biotronik, Berlin, Germany), both were was dilated at the same time. Despite expert effort in dilatation, the stenosis was observed to persist (Fig. c). Stent placement was considered, and the procedure was continued. A preprocedure intravenous bolus of 5000 IU of heparin was administered. By using two 0.014-inch guidewires (V14; Boston Scientific, Natick, MA, USA), the interventional radiologist guided the stent to cross the upper and lower branches, respectively, through the same vascular sheath (Fig. b). Two balloon expandable stents measuring 4 mm × 18 mm and 5 mm × 18 mm (Biotronik) were placed in parallel (kissing) and simultaneously inflated both branches. A good angiographic result was revealed (Fig. d) with no need for further ballooning. Angiography contrast media (Omnipaque 350; GE Healthcare, Shanghai, China) were used. Volumes of 25 ml of contrast agent were injected at a flow rate of 5 ml/s. The final angiogram was obtained to confirm the position of the stent, the patency of the lumen, and distal blood flow. Finally, the femoral access site was closed with Perclose ProGlide (Abbott Vascular, Chicago, IL, USA). After the procedure, the patient was admitted in the ambulatory room for further observation. Her blood pressure was monitored and recorded, it showed a significant reduction of blood pressure to 128/87 mmHg. After 24 h of observation, the patient was discharged to home with aspirin (100 mg/day) and clopidogrel (75 mg/day for 3 months). During 12 months of follow-up, the patient remained well with blood pressure of 126/87 mmHg. Renal ultrasound showed bilateral kidneys of normal size and shape with good cortical medullary differentiation. A bilateral renal Doppler study appeared normal. |
pmc-6598291-1 | A 36-year-old white man presented in April 2017 with a 2-week history of bilateral cruralgia. Following a diagnosis in December 2014 of a right temporoparietal grade III oligodendroglioma with IDH1 mutation and 1p/19q codeletion, he underwent emergency surgical cerebral decompression for a comatose state secondary to brain herniation, with incomplete resection due to massive cerebral edema. A second surgical resection 1 month later remained incomplete, with residual in-depth disease. He was treated with cranial RT with concomitant temozolomide chemotherapy. Identical chemotherapy treatment was continued from March to December 2015 (standard protocol for high-grade gliomas), receiving six series of treatment that ended 11 months after the second surgery []. In January 2016, a cranioplasty was carried out to treat infected craniotomy bone flaps. He was monitored for the following 9 months with regular MRI scans. In August 2016, that is 20 months after surgical resection, a local tumor recurred and was treated with a third subtotal resection. Second-line procarbazine, lomustine, and vincristine (PCV) chemotherapy was initiated following surgery, 4 months before the current presentation.
A physical examination revealed motor deficits of the lower limbs in addition to pre-existing left-sided hemiparesis and a swollen left supraclavicular lymph node. A computed tomography (CT) scan showed multiple osteoblastic bone lesions scattered throughout his spine, his pelvis and to a lesser extent his ribs, but no lymph adenopathy was identified (Fig. a). A positon emission tomography (PET)-CT scan confirmed the presence of the lesions identified in the CT scan and revealed further bone lesions in his pelvis (the right ischium, the pubic area, the left acetabulum, the left part of the sacrum, and the right and left iliac wing), in his sternum with a maximum standardized uptake value (SUVmax) of 4.8, in his right (SUVmax = 5.2) and left humerus (SUVmax = 4.3), and in his right scapula (SUVmax = 4.8). No soft tissue lesions (Virchow’s node included) were found, confirming the exclusive involvement of bones (Fig. ). The analysis of lymph acquired through fine-needle aspiration of his left supraclavicular lymph node excluded lymph node metastasis. A brain MRI showed local disease progression with an increase in the volume of the right temporoparietal tumor, which had spread to the left temporal region and the superior sagittal sinus. Cytological and biochemical analysis of cerebrospinal fluid excluded carcinomatosis meningitis. Immunohistochemical analyses were carried out on a bone marrow sample from his left iliac crest. A tumoral proliferation of ovoid cells was observed in the medullary cavity. Cells were hyperchromic, had pale cytoplasm and irregular nuclei, and mitosis was occurring: this morphological aspect perfectly reflected the diagnostic for the initial anaplastic oligodendroglioma brain tumor. Immunostaining was positive for glial fibrillary acidic protein (GFAP) and the mutated form of IDH1, and therefore excluded any diagnosis other than oligodendroglioma metastasis (Fig. ). The second-line PCV chemotherapy, initiated following the third subtotal resection 4 months before the current presentation, was continued with two additional cycles in the absence of a real therapeutic alternative and at our patient’s request. It was stopped due to the worsening of his clinical status with positional vertigo, nausea, vomiting, and headache compatible with carcinomatous meningitis, followed by status epilepticus and lethargy; he died after 4 months after the diagnosis of metastases. |
pmc-6598353-1 | A 72-year-old Chinese female (non-smoker), who has suffered from blood hypertension for over 30 years, chronic bronchitis for over 20 years, and diabetes for 6 years, was admitted to our hospital due to a productive cough for three weeks followed by severe symptoms for another week.
Respiratory sounds were weak and coarser in the right lung field. Laboratory examination revealed a high percentage of monocytes, a low level of hemoglobinn and a low mean corpuscular hemoglobin concentration. A hypermetabolic mass in the upper lobe of the right lung as well as the enlargement of right hilar and subcarinal lymph nodes were determined by F-FDG PET-CTA, suggesting lung cancer and lymph node metastases. The tumor was measured as 2.8 × 2.2 × 3 cm and ulcerated.
Routine histologic sections stained with hematoxylin-eosin showed that tumor cells grew infiltrative in fibrous interstitium and arranged in sheets and syncytial pattern with marked pleomorphism. Neoplastic cells presented vacuolar nucleus with prominent nucleoli and a marked lymphocytes infiltration (Fig. ). Considering the high similarity of histology features between LELC and nasopharyngeal lymphoepithelioma, we first confirmed the absence of a primary lesion in the nasopharynx. Subsequent immunohistochemistry staining was performed on formalin-fixed paraffin sections to confirm the diagnosis. In line with previous LELC reports [, ], the tumor cells were strongly positive for CK5/6 and P40 (Fig. ), excluding the large-cell lymphoma. Besides, the tumor cells showed negative immunostaining of Napsin A, TTF1, CD56, CgA, and Syn, further excluding the possibilities of lung adenocarcinoma and neuroendocrine carcinoma [, ].
In addition, latent membrane protein (LMP1) expression of the Epstein-Barr virus was positive in tumor cells (Fig. ). Chemiluminescence analysis of EB virus antibodies showed that EBV-EA IgA and EBV-VCA IgG were both positive, confirming EBV infection in this patient. The patient was formerly infected by cytomegalovirus (CMV), so the CMV-Ab IgG was positive as well.
Microscopic examination further excluded the vessel invasion, nerve invasion, and pleural invasion. No metastasis was found at the resection margin of the bronchus or in group 7 lymph nodes, but in the bronchial lymph nodes. The patient’s vital signs were stable without apparent productive cough, chest pain, chest tightness and other subjective discomforts after thoracoscopic-assisted radical resection of right lung cancer (right upper lobe lobectomy and lymph node dissection) and resection of middle lobe of right lung. |
pmc-6598355-1 | A 29-year-old male patient had presented with a history of 2-h chest pain and numbness of left upper arm before 5 days. The electrocardiogram (ECG) indicated acute inferior wall myocardial infarction (MI) and he refused any treatment at that time. Five days later he was admitted to our hospital for further examination. Physical examination showed no abnormal including arcus corneae and xanthelasma in eyelid, extensor tendon and achilles tendons. He had no histories of diabetes mellitus, hyperthyroidism, heart disease, hepatic or renal disease and no family history of FH. The ECG showed deep Q wave and inverted T wave in leads II, III and aVF (Fig. ) and the echocardiogram revealed the diastolic dysfunction of left ventricular with a decreased LV ejection fraction (EF, 48%). The lower extremities ultrasound revealed atherosclerotic plaque in the posterior wall of right common femoral artery. Blood tests showed CK-MB of 21.4 U/L, lactate dehydrogenase of 452 U/L, hs-CRP of 71.2 ng/L, triglyceride (TG) (Triglyceride Kit method) of 0.88 mmol/L, total cholesterol (TC) of 6.87 mmol/L (Cholesterol Kitmethod), low density lipoprotein cholesterol (LDL-C) of 5.90 mmol/L and high density lipoprotein cholesterol (HDL-C) of 1.09 mmol/L (Direct Method-Surfactant Clearance Method).Further laboratory tests revealed highly elevated anticardiolipin antibody (ELISA method) of more than 120RU/ml (0-12RU/ml) and no other abnormal auto-antibodies, including β2-glicoprotein antibodies IgM, IgA, IgG, lupus anticoagulant (LA). DNA analysis for antiphospholipid antibody syndrome (APS) was not performed. Coronary artery angiography (CAG) demonstrated predominant right coronary artery (RCA) and diffuse lesions in the middle and distal segments of the left anterior descending (LAD) artery with the stenosis up to 40~50% (Fig. a) and total occlusive RCA from the middle segment (Fig. b) with LAD-RCA collateral circulation. With the treatments of anticoagulation (heparin), double antiplatelets (aspirin and ticagrelor) and lipid-modulating (rosuvastatin), he was implanted a stent at the middle segment of the RCA (Fig. c). Four days later, he was discharged without any complication. The ECG at discharge showed that the inverted T waves were deeper than those at admission in leads II, III and aVF (Fig. ). At 6-month follow-up, the laboratory test showed the level of anticardiolipin antibody (ELISA method) was less than 2.0 RU/ml (0-12RU/ml). Lipid profile revealed TG of 0.98 mmol/L, TC of 6.22 mmol/L, LDL-C of 5.53 mmol/L and HDL-C of 0.99 mmol/L.CAG showed 70% in-stent restenosis of the RCA. ECG revealed deep Q waves and inverted T waves (Fig. ). The patient looked good without any activity restriction and discomfort. At 8-month follow-up, the level of anticardiolipin antibody is less than 2.0 RU/ml and the lipid profile showed TG 0.64 mmol/L, TC 4.15 mmol/L, LDL-C 3.47 mmol/L and HDL-C 1.01 mmol/L. |
pmc-6598373-1 | A 68-year-old asthmatic male patient presented to our center with 12 days history of melena. He denied any previous episode of melena or hematochezia or bleeding from another site. The patient did not have any other associated symptom, and had no other co-morbidities, or medication use. Upon referral, he was uncomfortable and looked pale. He was vitally unstable, with a blood pressure of 90/60 mmHg and a pulse rate of 120 beats/min. The examination revealed the presence of clotted blood on the anal verge, and some tarry stool on digital rectal examination. The hemoglobin level was 7.7 g/dl, the hematocrit was 22.8, and the blood urea nitrogen was 8 mg/dl. The prothrombin time and the partial thromboplastin time were normal.
Resuscitation was performed with transfusion of 2 units of packed red blood cells and intravenous fluids. He was admitted to the ICU for intensive monitoring. After admission and stabilization, upper and lower endoscopies were performed without demonstrating the bleeding site. They only revealed clotted and red blood throughout the colon.
Technetium-labeled red blood cell bleeding scan was done to localize the site of bleeding. This scan showed no evidence of early focal increased uptake in the abdomen to indicate active gastrointestinal bleeding during early images, but in the delayed images, it revealed that there was a focal uptake in the right and transverse colon. After that, capsule endoscopy was also performed without findings. As the angiography became available, the patient underwent selective angiography without findings noted at that time. These tests were inconclusive because they were performed while the episodes of bleeding ceased.
After 8 days of conservative management and negative investigations to define the cause of the bleeding, a sudden drop in hemoglobin level from 10.8 mg/dl to 6.9 mg/dl occurred over 12 h, which mandated operative management. Exploratory laparotomy was performed. Extensive jejunal saccular pouches were found 10 cm distal to duodenojejunal junction extending 1.6 m distally Fig. . The bleeding was difficult to control and the decision to clamp the major branched was performed. Division of the small bowel proximal and distal to the diseased part using gastrointestinal stapler was performed with side to side primary anastomosis Fig. . The specimen was a part of small bowel, 117 cm in length, with congested wall and multiple pouches at the mesenteric site. Opening of the specimen showed normally looking mucosa with active bleeding that stopped after awhile. No polyps or masses were detected. We reviewed the angiography achieve after that and a suspicious shadow reflecting the diverticular outpouching was detected.
Microscopic examination of the specimen revealed many diverticula; some of which being true diverticula, while the others are devoid of muscularis propria (false diverticulae). Within the diverticula and in the intervening portions of the bowel wall, there were numerous dilated thick- and thin-walled small blood vessels in the submucosa. Additionally, submucosal intermediate-sized vascular clusters and feeder vessels in the muscularis propria and serosa were present. The overall features were those of small intestinal diverticulosis and arteriovenous malformations. The latter involves the diverticula and intervening portions of the bowel wall Fig. .
Postoperatively, the patient was doing well, discharged home on day 5 postoperatively, with an uneventful postoperative course. He was followed up 2 years after that without complications. |
pmc-6598396-1 | An 8 days old male neonate was born to an Asian mother through vaginal delivery at 37 weeks of gestation, weighed 2,380 g, and had APGAR scores of 9 and 10 at 1 and 5 min, respectively. He was admitted to our hospital with a 2 days history of fever of up to 39°C but did not have respiratory or gastrointestinal symptoms. The infant's family denied any medical history and TB contact. His physical examination at admission documented smooth respiration, clear breathing sound, and no hepatosplenomegaly. The complete blood count indicated a total white blood cell count of 17,500/μL with 69% neutrophils, 20% lymphocytes, 9% monocytes, and 2% eosinophils. The C-reactive protein level was 7.3 mg/dL. The findings of the cerebrospinal fluid (CSF) analysis were normal. Bacterial cultures of the blood, urine, and CSF were negative. Intravenous antibiotics, namely cefotaxime and ampicillin, were administered after admission on the basis of suspicion of neonatal fever. Despite the administration of the antimicrobial combination therapy, the fever persisted and the neonate developed abdominal distension when he was 12 days old. Abdominal radiography exhibited nonspecific dilated bowel loops. Because no improvement in the condition of the patient was observed after changing antibiotics, infection caused by some virus and other atypical pathogen, including Mycobacterium tuberculosis, was considered. Tests for herpes simplex virus, Epstein–Barr virus, cytomegalovirus, hepatitis B virus, rubella, Chlamydia trachomatis, and Toxoplasma gondii were all negative. The repeat C-reactive protein level was elevated to 14.4 mg/dL. Coagulopathy with 323.7 μg/mL of abnormal fibrin degradation product and more than 20 mg/L of D-dimer were also noted. Antibiotics were switched to vancomycin and ceftazidime empirically. Chest radiography displayed only increased right lung field infiltration when the infant was 12 days old (), and chest computed tomography (CT) imaging exhibited a large amount of right pleural effusion with mild inflammatory changes in the right lower lobe when the infant was 15 days old (). Pleural effusion drainage was suggested but refused by his parents at that time. Gastric lavages for acid-fast staining and culture were examined when the infant was 20 days old after his parents agreed to further testing, and one of the three acid-fast stains of gastric lavages yielded few acid-fast bacilli. Repeat chest and abdomen CT imaging performed when the infant was 24 days old indicated patchy consolidation in the right upper lung, multiple new nodules in both the lungs, moderate pleural effusion, and multiple low-density nodules in the spleen and hepatic hilar region without hepatomegaly (). Subsequently, pigtail catheter insertion for pleural effusion drainage was performed. The findings of pleural fluid analysis indicated a total white blood cell count of 10,800/μL with 6% neutrophils, 57% lymphocytes, and 37% mesothelial cells; a total protein level of 4.6 g/dL, a lactic dehydrogenase level of 250 IU/L, and a glucose level of 164 mg/dL. TB infection was strongly suspected. The neonate was administered isoniazid (15 mg/kg/day), rifampicin (15 mg/kg/day), and pyrazinamide (20 mg/kg/day) when he was 24 days old. After initiating anti-TB treatment, the neonate's symptoms and signs subsided gradually. Finally, both gastric lavage and pleural effusion cultures showed M. tuberculosis complex.
The neonate's mother was 33 years old, gravida 1, para 1. Her Group B streptococcus test was negative. She had been healthy with no previous medical history and TB contact history; however, she developed a mild dry cough 1 week after delivery, experienced persistent general weakness, and was admitted to our medical intensive care unit because of altered mental status 24 days postpartum. Laboratory examinations indicated leukocytosis, thrombocytopenia, coagulopathy, acute hepatic failure, and acute renal failure. The HIV serology test was negative. A chest X-ray exhibited a miliary TB pattern (). A chest CT image displayed diffuse interlobular and intralobular septal thickening with ground-glass opacities (). Because her neonate was highly suspected to have TB infection at that time, acid-fast staining and TB polymerase chain reaction (PCR) of the sputum were performed. Both tests were strongly positive. The mother was administered anti-TB therapy immediately, but she died 3 days after hospitalization. M. tuberculosis infection was confirmed through sputum culture. |
pmc-6598538-1 | A 50-year-old man experienced amputation of the thumb, index finger, and middle finger of the right hand in a rubber cutting machine in a work-related accident and was brought to our hospital as an emergency. The thumb and index fingers were completely amputated at the position of zone I [,] and the middle finger was amputated at zone II (). He was a right-handed field worker who cut rubber. We used a composite graft for the thumb and the index finger. Replantation of the middle finger was abandoned due to severe damage, and reconstruction with a reverse vascular pedicle digital island flap was performed on the day of injury because the bone was exposed at the wound and he wanted to keep the finger length as long as possible.
Surgery was performed under general anaesthesia. All surgical steps were performed under a microscope. A flap of 25 × 20 mm was made on the radial side at the base of the proximal phalanx of the right middle finger (), the vascular pedicle was ligated proximally after clamping to confirm finger blood circulation and isolated from the digital nerve, and the flap was elevated. At the same time, the dorsal branch of the digital nerve was identified in the middle phalanx, and the flap was passed under the nerve to preserve the nerve (). The fingertip defect was covered with the flap, and the donor site was closed with a skin graft. The flap survived without any venous congestion.
The postoperative sensory recoveries of the flap and the dorsal skin of the distal phalanx were excellent. In the Semmes–Weinstein monofilament test, the sensation of the flap returned to 3.22 (blue) and the dorsal sensation of the radial side recovered to 2.83 (green) early after surgery (). At half a year after the operation, there was no limitation in the range of motion, and the contour was good (). |
pmc-6598597-1 | A 51 year old Caucasian woman presented with a diffuse skin rash associated with abdominal pain and diarrhea with a 2 weeks duration. Her past medical history was remarkable for a B2-type thymoma which was diagnosed about 7 years earlier. The patient underwent complete surgical resection of the tumor and then received adjuvant radiotherapy (50.4 Gy). Few months after surgical removal of the thymoma, the patient developed diffuse muscle weakness and was diagnosed with MG. She was started on azathioprine and pyridostigmine resulting in a good clinical control of her symptoms. Physical examination revealed erythematous plaques with shallow erosions and overwhelming yellow-to-brown crusts, involving the trunk, mainly back, upper and, to lesser extent, lower limbs, dorsal aspect of hands, face, and scalp (). There was no mucosal involvement. The results of the routine laboratory investigations were unremarkable except for elevated serum concentrations of the transaminases, GOT and GPT.
