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pmc-6559500-1 | A 28-year-old woman initially presented with blurry vision that developed over the span of approximately one month. The blurry vision was initially most prevalent on horizontal gaze but progressed to include vertical gaze. It resolved with closure of one eye. She reported a history of gradually worsening headache over the past several years. Her headaches both worsened in intensity and increased in frequency, until it was quite debilitating and occurred daily. She described the headache as an intense pressure in both the front and back of her head. She also noted a “whooshing” sound in her right ear. She denied any nausea or vomiting and had not had any syncope, numbness, weakness, facial droop or slurred speech. Furthermore, she had no history of bladder or bowel dysfunction.
Her medical history was pertinent only for obesity with a body mass index (BMI) of 39. On physical exam she was noted to have papilledema. Her neurological exam was unrevealing with the exception of a subtle sixth cranial palsy.
A magnetic resonance image (MRI) was obtained which showed a T1 hypointense and T2 hyperintense cystic lesion arising from the pineal gland measuring 2.0 x 1.1 cm in the sagittal plane with mild mass effect on the tectum and partial effacement of the cerebral aqueduct (Figures , ). The lesion demonstrated a thin rind of contrast enhancement and had thin enhancing internal septations. The lateral ventricles were mildly enlarged. There was no restricted diffusion and no loss of gray white differentiation. Cine flow study noted cerebral spinal fluid (CSF) flow through the cerebral aqueduct. Based on the radiographic images, the most likely diagnosis was an atypical pineal cyst.
Given the rapidity of the vision changes, the decision was made to pursue surgical intervention. An endoscopic third ventriculostomy (ETV) with pineal cyst fenestration was performed without complication. A computed tomography (CT) scan obtained post-operatively noted questionable decompression of the lateral ventricles but the patient reported no improvement in symptoms (Figure ). Ophthalmologic evaluation noted worsened papilledema. At this time the patient underwent a lumbar puncture, which noted an opening pressure of 32 cm H2O. Subsequent catheter venography noted severe stenosis of the right transverse sinus associated with a 9 mm Hg trans-stenosis gradient (Figure ). Placement of a venous sinus stent obliterated the pressure gradient (Figure ).
At six-month follow-up, her blurred vision, headaches and papilledema had all resolved. She reported complete resolution of her symptoms and plans were made for continued annual follow-up to monitor symptoms and ensure patency of the stent. |
pmc-6559625-1 | A 12-years-old boy was admitted to the hospital with episodes of chest pain triggered in effort and repose. He was subjected to an electrocardiogram and echocardiogram with normal results. The laboratory tests showed an elevation of high-sensitivity troponin T (hs-TnT) of 51 ng/L (99th percentile = 14 ng/L), creatine kinase (CK) within the reference range and preserved renal function. Exercise test was within normality range and thus acute process by ischemia, pericarditis or myocarditis was discarded.
Blood tests were repeated 4 months later and an increase of hs-TnT up to 98 ng/L was found, while CK and other parameters were within normal ranges. A second echocardiography was performed and no pathological alterations were detected.