Initially, after surgical removal of the thymoma, direct immunofluorescence (DIF) from perilesional biopsy of the scaly erythematous skin rash revealed deposits of both IgG and C3 on the surface of epidermal keratinocytes (). Another DIF which was taken later at the time of GVHD-like dermatitis revealed instead linear deposits of IgG and C3 along the dermal-epidermal basement membrane zone (BMZ) (). Indirect immunofluorescence (IIF) on normal human skin, 1M NaCl-split human skin and monkey esophagus showed neither IgG autoantibodies to either the surface of epithelial cells nor on the dermal-epidermal BMZ (not shown). In addition, IIF on rat bladder was negative on transitional epithelia (not shown). Of note, the patient had IgG autoantibodies against Dsg1 (719 relative units (RU)/ml, cutoff <20 RE/ml) and desmocollin 1 (Dsc1) (0.448 OD, cutoff <0.200 OD) by ELISA and IgG autoantibodies against laminin 332 by immunoblot analysis ().
Based on clinical, histologic, and immunologic findings, the diagnosis of PF with additional anti-BMZ IgG reactivity was established. As there was neither evidence for IgG antibodies against desmosomal plaque proteins nor the 170 kDa alpha2-macroglobulin-like protein-1, the diagnosis of PNP was abandoned.
The patient initially received a cycle of intravenous immunoglobulins (IVIg) at 2 g/kg/cycle, followed by infusions of rituximab 2 × 1 g two weeks apart (, ). The patient's skin erosions improved significantly and fully regressed eventually, in association with the decrease of anti-Dsg1 serum IgG antibodies.
Several months later, she developed diffuse erythroderma (). Erythematous targetoid plaques, resembling erythema multiforme (EM), and hyperkeratotic plaques appeared at her lower limbs and soles, respectively (). A skin biopsy from the erythrodermic skin revealed liquefactive degeneration and apoptotic keratinocytes and a band-like lymphocytic infiltrate along the BMZ (). These cutaneous symptoms were associated with persistent diarrhea and elevated liver enzymes and were thus considered as thymoma-associated GVHD-like disease. A chest X-ray and magnetic resonance imaging revealed a large mass in the left anterior mediastinum which was diagnosed by histopathology as a recurrent type-B2 thymoma. Prior to surgical removal, the patient received a cycle of intravenous cyclophosphamide (1,300 mg total dose) and IVIg (2 g/kg given on three consecutive days). After tumor resection, erythroderma with multiform lesions gradually regressed () and eventually disappeared (). Of note, MG significantly improved and anti-Dsg1 serum IgG antibodies were no longer detectable (). A third skin biopsy revealed findings consistent with GVHD-like erythroderma (). Despite the clinical response, the patient eventually died because of an opportunistic bacterial infection leading to fulminant sepsis. |
pmc-6598598-1 | Clinical Presentation: A 58-year old woman is treated with combination Ipilimumab/Nivolumab therapy for stage IV non-small-cell lung carcinoma (NSCLC), and presents with a 3-week history of a left, swollen, and painful left knee.
Arthralgia and inflammatory arthritis (IA) are the most commonly encountered rheumatic irAEs (, ). ICI-induced IA can have a variable timing, with a median onset 5 months (range 1–24 months) after ICI initiation (). The clinical presentations of IA are variable with oligoarthritis, polyarthritis, and reactive arthritis-like manifestations being described (). Cappelli et al. reported that patients who received combination ICIs were more likely to present with large joint involvement and to already have another irAE, while patients treated with ICI monotherapy were more likely to have initial small joint involvement and to have IA as their only irAE (). Other rheumatic irAEs include polymyalgia-like syndrome, vasculitis, sicca syndrome, and inflammatory myopathies (). The data regarding the incidence of rheumatic complications is highly variable, with rates of arthralgia ranging from 1 to 43%, with reports of other manifestations ranging from 0.7 to 5.1% (, ). This is potentially related to the variability in potential coding of these events in clinical trials, using CTCAE criteria.
Patients should undergo a full musculoskeletal evaluation. Laboratory studies including ESR (Erythrocyte sediment rate), CRP (C-reactive protein), RF (rheumatoid factor), ACPA (anti-citrullinated peptide/protein antibodies), ANA (anti-nuclear antibody), and HLA-B27 (Human Leukocyte Antigen B-27) should be sent, to help differentiate between phenotypes of IA that may have treatment implications. The majority of patients are seronegative, but a seropositive subgroup has been described (). Imaging including joint ultrasound or MRI should be completed to assess for effusion, erosive disease and tenosynovitis. In the above patient, diagnostic evaluation was notable for left knee effusion (see ) with unremarkable synovial fluid analysis, elevated inflammatory markers, and seronegative disease.
Early recognition of IA is critical to avoid erosive joint damage. ICI can be continued for grade 1 toxicities and treated with simple analgesia consisting of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs). However, in this patient with grade 2 IA, ICI was temporarily held while she received treatment with acetaminophen, NSAIDs and oral corticosteroids of prednisone 20 mg/day for 4 weeks. Given large joint involvement, she also received an intra-articular corticosteroid injection. Corticosteroid dose can be adjusted pending clinical response with taper over 4–6 weeks in the instance of clinical improvement, or, in presence of progressive IA, treatment can be escalated with addition of other immunomodulatory medications such synthetic or biologic disease-modifying anti rheumatic drugs (DMARDs). This patient demonstrated improvement and prednisone was tapered over 4 weeks. Ipilimumab/Nivolumab therapy was resumed when IA symptom control was reached, and the patient was taking a prednisone dose of 10 mg daily. A notable feature of rheumatic irAEs, in particular ICI-induced-IA, is their predilection for persistence despite cessation of ICI therapy which may require long-term immunomodulatory therapy for months to years after diagnosis (). Due to likely prolonged treatment requirements, physicians should consider starting immunomodulatory medications earlier than one would with other irAEs. DMARDs should be considered in all patients with grade 3 or 4 disease, as well as grade 2 patients that display progression of disease with corticosteroid therapy. In steroid-refractory cases, a common approach is to start with Methotrexate, with escalation to biologic agents such as infliximab in the absence of adequate clinical response. |
pmc-6598598-2 | Clinical Presentation: A 76-year old man with advanced urothelial presents with temporal headache and jaw claudication 10 days after cycle two of durvalumab.
Both polymyalgia-like syndrome and giant cell arteritis (GCA) have been reported following treatment with ICI. A recent analysis of WHO's VigiBase found that patients who received ICI had a reporting odds ratio of GCA 13 times greater than patients not treated with ICI (). This study also reported that the median time of onset from last dose of ICI was 55 days (range: 21–98) with a greater predilection for elderly patients, Caucasian patients, and those with melanoma (). ICI-induced GCA symptoms mirror those of traditional GCA, including temporal headache, jaw claudication, monocular vision loss, unexplained fever, and fatigue.
Early diagnosis is vital to prevent devastating ocular and cerebrovascular complications of GCA. Visual impairment has been reported in 28% of patients with ICI-induced GCA (). The diagnosis of GCA should not be made based upon symptoms alone and investigations including complete blood count (CBC), ESR, and CRP. Temporal artery biopsy is the gold standard diagnostic test and provides definitive diagnosis, but should not delay treatment. In this patient, physical examination was notable for temporal artery tenderness with intact vision. Initial investigations were notable for markedly elevated ESR and CRP.
Given intact vision, the patient was commenced on prednisone 60 mg/day to complete 2 weeks of therapy followed by a taper every 2 weeks. Durvalumab was held pending clinical response. Temporal artery biopsy confirmed the diagnosis. This management was instituted with the input of a rheumatology consult.
Patients with suspected ICI-induced GCA should be managed as per traditional rheumatic GCA with the addition that ICI therapy should be held pending clinical improvement in GCA. In patients without visual loss at diagnosis, treatment should comprise prednisone 1 mg/kg/day (maximum dose of 60 mg daily). Patients with threatened or established visual loss at diagnosis should be commenced on intravenous pulse corticosteroids (1 g methylprednisolone daily) for 3 days followed by high dose oral therapy (). Oral corticosteroids should be maintained for 2–4 weeks followed by a two-weekly interval taper. Typically, prednisone will be tapered by 10 mg every 2 weeks until a dose of 40 mg/day is reached, at which point the dose will be reduced by 5 mg decrements every 2 weeks until a dose of 20 mg/day is reached. At this point, the rate of the corticosteroid taper is slowed.
In the case of relapsed GCA symptoms despite high-dose corticosteroids, abatacept has demonstrated efficacy (), while methotrexate and tocilizumab are alternate therapeutic options. Resumption of ICI therapy can be considered once prednisone dose is <10 mg/day, ideally in consultation with rheumatology. |
pmc-6598598-3 | Clinical presentation: A 65-year old man with advanced renal cell carcinoma presents with chest pain and dyspnea following 1 cycle combination Ipilimumab/Nivolumab therapy.
Myocarditis is the most commonly documented cardiac irAE (). Cardiovascular complications of ICIs are less well-recognized, but these complications can be potentially fatal (, ). The absolute incidence of cardiac irAE is reported at <1%, however the true incidence is likely higher given prior under-recognition of cardiac toxicity (). Recently, Salem et al. reported that the odds of myocarditis in patients receiving ICIs was 11 times greater than patients who did not receive ICI (), with a median time of onset 30 days after initial exposure to therapy. Wang et al. recently found that myocarditis has the highest fatality rate of any irAE (). Manifestations of myocarditis are variable, with a clinical spectrum ranging from fatigue, chest pain, acute heart failure to cardiogenic shock, arrhythmias, and sudden death (, ). Pericarditis, conduction disease and ventricular arrhythmias are other reported cardiac irAEs, but acute myocardial ischemia, new onset systolic dysfunction and Takotsubo syndrome can also occur ().
Myocarditis is characterized by elevated cardiac enzymes (troponin, pro-BNP), with/without the onset of left ventricular dysfunction and evidence of myocardial inflammation on cardiac MRI or PET/CT; all of these parameters should be investigated. In cases of uncertainty, endomyocardial biopsy can be useful although non-invasive investigations are preferred. Initial evaluation of this patient was notable for marked hypervolemia and pulmonary edema. Diagnostic workup was notable for non-specific ST-segment changes on ECG, marked elevation of cardiac markers and new reduced ejection fraction on transthoracic echocardiogram. Cardiac MRI was notable for late gadolinium enhancement overlying the basal left ventricular lateral wall (see ).
The patient was transferred to the Cardiac Care Unit under the care of the cardiology team. ICI was permanently discontinued. The patient was monitored on continuous telemetry and commenced treatment with daily intravenous 1 g methylprednisolone and diuretic therapy. His hospital course was complicated by complete heart block that was managed with transvenous pacing, however, progressive clinical deterioration followed, resulting in cardiac arrest from which he could not be resuscitated.
All grades of cardiac toxicity warrant evaluation given the risk of cardiac compromise. Effective management requires close monitoring with a multimodal therapeutic plan consisting of ICI cessation, high-dose corticosteroids (1–2 mg/kg of prednisone/day or equivalent) and early cardiology consultation with management of cardiac complications. Steroid-refractory cases may necessitate the addition of mycophenolate, infliximab, or anti-thymocyte globulin, and there are no specific data that demonstrate a superior approach of these three options. Conduction disease is emerging as a common and potentially serious cause of ICI-medicated sudden death, even in the absence of myocarditis (). Electrophysiology consultation should be completed for consideration of insertion of cardiac device (pacemaker or defibrillator) if there is concern for ICI-induced conduction disease. In the instance of cardiac device insertion, the decision to proceed with ICI therapy should be made in conjunction with the patient, cardiology, and oncology. A surveillance strategy has recently been proposed that suggests a baseline cardiac assessment for all patients including baseline cardiac risk factor assessment, electrocardiogram, cardiac troponin, and pro-brain natriuretic peptide (pBNP) in addition to a non-invasive surveillance protocol for patients with cardiac risk factors defined as pre-existing coronary artery disease, hypertension, diabetes mellitus, obesity, smoking history, or positive family that should be completed within the initial 12 weeks of therapy (). Given the mortality risk of these complications this approach may be appropriate, but should be evaluated in prospective studies. |
pmc-6598598-4 | Clinical presentation: A 61-year old woman with Merkel cell carcinoma presents with a pruritic rash after cycle two of Avelumab therapy. She denies mouth pain, eye pain, fever, or constitutional symptoms.
Cutaneous toxicities are the most commonly encountered irAE, and has been reported in 30–50% of patients receiving ICI therapy (), with 37–70% of patients receiving CTLA-4 and 17–37% of patients receiving PD1/PDL-1 therapy experiencing dermatologic toxicities, respectively (, ). Of these, <3% experience greater than grade 3 toxicity. Dermatologic irAEs are challenging as they have variable clinical presentation and timing of onset. Clinical manifestations range from pruritus, vitiligo, inflammatory rashes (maculopapular eruption, dermal hypersensitivity reactions, acneiform, exfoliative, and psoriasiform lesions), bullous dermatoses (bullous pemphigoid, bullous drug reaction) to severe cutaneous adverse reactions (Stevens Johnson Syndrome, Toxic Epidermal Necrolysis, Drug-induced hypersensitivity syndrome/Drug reaction with eosinophilia and systemic symptoms). Time to onset can vary between 2 weeks and several months from onset of therapy (, ).
In patients with cutaneous irAE, a thorough clinical history and physical examination should be obtained. Clinicians should perform a close evaluation of all skin surfaces, mucus membranes, and lymph nodes with a specific focus on the percentage body surface area that is involved and the presence or absence of blistering. A positive Nikolsky sign (induction of blistering via mechanical pressure) should prompt concern for severe cutaneous reaction (SJS/TEN), which will characteristically include mucosal and systemic involvement (fever, constitutional symptoms). On examination, this patient was noted to have tense blisters and erosions on her extremity flexures that involved 15% body surface area. Nikolsky sign was positive. There was no evidence of ocular of mucosal involvement. Hematological and biochemical investigations were normal. She was evaluated by a dermatologist and underwent lesional and perilesional biopsies that confirmed the diagnosis of bullous pemphigoid. Skin biopsy revealed linear immunoglobulin G (IgG) and linear C3 staining along the basement membrane zone, which is present in >90% of cases (). If biopsy is not possible, serum can be sent for antibodies to BP180 and BP230 (ELISA testing) to confirm the diagnosis ().
The patient was treated with betamethasone topical therapy and oral prednisone 1 mg/kg, tapered over 4 weeks. The patient was monitored closely with serial photography for progression but displayed evidence of improvement. Avelumab was initially held, but resumed upon resolution of symptoms to less than grade 1 severity.
With the exception of bullous disease, most grade 1 and 2 cutaneous toxicities can be managed with topical therapies (emollients, corticosteroids) and continuation of immunotherapy. Escalation of dermatologic care includes holding immunotherapy, increasing the potency of topical corticosteroids and starting systemic corticosteroids. Grade 4 toxicities should be treated with intravenous methylprednisolone dosed at 1–2 mg/kg. Patients with >30% body surface area involvement should be managed in specialist burns unit. In steroid-refractory cases, IVIG or cyclosporine can be considered in conjunction with dermatology. Notably, cutaneous irAEs have been recognized as a barrier to ICI compliance (). Interestingly, development of cutaneous toxicities may correlate with clinical response in patients with metastatic melanoma, with a greater survival benefit reported in melanoma patients who developed rash or vitiligo after pembrolizumab or nivolumab therapy, respectively (, ). Development of new vitiligo has also demonstrated a significant association with both progression-free survival and overall survival in a meta-analysis of 27 studies of melanoma patients treated with a wide variety of immunotherapeutic strategies (139 treatment arms comprising 11 general immune stimulation, 84 vaccine, 28 antibody-based, and 16 adoptive transfer)(). |
pmc-6598598-5 | Clinical presentation: A 58-year old woman with stage IV PD-L1+ NSCLC was noted to have asymptomatic creatinine (Cr) elevation to 2.5 mg/dl (baseline 0.9 mg/dl) after 2 cycles of Pembrolizumab.
Nephritis is the most common renal toxicity of anti-PD-1/PD-L1 therapy, and is more common in patients with NSCLC treated with the combination of chemotherapy and immunotherapy, which is now standard first-line therapy for patients with advanced NSCLC (). Hyponatremia may also be encountered in these cases, however this occurs more commonly in the setting of hypophysitis (). There is significant heterogeneity in the onset of kidney injury; with CTLA-4 nephrotoxicity occurring earlier (range: 2–3 months), compared to the later onset of injury with PD-1 related nephrotoxicity (range: 3–10 months) (–). Acute interstitial nephritis is the most prevalent pathologic lesion, with one report of thrombotic microangiography (). While initial data suggest that ICI-mediated renal injury ranged from 1 to 2% in monotherapy and 4.5% in combination therapy (), more recent studies have suggested a higher incidence ranging from 9.9 to 29% ().
Patients with renal irAEs are frequently asymptomatic and therefore, routine monitoring of renal indices (serum creatinine, electrolytes) is necessary to ensure prompt detection. Symptomatic patients may present with nausea, vomiting, fatigue, altered mental status, reduced urinary output, peripheral edema, or dyspnea. All patients should undergo complete renal evaluation including urinalysis, serum creatinine, serum electrolytes, and consideration for renal ultrasound to evaluate for other potential etiologies. In this asymptomatic patient with Cr 2.5 mg/dl, urinalysis was notable for pyuria with mild peripheral eosinophilia on CBC. Investigations may reveal pyuria (68%), hematuria (16%), and/or proteinuria on urinalysis with eosinophilia (21%) on CBC (, ).
Therapy should be temporarily withheld while evaluation for an underlying cause of nephrotoxicity is completed. Should no alternate cause be identified, patients should be presumed to have immune-mediated toxicity. Reflex kidney biopsy is not recommended until corticosteroid treatment has been attempted. Corticosteroids are the mainstay of treatment. Additional immunosuppression including mycophenolate can be considered in steroid-refractory cases. In this patient, Pembrolizumab was held temporarily. Nephrology were consulted and she was commenced on prednisone 1 mg/kg/day. At 2-week follow up Cr had improved to 1.8 mg/dl. Prednisone was tapered over 4 weeks with improvement in renal indices to baseline. Following discussion with the patient regarding risks and benefits, pembrolizumab was resumed. |
pmc-6598598-6 | Clinical presentation: A 62-year old female with stage IV renal cell carcinoma presents with headache and altered mental status 1 week following Ipilimumab/Nivolumab therapy.
Neurological toxicities, while uncommon, are of special interest due to their potential severity. These complications encompass dysregulation of both central and peripheral nervous systems. Central manifestations include encephalitis, aseptic meningitis, transverse myelitis and posterior reversible encephalopathy syndrome (PRES). Encephalitis is estimated to occur in 0.1–0.2% of patients (). Patients may present with headache, altered mental status, motor or sensory deficits, abnormal behaviors, personality change, speech disorders, or movement disorders. A meta-analysis of 9,208 patients who received ICI therapy reported that incidence of neurologic irAEs ranged from 3.8 to 6.1% with anti-CTLA4 and anti-PD-1 monotherapy, respectively, and up to 12.0% with combination therapy. High-grade events were reported at an incidence of <1% across all ICIs (). The median time of onset to encephalitis is 6 weeks. Most neurological irAEs present initially with non-specific symptoms such as headache, dysgeusia and sensory impairment (, ).
A baseline complete blood count, liver, renal, and thyroid function should be sent as well as assessment of the pituitary axis. If there is concern for a vasculitic process, ESR, CRP, and ANCA should be sent. Lumbar puncture should be completed to evaluate for infection and leptomeningeal disease. Anti–N-methyl-D-aspartate receptor (anti-NMDAR) antibody should also be sent. Contrast-enhanced MRI brain scan and EEG monitoring can be completed to assesses for vascular insult, brain metastasis and subclinical seizure activity. In this patient, the diagnostic evaluation revealed an intact pituitary axis, with a subtle hyperintensity of the right hippocampus on MRI (see ). CSF analysis was notable for a lymphocytic pleocytosis with negative infectious, paraneoplastic and cytopathology panel. EEG showed diffuse non-specific slowing.