A new blood sample was collected one month later and high concentration of hs-TnT (52 ng/L) was observed again. Given the absence of compatible symptoms, a falsely positive result caused by interference was suspected. |
pmc-6559675-1 | A 62-year-old Caucasian male with a past medical history of hepatitis C and alcohol-induced liver cirrhosis was admitted for progressive fatigue after sustaining a fall at home. Home medications included furosemide, spironolactone, lactulose, and rifaximin. He was afebrile and vital signs were stable. He was awake, alert, and fully oriented. His physical examination was remarkable for periorbital bruising, skin abrasions, deep jaundice, dry oral mucosa, tense ascites, and mild asterixis. Computed tomography (CT) brain did not reveal evidence of intracranial bleeding. Initial chest X-ray showed a moderate-sized right pleural effusion. Laboratory studies revealed a white cell count of 10,960/μL with 22% bands. Serum sodium level was 119 mg/dl and serum creatinine was 1.3 mg/dl. Model for end-stage liver disease (MELD) sodium score on admission was 33. Intravenous (IV) rehydration was started and diuretics were discontinued. Blood cultures on admission grew gram-positive rods after Day 1. The patient was started on empiric piperacillin/tazobactam. The highest temperature reported was 100.4 F (Fahrenheit) on Day 2. On Day 3, the patient underwent diagnostic paracentesis. Ascitic fluid analysis showed 492 neutrophils/μL, which pointed to spontaneous bacterial peritonitis (SBP); however, ascitic fluid cultures were negative. Repeat blood cultures on Days 2 and 3 also grew gram-positive rods as well. Antibiotic coverage was broadened to IV meropenem and vancomycin. By Day 5, four out of four blood cultures grew Clostridium tertium sensitive to penicillin, meropenem, and metronidazole (Figure ). Subsequent cultures after the initiation of meropenem were negative. Paracentesis was repeated on Day 9; 5.5 L were drained. Ascitic fluid analysis confirmed the resolution of SBP. The patient initially improved and intensive workup was undertaken in order to list him for liver transplantation in light of severe hepatic decompensation. However, the patient developed severe hepatic encephalopathy following upper gastrointestinal bleeding. Despite supportive care in the intensive care unit, he had recurrent seizures, shock, and respiratory failure, necessitating vasopressor and ventilatory support. He died on Day 18 of admission. |
pmc-6559678-1 | A 51-year-old female patient with a past medical history of stage IIIa (T1c, N2a, M0) right breast cancer, hepatitis C infection, and hypertension presented to emergency department (ED) with bilateral hand swelling, redness, and edema that started three days before coming to ED. Swelling and redness started only one day after starting docetaxel chemotherapy. She received a single dose of 117 mg (75 mg/m2) intravenous docetaxel. Also, she received prednisone before starting chemotherapy. She denied any recent fever or chills. Vitals signs were stable on admission; no fever was documented. Physical examination revealed bilateral swelling, redness, and tenderness of both hands up to the wrists (Figure ). No upper limb weakness was found on physical examination. No skin rash was observed in other body parts.
Lab investigation showed normal white blood cells count of 7.24 thousand cell/ul (normal range: 3.70-11.00 k/uL). Sepsis lactate was checked and was found to be 1.3 mmol/L (normal range: 0.5-2.0 mmol/L). Basal metabolic panel, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on admission were unremarkable. Blood cultures were done and did not grow any microorganism. No imaging studies were done.
The patient was given vancomycin for one day without any improvement in skin rash or hand edema. On the next day antibiotics was stopped by the infectious disease team. She was then started on intravenous 40 mg methylprednisolone. Swelling, redness, and pain started to improve 24 h after steroid initiation. The patient was discharged on prednisone 20 mg three times daily for another seven days. She was diagnosed with HFS erythrodysesthesia. |
pmc-6559679-1 | A 74-year-old Caucasian woman presented to the emergency department with nausea, vomiting, and bloody diarrhea for five days. She had presented to her primary care physician on the third day of illness and was treated with supportive measures for presumed viral gastroenteritis. Her nausea and diarrhea improved, but she continued to have poor oral intake and increased weakness. The patient reported a history of consuming meatloaf from a local store, three days prior to the onset of symptoms. On presentation to the emergency department, vital signs were stable and physical examination was remarkable only for dry mucous membranes. Initial laboratory findings showed hemoglobin of 12 g/dl (which was reduced from 15.4 two months ago), white blood cell (WBC) 8.8 x 103/mL, platelet of 47 x 103/mL (which was lower than 161 two months ago), sodium of 119 mmol/L, potassium 4.4 mmol/L, creatinine of 6.7 mg/dl (baseline creatinine was 1.0 mg/dl), and blood urea nitrogen of 99 mg/dL. Urinalysis was concerning for urinary tract infection. A peripheral blood smear showed mildly increased schistocytes (2/high power field), normochromic normocytic erythrocytes, and marked thrombocytopenia. Hemolytic workup was significant for an elevated reticulocyte count of 3.08%, lactic acid dehydrogenase (LDH) elevated to 480 IU/L (normal: 110-240 IU/L), normal bilirubin, haptoglobin of 163 mg/dL (normal: 30-200 mg/dL), and free hemoglobin was elevated to 115 mg/dL (normal: <10 mg/dL). Urine culture grew Enterococcus faecalis, and the patient received ampicillin.