Prompt recognition and expeditious management carries the potential of complete neurological recovery (, ). In this patient, ICI was held and she was commenced on IV acyclovir that was discontinued on receipt of negative viral PCR panel. Neurology were consulted. She was treated with pulse corticosteroids (methylprednisolone 1 g IV daily for 5 days) as well as IVIG 2 g/kg over 5 days. Following 8 days of therapy with corticosteroids and IVIG, she demonstrated full neurological recovery. A recent case series of nine patients with ICI-induced neurological toxicity reported that 77.8% of patients showed marked symptomatic improvement following discontinuation of immunotherapy and management with corticosteroids (). In steroid-refectory cases, additional therapeutic modalities such as IVIG, rituximab or plasmapheresis can be considered, since this toxicity is autoantibody-mediated. |
pmc-6598598-7 | Clinical Presentation: A 67-year old man with metastatic colorectal cancer presents with diplopia 1 week following the first cycle of Nivolumab therapy.
Myasthenia gravis is estimated to occur in 0.1–0.2% of patients receiving immunotherapy (, ). Presentation is typically within 2–3 weeks of treatment initiation (, ) with symptoms of fluctuating motor weakness and fatigue that is often associated with ocular and bulbar dysfunction. Peripheral neurotoxicity can also manifest as peripheral neuropathy, autonomic neuropathy, Guillain-Barre syndrome, and necrotizing myositis.
Any concern for myasthenia gravis warrants rapid evaluation and intervention given the potential for respiratory compromise. In this patient, acetylcholine receptor antibodies were positive. Serial pulmonary function test with negative inspiratory force (NIF) and vital capacity did not reveal respiratory compromise. Electrophysiologic testing (Single fiber EMG) confirmed the diagnosis of myasthenia gravis. Other investigations including creatinine kinase, aldolase, ESR, and CRP should be sent to assess for concurrent myositis. High clinical suspicion for concurrent myositis and myocarditis is warranted given possibility of coexisting myasthenia gravis, myositis and myocarditis in a subset of patients as evidenced in 25% of cases of nivolumab-related myasthenia gravis ().
ICI-induced myasthenia gravis has been associated with a higher incidence of myasthenic crisis than idiopathic myasthenia gravis (, ). Thus, a high level of suspicion and rapid initiation of corticosteroids are mandatory to prevent clinical deterioration, which can result in respiratory failure and death. In this patient, nivolumab therapy was held. Neurology were consulted and he was commenced on pyridostigimine 30 mg four times per day as well as prednisone 1 mg/kg/day. With clinical improvement, prednisone was slowly weaned in 5 mg decrements every 2 weeks. Patients with grade 3 or 4 toxicity should be monitored in the intensive care setting given risk of respiratory compromise. Pyridostigimine can be titrated to achieve optimal relief of symptoms. Additional therapeutic modalities include IVIG or plasmapheresis that should be initiaited for grade 3 or 4 disease. |
pmc-6598598-8 | Clinical Presentation: A 71-year old man with history of urothelial cancer noted onset of right eye pain 5 weeks following cycle 1 of Atezolizumab therapy.
Ophthalmic irAEs affect <1% of ICI-treated patients and typically manifest as uveitis and/or dry eye (, ). Ocular irAE have a median onset of 2 months and are more commonly associated with other concurrent irAEs (). Patients can present with eye pain, erythema, pain with eye movement, visual disturbance, diplopia, or photophobia. Less commonly encountered ocular manifestations include inflammatory orbitopathy, keratitis, choroidal neovascularization, serous retinal detachment, retinopathy, neuroretinitis, and ocular myasthenia gravis.
Ocular irAEs are commonly seen in associated with other systemic irAEs, therefore clinical suspicion for other manifestations should be high. This particular patient endorsed the presence of visual floaters, but denied pain with eye movement, change in color perception, visual change, or photophobia. On examination, the patient's right pupil was mildly constricted, reactive to light with erythema of the limbus. Left pupil was round and reactive. Color vision and visual acuity were intact. Red reflex was present bilaterally. There was no evidence of concurrent irAE.
The patient was prescribed topical corticosteroid, 1% cyclopentolate (topical cyclopegic agent) and prednisone 60 mg daily. An urgent ophthalmology appointment was scheduled within a week. Atezolizumab was temporarily held until completion of corticosteroid taper over 2 months.
The majority of ocular irAE do not necessitate discontinuation of ICI and are managed with topical therapies. All patients should be referred to ophthalmology for slit-lamp and dilated fundus examination to assess for presence of leukocytes in the anterior chamber of the eye as well as to examine the extent of inflammation. In this case, ICI was temporarily held in the setting of grade 2 toxicity. However, ICI should be permanently discontinued with emergent ophthalmology assessment in higher grade irAEs. Additional therapeutic strategies include systemic and topical/intravitreal corticosteroids. Infliximab can be considered in steroid refractory cases (). |
pmc-6598598-9 | Clinical presentation: A 54-year-old man with advanced urothelial carcinoma presents following the fifth dose of Durvalumab with dyspnea.
Checkpoint-inhibitor pneumonitis (CIP) is defined as the development of new infiltrates on chest imaging with dyspnea or other respiratory symptoms in the absence of infection, cardiac dysfunction or tumor progression. Presentations can be heterogeneous, ranging from asymptomatic radiographic findings, chest pain, cough, or dyspnea, to life-threatening respiratory compromise (). The overall incidence of CIP ranges from 0 to 10%, with a median time to onset of ~3 months reported by Naidoo et al. (). Patients receiving combination ICI therapy are at increased risk of CIP (10 vs. 3%, respectively; p < 0.001), with evidence to suggest that these patients experience symptoms earlier in the clinical course (, ). In a study of fatal ICI-associated toxic effects, anti–PD-1/PD-L1–related fatalities were often from pneumonitis, consisting of 35% of all fatalities (). The data would suggest that higher grade CIP tend to occur within the first 100–200 days of therapy initiation (). Emerging data from the Johns Hopkins Hospital group has shown that tumor histology may be a risk factor for CIP in NSCLC patients (). Furthermore, multistate modeling has demonstrated that NSCLC patients who develop CIP may have a poorer survival ().
The patient underwent thorough history and physical examination that was notable only for hypoxia with O2 saturation of 88% on room air. Physical examination in CIP can be very unrevealing and thus clinicians must be vigilant for early detection. The differential diagnosis should include respiratory infection, rare respiratory infections such as PCP or aspergillosis (especially if being treated with high-dose corticosteroids), tumor progression, radiation-induced pneumonitis, and ICI-induced myocarditis/cardiac failure. Further diagnostic evaluation should include infectious evaluation (urine, respiratory culture, viral culture/swab, blood cultures, serum galactomannan), CT imaging and consideration for bronchoscopy with bronchoalveolar lavage (BAL) +/– lung biopsy. This patient underwent CT imaging with findings as illustrated in . Infectious evaluation was negative for the presence of an infectious organism. Bronchoscopy with BAL was notable for the presence of chronic lymphocytes and macrophages with type-II pneumocyte hyperplasia. High-resolution CT chest is the imaging modality of choice, with common manifestations including ground-glass opacities or patchy nodular infiltrates, predominantly in the lower lobes (). This should ideally be done with contrast, to rule out the presence of a pulmonary embolus. Five distinct types of radiologic abnormalities of CIP have been described, including cryptogenic organizing pneumonia (COP) like ground glass opacities, interstitial, hypersensitivity, and pneumonitis not-otherwise-specified ().
Corticosteroid therapy is the mainstay of CIP management, with >80% of CIP patients having their pneumonitis improve or resolve with corticosteroids alone. Pulmonology assessment is often warranted in any patient with suspected CIP, to evaluate for bronchoscopy or help to rule out alternative etiologies. In this patient with grade 2 CIP, ICI was temporarily held while the patient was treated with prednisone 1 mg/kg/d, followed by 5 mg/week taper over 4 weeks. Interval CT imaging at 4 weeks was notable for improvement in radiographic findings. In this case, since CIP resolved, the patient's ICI-therapy was restarted. While grade 1 or 2 CIP can be managed with low-dose corticosteroids and close observation, higher-grade CIP should be treated with high-dose corticosteroids (methylprednisolone IV 1–2 mg/kg/d). Infectious disease should be consulted in addition to the pulmonary team to rule out common or unusual infections, and in some cases, empiric antimicrobials may be given when infection cannot be completely excluded. Lung biopsies are typically not warranted, but may be useful rule out infection or lymphangitic tumor spread. Patients that do not demonstrate clinical improvement in CIP within 48–72 h should be considered for second-line therapies, options include infliximab, mycophenolate mofetil, IVIG, or cyclophosphamide. Retrospective studies have noted that up to 86% of CIP improves with corticosteroid treatment, however, of concern there was very poor response to additional immunosuppression (, ). In addition, a recent retrospective analysis has found that pneumonitis is associated with worse survival (). There is currently a deficit in evidence for salvage treatment in steroid refractory patients. This is an area under current development to ameliorate the morbidity and mortality associated with respiratory-induced adverse events. |
pmc-6598598-10 | Clinical presentation: A 70-year old male with advanced renal cell carcinoma receiving Ipilimumab/Nivolumab, presents with new-onset fatigue and dizziness after 2 cycles of therapy.
Immune-related endocrine events pose a clinical challenge as symptoms are often subtle. Patients can present with non-specific symptoms including nausea, vomiting, dizziness, headache, fatigue, and malaise. The pituitary, thyroid, pancreas, and adrenal glands are the organs most commonly affected, although parathyroid involvement has also been reported (). The incidence of immune-related endocrinopathies was approximately 10% in a recent meta-analysis of 7,551 patients that received ICI (). The risk of endocrine irAE is greatest with combination therapy, with rates of hypothyroidism (17%), hypophysitis (13%), and hyperthyroidism (10%) reported (, ).
In this particular patient, a physical examination was notable for intact visual fields, however, laboratory assessment showed mild hyponatremia, with both low TSH and free T4. Morning ACTH and cortisol were also low. MRI brain was notable for pituitary enhancement.
In patients with suspected hypophysitis, the pituitary-hypothalamic axis should be examined including free T4, TSH, LH, FSH, ACTH, and cortisol, as well as serum electrolytes. It is imperative to discern between primary vs. secondary hormonal deficiencies, as this will guide appropriate management. Clinicians should recognize that hypophysitis can result in secondary adrenal insufficiency and hypothyroidism. Failure to recognize this disease entity can have negative consequences for patient care; replacing thyroid hormone prior to cortisol repletion can precipitate adrenal crisis.
Ipilimumab/Nivolumab therapy was temporarily held. In consultation with endocrinology, the patient was started on hydrocortisone 10 /5 mg in morning and afternoon, respectively. One week later he was started on a weight-based dose of levothyroxine. The patient was provided with “sick day” instructions for stress dosing of hydrocortisone and a medical alert bracelet. The patient demonstrated clinical improvement and was restarted on PD-1 monotherapy.
It is recommended that ICI is held for any-grade hypophysitis. Once patients demonstrate stability on hormonal replacement, ICI can be restarted. Higher-grade hypophysitis (grade 3+) can be managed with an initial pulsed dose of corticosteroids. Free T4 should be monitored for levothyroxine replacement. Key concepts of management include high index of clinical suspicion, appropriate localization of endocrine dysfunction, replacement of hormones and close monitoring. Immune-related endocrine events are unique as the manifestations are often irreversible and patients often require lifelong hormone replacement (). |
pmc-6598598-11 | Clinical presentation: A 60 year old female patient with stage-III lung adenocarcinoma treated with durvalumab, has a thyroid stimulating hormone (TSH) of 8.5 mIU/l with normal free thyroxine (fT4). She was asymptomatic.
Hypothyroidism is one of the most common irAEs from anti-PD-1, anti-PD-L1, and anti-CTLA-4 ICIs. A systematic review and meta-analysis by Barroso-Sousa et al. demonstrated that the overall incidence of hypothyroidism was 6.6% (). Hypothyroidism can present with fatigue, unintentional weight gain, cold intolerance, constipation, myalgia, and dry skin.
Physical examination may be notable for goiter, bradycardia, diastolic hypertension, or delayed deep tendon reflexes. TSH and fT4 should be completed prior to initiation of ICI therapy and should be monitored every 4–6 weeks. It is important to differentiate primary from secondary hypothyroidism as discussed above, as well as differentiate hypothyroidism from late-phase thyroiditis. Elevated TSH with low fT4 is indicative of biochemical hypothyroidism. Upon detection, thyroid peroxidase (TPO) antibody should also be sent.
Durvalumab therapy was continued. At 4 week follow-up, TSH level was noted to be elevated to 12 mIU/ml with normal fT4. She remained asymptomatic. However, given TSH >10 mIU/l, she was commenced on 75 mcg of levothyroxine daily. In patients with grade 1 hypothyroidism, ICIs may be continued with close monitoring of TSH and fT4. For grade 2 toxicity, appropriate thyroid supplementation should be administered with either continued ICIs or temporary withholding until symptomatic patients with any level of TSH elevation or in asymptomatic patients with TSH levels that persist >10 mIU/l (measured 4 weeks apart) improve. Grade 3 and 4 toxicities should be treated as grade 2 unless signs of myxedema (decreased mental status, hypotension, hypoglycemia, bradycardia, hypothermia) are present, in which case hospitalization for supportive therapy may be recommended. In general, TSH should be monitored every 6–8 weeks while titrating hormone replacement until a normal TSH is reached, with repeat testing annually or as clinically indicated. |
pmc-6598598-12 | Clinical presentation: A 50-year old female with PD-L1+ metastatic lung adenocarcinoma presents with petechiae after 3 cycles of pembrolizumab treatment.
Hematologic irAE that may occur from anti-PD-1/PD-L1/CTLA-4 include autoimmune hemolytic anemia, acquired thrombotic thrombocytopenia, hemolytic uremic syndrome, immune mediated thrombocytopenia, lymphopenia, and acquired hemophilia. Thrombocytopenia due to ICI is relatively infrequent, with reports ranging from 1 to 28% of patients (–).
In patients who develop thrombocytopenia during ICI therapy, other etiologies for this presentation should be considered, including bone marrow suppression, infiltration, platelet destruction, or platelet sequestration, with a differential diagnosis of myelodysplastic syndrome, disseminated intravascular coagulation, ICI-mediated thrombocytopenia, acquired thrombotic thrombocytopenia (TTP), and hemolytic uremic syndrome (HUS). A thorough history is important to evaluate for drug/toxin exposures or viral infections that may have led to thrombocytopenia. In this patient, CBC was notable for normal hemoglobin with grade 2 thrombocytopenia (platelets 70,000/μl). Renal function was normal. There was no evidence of platelet consumption or hemolysis on a peripheral blood smear. Hemolysis labs including serum lactate dehydrogenase (LDH), haptoglobin, indirect bilirubin, and CBC were normal. HIV, hepatitis B/C virus and H. pylori were negative. Thus, ICI-mediated immune thrombocytopenia was the most likely diagnosis.
In this patient, ICI was held for 2 weeks, and a repeat CBC did not show improvement in platelet count until prednisone 1 mg/kg/dose was started. Re-evaluation at 2 weeks revealed improvement to grade 1 thrombocytopenia (Platelets 90,000/μl). Prednisone was tapered over 4 weeks, and the patient was able to be recommenced on pembrolizumab.
Most patients with low-grade thrombocytopenia improve with ICI withholding and initiation of oral corticosteroids. For higher-grade toxicities, a hematology service should be consulted for consideration of additional therapies for severe toxicity, such as IVIG, rituximab, cyclosporine A, mycophenolate mofetil, cyclophosphamide, or thrombopoietin receptor agonists. If indicated, IVIG initial dosing is recommended at 1 g/kg as a one-time dose which can be repeated if necessary (). |
pmc-6598598-13 | Clinical presentation: A 45-year old male with advanced melanoma presents to the ED with abdominal pain, non-bloody diarrhea (>7 bowel movements per day) and fever 2 days after receiving 3rd dose of combination Ipilimumab/Nivolumab therapy.
The most common GI toxicities reported from anti-CTLA-4 ICIs are diarrhea and colitis. Colitis is defined as inflammation of the lining of the colon, as opposed to diarrhea that is defined as increased number of bowel movements.
The incidence of colitis ranges from 8 to 27% with rates of diarrhea reported up to 54% of CTLA-4 treated patients. The incidence is greatest in patients treated with CTLA-4 monotherapy vs. CTLA-4/PD-1 combination therapy (, ). When PD-1 inhibitors were compared directly with CTLA-4 inhibitors, the relative risk of all-grade diarrhea and colitis was 0.58 and 0.16, respectively (). Combination PD-1/CTLA-4 related deaths were recently found to be most frequently from colitis, accounting for 37% of fatalities (). The time of onset is typically 5–10 weeks following initiation of therapy (). ICI-induced hepatotoxicity has also been well-described, with incidence of 2–10% of patients receiving monotherapy () and 25–30% of patients being treated with combination PD-1/CTLA-4 therapy (). Hepatitis has been found to be the second most common irAE leading to fatal outcomes anti–PD-1/PD-L1 therapy (). The time of onset of hepatitis may also occur early in a patient's treatment course; typically commencing within the first 6–12 weeks after treatment initiation (). Other less frequently reported GI toxicities include dysphagia, gastritis, duodenitis, and pancreatitis ().
Diagnostic work-up for colitis includes standard laboratory testing to assess for infectious vs. non-infectious etiologies including CBC, CMP, ESR, and CRP. Stool cultures (bacterial, viral, ova, and parasites) should be obtained as well as stool calprotectin or lactoferrin to monitor disease activity, extrapolated from the management of inflammatory bowel disease. In patients with severe colitis, tuberculosis testing should be completed in potential preparation for the use of anti-TNF-α inhibitors for steroid-refractory colitis. Patients should also undergo radiologic imaging with a CT abdomen, which may show mesenteric vessel engorgement, colonic wall thickening, colonic distension, and pericolonic fat stranding (). In severe cases, in those in which the diagnosis is uncertain, and to evaluate the severity of colitis, direct visualization of the colon with either a colonoscopy or flexible sigmoidoscopy should be considered. The presence of ulceration on direct visualization is associated with a corticosteroid-refractory course, and early infliximab can be considered in these cases. ICI-induced colitis has been reported to have greater predilection for descending colon (see ) (, ). Endoscopy is also useful in monitoring colitis, particularly when resumption of therapy is being planned.
This patient underwent extensive evaluation as delineated above. CT imaging revealed thickening of descending colon with pericolonic fat stranding. Gastroenterology were consulted who completed colonoscopy, which demonstrated diffuse ulceration at the descending colon.
The patient was managed with intravenous fluids and prednisone 1 mg/kg/day. This resulted in clinical improvement, with reduction in bowel movement to three times per day. The patient was continued on the initial corticosteroid dose for a further 4 days, and then steroids were tapered over 4 weeks. Upon completion of the prednisone taper, nivolumab monotherapy was resumed.
Patients with grade 2+ colitis should have ICI withheld, and treatment should only be resumed if toxicity improves to <grade 1. Cases of grade 3+ colitis often imply permanent discontinuation of anti-CTLA-4 therapy (). Early intervention with corticosteroids and best supportive care with hydration, electrolyte repletion and antidiarrheal agents is crucial. If patients do not demonstrate adequate clinical response within 48–72 h of corticosteroid therapy, TNF-blocker therapy with infliximab should be commenced. This can be repeated again at a 2-week interval. Vedolizumab, an anti-integrin α4β7 antibody, should be considered in patients who develop colitis that is refractory to infliximab or in cases that anti-TNF- α therapy is contraindicated. |
pmc-6598600-1 | A 65 year-old female was referred to ENT department with complaint of throat pain for one month. There was no history of smoking and alcohol consumption. History of dysphagia or dyspnea was denied but odynophagia was present. The initial treatment with antibiotics was administered by her primary care physician but was not effective. Physical examination revealed an enlarged right palatine tonsil with ulcerating mucosa and fullness of her anterior tonsillar pillar. The left palatine tonsil and other pharyngeal mucosal surfaces were normal. The remainder examination of head and neck was negative. A computed tomography (CT) scan of the neck showed a 3.5 × 2.8 cm well-circumscribed, enhancing, necrotic appearing mass posterior to the right submandibular gland and increased attenuation within the right tonsil. A CT scan of the chest, abdomen and pelvis was unremarkable. Whole body positron emission tomography – computed tomography (PET-CT) showed a prominent collection of fluorodeoxyglucose within right tonsillar fossa without any evidence of distant metastatic disease. Fine-needle aspiration of the right neck mass performed at an outside hospital was positive for poorly differentiated carcinoma. On endoscopy, a very small exophytic tumor involving the right palatine tonsil was seen. Several biopsies were taken and sent for histology. Histologic examination revealed small round to oval tumor cells arranged in cords or nests, containing hyperchromatic nuclei and scant cytoplasm, nuclear molding, numerous mitotic figures and apoptotic bodies (A and B). Immunohistochemical staining showed that tumor cells were strongly positive for neural cell adhesion molecule (CD56), Synaptophysin, Chromogranin, NSE and negative for leukocyte common antigen (LCA) and CD 20 (A and B). The patient was diagnosed with poorly differentiated neuroendocrine carcinoma (SCC) of the right tonsil. Thus the right palatine tonsil was confirmed as the primary lesion and there was no evidence of distant metastasis. As she refused surgery or radiotherapy, six cycles of Cisplatin combined with Etoposide were given and the mass showed initial complete response at that time. The patient refused any further treatment and was lost to follow-up. |
pmc-6598601-1 | The patient is a 36-year-old male with no significant past medical history. He presented to a local hospital with a complaint of left-sided abdominal pain for several days. He was initially managed conservatively as a non-specific abdominal pain and discharged home. Two months later, he re-presented with severe abdominal pain associated with signs and symptoms of sepsis. Computed tomography (CT) scanning of the abdomen revealed a phlegmon in the LUQ and free fluid (A). A diagnostic laparoscopy was performed, and showed extensive peritoneal deposits of thick mucoid material. Biopsies were taken, washout was performed, and drains were inserted. Later, his sepsis resolved, and the biopsies showed LAMN.
He was then referred to our hospital for further management. Upon evaluation, upper and lower gastrointestinal scopes were performed and showed no evidence of pathology.
Reviewing the CT imaging identified the abnormal anatomy of the bowel where the right colon runs retroperitoneally behind the mesentery of the small bowel. The cecum with the appendicular mass was found in the left side of the abdomen joining the colon at the splenic flexure. The duodenojejunal (D–J) junction was found slightly to the right side of the midline, and the inferior mesenteric vein to its left side. In addition, a large right kidney, an atrophied left kidney, and two ureters were noted (B).
The case was discussed in a multidisciplinary meeting (Tumor Board), where the committee advised to proceed management with CRS/HIPEC.
Exploratory laparotomy revealed extensive deposits all over (A), giving a Peritoneal Cancer Index (PCI) of 39. The abnormal anatomy was clarified as described in the CT scan. The duodenum was partially intraperitoneal (B). There were congenital adhesions between the sigmoid colon and the small bowel mesentery. Severe adhesions were also apparent in the LUQ—phlegmon-like—involving the greater omentum, cecum, appendix, splenic flexure and spleen. This phlegmon was resected en-bloc to include the spleen, greater omentum, terminal ileum, and part of the ascending, distal transverse, and splenic flexure colon. However, most of the left colon, sigmoid, and the intraperitoneal rectum were also heavily diseased. Thus, the resection was extended to include the entire colon beyond the distal transverse with the upper two-thirds of the rectum (A and B). Complete cytoreduction was achieved through stripping the entire peritoneum, including the peritoneal lining of the diaphragm, burning the liver surface, and resecting both the greater and lesser omentum. In addition, small bowel mesentery and its surface were cleared from the disease.
Creating a tension-free anastomosis with good vascularity between the remaining transverse colon and the low rectum constituted a great challenge. The segment was dependent on the middle colic pedicle, and could not reach to the low rectum in the current anatomical position. Considering this unusual challenge, we aimed to preserve the transverse colon by rotating the colon along the axis of the middle colic pedicle from left to right after scoring the peritoneal surface of the mesentery. At this position, the distal end of the transverse colon reached the low rectum without tension through the right side (A and B).
Given this procedure has not been described before, we questioned the perfusion and tension in that new position. Therefore, the colon was left in the proposed position for 90 minutes, during which we performed the HIPEC by infusing heated intraperitoneal mitomycin C and doxorubicin, in addition to intravenous 5-fluorouracil and leucovorin.
Upon completion of HIPEC, the colon retained normal vascularity and viability in the new rotated position. Therefore, we proceeded with the anastomosis by connecting the low rectal stump to the rotated distal transverse colon, using the stapled technique (). After washing the abdominal cavity with warm water and re-inspecting the bowel, drains were placed intraabdominally and bilateral chest tubes were inserted. The midline laparotomy wound was closed, and a double-barrel stoma was created with the distal ileum as one end, and the proximal part of the remaining colon as the mucous fistula ().
The patient was extubated at the end of the procedure, and transferred to the intensive care unit (ICU), where he recovered gradually for several days, and was then transferred to the surgical ward. Heparin infusion was initiated eight hours postoperatively as an attempt to protect against a concerning risk of thrombosis in the rotated vascular pedicle, which could endanger the blood supply to the remaining colon. Unfortunately, during his early postoperative days, he developed a subsegmental pulmonary embolism despite being on mechanical venous thromboembolism (VTE) prophylaxis and heparin infusion. However, all other aspects of his postoperative course were uneventful. Postoperative abdominal CT scan was performed with barium injected through the stoma, which showed no leak or collection (). Four weeks following his surgery, he was discharged home in a good condition.
The final histopathology proved the diagnosis of LAMN in all resected specimens. He was regularly followed up in the clinic. His last visit was seven months after surgery, where he appeared well and had no complaints. Closure of the stoma is planned after one year and following reevaluation for any possible recurrence. |
pmc-6598602-1 | A 14-year-old boy presented as an emergency with 3-days history of pain in abdomen and distention.The nature of pain was the sharp, severe and non-radiating type. He also complained of nausea and vomiting. There was a history of constipation for which he dad to take laxatives regularly. He has a significant medical history of premature birth at 32 weeks, developmental 3 delay and mental retardation. He denied other past surgery and relevant family history. On examination, the patient was ill looking, dehydrated. He had cold extremities and sunken eyes. Blood pressure was 100/70 mmHg, Pulse rate 110 per minute with low volume. No abnormality was detected in respiratory, cardiovascular and nervous systems. Abdomen examination revealed gross distention, hyper-resonance with mild tenderness. Bowel sounds were sluggish and per rectal examination was unremarkable. Patient resuscitated with a bolus of intravenous fluid (normal saline) antibiotics, analgesics and nasogastric decompression. On investigation, white blood cells were 12,000 cells/mm3, hemoglobin 11 gm/dL platelet count 150,000 cells/mm3, serum sodium 140 mEq/L and potassium 4.2 mEq/L. Plain X-ray abdomen showed dilated loops of large bowel loop in the left upper quadrant (bent inner tube/omega sign) (). The patient was taken for laparotomy with a diagnosis of sigmoid volvulus. During laparotomy, midline incision released 300 mL of serous fluid. A volvulus of the sigmoid colon with 360-degree clockwise rotation was found (). The redundant sigmoid colon was hugely dilated which was resected after detortion and resection anastomosis was performed. The patient was discharged from hospital on 8 th postoperative day. Post-operative period was uneventful. |
pmc-6598605-1 | A 38-year-old man with a hypervascular mass lesion in the pancreas (Figure ) detected on Computed Tomography (CT) was referred to our institution for a 68Ga DOTATATE PET/CT to identify metastatic disease. 68Ga DOTATATE is an imaging agent targeting somatostatin receptors (SSTR). 68Ga DOTATATE PET/CT is an established method in the work-up for neuroendocrine tumors (NETs), because SSTRs are over-expressed by the majority of well-differentiated NETs.
PET images showed a focus of uptake in the pancreas (Figures and , arrows) and moderate tracer uptake foci (arrows) in the spinous process of the first thoracic vertebra (Figures and ), the bodies of the fifth and eighth thoracic vertebras (Figures , , and ), and the right iliac wing (Figures and ). These uptakes of 68Ga DOTATATE could be taken for bone metastases. The corresponding CT images, however, showed characteristic appearances of hemangiomas, consisting in bone demineralization with vertical striation due to thickened trabeculae (“Corduroy sign” on the sagittal planes) and a “polka-dot” appearance on the axial slices where the thickened trabeculae are seen as small punctate areas of sclerosis (Figure , arrows). |
pmc-6598606-1 | A 72-year-old male presented to the emergency department with complaints of abdominal pain for six days, decreased appetite and diarrhoea for 3–4 months. Clinical examination revealed a periumbilical mass, not yet noticed by the patient. Routine haematological tests showed a slightly elevated C-reactive protein (36 mg/L) and mild hypernatremia (149 mmol/L). The medical history mentioned a positive immunochemical faecal occult blood test (iFOBT) eight years ago that led to resection of two mildly dysplastic colon polyps. Abdominal computed tomography (CT) was performed after administration of oral and intravenous iodine-based contrast. A notable irregular bowel wall thickening was detected in a jejunal loop, extending through the entire circumference and over a length of nearly 15 cm. The wall broadening went along with widening of the lumen, making it apparent as an aneurysmal dilated tumoral mass containing air-fluid level (Figures and , large arrows). CT also demonstrated numerous enlarged mesenteric and retroperitoneal lymph nodes (Figures and , small arrows). A close spatial relationship was noted between the jejunal tumoral changes and the voluminous lymph nodes. These CT signs were highly suggestive of a small bowel lymphoma with locoregional lymphadenopathy. A diagnostic laparoscopy yielded similar abnormalities, and biopsies were obtained. Finally, histopathologic analysis confirmed a diffuse large B-cell lymphoma of the jejunum. |
pmc-6598616-1 | A 19-year-old male patient with the homozygous sickle cell trait was admitted to the hospital due to a sickle cell crisis. His main complaint was unbearable pain in the extremities. The patient’s history was remarkable for multiple previous admissions for sickle cell crises. During his admission he developed a swollen left eye, with discrete ptosis of the upper eyelid and minimal exophthalmia. There were no visual disturbances and eye movement was unimpaired. A contrast-enhanced computed tomography (CT) of the orbits showed a lens shaped extraconal mass lining the lateral wall of the left orbit (Figure ). The lesion measured 3.1 × 1.2 cm with high attenuation due to enhancement or spontaneously dense compounds. The underlying frontal and sphenoid bones were unremarkable. The patient was referred for MRI the same day for further work-up. The lesion was markedly hypointense on T2-weighted images with fat suppression (Figure ). T1-weighted sequences showed an isointense signal comparable to the adjacent bone (Figure ). There was no lesional enhancement after injection of gadolinium and faint perilesional enhancement (Figure ). Imaging findings were compatible with an acute subperiosteal orbital hematoma (SOH). Additionally, MRI revealed a new extracranial subperiosteal hematoma lining the external table of the frontal bone on the left side (Figure ). This hematoma was less hypointense on T2-weighted images and exhibited more prominent perilesional enhancement. The frontal bone and left greater wing of the sphenoid bone showed discrete bone oedema on T2-weighted images (Figure ) and asymmetrical low signal intensity on contrast-enhanced T1-weighted images (Figure ), suggesting areas of infarction. The patient received supportive treatment after diagnosis, and the eye swelling diminished spontaneously over time. |
pmc-6598618-1 | A 59-year-old woman presented eight months after whiplash trauma with persisting cervical pain. Radiography of the cervical spine showed no traumatic lesions (not shown). Computed tomography (CT) and 3D reconstruction of the cervical spine showed an incidental asymmetrical craniocervical junction with a supernumerary occipital condyle on the right (Figures and , yellow arrow), lateral to the proper occipital condyle (Figures and , green arrow). This extra condyle articulated with a hypertrophic right transverse process of the atlas. Signs of neo-articulation with degenerative changes such as subchondral sclerosis, osteophytosis, and dystrophic calcifications are documented. Other findings included an unfused posterior arch of C1 (Figure , blue arrow), rotation of C2 on C1 (13°) despite the neutral position of the head (Figure ), a mild sinistroconvex cervical scoliosis (Cobb angle 11°), and an asymmetrical right-sided uncovertebral degeneration from C3 to Th2 (Figure ). Furthermore, an elongation of both styloid processes (approximately 4 cm) was also present (Figure ). |
pmc-6599089-1 | The first case () was a 41-year-old male who sustained a severe crush injury to the left middle finger requiring amputation at the proximal interphalangeal joint. However, the soft tissue envelop of the crushed middle phalanx was still viable based on the ulnar neurovascular bundle. The adjacent ring finger had an intra-articular fracture of the head of the proximal phalanx as well as extensor tendon injury and skin loss over the dorsal aspect of the proximal interphalangeal joint. The tendon was repaired and k-wires were used to stabilized the joint. The soft tissue defect was then reconstructed with a ‘spare-part’ fillet cross-finger flap from the adjacent middle finger. The flap was divided in 17 days and the k-wires were removed 4 weeks after injury. At the final follow-up, 6 months later, the range motion of the ring finger was: 0–80° at the metacarpophalangeal joint, 15°-90° at the proximal interphalangeal joint, and 0–50° at the distal interphalangeal joint. The patient was satisfied with the outcome and return back to his original job as a manual worker. |
pmc-6599089-2 | The second case () was a 35-year-old male who sustained a heat-press injury to his left hand. Most of the contact area was to the dorsal aspect of the index finger ray leading necrosis of the dorsal skin and extensor tendons. Since the patient was a manual worker, decision was made to do a ray amputation of the index finger so that he would be able to use his uninjured middle finger as an index finger. The volar skin of the index finger was still viable. Another area of contact to the heat press was the radial aspect of the thumb. Debridement of the burnt area in the thumb resulted in a complex defect exposing the collateral ligaments of the interphalangeal joint and the radial digital nerve. The radial digital artery was thrombosed. Reconstruction of the complex thumb defect was done using a ‘spare-part’ fillet flap from the index finger. A meshed split- thickness skin graft was used to cover the pedicle of the fillet flap. The flap was divided 18 days later. The skin graft was removed from the flap pedicle and the pedicle was then used to cover the amputation stump of the index finger ray amputation. At final follow-up 8 months later, there was full range of motion of the remaining fingers. There was also full range of motion of thumb at the carpo-metacarpal and the metacarpophalangeal joints. At the interphalangeal joint, the range of motion was 0–50°. The patient was satisfied with the outcome and went back to his original job as a manual worker. |
pmc-6599090-1 | A 58 year-old female with a past medical history of diabetes mellitus and thyroid disease presented for weight loss consultation. There was no other pertinent surgical history. Prior to her endoscopy, her only subjective finding was mild occasional gastrointestinal reflux disease (GERD).
The patient underwent a pre-operative esophago-gastro-duodenoscopy (EGD) and was found to have a 3 cm submucosal mass along the anterior aspect of the gastric body, near the incisura angularis; biopsy at that time was indeterminate. As such, the patient was referred to gastroenterology for repeat EGD and endoscopic ultrasound (EUS).
Subsequent EGD re-demonstrated a 3 cm mass near the incisura. This had a positive pillow sign (pillowing of the surface of the lesion when prodded). Stack biopsies were obtained, with apparent fat within the biopsy, consistent with lipoma (). EUS was performed, revealing a 3.3 x 1.6 cm relatively echogenic mass arising from the gastric submucosa in the area of the gastric lesion consistent with lipoma (). Pathology was consistent with submucosal lipoma. Ancillary H. pylori biopsy was negative. CT scan re-demonstrated the lesion, confirming a lack of extra-gastric component ().
Due to the lipoma's location, resection was critical, as it would have led to obstructive symptoms following sleeve gastrectomy. The patient underwent a simultaneous laparoscopic vertical gastrectomy, gastric lipoma excision, EGD, and laparoscopic cholecystectomy. A longitudinal gastrotomy was made on the greater curvature. Exposure was achieved using retraction sutures. Following this, a laparoscopic submucosal resection of the lipoma was performed. We then used electrocautery to open the mucosa overlying the lipoma. Blunt and ultrasonic dissection were used to mobilize the lipoma. We then identified the vascular pedicle and divided this using the harmonic scalpel. A primary closure of the mucosa and greater curvature followed. The gastrocolic and gastrocolic omentum was taken down using the harmonic scalpel. We then used the linear cutting staple to perform the sleeve gastrectomy. Concurrent endoscopy was performed during the first two stapler firings to ensure that the mucosal suture line was not crossed by the stapler. We then inserted a 40 French Bougie and completed the sleeve in standard fashion. At 3 month follow up the patient was doing well. |
pmc-6599270-1 | A 66-year-old man was referred to our surgical outpatient clinic because of an endoscopic report that was indicative of a small irregular ulcerative lesion in the fundus of the stomach. The histopathological report was consistent with gastric squamous carcinoma (AE1/AE3+, p40+, Chromogranin A−, Synaptophysin−, c-erB-2/HER2−). The patient complained of epigastric pain and abdominal cramps for the last 2 months with no incident of hematemesis, melena, or hematochezia. He had an unintentional weight loss of approximately 10 kg during the last 4 months. He was suffering from type 2 diabetes with a past medical history of smoking, 100 packs per year approximately. The patient had never undergone a surgical operation before.
His blood tests showed chronic anemia and his tumor markers (CEA, CA 19-9, aFP, and PSA) were within normal limits. The abdominal computed tomography (CT) revealed no other sites of tumor location or other primary sites of squamous malignancy (Fig. ). Maximum diameter of the tumor was 3 cm in the fundus of the stomach with no suspicious lymph nodes, while the chest CT was normal. The multidisciplinary team decided to proceed to surgery. Three weeks after the multidisciplinary team meeting due to the high volume of the patients, the patient underwent total gastrectomy with Roux-en-Y reconstruction, along with splenectomy and D2 lymphadenectomy. The postoperative recovery was uneventful and the patient was discharged on postoperative day 12.
Pathological assessment of the specimen revealed a 4.7 × 3 × 2.5-cm mass located in the fundus of the stomach invading the subserosa. Out of 48 lymph nodes resected, 9 of them were positive for tumor infiltration. Perineural invasion and extramural venous invasion were also found. The resection margins were free and the final TNM stage was T3N3aM0 (WHO 2017). Microscopically, the tumor was a poorly differentiated gastric squamous cell carcinoma with clear cell characteristics, chronic inflammatory, and desmoplastic stromal reaction (Fig. ). Immunohistochemistry of gastric tumor confirmed the diagnosis with positive CK14 stain, cyclin-D1 stain, p53 stain, EGFR stain, co-expression of CK5/6, and p63 stains (Figs. and ). In order to rule out other possible diagnoses or other occult primary tumors, extensive immunohistochemistry check including MUC1, uroplakin III, PAX8, RCC, and PAS was performed without positivity.