Due to concerns of new-onset thrombocytopenia, anemia, and acute kidney injury, TMA was suspected. Further evaluation of TMA showed normal ADAMTS13 activity (reported as 92%), C3 complement, C4 complement, and complement CH50 (Table ). The atypical hemolytic uremic syndrome panel was negative for any known mutations. Stool sample for culture and Shiga-like toxin could not be obtained, as the patient was constipated during the hospital stay. Nephrology was consulted for the possible need for renal replacement therapy. Despite significantly worsened renal function, the patient did not develop anuria or oliguria. The patient’s kidney function improved with supportive measures and did not require renal replacement therapy measures. Platelet count recovered to 186 x 103/mL on the fourth day of admission and her creatinine continued to improve after she was discharged. At two-months follow-up in the clinic, the patient was asymptomatic with creatinine 1.33 mg/dl and normal hemoglobin and platelet counts. |
pmc-6559679-2 | A 79-year-old Caucasian woman was transferred from an outside hospital facility with complaints of diffuse crampy abdominal pain, nausea, vomiting for three days, and diarrhea associated with blood for a day. The patient also complained of shortness of breath, decreased urine output, and swelling of lower extremities. She denied a history of fever, mental status change, or recent sick contacts. She reported a history of consuming meat from a local restaurant a day prior to the onset of symptoms. Past medical history was significant for metastatic non-small cell lung cancer and she was on treatment with osimertinib for months. On presentation, the patient was afebrile, with a blood pressure of 105/64 mmHg, heart rate of 108 bpm, respiratory rate of 16 per minute, and saturation of 98% on room air. The physical examination was significant for dry mucous membranes, distended abdomen with generalized tenderness, and pitting edema on bilateral lower extremity extending up to the knees. Initial laboratory work showed white blood cell count of 7.5 x 103/mL, hemoglobin of 11 g/dL, and platelet of 19 x 103/mL. The basal metabolic panel showed sodium of 129 mmol/L, potassium 4.1, chloride 96, bicarbonate 18, anion gap 15, blood urea nitrogen (BUN) 42 mg/dl, and creatinine 2.01 mg/dl. The peripheral blood smear revealed normocytic normochromic anemia with two to four schistocytes/hpf and severe thrombocytopenia supporting the microangiopathic hemolytic process. Subsequent workup showed elevated indirect bilirubin (total 2.7 mg/dL and direct bilirubin 0.7 mg/dL), elevated lactate dehydrogenase of 994 IU/L, and negative direct Coombs test (Table ). Abdominal imaging did not show any evidence of an acute abdominal process.
The patient was admitted to the medical intensive care unit for concerns of TMA and suspected sepsis. She was empirically started on broad-spectrum antibiotics. The following day, the patient became hypotensive, requiring vasopressor support, and her renal function deteriorated with anuria. Nephrology initiated continuous renal replacement therapy and the vasopressor medications were weaned off over the next two days. Her ADAMTS13 activity resulted in 92% and an atypical HUS panel could not be sent. The stool culture and stool test for enterohemorrhagic E. coli (EHEC O157:H7) performed outside the hospital were negative. Due to the unfavorable prognosis of her metastatic lung cancer, the patient and the family members decided to opt for hospice care, and she was subsequently transferred to the inpatient hospice. The patient later passed away at the hospice facility. |
pmc-6559680-1 | A 17-year-old girl presented with a 15-day history of headache (holocranial and predominantly bifrontal) with occasional vomiting and ataxia of gait with no diplopia. She complained of short-lasting episodes of fever for a few days before consulting the doctor. On examination, she had no cranial nerve involvement, no meningeal signs, and a normal fundus examination. She had mild misbalancing on tandem gait. The patient was investigated further and a routine workup was done. Routine hemogram, liver function tests, renal function tests, and serum electrolytes were normal. Serum antinuclear antibody (ANA) and cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) levels were normal. Venereal disease research laboratory test (VDRL) and rapid plasma reagin (RPR) antigens were negative. Cerebrospinal fluid (CSF) examination revealed 30 cells (all lymphocytes), an increased protein level of 81 mg/dL (normal range: 12 - 60 mg/dL), and a normal glucose level of 57 mg/dL (normal range: 40 - 70 mg/dL). The CSF examination for fungus and gram stain was negative. No oligoclonal bands were seen. Scrub typhus, Leptospira, dengue, Japanese encephalitis, and toxoplasmosis serologies were negative. Chest computed tomography (CT) and chest x-ray were normal.