Because of the rarity of this specific type of tumor in the stomach, the tumor board decided to rule out other possible primary sites of squamous malignancy. The patient underwent a cranial, abdomen, and chest CT, which revealed enlarged lymph nodes in the mediastinum, in right and left paratracheal area, as well as 4 small bilateral possible secondary lung lesions (Fig. ). Interestingly enough, these findings were not apparent in the preoperative CT scan. However, they were evident 3 weeks after surgery, while preoperative chest CT scan was unremarkable, a fact that underlines the aggressive behavior of this malignancy. Following that, the patient also underwent bronchoscopy which did not reveal any lesion. Endobronchial brushing results were normal. Full-body FDG PET/CT scan showed multiple metastatic chest lesions of maximum diameter 11 mm (Fig. ). The patient received adjuvant chemotherapy with paclitaxel and carboplatin. To date, 12 months after the initiation of the chemotherapy, there is no progression of the disease, with minor regression of the metastatic chest lesions. |
pmc-6599300-1 | A 59-year-old woman, previously independent in activities of daily living and self-employed in the family business, presented with a progressive, over the period of 10 years, decline in cognitive function manifested as increasing social withdrawal, inattentiveness followed by progressive memory impairment, inappropriate behaviour, urinary incontinence and problems with balance. Furthermore she had episodes of an emotional lability, alternating between depressive symptoms with psychomotor retardation and agitation with paranoid ideation, insomnia and confusion. Patient’s presentation was complicated by a spontaneous (8 mm) subdural haematoma treated with craniotomy and evacuation in year 2014 as well as by a single seizure during the perioperative period with a subsequent pulmonary embolism requiring temporary use of anticoagulation. Despite surgical evacuation of her subdural haematoma, patient’s cognitive status continued to deteriorate due to superimposed episodes of delirium requiring multiple, 2nd monthly hospitalisations. Comprehensive geriatric assessment, performed in between hospitalisations, confirmed an impairment of the patient’s executive function with impaired reasoning and problem solving skills. Her Mini-Mental state examination (MMSE), a brief (5–10 min) mental status questionnaire, assessing attention, orientation, memory, language and visuospatial copying, revealed a score of 24/30, suggestive of cognitive decline. 3 months prior to the neurosurgery her executive function severely declined to the point of requiring fulltime assistance with all daily living activities including her personal care and the need for regular antipsychotics and antidepressants with haloperidol, mirtazapine and levetiracetam. On her preoperative assessment (Barthel Index of activities of daily living, total score range from 0 to 20) the patient scored only 7 points, indicative of her severe limitations in activities of daily living [].
The patient’s past medical history included hypertension, type 2 diabetes mellitus, thyrotoxicosis successfully resolved with I-131 treatment, osteoporosis with L5 vertebral compression fracture, recurrent urinary tract infections requiring supra-pubic catheterisation and hyperandrogenism with an onset after 40 years of age. |
pmc-6599305-1 | A 60-year-old Caucasian male presented to the Department of Ophthalmology in Poznan with a complaint of bilateral ocular redness, pain, severe photophobia, and progressive deterioration of vision in April 2015.
Three months earlier, he had been diagnosed with bilateral conjunctivitis, which did not respond to standard treatment. His past medical history was significant for hypertension and tinnitus of the right ear for several months. No other symptoms or signs of systemic diseases were recorded.
In the meantime, the patient was admitted to the Department of Cardiology-Intensive Therapy with cardiogenic shock due to complete atrioventricular (AV) block. He underwent temporary pacing, followed by permanent dual-chamber pacemaker insertion. Two weeks later, because of the exacerbation of his eyes problems, he was referred to us with the diagnosis of bilateral anterior uveitis.
At presentation, his best-corrected visual acuity (BCVA) in the right eye (RE) was 0.7 and in the left eye (LE) was 0.25. The corneal reflex of the LE was decreased.
Ocular examination revealed a non-necrotizing diffuse scleritis, mild paralimbal keratitis, anterior chamber cells (1+) and flare (2+), and posterior synechiae in both eyes, more marked in the LE (Fig. , a and b). The view of the fundus with indirect ophthalmoscope was limited, and the quality of standard photographic documentation was inadequate. Ultrasound evaluation elicited bilateral inflammation of the vitreous body, and exudative retinal detachment (Fig. , c and d). Head computed tomography scans revealed anterior inflammation of the eyewall, retinal detachment, and an enlargement of the left lacrimal gland (Fig. ).
Due to progressive visual acuity decline (0.25 in RE; hand motion in LE) within a week, accompanied by the elevation of acute phase reactants, the detailed diagnostic investigation was performed.
The erythrocyte sedimentation rate, C-reactive protein, and plasma fibrinogen levels were increased, reaching maximum levels of 88 mm/h, 67 mg/l, and 968 mg/dl, respectively. Serological test for toxocariasis, Lyme disease, tuberculosis, syphilis, viral hepatitis, HIV, rheumatoid factor, anti-CCP, and tumor markers were negative. Despite elevated IgG antibody titers of toxoplasmosis, HSV-1, and CMV, they were not of diagnostic importance. Strongly positive serum cytoplasmic ANCA (c-ANCA), which specifically react with proteinase 3, showed a diffuse granular cytoplasmic staining pattern in a method of indirect immunofluorescence. The urinalysis was unremarkable, and serum creatinine level (0.84 mg/dl), as well as estimated glomerular filtration rate (115.02 ml/min/1.73 m2), were within the normal range. A radiographic study showed a narrowing of right sacroiliac joint space and no chest abnormalities. Abdominal ultrasound examination was normal. Our patient was also HLA-B27 positive.
Because c-ANCA were highly specific for GPA, conjunctival and musculocutaneous biopsies were obtained. The histopathological examination did not disclose any evidence of the disease.
Notwithstanding the negative biopsy results, we made a tentative diagnosis of GPA based merely on positive c-ANCA and ocular involvement.
The patient was referred to the Department of Rheumatology and Internal Medicine, where our diagnosis of GPA was upheld. The patient started therapy with cycles of intravenous steroids and cyclophosphamide along with oral steroids q.d. The response to the treatment was excellent, and ocular inflammation diminished. After the second cycle of therapy, his BCVA increased to 1.0 in RE and 0.2 in LE. The vitritis and exudative retinal detachment resolved completely (Fig. ). Uneventful cataract surgery was performed in the LE that further enhanced his vision to 0.5 after 3 months. At this time, the total dose of cyclophosphamide administered over the 3 years was 9800 mg. |
pmc-6599311-1 | The authors report a case of a 29-year-old Saudi woman who was G4T2P0A1L2 at 21 weeks of gestation. She was free from medical illness and she had had no previous surgical procedures. She is a housewife; she never smoked tobacco or drank alcohol, and she had no history of recent travel to endemic or pandemic areas. She was referred based on an antenatal ultrasound finding that showed multiple fetal anomalies. This ultrasound had been conducted at another hospital for evaluation and management. Her past obstetrical history was uneventful with two normal term vaginal deliveries and a history of first trimester unexplained miscarriages. She is married to a first-degree cousin working in a governmental institute; there is no history of genetic or congenital anomaly in either of their families.
Her current pregnancy was spontaneous with no history of illicit drug use or exposure to infection or radiation. Her initial early antenatal scan diagnosis showed suspicion of possible fetal diaphragmatic hernia and required further validation which was not possible at the maternal–fetal medicine (MFM) unit at the hospital which also did not have available sonographic specialists. During her first antenatal visit at 21 weeks + 0 day of gestation, the results of her anatomy scan revealed a single viable fetus with estimated fetal weight (EFW) on 50th percentile with normal biometry measurements.
Further detailed anatomy scan findings revealed a male fetus with both kidneys appearing small in size, hyperechoic dysplastic, both ureters were dilated, urinary bladder looked abnormal in shape with thickened bladder wall, and umbilical cord at fetal insertion side appeared thickened. In addition, the diaphragm was seen clearly separating the chest from the abdominal compartments with no evidence of diaphragmatic hernia. Both feet were clubbed and open hands were seen with no other anomalies or any soft marker seen (see Fig. .) Based on the multiple fetal structural anomalies discovered, the couple was counseled about the scan findings and advised for further workup, such as: perinatal invasive testing; toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus, and herpes (TORCH) screening; and fetal echocardiogram to exclude syndromic or chromosomal causes. This would support reaching a better diagnosis and allow for further discussion on the options available such as the continuity of the pregnancy or termination based on the severity of the fetal condition (see Table ).
Our patient had some social issues and was also following her condition in another institute and only revisited our center at 32 weeks and 4 days of gestation. At our center another follow-up scan revealed a single viable fetus, cephalic in presentation, anhydramnios with normal head and femoral length biometry. Unfortunately, the abdominal circumference (AC) was not taken due to the extremely distended abdominal wall that prevented any further visualization by ultrasound. The right kidney measured 3.4 × 1.1 cm with a small cyst, the left kidney measured 2.9 × 1.3 cm with bilateral hugely dilated ureter and urinary bladder (mega cyst) (see Fig. ).
TORCH screen test results were non-reactive. Amniocentesis was performed and showed normal chromosomal results. A fetal echocardiogram allowed for limited examination due to anhydramnios; however, no obvious cardiac anomalies were noted. Lungs appeared compressed due to severely distended abdomen from the progressively enlarged urinary system, otherwise no other abnormal findings noted. The couple was counseled by the MFM team about the worsening condition from the recent scan findings and were told about the poor fetal prognosis and the high mortality rate, secondary to severe lung compression with the presence of anhydramnios which would lead to lung hypoplasia and cause fetal demise.
It was explained that the entire urinary system was affected with severe dilatation causing severe abdominal wall dilatation and for this reason measuring fetal AC had been difficult antenatally. Options were discussed with the couple:Termination of pregnancy to avoid obstetrical complication during labor which is fetal abdominal dystocia as it was difficult to measure the abdominal wall antenatally with the severe progressive renal system dilation with advancing gestational age versus To wait until term pregnancy while knowing the poor fetal prognosis
Furthermore, antenatal interventions were offered to the couple including tapping of the fetal bladder and ureters prior to induction of labor and to then send the amniotic fluid sample for further genetic testing. Our patient’s case was initially discussed by a multidisciplinary team which included a perinatologist and a neonatologist before finally making a combined agreement and alignment with the couple who decided to terminate the pregnancy; a caesarian section would be preserved for maternal indication and comfort care post-delivery to born infant were also explained.
At 32 weeks and 5 days of gestation, tapping of the fetal bladder and ureter was performed and samples of amniotic fluid were sent for whole exome sequencing (WES) test; however, unfortunately, after waiting a few weeks for the results, no results could be determined due to a laboratory error.
Our patient underwent induction of labor to terminate the pregnancy and delivered vaginally a male neonate with Apgar score of 2 in 1 minute and 5 in 5 minutes, weighing 1800 grams without any complications. The vital signs revealed blood pressure of 90/60, pulse 100 beats /minute, and temperature of 36 °C. Clinical examination of the newborn revealed distended abdomen and thin wrinkled skin, retracted chest, cryptorchidism, and clubbed feet; no facial anomalies were noted and the features were most likely to be suggestive of PBS (see Fig. ). The newborn died 2 hours post-delivery.
The placenta was sent for a histopathology examination as a part of the workup and the result revealed normal findings.
A postmortem examination was not offered to the couple since this is not conducted in the center. The couple was counseled prior to discharge regarding future pregnancy plans, despite low reoccurrence. It was also highlighted to them the importance of having early prenatal testing in a center in which there were well-trained sonographers and a high risk in pregnancy unit available. They were also informed about the lack of result of WES test due to laboratory error and they were fine. |
pmc-6599372-1 | A 32-year-old man with tonsillar hypertrophy detected during a physical examination was referred to us. The physical symptoms first appeared three years prior. No inciting events were associated with the appearance of tonsillar hypertrophy. His vital signs were as follows: body temperature 36.5 °C, pulse 78 beats per minute, respiratory rate of 18 breaths per minute, and blood pressure 120/79 mmHg. His physical examination revealed nonspecific findings with the exception of tonsillar hypertrophy. He had no signs or symptoms of an autoimmune disease. His family history did not suggest the presence of any familial disease. No lymphadenopathy, POEMS syndrome, lymphoma, or other cancers were present. Tests were negative for anti-HCV antibody, treponema pallidum-specific antibody (TP-Ab) and HIV antigen/antibody. The test results for HBV indicators were as follows: HBsAg 0.23 (negative), HBsAb 30.78 (positive), HBeAg 0.38 (negative), HBeAb 0.23 (negative), and HBcAb 1.85 (negative). Other laboratory tests also revealed no abnormal findings.
Laryngoscopy revealed the following: tonsillar hypertrophy (right, grade 3; left, grade 2), an elongated uvula, and posterior pharyngeal wall lymphoid hyperplasia (Fig. a-f). The nasopharynx was smooth and symmetrical. Based on the physical examination and related laboratory tests, the initial diagnosis were tonsil hypertrophy and chronic tonsillitis. The patient underwent a low-temperature plasma tonsillectomy under general anesthesia. Two lesions were sent for pathological examination. The larger lesion was 3.4 cm × 2.0 cm × 1.5 cm, and the smaller lesion was 2.0 cm × 1.3 cm × 0.9 cm. Cut sections demonstrated a smooth, yellow-brown to red-brown, and waxy appearance that was not well demarcated.
Sections of the tonsillar mass revealed the characteristic findings of HVCD. Microscopic examination of permanent sections showed polypoid masses unseparated from the surrounding normal tonsil, which were covered by well-differentiated squamous epithelium. No tonsil crypt structure was observed. Lymphoid follicular hyperplasia was the main pathologic finding, a portion of which appeared to be a fusion of nodular hyperplasia (composed of lymphoid follicles of variable size and shape) (Fig. a-c). These distinctive follicles with atrophic hyalinized germinal centers (depleted of centroblasts and centrocytes) and a broad mantle zone of small lymphocytes formed concentric rings (a so-called onion-skin arrangement). Both single follicles and confluent follicles with a single mantle zone were observed (Fig. a and e). Medium-sized vessels and a plethora of capillaries were present in the center of lymphatic follicles, mantle zones, and interfollicular areas (Fig. b-d). A characteristic lollipop appearance was also observed due to the onion-skin arrangement of the expanded mantle zone lymphocytes with a vessel penetrating the germinal center (Fig. f).
To exclude the possibility of low-grade malignant lymphoma, a comprehensive immunostaining panel was performed. A meshwork of follicular dendritic cells in the germinal centers was highlighted by CD21 and CD23 staining (Fig. a and b). Cells constituting the expanded mantle zones expressed CD20 and CD79α (Fig. e and f). The B-cell population within both the follicles and interfollicular areas demonstrated polytypic expression of Ig light chains. The interfollicular areas were comprised predominantly of T-cells (immunoreactive for CD3, CD5, and bcl-2) admixed with scattered B-cells (immunoreactive for CD20, CD79a) (Fig. c-g). Bcl-2 staining also indicated small and mature lymphocytes in the mantle zone. The onion-skin arrangement was clearly visible via bcl-2 immunohistochemical staining (Fig. h). The small lymphocytes in the expanded mantle zone were negative for cyclin D1 (Fig. i). Ki-67 staining indicated proliferating cells, which were mainly observed in the germinal centers (Fig. j). Immunostaining with HHV-8 was negative (Fig. k). Epstein Barr virus (EBV) was not detected in the tonsillar lesion by in situ hybridization (ISH) for EBV-encoded small nuclear mRNA (EBER). EBER is an EBV-encoded small nuclear mRNA.
Based on these microscopic features and immunohistochemical findings, a diagnosis of HVCD was rendered. The patient was treated with local excision without any other therapy based on the diagnosis of HVCD. At the 7-month follow up, the patient had no recurrent symptoms or masses. |
pmc-6599409-1 | We present the case of a 7 year old boy who presented with effort intolerance and no cyanosis. Clinical examination was unremarkable. Doppler echocardiography revealed left sided pulmonary veins opening into left innominate vein. Right pulmonary veins were seen draining normally into the left atrium. There was no ASD and right atrium and right ventricle were dilated. CTPA ( & ) aided in defining the anatomy. Left pulmonary veins were shown to be joining to form a common channel and draining into superior vena cava via left brachiocephalic vein suggestive of left supracardiac PAPVC thus confirming the preliminary diagnosis of isolated left sided PAPVC.
Pt. was successfully surgically managed. Median sternotomy approach was chosen.
Innominate vein and superior vena cava were found to be dilated. Also, the right atrium and the right ventricle were dilated (). Vertical vein was seen opening into innominate vein. Left Pulmonary veins were seen opening into the vertical vein. Patient was operated without cardiopulmonary bypass (CPB) support. A 15 mm opening was made in the common chamber horizontally after applying a Cooley’s clamp. Another opening of similar dimension made over LA appendage. Vertical vein was anastomosed to left atrial appendage posteriorly with 6-0 prolene in side-to-side fashion. The vertical vein-innominate confluence was ligated at the end of the procedure. Chest was closed in standard fashion. Mechanical ventilation was required for 12 h. Patient recovered uneventfully and was discharged on Day 10. |
pmc-6599410-1 | An 18 month-old, latin, male, diagnosed with Rickets and Crouzon syndrome, received pharmacological treatment for rickets during three months. He was referred to neurosurgery due to occipital protrusions and skull deformity. A cranial remodeling was performed, the surgery concluded successfully without complications, a surgical drain was placed and antimicrobial prophylaxis (cephalothin) was given. On the first postoperative day, the patient presented fever (38.6 °C) tachycardia, tachypnea and dyspnea. Laboratory results, showed a white cell count of 3.9 × 103/mm3 and platelets of 82 × 103/mm3. Over the next 48 h, antibiotic therapy was changed to third generation cephalosporin (ceftriaxone) due to the persistence of fever and the presence of diarrhea.
Over the next hours, tissue edema was observed in the cephalic region at the surgical wound. A Computed Tomography scan of the head was performed, an infiltrative soft tissue edema with a probable hemorrhagic component was observed. Antibiotic therapy was adjusted to ceftriaxone and clindamycin due to probable infection of the surgical wound. Two days later, bilateral areas of ecchymosis developed in the cervico-maxillary region. A blister in the right cheek spontaneously ruptured and drained thick yellowish material. Indurated skin and violaceous and well delimited lesions were noticed in some areas with scab formation (A). The antibiotic therapy was changed to meropenem and vancomycin. Despite of the use of broad spectrum intravenous antibiotics his clinical condition worsened. A new clinical examination showed weak pulses, poor skin perfusion and respiratory failure. The patient was placed in mechanical ventilatory support and he was diagnosed with septic shock.
Over the next 48 h, necrotic areas developed in the occipital, frontal, parietal, cervical and upper back regions (B), a new head computed tomography scan of the head showed soft tissue edema and a subgaleal fluid collection with defined borders. The gram stain of the cervical wound revealed gram positive short bacilli suggestive of anaerobes. Surgical lavage and debridation of necrotic tissue up to the muscular plane and some areas of the head were required for the next days, the clinical condition improved, an increase of the platelet count was observed up to 214 × 103/mm3 allowing the decrease of ventilatory parameters.
Regardless of the clinical improvement, the patient persisted with fever and hemodynamic instability. An angioresonance showed an inflammatory process in the bilateral frontotemporal occipital areas with epidural, right parietal and periorbital fluid collections, a subdural empyema in the left parietal area, and a suggestive image of temporal artery thrombosis. Candida albicans was isolated from a neck tissue sample, Staphylococcus epidermidis was isolated from a central venous catheter culture and Acinetobacter baumannii was isolated from a head tissue sample in different times. Antibiotic therapy with meropenem and vamcomycin was continued and fluconazole was added to the treatment.
After multiple surgical lavages and debridement of necrotic tissue and skin grafting of the neck and cheeks, the patient showed clinical improvement and was able to extubate.
In order to cover the skull and because of a very large uncovered area, an artificial skin graft was placed in the temporoparietal area, where after few days an infection developed presenting a green secretion under the graft where Pseudomonas aeruginosa was isolated, ciprofloxacin was added to the treatment according to the sensitivity pattern (C). The patient presented acute osteomyelitis of the frontoparietal area and surgical lavages and bone debridement was required, the green secretion persisted despite of the treatment. VAC (vacuum assisted closure) therapy and hyperbaric oxygen therapy was added to the management.
The antibiotics, surgical lavages, VAC and hyperbaric oxygen continued until the cranial area was clean and autologous skin grafts from the leg were placed in the skull until the whole skull was covered with tissue and skin (D). After 2 months of intensive care, the patient was discharged from the hospital with oral ciprofloxacin to complete the treatment for cranial osteomyelitis in good general conditions (E).