Later, she underwent a contrast-enhanced MRI of the brain which revealed hyperintense T2-weighted/fluid-attenuated inversion recovery sequence (T2-FLAIR) signals involving the midbrain, pons, right cerebellar peduncle, bilateral subthalamic, body and splenium of the corpus callosum, left capsular, and right occipital regions. No restriction on diffusion-weighted imaging (DWI) was seen (Figures -).
On contrast enhancement, multiple foci of peppered enhancement were seen in these areas, especially the midbrain, the pons and body, and the splenium of the corpus callosum, distributed in a perivascular pattern (Figure ).
On the basis of the history, a presumptive diagnosis of acute disseminated encephalomyelitis (ADEM) was made and treatment was started in the form of intravenous (IV) methylprednisolone (1 gram daily for five days). The symptoms of the patient improved, and she was discharged on steroids with no follow-up.
She was again readmitted after a few days for recurrence of headache and complained of fever for three days prior to admission. She had also complained of right-sided ptosis during the episodes of fever. She was again treated with IV methylprednisolone, 1 gm daily for three days, and she improved completely. A repeat routine hemogram, liver function test (LFT), renal panel, and chest x-ray did not reveal any significant finding. Blood culture was negative. Thyroid profile and Vitamin B12 levels were within normal limits. Again, on recurrence of headaches, she was asked to get a repeat MRI scan of the brain (plain and contrast) which revealed similar findings as the previous MRI done almost a month earlier; however, the lesions had increased in size. The patient’s symptoms and radiological imaging findings responded to treatment with high-dose steroids and methotrexate (Figure ), but after several trials to taper the dose of steroids, the symptoms reappeared and were progressive in nature. |
pmc-6559681-1 | A 78-year-old Caucasian man presented to the emergency room with a sudden onset of severe, intermittent, cramping right upper quadrant abdominal pain with non-bloody, non-bilious vomiting for one day. His personal history included atrial fibrillation and atrioventricular block with an implanted pacemaker. On examination, the abdomen was soft with mild epigastric tenderness, decreased bowel sounds and distension. Labs revealed leukocytosis of 12.46 TH/MM3, alkaline phosphatase of 321 IU/L, aspartate aminotransferase of 52 IU/L, alanine aminotransferase of 47 IU/L, total bilirubin of 1.8 mg/dl, and serum lipase of 161 U/L. An abdominopelvic computed tomography (CT) revealed a 6.6 x 4.4 cm gallstone in the proximal duodenum with surrounding inflammation, cholecysto-duodenal fistula, and pneumobilia (Figure ).
Upper endoscopy was performed revealing complete obstruction of the duodenum due to the impacted stone (Figure ).
Several endoscopic foreign body and stone retrieval devices, as well as lithotripsy, were attempted to remove or fragment the stone. However, the stone was impacted and exceedingly larger than the available endoscopic retrieval devices. Another attempt was made to inflate the controlled radial expansion (CRE) dilation balloon beyond the impacted stone and drag the stone into the stomach for fragmentation, but it was unsuccessful (Figure ).
Endoscopic guided electrohydraulic lithotripsy (EHL) was performed, which led to partial fragmentation of the stone. We were able to create a tunnel through the stone but was unable to break the outer shell despite using multiple probes at high power. Laparoscopy was then attempted although he eventually required laparotomy due to adhesions. The stone was successfully extracted through duodenotomy as seen in Figure , followed by closure of the cholecysto-duodenal fistula, cholecystectomy, and placement of a temporary feeding gastrojejunostomy tube. The postoperative course remained uneventful, and the patient was discharged after four days. |
pmc-6559684-1 | A 40-year-old Hispanic man with a past medical history of human immunodeficiency virus (HIV) was brought to the emergency department complaining of right upper extremity (RUE) weakness and numbness for four days with associated bitemporal headache and generalized fatigue. The patient reported first time use of intranasal cocaine and heroin, after which he lost consciousness and woke up approximately four hours later with new onset RUE and headache. His cluster of differentiation 4 (CD-4) count was reported above 500 cells/mm3 and viral load (VL) was undetectable. The patient did not have any known CNS complications in the past.
On physical examination, his blood pressure was 151/97 mm Hg and pulse was 82 and regular. He was alert and cooperative. His cranial nerves were intact. His motor exam, however, was abnormal in the RUE with 3/5 arm strength and wrist drop; the strength and tone of the other extremities were normal throughout. Deep tendon reflexes were normal bilaterally, but his gait could not be evaluated. His sensory function decreased to pin sensation at the RUE and normal sensation was noted in the rest of the extremities and face. Laboratory testing was normal except for an elevated creatinine of 6.9 mg/dl, creatine phosphokinase (CPK) of 7855 IU/l, alanine transaminase (ALT) of 139 IU/l, and aspartate transaminase (AST) of 109 IU/l. Urine toxicology was positive for metabolites of cocaine and heroin. Magnetic resonance imaging (MRI) of the brain was done and it revealed two areas of increased T2/FLAIR signal within the medial aspect of both basal ganglia, measuring 16 mm in the right and 12 mm on the left involving each globus pallidus and the genu of the internal capsule, as can be seen in Figures -. His chest radiography was normal, computerized tomography (CT) of the brain, as can be seen in Figure , and cervical spine were normal. His electrocardiogram was normal.
In the subsequent days, his kidney function and rhabdomyolysis improved. The patient remained fully awake, alert and oriented, but the weakness of his RUE persisted. The patient decided to leave against medical advice despite full explanation of the risk of leaving.
The patient was contacted over the phone and he informed us that he followed up with his primary care physician and reported improvement of the weakness. He received physical therapy and was independent in all activities of daily living and functional mobility. His only limitation was a moderate decrease in fine motor coordination of the RUE. |
pmc-6559686-1 | A 22-year-old male with no significant past medical history and a five-year history of synthetic cannabinoid use presented to the emergency department with complaints of hematuria and epistaxis. The patient had stable vital signs, and his physical examination revealed a right conjunctival hemorrhage, active epistaxis of the left nostril, and blood-tinged urine. Laboratory workup revealed a prothrombin time (PT) greater than 106 s and a partial thromboplastin time (PTT) of 79.5 s. His international normalized ratio (INR) was not determinable.
The patient admitted to adding rodenticides to his synthetic cannabinoids in order to increase their euphoric effect. He was subsequently admitted to the hospital for monitoring and management of blood loss in the setting of an acute chemical-induced coagulopathy. He was given an initial dose of intravenous vitamin K1 50 mg and the poison control center was notified. The patient then received two doses of oral vitamin K1 50 mg over the next two days until his PT normalized. |
pmc-6559688-1 | A 16-year-old male presented to the emergency department following a high-speed front-end collision with another vehicle. He was restrained and occupied the front seat of the vehicle that was struck head-on. The speed at the time of the collision was estimated to be in excess of 79 miles per hour. On arrival, the patient was unconscious and not breathing independently. Attempted intubation at the scene was unsuccessful and the patient was pronounced dead soon after arrival to the hospital.