The patient continued with ambulatory lavages of the head, one month later the patient presented a fistula with yellowish and sometimes green secretion on the right temporal area, a bone scintigraphy with Indium111 and Technetium99 was performed; the bone scan images showed an abnormal increased uptake of the Indium111 in the right temporal region of the skull, confirming chronic osteomyelitis (F). The patient was admitted to the hospital for surgical resection of the affected bone, surgical lavage and skin graft; 2 strains of multi-resistant Pseudomonas aeruginosa with different patterns of sensitivity were isolated from the lesion; one was only sensitive to tobramycin which was not available in México and the other one was sensitive to piperacillin/tazobactam. A synergic testing method (the checkerboard) [] was used to measure in vitro efficacies of various antimicrobial combinations with intermediate sensitivity against the multi-resistant Pseudomonas aeruginosa. Ceftazidime and gentamycin were synergistic and together with piperacillin/tazobactam were used to treat the patient during hospitalization. A subclavian catheter was placed and the patient was discharged from the hospital and received ambulatory antibiotic treatment for 6 weeks. One week later after the discharge tobramycin was imported from United States of America and gentamicin was exchanged for tobramycin. The patient fully recovered and is in good condition, there is bone growth in the frontoparietal area. |
pmc-6599445-1 | A 50-year-old woman who was diagnosed with ypT3N1bM0 (stage III) moderately differentiated adenocarcinoma of the rectum was treated with a low anterior resection after preoperative chemoradiotherapy and adjuvant chemotherapy in 2013. The follow-up included clinical examination, serum carcinoembryonic antigen measurements every 3 months and abdominopelvic and chest computed tomography scan every 6 months for the first 2 years. After 14 months of the follow-up, she developed a recurrence of rectal adenocarcinoma in the right lower lobe of the lung and underwent curative wedge resection. Additionally, the patient was treated with eight cycles of XELOX (oxaliplatin and capecitabine). At the abdominopelvic computed tomography scan made in December 2015, several enlarged LNs were found in the gastrosplenic area (A). 18F-fluorodeoxyglucose positron emission tomography identified mild uptake (standardized uptake value max 2.8) in the gastrosplenic area (B), which was highly suspicious of rectal cancer relapse. At that time, the level of carcinoembryonic antigen, a tumor marker, was normal (0.78 ng/mL). To confirm this diagnosis, laparoscopic partial omentectomy was performed to remove a splenic hilum nodule. Gross examination revealed a well-encapsulated and lobulated mass 2.2 × 1.3 cm in size. The cut surface showed homogeneously solid and brown color (C). Microscopic findings showed a thick fibrous capsule in the periphery of the nodule with some LN features (A). Epithelioid cells occupied most of the LN, being arranged in a nested or alveolus-like architecture supported by branching thin-walled vascular spaces and/or delicate collagenous stroma (B). Individual epithelioid cells had clear to granular eosinophilic cytoplasm (C). Tumor cell nuclei were round to ovoid shape; mild atypia and prominent nucleolus were found. Spindle cells were not observed. Multinuclear tumor cells were seen infrequently. Melanin pigment granules were infrequently noted in tumor cell cytoplasm. Prominent necrosis was not observed, and mitotic activity was counted at up to 4 of 10 high-power fields (HPFs). In immunohistochemical studies, HMB45 and TFE3 were strongly and diffusely expressed (A and B). In contrast, Melan-A (C), smooth muscle actin, CK, and S100 were not expressed. On the basis of these histological and immunohistochemical findings, the diagnosis of PEComa with TFE3 expression was considered. We classified our case according to the Folpe’s classification of PEComas [], and this neoplasm was classified as “benign”. The patient did not receive additional adjuvant chemotherapy for this neoplasm. After 36 months following surgical excision, the patient remained healthy with no evidence of recurrence in the clinical and radiological follow-up. This study was approved by the Institutional Review Board of Kyungpook National University Chilgok Hospital (No. 2019-02-012). |
pmc-6599465-1 | A 74-year-old Caucasian male presented to the emergency department with complaints of shortness of breath, nausea, diarrhea, generalized weakness, and jaundice. He reported that he had started fluticasone-vilanterol for the management of chronic obstructive pulmonary disease (COPD) three days prior to presentation. He denied a history of liver disease, alcohol use, over-the-counter supplement use, recent antibiotic use, herbal product use, or acetaminophen use. His past medical history included asthma, tobacco use disorder, and non-insulin-dependent type 2 diabetes mellitus. His outpatient medications included metformin, vitamin D supplement, low-dose aspirin, and a rescue albuterol inhaler. The patient was an ex-smoker with a 25 pack-year smoking history and quit tobacco nine months prior to presentation. He also denied any other illicit substance abuse such as marijuana, cocaine, and heroin. His family history was notable for COPD and chronic renal failure, but he denied liver disease in the family. He denied any recent travel or recent sick contacts.
Prior to starting this new medication, the patient used an albuterol rescue inhaler and glycopyrrolate-formoterol fumarate combination for management of COPD. The latter medication was switched to fluticasone-vilanterol by his outpatient pulmonologist. Three days after starting this new medication, the patient noticed skin rashes, dyspnea on exertion, progressive nausea, vomiting, diarrhea, poor appetite, pruritus, anorexia, and weight loss. His condition deteriorated to the point that he was lethargic and icteric. Given these symptoms, the patient stopped taking this new medication and presented to the emergency department for evaluation. Upon admission, liver chemistries were performed, which showed the following: aspartate aminotransferase (AST) = 206 U/L (normal 12-55 U/L), alanine aminotransferase (ALT) = 371 U/L (normal 2-50 U/L), alkaline phosphatase (ALP) = 456 U/L (normal 30-99 U/L), total bilirubin (T Bilirubin) = 11.9 mg/dL (normal 0.1-1.5 mg/dL), direct bilirubin = 9.5 mg/dL (normal 0.1-1.5 mg/dL), albumin = 3.2 g/dL (normal 3.2-4.9 g/dL), and gamma-glutamyl transferase (GGT) = 800 U/L (normal 9-48 U/L) (Figures -). International normalized ratio (INR) was normal at 0.97 (normal 0.87-1.13). His white blood cell count and hemoglobin were within normal limits. He presented with acute kidney injury with a creatinine of 1.51 mg/dL (elevated from his baseline of 1.0 mg/dL) (normal 0.5-1.4 ml/dL) and blood urea nitrogen of 34 mg/dL (8-22 mg/dL). The patient also presented with non-anion gap metabolic acidosis with a bicarbonate level of 17 mEq/L (normal 22-28 mEq/L) secondary to acute kidney injury. Urinalysis was positive for bilirubinuria. No peripheral eosinophilia was noted. Serum acetaminophen was undetectable on admission. Viral hepatitis serologies were negative for hepatitis B (HBV) sAg, hepatitis C (HCV) Ab, and hepatitis A (HAV) Ab. A urine drug screen was negative for cannabis, opiates, benzodiazepines, and cocaine metabolites. Ultrasound of the abdomen was completed and revealed heterogeneous liver texture, hepatopedal portal vein flow, contracted gallbladder without biliary ductal dilatation, and normal partially visualized pancreas (Figures ).
Due to the significant hepatocellular dysfunction along with cholestatic picture at presentation, magnetic resonance cholangiopancreatography (MRCP) was performed to rule out biliary obstruction. It showed gallbladder sludge without choledocholithiasis, pancreatic divisum, mild hepatomegaly, and small renal cysts (Figure ). The common bile duct (CBD) measured 7 mm proximally and tapered at the pancreatic head (normal 4-8 mm). There was no intrahepatic biliary ductal dilatation. Chronic liver disease workup including celiac panel (tissue transglutaminase, endomysial antibody, and total IgA), smooth muscle antibody titer, antinuclear antibody titer, and hemochromatosis panel (ferritin and iron levels) was normal. After discussion with the radiology department, a hepatobiliary scan (HIDA) was performed, which showed prompt hepatic uptake, but prolonged hepatic activity and lack of hepatic transit/excretion (Figure ). The results were consistent with diffuse hepatocellular injury. The biliary products and gallbladder were not seen due to lack of radionucleotide excretion; therefore, cystic or biliary duct obstructions were not excluded. Due to the possibility of choledocholithiasis or sludge not seen on MRCP, endoscopic ultrasound with endoscopic retrograde cholangiopancreatography was considered for biliary decompression. However, the patient refused. Ultrasound-guided liver biopsy was performed through interventional radiology. Liver biopsy showed a predominance of eosinophils in the portal tracts compatible with a drug reaction. The portal tracts were moderately inflamed and showed features of mixed inflammatory infiltrate with lymphocytes, eosinophils, and rare neutrophils. No lobular or interface hepatitis was present. Lobular hepatocytes featured increased deposition of lipofuscin in the cytoplasm but no canalicular bile plugs to indicate cholestasis. No steatosis, ballooning degeneration, or necrosis of the hepatocytes was appreciated. Iron and periodic acid-Schiff staining (PAS) were normal. According to Batts-Ludwig criteria, activity grade was 2 and fibrosis stage was 0.
The patient’s hepatic panel normalized one week after stopping the offending agent. There was a concomitant improvement of his symptoms of pruritus, lethargy, and generalized weakness. The patient was asked to report fluticasone-vilanterol as an allergy. Re-challenge was not performed. |
pmc-6599468-1 | The clinical case we report here is of an 81-year-old female with a significant past medical history of diabetes, hypertension, and degenerative joint disease of the right hip joint. She reported neck weakness for two weeks, which she described as an inability to hold the neck straight. It began without any preceding trauma, infection, or significant stressor. Neck weakness started suddenly, worsening throughout as the day progresses, causing mild pain with no notable aggravating or alleviating factors. Staff at the nursing home noticed that the patient was having difficulty in extending her neck. There appeared to be no diplopia, ptosis, dysphagia, dysarthria, dysphonia, regurgitation, neck stiffness, photophobia, fever/chills, or difficulty breathing. There is no significant family history of autoimmune diseases except for hypothyroidism in the mother.
Detailed examination revealed 3/5 strength of the neck musculature but intact strength in the upper and lower extremities. Spurling and Lhermitte’s signs were negative. No sensory impairment was noticed. Deep tendon reflexes were 2+ symmetric all over, with Babinski negative. The differential diagnosis at this point included degenerative joint disease, vertebral compression fracture, muscular dystrophy, neuromuscular disease, and paraneoplastic process. Initial blood tests were within normal limits. The patient underwent a cervical spine X-ray and blood tests for inflammatory markers and metabolic panel. The X-ray was unremarkable, and there were no signs of inflammation or infection on complete blood count (CBC) and comprehensive metabolic panel (CMP). Liver function tests (LFTs), including aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), were within normal limits, excluding muscular inflammation. Autoimmune markers came out normal as well. The erythrocyte sedimentation rate (ESR) was 15 mm/hr, and the serum creatine phosphokinase (CPK) levels were mildly elevated at 350 U/l (normal 22-198 U/l).
The patient presented two weeks later with a progression in neck weakness and difficulty in holding her neck still. Chest X-ray was unremarkable, with no signs of thymoma. The anti-acetylcholine receptor binding antibody was 12.04 nmol/L (normal <0.40 nmol/L), blocking antibody was 52% (normal <26%), and modulating antibody was 84% (normal <45%), which are consistent with a diagnosis of myasthenia gravis. Depending on the clinical picture and laboratory results, we decided to prescribe cholinergic agonists rather than performing electromyography to diagnose myasthenia.
The patient was introduced on pyridostigmine (Mestinon 60 mg QID) therapy. We advised her to follow up in three days. Her symptoms improved drastically following the commencement of pyridostigmine therapy. The disease was not aggressive in course. The patient is stable on the medication since then, with no recurrence of weakness. There have been no reported adverse effects of therapy. The patient returned to her previous baseline lifestyle without any troubles with vision, swallowing, speech, or gait. |
pmc-6599469-1 | A 13-year-old girl from a rural area was admitted to the Surgery Department of Civil Hospital, Karachi, Pakistan with a history of painful rectal bleeding and protrusion of a red mass through anus after defecation for the last two years. Initially, the mass was small in size although it progressively increased in size, which protruded on defecation and had to be reduced manually. It was associated with fresh bleeding and pain after passing stool. She developed pallor and generalized body weakness over time. However, the patient had no significant history of nausea, vomiting, diarrhea, constipation, blood transfusion or any surgery. Her family history was also negative for colonic polyps and cancer. She was taken to a local general physician in her area but her condition did not improve. Then, she was referred to tertiary care hospital for further management.
On general physical examination, she was ill-looking and lethargic. Her pulse was 90 beats/minute; blood pressure 90/60 mmHg; respiratory rate 20 breaths/minute; afebrile. There were no signs of jaundice, cyanosis, clubbing or koilonychia. On abdominal examination, her abdomen was soft, mildly tender with audible gut sounds. The digital rectal examination was performed which revealed friable, easily prolapsed and bloodstained multiple pedunculated polypoid masses with normal anal sphincter tone and anal canal (Figure ). All other systemic examinations were unremarkable.
The full blood count showed hypochromic microcytic anemia with hemoglobin of 10 g/dl, packed cell volume of 28.6% and a mean corpuscular volume of 66.8 fl. The white blood cells count indicated neutrophilic leukocytosis of total leukocytes 16.7x109/L and neutrophils 79%. Other laboratory tests were within normal ranges. The chest X-ray and ultrasound scan of the abdomen were normal. Small multiple erosions in fundus were found on upper gastrointestinal tract endoscopy while the rest was unremarkable. Colonoscopy illustrated hundreds of pedunculated polyps throughout the colon. Double contrast barium enema was performed which demonstrated various filling defects, scattered diffusely in the large bowel up to the rectum (Figures -).
Contrast computed tomography (CT) scan of abdomen depicted distended large bowel which was studded with numerous, pedunculated and broad-based soft tissue density filling defects of variable sizes throughout the transverse colon, descending colon, sigmoid colon, and rectum; largest of them found in the mid rectum was measured 2.3x2.07cm. A large, irregular, heterogeneously enhancing polypoidal like mass lesion was seen at the hepatic flexure, inferiorly extending up to the ascending colon and caecum, measuring up to 3.9x4.9x3.0 cm (CCxTVxAP dimensions), also causing colo-colic intussusception. Multiple enlarged solid enhancing lymph nodes were found and the largest of them measured 1.3x1.0 cm at the ileocolic region. Histopathology report confirmed benign juvenile polyposis, showing a number of polyps with cystically dilated, hyperplastic glands, lined by tall columnar epithelium with basally placed nuclei. Some glands were filled with fibrin and intervening stroma was inflamed and showed congested blood vessels. Most of the polyps were covered by granulation tissue but indicated no evidence of dysplasia or malignancy.
Genetic testing was unavailable at our hospital. A pan-proctocolectomy with ileoanal J pouch anastomosis was planned. After consent and counseling on long-term risk of colorectal cancer associated with polyposis; exploratory laparotomy was performed and numerous polyps in colon and rectum were found. The entire colon and enlarged lymph nodes were resected (Figure ) and ileoanal J pouch anastomosis was made. Postoperatively family was counseled on proper fluid intake, soft and small meals, and hygiene, given their rural background. The patient was also informed to have regular checkups and to take part in routine tasks actively. There were no active complains within one-month follow-up post discharge. |
pmc-6599527-1 | An 88-year-old Japanese woman was noted to have an abnormal chest shadow, which was characterized on the basis of computed tomography (CT) as a mixed ground-glass opacity nodule in the upper and middle lobes of the right lung (Fig. ). She had no symptoms. Because of her age, the patient and her family did not desire further examination. A tentative diagnosis of bronchioloalveolar carcinoma was made. Follow-up chest CT every 3 to 6 months for 15 months showed stability of the pulmonary nodules. Fifteen months after the first visit, she was referred to our hospital from a nearby clinic because of dyspnea, mild cough, and chest x-ray findings of consolidation in the right lung.
She had a medical history of hypertension, for which she was receiving oral azilsartan 40 mg once daily and amlodipine 5 mg two times daily. Her social and family history was unremarkable, and she had no smoking history. Her environmental history revealed no abnormalities. She was a housewife.
Her physical examination upon admission revealed blood pressure of 140/70 mmHg, pulse rate of 120 beats per minute, temperature of 37.9 °C, and percutaneous oxygen saturation of 91% on room air. Coarse crackles at the right lung base were noted, but she had no palpable superficial lymph nodes. The result of her cardiovascular examination was normal, and her abdominal examination was unremarkable with no hepatosplenomegaly. A neurological examination revealed no abnormalities, and no skin lesions were appreciated.
Laboratory findings showed a normal white blood cell count (6200/μl) and elevated levels of serum C-reactive protein (14.25 mg/dl) and carcinoembryonic antigen (6.8 ng/ml). The laboratory findings showed that serum aspartate aminotransferase was 76 U/L, serum alanine aminotransferase was 65 U/L, and lactate dehydrogenase was 364 U/L. The serum levels of electrolytes, creatinine, and blood urea nitrogen were normal. Antineutrophil cytoplasmic antibody was negative. Sputum culture results were all negative for a causative organism. A chest x-ray showed areas of consolidation, mainly in the right lower lung (Fig. ). Chest CT images showed areas of consolidation in the right middle and lower lobes with ground-glass opacities and interlobular septal thickening (Fig. ).
Upon admission, she was treated with intravenous levofloxacin (500 mg/day). However, her symptoms and chest radiologic findings worsened; therefore, intravenous meropenem (1 g/day) was added. In addition, dexamethasone (6.6 mg/day) was started because of the possibility of carcinomatous lymphangitis. The patient and her family did not wish for her to receive aggressive medical treatment, so we did not perform bronchoscopy. Corticosteroid therapy temporarily ameliorated the patient’s fever and dyspnea, but she rapidly developed respiratory failure and died 14 days after disease onset. Her clinical course is shown in Fig. .
After consent from her family was secured, an autopsy was performed, which revealed hemorrhagic infarction of the bilateral lower lobes of the lungs due to pulmonary arterial thrombosis (Fig. ). Histologic examination of the lungs showed bilateral diffuse infiltration of atypical lymphocytes in the alveolar septum and pulmonary arteries, with thrombus formation (Fig. ). The infiltration of atypical lymphocytes was found in the bilateral lower lobe mainly, bilateral upper leaves, and middle right lobe. Immunohistochemical (IHC) analysis showed that the atypical lymphocytes were positive for CD3, CD4, CD8, and CD7 and negative for CD20, CD5, CD56, granzyme B, and perforin (Fig. ). Epstein-Barr virus-encoded small RNAs were negative on the basis of in situ hybridization analysis. T-cell receptor (TCR)-β and TCR-γ gene rearrangement was not detected by polymerase chain reaction (PCR) analysis.
Based on these findings, a diagnosis of peripheral T-cell lymphoma was made. Further review showed atypical lymphocyte infiltration with resulting thrombus formation in the bilateral renal arteries and hemorrhagic infarction of both kidneys (Fig. ). The atypical lymphocyte infiltration was not observed in the other organs, except in the lungs and kidneys. Moreover, well-differentiated adenocarcinoma with a bronchioloalveolar carcinoma growth pattern was observed in the right upper lobe S3 of the lung, but there were no lymphatic or hematogenous metastases (Fig. ). |
pmc-6599698-1 | A 9-year-old female leucoderma patient presented to the stomatology department of a public hospital in Rio de Janeiro, Brazil. She complained of small nodules in the left parotid region that had developed over the course of 2 years. Her main complaint was of recurring periods of worsened symptoms characterized by the exacerbation and remission of gland volume that was possibly triggered by occasional otolaryngologic infections or unrelated to these infections. These symptoms suggest juvenile recurrent parotitis. Facial panoramic radiography revealed the presence of multiple circular radiopaque masses in the left parotid region (Fig. ). The ultrasound revealed increased volume of the left parotid, with imprecise borders, heterogeneous echotexture with hypoechoic and hyperechoic areas within it. These features were suggestive of an inflammatory process associated with calcifications in the parenchyma of the gland. CT scan revealed a dense mass in the left parotid; it was heterogeneous and included calcifications in its center (Fig. ). Because of the association between the patient’s clinical history, her clinical presentation, and the imaging findings, the possible origin of the calcified materials was questioned. There was evidence of sialoliths or dystrophic calcification associated with recurrent inflammation/infection. Sialoliths are typically symptomatic because of their association with secondary bacterial infections, which are generally treated with systemic antibiotic therapy. Spontaneous remission of bacterial sialadenitis associated with sialoliths is not expected. In addition, sialoliths generally observed as oval-shaped calcified masses or fusiforms on imaging. Because of the pediatric nature of this case, the clinical conduct selected to treat this patient was clinical follow-up and the use of imaging and functional assessments of the gland affected every 6 months or when any signs and/or symptoms appeared. After 48 months, the patient is asymptomatic, without periods of exacerbation of the condition. Recent ultrasound (Fig. ) demonstrates an improvement in the inflammatory aspect of the gland. Clinical and imaging follow-up will be maintained. |
pmc-6600042-1 | A 56-year-old man was referred to our hospital with a 6-month history of abdominal distension and discomfort (A). He had a medical history of schizophrenia. His abdomen was markedly distended, and severe edema was present in both lower limbs. He had no symptoms of gastrointestinal obstruction. Neurological examination findings were normal. He had slight anemia (hemoglobin of 10.5 g/dl), and other laboratory data were within normal limits. A computed tomography (CT) scan demonstrated a 30- × 18- × 30-cm giant mass located between the stomach and transverse colon. It included a large cyst and solid component that showed enhancement (B). The main feeder artery for the tumor seemed to be the right gastric artery. Magnetic resonance imaging (MRI) also showed a huge heterogeneous soft tissue mass. The solid component showed high signal intensity on T2-weighted imaging and diffusion-weighted imaging (C, D). Upper and lower endoscopy was not performed because the patient declined. CT-guided biopsy was not performed to avoid dissemination. Our preoperative differential diagnoses were sarcoma with a mucinous component, gastrointestinal stromal tumor, lymphangioma, and mesenteric cyst. A histological diagnosis was not obtained preoperatively, and the tumor was too large to identify its boundary with the surrounding organs by radiological examination. We expected that the tumor was arising from the stomach, transverse colon, or mesenterium.
We decided to perform surgery because the tumor showed the tendency to grow. During laparotomy, we identified a huge encapsulated tumor. The tumor occupied most of the pelvic cavity, but the caudal side of the tumor had no adhesions with pelvic organs. We gradually dissected along the capsule and moved the tumor outside the body (A). Finally, we found that the tumor was adhered to the stomach and transverse colon. We resected the distal stomach and 15 cm of the transverse colon with the tumor. Reconstruction was performed using Billroth-I anastomosis for the stomach and end-to-end anastomosis for the colon. We identified the resection margin of the tumor, and we did not perform intraoperative histological examination or lymph node dissection because no enlarged lymph nodes or disseminated nodules were found. The tumor was completely removed. The postoperative course was uneventful, and the patient was discharged on postoperative day 17.
Macroscopic examination revealed a 38- × 20- × 19-cm tumor weighing 13,000 g (B). No abnormalities were found on the intraluminal surface of the stomach or transverse colon wall. On histological examination, the tumor was composed mainly of short spindle and vacuolated cells, including lipoblasts and mature adipocytes, with a myxomatous matrix. The main mass was located in the abdominal cavity, but the tumor base was broadly adhered to the gastric wall and seemingly grew from the gastric submucosa, suggesting that the tumor had likely arisen from the stomach (). The transverse colon was intact. Immunohistochemically, the tumor cells were negative for smooth muscle actin, c-kit, and MDM2. These features were consistent with myxoid liposarcoma. The patient was still doing well 2 years postoperatively. |
pmc-6600383-1 | A 50-year-old woman presented to our institution 14 years ago with a past medical history significant for polycythemia diagnosed at age 7. An obstructive mass in the head of the pancreas was found and resected at age 36, using the Whipple procedure. Blood pressure was labile during the procedure. Histology confirmed duodenal ampullary somatostatinoma and additional multiple abdominal paragangliomas. She was at that time referred to our institution for investigation of suspected metastatic paraganglioma. Blood chemistries () and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT) confirmed metastatic and/or additional paragangliomas with foci present in the left para-aortic region at the level of the kidney and throughout the abdomen, corresponding to 123I-metaiodobenzylguanidine (123I-MIBG) activity on subsequent scan. She underwent 131I-MIBG-directed radiotherapy and resection of these tumors at an outside institution. Identification of the EPAS1 gain-of-function mutation in the resected tumor tissues and circulating leukocytes confirmed the underlying syndrome. At present, tumor burden is stable, polycythemia has resolved although erythropoietin levels are mildly elevated, and the patient is asymptomatic.
Imaging of the chest, abdomen, and pelvis showed stable tumor size and occult sacral dysraphism and segmentation defect. l-3,4-dihdroxy-6-[18F]fluorophenylalanine (18F-FDOPA)-PET/CT scan revealed focal tracer uptake at the skull base consistent with a glomus jugulare tumor (probably paraganglioma) and tracer uptake within several lumbar vertebral bodies. CT and MRI of the head were diagnostic of Chiari malformation type I with tonsillar displacement 7 mm below the foramen magnum (A). Reduced ossification of the occipital bone and uncalcified petroclival synchondrosis were evident on CT (B–D).
No family members have history of pheochromocytoma/paraganglioma, polycythemia, thyroid disease, parathyroid disease, adrenal disease, or history of Chiari malformation. Her mother died from lymphoma at age 62. Her father died of bladder cancer at age 75. |
pmc-6600383-2 | A 29-year-old male presented to our institution with a past medical history significant for polycythemia diagnosed at 28 months by routine phlebotomy. At age 14, a left chest wall tumor was found at level of the 4th rib on CT scan performed for evaluation of hypertension and syncopal episodes. Blood chemistries () and histopathology of three resected chest wall masses at age 17 confirmed paragangliomas. He was referred to our institution for genetic evaluation after resection of multiple paraortic and lumbar paragangliomas. Somatic mosaicism of EPAS1 gain-of-function was confirmed in the resected tumors and circulating leukocytes. His follow-up included routine phlebotomy for polycythemia and measurement of plasma and urinary metanephrines and imaging for tumor surveillance and detection.
18F-FDOPA scan revealed a focus of tracer uptake in the right lower lobe and six retroperitoneal foci in the aortocaval and right paracaval regions; the para-aortic lesions were also positive on 68Ga- DOTATATE PET/CT. MRI of the brain with contrast performed for evaluation of metastatic disease detected Chiari type I malformation with tonsillar displacement 8 mm below the foramen magnum (A–C). A developmental venous anomaly of the Vein of Galen confluens and choroid plexus involving the velum interpositum was also found (D–E). Sacral dysraphism was also present (F–H). Imaging follow up over several years in patient 2 demonstrated that the Chiari I malformation was stable. |
pmc-6600853-1 | A 50 years old Aryan female from Lalitpur district, Nepal, presented to Patan Hospital Emergency Department in December 2018 with complaints of abdominal pain that had persisted for two days. She had multiple episodes of vomiting. In terms of the patient’s history, she had been treated with amlodipine and atenolol for hypertension and undergone a total abdominal hysterectomy 5 years prior for fibroids. She was a farmer living in suburban area of Lalitpur and involved in growing of vegetables and rearing of cows and poultry. On assessment, her blood pressure was 170/100 mmHg and her pulse rate was 88 beats per minute. Temperature was 98 degree Fahrenheit. Abdominal examination showed tenderness in the right upper quadrant.
Below are the laboratory parameters with normal range in parentheses:
Complete blood count : white cell count 8.4 (4-10) X 10^9/L ; neutrophils 60 % ; lymphocytes 37 % ; monocyte 1 % ; eosinophil 2 % ; red blood cells 4.8 (4.2–5.4) × 10^12/L; hemoglobin 12.5 ( 12-15) g/dL ; platelets 145 ( 150-400) X 10^9/L
Biochemistry: random blood sugar 124 (79-160) mg/dL; urea 28 (17-45) mg/dL; creatinine 0.7 (0.8-1.3) mg/dL; sodium 135 (135-145) mmol/L; potassium 3.8 (3.5 – 5) mmol/L; calcium 8.5 (8.4-10.2) mg/dL; albumin 3.4 (3.5-4) gm/dL; magnesium 1.8 (1.6-2.3 mg/dL); amylase 45 (30-125) U/L; lipase 56 (10-150) U/L.
Hepatic panel: bilirubin total 2 (0.1-1.2) mg/dL and direct 0.5 (0-0.4) mg/dL; alanine transaminase 53 (5-30) units/L; aspartate transaminase 47 (5-30) units/L; alkaline phosphatase 76 (50-100) IU/L
Ultrasound of the abdomen revealed a gallstone with a thickened gall bladder wall. She was admitted to the surgical ward with a provisional diagnosis of biliary colic, and managed conservatively with intravenous fluids, anti-emetics and analgesics. Her pain subsided. and her blood pressure also fell down to normal range with analgesia. But she developed a headache from 2
nd day and fever of 101 degrees Fahrenheit on the 4
th day. Injection ceftriaxone 1 gram twice daily was started empirically. The next day, she developed altered sensorium. Neurological examination revealed disorientation to time, place and person with neck stiffness but no papilledema or any focal neurological deficit. Plantar reflex was normal bilaterally.
Plain computed tomography (CT) of the head was normal. Cerebrospinal fluid (CSF) analysis revealed the following (with normal range in parentheses): Red blood cells= 6 (0–10)/mm^3; white blood cells = absent (0–5/mm^3); protein= 45 (20–45) mg/dL; sugar= 71 (45–80) mg/dL; lactate= 2 (1.1–2.8) mmol/L; adenosine deaminase (ADA) = 6.2 U/L; GeneXpert was negative for Mycobacterium Tuberculosis; CSF India ink staining was negative; Bacterial culture showed no growth over 48 hours. However, CSF cryptococcal antigen was positive by latex agglutination (Latex-Cryptococcus Antigen Detection System; IMMY). Serological test for HIV were negative.
With the diagnosis of cryptococcal meningitis, she was transferred to the intensive care unit (ICU) and liposomal amphotericin B (4 mg/kg/day) and Fluconazole (800 mg daily) were prescribed while ceftriaxone was continued. Unfortunately her family members could not afford the expensive liposomal amphotericin B. The government of Nepal provides liposomal amphotericin B (single dose of 10 mg/kg) free of cost to patients with visceral leishmaniasis (VL)
. We wrote an application letter to the relevant authority to request liposomal amphotericin B for the patient. We asked for a total of 56 vials of the medicine (each vial contained 50 mg of liposomal amphotericin B) that would be sufficient for a two-week course. The relevant government authority refused to provide liposomal amphotericin B to our patient stating that the drug is to be dispensed to patients with VL only, as per the government policy. She was then started on fluconazole alone, but her status deteriorated. In addition, she also developed right sided hemiparesis 3 days following the diagnosis. Magnetic resonance imaging (MRI) of the brain was performed that revealed an acute infarct involving the left parietal lobe and basal ganglia, with multiple acute lacunar infarcts in the bilateral frontal and parietal lobes and bilateral cerebellum. She was in sinus rhythm. Echocardiography was normal. Aspirin 75 mg and atorvastatin 40 mg daily were administered as a result.
In a few days, her family members provided the liposomal amphotericin B. They revealed that they had connections with influential politicians who helped them acquire the medicine from the same government center who had previously refused them. She then received the two-week course of liposomal amphotericin B along with fluconazole. The patient improved gradually. She had hypokalemia during treatment with Amphotericin B which was managed with a potassium chloride infusion at 5 mEq/hour. She started showing improvement in her higher mental functions after the 5th day of amphotericin B administration.
After completion of 2 weeks of Amphotericin B, her higher mental function had returned to normal, and she could walk on her own with some residual weakness in her right upper limbs. She was then discharged from hospital and daily fluconazole 800 mg was continued for 8 more weeks.
On first follow up 1 week following discharge she was doing well. She was last seen in February 2019 after completing 8 weeks of fluconazole 800 mg daily. She was asymptomatic and was prescribed a daily tablet of fluconazole 400 mg for 1 year. |
pmc-6600893-1 | A 78-year-old Asian woman presented to our outpatient department with chief complaints of coughing and fever. Her cough had persisted for several weeks, and her fever had developed on the previous day. The patient’s medical history included asthma and sinusitis. Although her sinusitis had been treated several years prior, she had not received treatment before hospitalization. The patient’s surgical history included knee joint replacement and two spinal fusion surgeries; the second spinal fusion had been performed 3 months before the current consultation.
Physical examination revealed hypoxemia, and auscultation revealed bilateral chest crackles with no sign of heart failure. Bilateral pleural effusion was detected on a chest radiograph (Fig. ). The patient developed yellowing of her fingernails and toenails following hospitalization (Figs. and ). This finding, combined with the patient’s pleural effusion and sinusitis, led to suspicion for YNS. Bilateral dorsum pedis lymphedema was confirmed during hospitalization. Blood analysis revealed a slight increase in inflammation. However, the patient’s test results for rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative. Her thyroid parameters and levels of soluble interleukin-2 receptor were normal. Her sputum culture and interferon-γ release assay results were negative. The result of her bacterial culture of pleural effusion was negative. Computed tomography failed to confirm the presence of a malignant tumor. A chest radiograph (Fig. ) obtained prior to the second spinal fusion procedure showed no pleural effusion. However, pleural effusion appeared 1 month after the second surgery. On the basis of these findings, the patient was diagnosed with YNS due to titanium exposure.
After diagnosis, vitamin E was administered for more than 1 year. After a half-year of vitamin E administration, improvement in the thickness of the nails on the patient’s hands was observed (Fig. ), but no effect was seen for the pleural effusion. Pleural effusion also failed to respond to pleurodesis. Pleural effusion drainage was therefore performed regularly. Currently, the patient visits our clinic every 1–2 months and undergoes chest radiography. Pleural drainage is performed if there is an increase in pleural fluid. |
pmc-6600896-1 | A 31-year-old female, gravida 2, para 2 (G2 P2), referred to the gynecologic clinic with a main complaint of secondary infertility during the last twelve months. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The patient had two previous C-sections. Her menstrual cycles were ovulatory. Spermogram was unremarkable and hormonal assay did not show any abnormality. HSG was performed and revealed a migrated copper IUD with its long tail out of the uterine cavity (Fig. ). Plain abdominopelvic radiography also indicated a rotated T-shaped IUD in the pelvis (Fig. ). A transvaginal ultrasound was also performed by a skilled radiologist who reported a copper IUD in the bladder lumen with a small portion of it within the bladder musculature. The patient had taken multiple courses of antibiotics for urinary tract infection (UTI), but her symptoms never disappeared. The patient also underwent cystoscopy for recurrent infection last year, but no pathological finding was detected. Eventually, the patient said that her symptoms were related to the possible adhesions following two previous operations. The patient had a history of IUD insertion following her last C-section about eight years ago. After three years, however, the patient decided to remove it due to recurrent vaginal secretions. Three years later, her IUD was expelled, and another copper IUD was inserted. The patient removed the other copper IUD for becoming pregnant about two years ago. The patient was very confident of its removal, but her recent HSG, interestingly, demonstrated a rotated copper IUD in the pelvic cavity. Physical examination was essentially normal. A baseline complete blood count, urea, and creatinine levels were normal. The patient was candidate for a hysteroscopic cystoscopy. Hysteroscopy was normal except for a small fibrotic defect at the lower segment of the uterus. During cystoscopy, the long tail of the copper IUD was found on the posterolateral border of the bladder far from ureteral offices (Fig. ). The two short arms adhered to each other were embedded in the mucosal and muscular layer (Fig. ). No calculus was observed within the bladder cavity. Using glycine as the media, a mono-polar loop entered the bladder. A gentle and brief cautery was applied on the mucosa where the shadow of a short arm of the device was observed. The copper IUD was safely removed through the urethra using a special grasper. There was no major defect in the place of the copper IUD in the bladder. The bleeding points were effectively cauterized (Fig. ). The patient was discharged the next day with an indwelling catheter. After catheter removal, the patient did not complain of any urinary symptoms. |
pmc-6601150-1 | A 62-year-old man, a heavy smoker, was admitted with resistant hypertension. He had been a known hypertensive for >10 years; the highest systolic and diastolic blood pressure was 220 and 140 mmHg, respectively. Treatment with oral calcium channel blocker, beta blockers, and diuretics had not controlled the blood pressure. Other medical history included new-onset diabetes for the last 2 months and hyperlipidaemia and coronary heart disease for the last 10 years. No abdominal and cardiovascular abnormalities were found. Conn’s syndrome was excluded by negative aldosterone screening in horizontal position and no abnormal adrenal CT scan. The creatinine level was 84.3 µmol/L (44–133 µmol/L). Renal artery US showed a peak systolic velocity of 358 cm/s, indicating severe stenosis of the right renal artery. Renal artery CTA showed local and ostial stenosis (95%) of the right renal artery (Figure ). RAG showed 95% ostial stenosis of the right renal artery (Figure ) using a 6 F RDC catheter. The stenosis was pre-dilated with a 4 × 20 mm balloon (Sapphire) at a maximal pressure of 18 atm and implanted with a 6 × 14 mm stent (Express SD) at a maximal pressure of 15 atm through a Fielder guided wire. The intervention was successful without any complications (Figure , Video S1). Dual antiplatelet therapy was then administered (aspirin 100 mg, one time daily, clopidogrel 75 mg, one time daily).
After 3 days, the patient developed sudden right lower abdominal pain. The abdominal and renal examination was negative, but defaecation had stopped. The electrocardiogram, myocardial enzyme levels, and myocardial infarction marker levels were all normal. Pancreatitis was excluded because the amylase levels were normal. The serum creatinine level increased slightly, to 100–108 µmol/L, the urine protein was weakly positive (+1), and the blood pressure was maintained at 110/70 mmHg. To determine the cause of abdominal pain, renal artery US was performed, which showed that the main trunk of the right renal artery was not clear, and the blood flow was significantly reduced. This indicated a possible complication of right renal artery stenting. Renal artery CTA showed an unobstructed right renal artery stent, a severely stenosed middle segment, and light right renal perfusion (Figure , , Video S2). Considering a diagnosis of thrombosis or dissection of the renal artery, treatment with low-molecular weight heparin anticoagulant and rehydration was administered. Simultaneously, examining the dual glomerular filtration rate (GFR) using nuclear imaging discovered a non-functional right kidney (GFR: right 0.6; left 75.6; Figure ). Therefore, RAG was repeated to identify the cause of blood flow reduction and rescuing kidney function; the right renal artery stent was found patent. Severe stenosis (90–95%) of the middle part of the renal artery with two branches involved was seen; however, there was no dissection or thrombus formation (Figure , , Video S3). To further determine the aetiology of the new lesion, IVUS was used, which showed that the IMH originated at the distal end of the stent, without an identifiable entry point, and the length was about 40 mm (Figure , , Video S4).