Radiographs at the time of the incident noted internal decapitation with AO assimilation specifically between the anterior arch of the atlas and the basiocciput (Figure ). No fractures were noted, including the odontoid process. There was no known past medical or surgical history and the AO assimilation was unknown to the family. |
pmc-6559690-1 | A 65-year-old male, former smoker, with a 44 pack-year smoking history presented with left upper extremity weakness and numbness that lasted for approximately half an hour. The patient denied any focal neurological deficits in other extremities. Computed tomography (CT) and magnetic resonance imaging (MRI) of the head showed intracerebral hemorrhagic metastases. CT of the chest/abdomen/pelvis showed right lower lobe lung lesions suspicious for cancer along with mediastinal and right inguinal adenopathy and a right acetabular lytic lesion. Biopsy of the right inguinal nodes showed cancer metastases morphologically and immunohistochemically identified to be adenocarcinoma, probably from lung primary as malignant cells were positive for cytokeratin AE1/AE3, thyroid transcription factor 1 (TTF-1) and cytokeratin 7 (CK7), while negative for CK20, p40, napsin, and CK5/6. The pathology report further revealed programmed death ligand 1 (PD-L1) > 100%, while epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and receptor tyrosine kinase (ROS1) mutations were negative. The patient was first treated with radiotherapy to the brain and right hip followed by immunotherapy with pembrolizumab. Subsequent CT of the chest/abdomen/pelvis showed complete resolution of the disease and an MRI of the brain did not show any new lesions, but the patient developed forgetfulness and shuffling gait and the etiology was unclear. Initial imaging showed response in both central nervous system (CNS) and systemic disease; however, repeat imaging after five months of therapy showed control of disease outside CNS while MRI of the brain showed disease progression as patient developed new sub-ependymal metastatic lesions (Figures , ). Biopsy was deferred as this was thought to be too invasive and the family refused it as well. Imaging findings and poor prognosis of the disease were discussed with the patient and his family, after which they decided to pursue hospice palliative care at home with no additional interventions. |
pmc-6559690-2 | A 61-year-old male with a 30 pack-year smoking history came for evaluation of fatigue, significant weight loss, and poor balance with multiple falls over a period of three months. Initial workup including CT of the chest/abdomen/pelvis showed a large right paramediastinal mass with metastatic lesions involving the liver, retroperitoneal and left gluteal lymph nodes. CT of the brain was concerning for metastatic lesions of the left occipital and frontoparietal lobes. Biopsy of a left gluteal lymph node revealed cancer metastasis morphologically and immunohistochemically consistent with pulmonary adenocarcinoma as tumor cells were positive for AE1/AE3, CK7, TTF-1, and napsin-A, while negative for CK5/6, p40, melan and CK20. The tissue sample was inadequate for PD-L1 testing but EGFR, ALK, and ROS-1 mutations were absent. The patient was started on conventional chemotherapy with follow-up MRI of the brain consistent with previous CT findings. Because of poor tolerance of chemotherapy and cytopenias, therapy was changed to nivolumab based on high tumor mutation burden detected by FoundationOne testing. The patient received nivolumab, and metastatic lesions in the brain were stable and significant reduction in lung cancer and metastatic lesions outside CNS was seen on MRI of the brain (Figures , ) and CT of the chest/abdomen/pelvis, respectively. Symptoms associated with the metastatic brain lesions disappeared completely and his general condition showed remarkable improvement. |
pmc-6559691-1 | A four-year-old male presented to the pediatric cardiology clinic with a three-week history of episodic chest pain, shortness of breath, diaphoresis, and pallor. Upon presentation, the patient was asymptomatic with an unremarkable physical exam. Office lab work was unremarkable. Electrocardiogram (EKG) showed sinus tachycardia. Echocardiogram showed a possible anomalous origin of the left coronary artery from the right facing sinus (Figure ).
The systolic function and the remainder of his cardiac anatomy were normal. A coronary computed tomography angiogram (CCTA) was performed, which showed both the coronary arteries originating high from the right coronary sinus at the level of the sinotubular junction (Figure ). The CCTA was performed on a single source 128-detector row Philips Ingenuity® CT scanner using a low-dose retrospectively ECG-gated helical scan protocol. The heart rate during the scan was 78 beats per minute after the patient received 10 mg of IV esmolol. There was an anomalous origin of the left main coronary artery (LMCA) from the right coronary sinus with a malignant interarterial course between the pulmonary trunk and descending aorta with mild stenosis. It was posited that the LMCA and the right coronary artery (RCA) had a common ostium. There was no evidence that the anomalous LMCA had an intramural course; however, there was a mild narrowing of the interarterial segment with an elliptical shape. This narrowed segment measured approximately 2.3 x 2.0 mm as compared to a more distal normal segment that measured 3.7 x 3.0 mm. Moreover, superficial myocardial bridging was noted with the left anterior descending (LAD) and two significant fistulae were found between the mid and distal LAD and the pulmonary trunk (Figures -).
The total dose length product (DLP) of radiation used during CCTA was 122.3 mGy cm and the calculated effective dose (ED) of radiation exposure during CCTA was 3.843 mSv (Table ).