After clarifying the cause of the new stenosis, we first used a 2.5 × 20 mm balloon, followed by a 4 × 20 mm balloon (Sapphire) at a low pressure to push out the haematoma and dilate the compressed renal artery from the proximal to the distal end. The cavity of the compressed renal artery increased gradually, and the blood flow improved. However, the residual stenosis was still more than 50%, limiting the blood flow. Therefore, another stent (5 × 19 mm Express SD) was implanted near the first stent; the distal segment of the renal artery was seen to be well-developed (Figure , , Video S5). After reoperation, dual GFR revealed that the right kidney function had partially recovered (GFR: right 10.3; left 66.3; Figure ), the creatinine reduced to 91 µmol/L, and the urine protein was negative (Figure ). After discharge, the patient continued to maintain dual antiplatelet therapy. At the third month follow-up, the abdominal pain symptoms had disappeared, the serum creatinine level was 79 µmol/L, the urine protein was negative, and the blood pressure was maintained at 125/83 mmHg without any antihypertension drug. Renal artery US showed that the right renal artery was unobstructed. |
pmc-6601201-1 | A 16-year-old man was referred to our institution with progressive weakness and arthralgia, mainly involving proximal part of superior limbs. He developed these symptoms during the last 3 months in association with intermittent fever and weight loss. As the patient reported, a skin rash was present for 6 months. He had not received any therapy for these symptoms and signs.
At admission he had a temperature of 37.4°C. Physical examination demonstrated significant hepatomegaly. Mucocutaneous examination showed lichenoid papules on the dorsal surface of the hands, typical of Gottron papules.
His jugular venous pressure was raised and his heart sounds were normal. The chest was clear to auscultation. His blood pressure was 90/60 mmHg with a heart rate of 82 b.p.m. The respiratory rate was 16 breaths per minute and the oxygen saturation was 98%.
Blood investigations revealed:
High alanine transaminase (78 IU/l) (reference range <35 IU/l) Very high creatine phosphokinase (736 UI/l) (reference range 60–174) Positive Rose-Waaler test. Positive anti-Jo1 antibody High NT-proBNP (3150 ng/l) (upper limit of normal: 900 ng/l).
In the proximal muscles, electromyography showed small, short, polyphasic actions potentials, with early recruitment motor unit action potentials, indicative of membrane irritability. These findings were more pronounced in the upper limbs. These findings suggested a diagnosis of DM.
A right quadriceps femoris biopsy showed B cells inflammatory infiltrated involving perivascular spaces and interfascicular septae, compatible with muscle fibre degeneration due to microvascular damage.
Muscular magnetic resonance showed generalized muscular oedema associated with atrophy and adipose infiltration.
The patient was diagnosed as having DM (Bohan and Peter’s criteria) and was started on corticosteroids therapy (1 mg/kg/day of oral prednisolone) together with methotrexate (15 mg, orally, once a week).
The 12-leads electrocardiogram showed a sinus rhythm with multiple ventricular premature beats.
The transthoracic echocardiogram (TTE) showed an atypical interventricular septal bounce into the left ventricular cavity because of ventricular interaction ( online, Video S1). Left ventricle and right ventricle (RV) systolic function was normal.
Transoesophageal echocardiogram showed a markedly thickened and calcified pericardium and demonstrated very clearly the interventricular septal bounce ( online, Video S2).
TTE-transvalvular PW Doppler flow studies showed a significant reduction of 31% in mitral inflow velocity and an increase of 25% in tricuspid inflow velocity during inspiration (Figures ). The increase in tricuspid flow during inspiration was less significant than mitral inflow velocity reduction. In contrast, an increase of mitral inflow velocity was noted during expiration with a reduced filling velocity to the right heart (Figures ). The aortic flow velocity decreased during inspiration and increased during expiration.
Tissue Doppler imaging (TDI) showed a medial eʹ velocity of 12 cm/s and a lateral eʹ velocity of 9 cm/s (annulus reversus). E/eʹ ratio (using average eʹ) was 9 (annulus paradoxus).
The echocardiographic findings were in keeping with constrictive pericarditis (CP).
Patient was diagnosed as having a CP.
At the time of diagnosis the NYHA class was 3 (dyspnoea induced by mild exertion).
The patient underwent radical pericardiectomy by total median sternotomy without significant post-operative complications.
He was discharged on day 10 with a medical therapy consisting of diuretics (furosemide orally 20 mg BID); corticosteroids (5 mg per day of oral prednisone), methotrexate (15 mg orally, once per week), antibiotics (amoxicillin orally 3 g/day for 2 weeks) and paracetamol (maximum 4000 mg/day, orally). Hepatomegaly disappeared 4 weeks after operation together with alanine transaminase normalization.
After pericardial resection, the interventricular septum bulging and the respiratory variation of filling velocities completely disappeared ( online, Video S3) (see also Table ).
On follow-up 2 years later, the patient had no symptoms. |
pmc-6601217-1 | A 74-year-old woman with past medical history of left breast cancer submitted to radical mastectomy 10 years ago was admitted to the emergency department for acute dyspnoea. Clinical observation showed tachycardia, blood pressure 89/54 mmHg, regular heart sounds, no heart murmurs, arterial oxygen saturation of 85%, tachypnoea, accessory respiratory muscles use, and bilateral rales with left hemithorax dullness at percussion. Electrocardiogram showed sinus tachycardia, right bundle brunch block, and left anterior hemiblock with 2 mm ST-elevation in leads aVL, aVR, and I (Figure ). Clinical condition deteriorated requiring intensive care unit admission, inotropic and vasopressor support, and mechanical ventilation. Bedside transthoracic echocardiogram (TTE) showed impaired LV function with anterior and lateral wall akinesia. A presumptive diagnosis of myocardial infarction (MI) presenting as cardiogenic shock was made and antithrombotic therapy including loading doses of aspirin (250 mg), ticagrelor (180 mg), and heparin (5000 UI) were administered. Emergent coronary angiogram was performed and showed diffuse non-significative three-vessels disease (Figure ). Cardiac biomarkers were elevated (high sensitivity troponin I 32 ng/mL, for a normal <0.07 ng/mL and BNP 528 pg/mL, for a normal <100 pg/mL). Based on radiological chest imaging, a mass in the left lung was suspected; TTE imaging review showed LV lateral and anterior wall akinesis due to infiltration by a heterogeneous echogenic mass (Figure ). Transoesophageal echocardiogram confirmed TTE findings, showing mild mitral regurgitation and a large mass invading the lateral LV wall. An urgent computed tomography (CT) scan was performed showing a neoformation located in the lower and mid sections of the left hemithorax, invading the lateral LV wall, pulmonary artery left branch, left pulmonary bronchi and anterior thoracic wall, compatible with an advanced lung cancer (Figure ). Despite supportive care, clinical status worsened and the patient died in the following hours. |
pmc-6601238-1 | A 79-year-old man was admitted to the intensive care unit on November 2017 for a ruptured penetrating atherosclerotic ulcer of the ascending aorta identified on CT scan (Figure).
He had a significant past medical history: end-stage renal failure undergoing dialysis, and myocardial infarctions with previous stentings (the last infarction dating back 10 months). Earlier in the day, the patient had presented with severe retrosternal chest pain for which a myocardial infarction was initially suspected, but the electrocardiography and the transthoracic echography performed in emergency excluded the diagnosis. A CT scan was realized and showed a local aortic plaque rupture of the ascending aorta with active contrast leakage, the patient was then transferred to our institution.
At admission the patient was haemodynamically stable with good blood pressure, a normal pulmonary auscultation with oxygen saturation at 100%, and no more pain. The patient was considered for open cardiac surgery but was evaluated at a high mortality risk based on his age, his medical history, and significant calcifications on his aorta. Our vascular surgical team decided then to perform an endovascular repair.
In emergency, an off the shelf endovascular stent graft was used. The rupture measured 12 mm and was located at just a few millimetres proximal to the IA. The ascending aorta measured 8 cm from the coronary sinuses to the IA. The largest diameter measured along the length of the ascending aorta was 33 mm (Figure). The shortest available off the shelf thoracic stent graft was the 10 cm length Conformable GORE® TAG® Thoracic Endoprothesis (WL Gore & associates, Flagstaff, AZ, USA).
In a hybrid operative room, first we performed an IA debranching with a left to right common carotid bypass through a cervicotomy using GORETEX vascular graft (8 mm). Via a transfemoral approach, the IA was embolized with a plug emplatzer (16 mm). Then, we considered a femoral approach to place the stent graft, but due to bad femoral access and after determining the working length of the delivery catheter would be insufficient to reach the most proximal landing in the ascending aorta, we decided a transapical approach would be necessary. A 24-Fr introducer sheath was placed through a left ventricular transapical approach by using a mini-thoracotomy. The endograft was deployed under rapid pacing with three-dimensional image fusion-guided thoracic endovascular aortic repair (Figure). The intra-procedural aortography demonstrated a well-positioned endograft with successful seal of the rupture.
During post-operative period, the patient underwent an ischaemic stroke with sudden right hemiparesis for 48 h followed by complete recovery. The patient was discharged from the intensive care unit at 19 days and from the hospital at 30 days with an antiplatelet therapy (aspirin 75 mg).
The post-operative CT scan showed a successful exclusion of the rupture (Figure). Eight months after surgical treatment, the patient is in an excellent neurological condition without sequelae, and he recovers a quality of life equivalent to the previous state. |
pmc-6601240-1 | A 58-year-old man was brought to the local hospital with chief complaints of lower extremity fatigue, severe bilateral lower extremity pitting oedema, particularly of the right leg, and intermittent, mild chest tightness. He first visited the neuropathy clinic. The CT, diffusion-weighted imaging, and angiography were unremarkable. Haemoglobin was 108 g/L (normal range within 130–175 g/L), urine protein was 0.43 g/24 h (normal range within 0.00–0.15 g/24 h), and albumin was 34.7 g/L (normal range within 40.0–55.0 g/L). Thyroid function was unremarkable.
The initial transthoracic echocardiogram indicated the internal diameter of the ascending aorta 32 mm, right ventricular outflow 30 mm, the left atrium 30 mm, left ventricular (LV) end − diastolic/systolic dimension 50 mm/29 mm, LV dimension 18 mm, and LV function was normal with an ejection fraction (LVEF) of 72%, fractional shortening (FS) of 42%, stroke volume (SV) of 88 mL, and cardiac output (CO) of 10.9 L/min. A moderate pericardial effusion was detected, and the depth of liquid at the left ventricular apex was 5 mm. The diaphragmatic surface of the right ventricle was 12 mm. After the treatment with diuretic, there was little improvement in lower extremity fatigue, oedema of the lower extremities, or chest tightness.
Therefore, the patient visited the outpatient clinic of cardiology for further treatment after new facial and ankle oedema appeared and his shortness of breath persisted. On admission to the cardiology department, a chest X-ray revealed bilateral pleural effusions (Figure). Echocardiogram showed normal left ventricular function with an LVEF of 65%, FS of 35%, SV of 76 mL, CO of 9.2 L/min, a small-medium pericardial effusion (left ventricular posterior wall 6.4 mm, right ventricular anterior wall 7.7 mm, apex of the heart 6 mm, right ventricular free wall 17 mm, left ventricular free wall 6 mm), increased size of the right heart (right atrial diameter 36 mm × 46 mm, right ventricle internal dimension 40 mm × 70 mm), dilation of the inferior vena cava (24 mm) and respiratory variation of the mitral peak E velocity of >25% (Figure). Electrocardiography showed sinus tachycardia, and T wave inversion (Figure). The coronary CTA and computed tomography pulmonary angiogram (CTPA) showed severe narrowing of the diagonal branch of left anterior descending artery (FigureA), as well as the presence of pleural effusion (FigureB) and peritoneal effusion. Thoracentesis of the left thoracic cavity using imaging guidance was performed to determine the cause of the excess pleural effusions and to relieve his shortness of breath. A total of an estimated 1180 mL of fluid was drained from the pleural effusion during hospitalization. Laboratory tests of the pleural effusion indicated leakage fluid with the following results: light yellow turbid liquid, Rivalta test (+), total cells count 152 × 106, monocytes accounting for 90% of total white blood cells, white blood cells count 140 × 106, protein 27.7 g/L, glucose 11.87 mmol/L, lactate dehydrogenase (LDH) 106 U/L, and adenosine deaminase (ADA) 4 U/L. Thoracentesis of the right thoracic cavity was also performed later. A total of 3050 mL of fluid was drained from the pleural effusion during hospitalization. Laboratory tests of the pleural effusion indicated leakage fluid with the following results: light yellow turbid liquid, Rivalta test (+), total cells count 352 × 106, monocytes accounting for 72% of total white blood cells, white blood cell count 287 × 106, protein 31.6 g/L, glucose 12.55 mmol/L, LDH 111 U/L, and ADA 4 U/L. Hyperplastic mesothelial cells and lymphocytes were found in the pleural effusion. The oedema and shortness of breath was significantly improved after thoracentesis. After removing the drainage tube due to the concerns of iatrogenic infection and discomfort, however, the bilateral pleural effusions quickly reappeared. Based on the CTA result indicating the severe stenosis of the diagonal branch of left anterior descending artery, antiplatelet and lipid-lowering medications, and a beta-blocker were prescribed because the symptoms of fatigue, chest tightness, and dyspnoea were partially thought to be due to ischaemic heart disease. However, these symptoms were unsuccessfully treated as ischaemic heart disease.
After being discharged from the department of cardiology without a clear aetiology, the patient complained of cough, expectoration, progressive dyspnoea, and bilateral lower extremity pitting oedema. He then visited the department of pulmonary medicine. After reviewing the initial CT results, a thickened pericardium was observed (FigureC–E). Though there was no evident Kussmaul sign, CP was considered and this urged the physicians to get informed consent to perform a pericardectomy. The gross view of the heart in situ originally observed during pericardectomy indicated fibrinous pericarditis, a massive haemorrhagic pericardial effusion, and thickened pericardium (FigureA and ). The maximum thickness of the pericardium was more than 6 mm (FigureB). Haematoxylin and eosin (H&E) staining of the pericardial tissue biopsy obtained from five different regions of the thickened pericardium showed massive chronic inflammatory cell infiltration (phlogocytes and leucomonocytes) and fibroid necrosis (hyaline degeneration). There were no pathological characteristics of TB or malignancy (). The patient was diagnosed as idiopathic pericarditis. Chronic, non-specific vascular inflammation was proposed to be responsible for the haemorrhagic pericardial effusion. All of the symptoms gradually disappeared 1 week after pericardectomy. Prior to discharge, the repeated X-ray () indicated disappearance of the cavity effusion. At the first scheduled follow-up visit 1 month after pericardectomy, the echocardiogram indicated normal left ventricular function with an EF of 76%, FS of 44%, SV of 75 mL, and CO of 7.8 L/min. At the 2-, 5-, 7-, and 12-month follow-ups, the patient had no complaints of discomfort. |
pmc-6601307-1 | A 59-year-old, right-handed woman, who had been treated for moderate arterial
hypertension, had an acute episode of right-side hemiplegia. A brain CT revealed an
intracerebral hemorrhage of approximately 50 milliliters with its center in the left
thalamus, which had ruptured into the ventricles (). She was submitted to external ventricular drainage with
continuous monitoring of intracranial pressure. The patient remained unconscious for
several weeks and was hospitalized for almost five months.
She was seen at the outpatient clinic 19 months after the stroke. She had remained at
home since leaving hospital, where she experienced severe limitation in daily
activities and was still using diapers. She was always in a good mood, seemingly
unaware of her condition.
At examination, she was in a wheelchair, with neglect of the right visual field,
right-sided hemiplegia and hemianesthesia. She was unable to perform on command or
to imitate simple gestures with her left arm.
Her spontaneous speech was very poor, restricted to simple words or monosyllables.
When she tried to say something else there were many phonemic paraphasias and
neologisms. Palilalia was also frequent. She was able to understand and respond to
simple commands such as “open your mouth”, but perseveration ensued almost
immediately. Naming was also severely impaired. She was able to name only one out of
ten simple drawings and she also had severe difficulty singling out an object after
hearing its name. Her performance fluctuated on almost all tasks, although was
consistently very poor.
Repetition of single words or familiar short sequence of words (such as the name of
the street where she had been living for years) was preserved.
She was able to repeat 4 digits forwards, but none backwards. Semantic verbal fluency
was zero and she scored 3 on the phonemic (FAS) test. She was able to read simple
phrases aloud such as “close your eyes”, but she did not obey the command. She was
unable to write, not even single letters, or to copy single figures, when closing-in
phenomena was observed.
Her speech improved for a few seconds when she was asked about her only son, but
after only two or three short phrases, her speech again became unintelligible and
non-fluent. Besides her ability to repeat words, she also could sing old songs
together with her caregivers.
MRI showed a residual cavity in the left thalamus with a confluent white matter
hyperintensity in the left centrum semiovale. The left hemisphere was slightly
smaller than the right hemisphere. Color fractional anisotropy map revealed loss
of anisotropy in the left centrum semiovale, and tractography focusing on
anterior thalamic radiations showed normal appearance on the right side, yet
almost no clear fiber identification on the left side. (-).
The F-Fluor-dexoxi-glucose PET (F-FDG-PET) scan showed severe glycolytic
hypometabolism in the left cerebral hemisphere and contralateral cerebellar
hemisphere. Coronal views showed that metabolism was less reduced in the
transverse cortical gyri. On the lateral surface of the left hemisphere, only
the occipital cortex, frontopolar region and a small area corresponding to the
superior temporal gyrus were less involved when compared with the database
control. A Z-score mapping system showed a marked reduction of meta bolism in
the left cortical hemisphere, but an area corresponding to the left superior
temporal gyrus and a small area of the left inferior frontal gyrus had better
preserved metabolism than other areas in the left hemisphere. Analyses of the
images using Statistical Parametric Mapping (SPM) showed better preserved metabolism in the superior temporal
gyrus, in a region of the inferior frontal gyrus roughly corresponding to
Broca’s area, compared to a normal volunteer database group, (-) and also in the region corresponding to the calcarine fissure
(Figure 4 - shown at: ). She did
not improve with transdermal rivastigmine and with repetitive transcranial
magnetic stimulation (r-TMS), which was performed with a MagPROX100 device
(Magventure® Tonika Elektronik, Farum, Denmark) at 10Hz, using a butterfly
double-cone D-B80 cooled coil, held tangentially to the scalp using previously
described protocols. The total
treatment consisted of sessions five days per week for two weeks.
Neuropsychological evaluations were performed before, after the first and after
the second weeks. 18F-FDG-PET scans performed before and immediately after the
end of the r-TMS also failed to show a difference. |
pmc-6601469-1 | Case 1. An 80-year-old male presented with bilateral posterior uveitis and CME with onset 5 months after initiating nivolumab (Opdivo) for treatment of metastatic cancer due to an unknown primary tumor. Best corrected visual acuity (BCVA) was 20/70 OD and 20/40 OS. Oral prednisone, topical difluprednate (Durezol), and nepafenac (Nevanac) were started. CME had resolved with improved BCVA (20/30 OU) after 6 months of therapy. 9 months later, foveal thinning developed which progressed to a FTMH one month later (), reducing BCVA to 20/60 OS. Scheduled macular hole surgery (MHS) was cancelled when the vision improved to 20/40. OCT showed a closed MH, with residual subretinal fluid (SRF) (). The condition remained stable until three months later when the patient presented with decreased VA (20/150). OCT showed reopening of the MH (). The patient scheduled MHS but wanted to wait for 3 months, hoping for spontaneous resolution. 3 months later, MH spontaneously closed () with improved VA to 20/80 OS. The condition has remained stable with 20/70 BCVA. |
pmc-6601469-2 | Case 2. A 73-year-old male patient presented with a 2-month history of decreased vision OD (20/60). OCT showed a thinned fovea, progressing over 2 weeks into a tiny MH (). The patient was counseled about the treatment options and MHS was scheduled. 6 weeks later, vision improved (20/50), and OCT showed a closed MH although with residual CME (). 3 months later, MH had reopened () with decreased vision (20/70), but the patient deferred MHS. Over 3 months, MH gradually reapproximated and closed with residual intraretinal CME and SRF which resolved slowly over 6 months () with improved BCVA to 20/50 and remained stable during the next 7 months. |
Subsets and Splits
Exclude ER emergencies
Retrieves 100 descriptions that do not contain the terms 'ER' or 'emergency', providing a basic filter of the dataset.