The patient underwent surgical intervention which showed that the LMCA indeed arose from the right coronary sinus and coursed between the aorta and pulmonary artery. The orifice of the LMCA and RCA were so closely positioned together that they made a single coronary artery. The LMCA was mobilized and freed of its attachments followed by unbridging of the LAD. The main pulmonary artery was translocated leftward towards the left pulmonary artery to reduce pressure on the interarterial LMCA. At the end of the surgery, there was excellent flow in all the three coronary arteries. |
pmc-6559692-1 | A 16-year-old female patient presented to us with bilateral reduction of vision since the last 10-12 days. She first presented to the emergency department with complaints of severe headache and fever since the preceding two-three days. She underwent a detailed systemic evaluation. Magnetic resonance imaging (MRI) scan at this time showed multiple ring-enhancing lesions in the brain and a chest computed tomography (CT) showed tiny miliary nodules scattered throughout both lung fields. She was diagnosed as a case of miliary tuberculosis (pulmonary and cerebral). Dilated fundus exam revealed yellow-white choroidal lesions consistent with miliary tubercles. She was started on first-line anti-tubercular treatment with rifampicin (450 mg/day), ethambutol (800 mg/day), pyrazinamide (1500 mg/day), and isonicotinylhydrazide (INH; 300 mg/day).
Two months later, following a poor clinical response and a drug sensitivity test (DST), she was started on kanamycin, moxifloxacin, ethionamide, and clofazimine in addition to the earlier drugs.
A worsening headache led to a repeat MRI scan a month later that detected a leptomeningeal enhancement. Subsequently, linezolid was started but was withdrawn a month later due to gastric intolerance. Following five months of treatment of ethambutol, she noticed the onset of reduced vision and was referred to us.
On examination, her best-corrected visual acuity was 6/60 in the right eye and 6/120 in the left. Extraocular movements were normal as was her anterior segment examination, including her pupillary reactions. Dilated fundus examination revealed normal findings in the right eye and normal disc and macula with a single choroidal tubercle along the superotemporal arcade in the left eye.
She underwent a visual field examination (central 30-2, SITA-Fast), which revealed an incomplete left homonymous hemianopia with additional defects in the inferior quadrants of the right eye (Figure ).
The specific clinical picture suggested ethambutol toxicity, which was then stopped and she was advised to follow-up. At last follow-up (three months), her visual acuity had returned to normal and she was referred back to her physician. |
pmc-6559692-2 | A 65-year-old male patient presented with complaints of bilaterally reduced vision. He had been investigated and been treated earlier for small cell cancer of the lung and had undergone chemotherapy for the same. Seven months earlier, following persistent breathlessness, he underwent radiological investigations and was found to have a pleural effusion. A routine examination of the pleural fluid revealed mycobacterial infection of the pleura that was the treated with rifampicin (450 mg/day), ethambutol (800 mg/day), pyrazinamide (1500 mg/day) and INH (300 mg/day). Following drug-induced hepatitis, the regimen was reduced to rifampicin and ethambutol with the addition of levofloxacin.
On examination, his best-corrected visual acuity was 6/15 in either eye. The extraocular movements and his anterior segment examination were normal. Dilated fundus examination was normal. He underwent routine testing. A visual-evoked potential (VEP) testing showed reduced amplitude and prolonged latency on either eye, suggestive of bilateral optic axonopathy. An MRI scan revealed multiple round peripherally enhancing lesions in both cerebral hemispheres and in the right cerebellum. Central 30-2 perimetry revealed an incomplete left homonymous hemianopia with additional inferior temporal defects in the right eye (Figure ). A diagnosis of ethambutol toxicity was made, as the lesions in the cerebral hemispheres were not consistent with the perimetric findings.
The patient declined all further treatment and was lost to follow-up. |
pmc-6559692-3 | A 30-year-old female patient presented to us with complaints of blurred vision for a month. Eight months earlier, she had undergone a routine uncomplicated laparoscopic myomectomy. Two months following this procedure, she revisited the gynecologist with complaints of abdominal pain and a feeling of hardness over the anterior abdominal wall. An ultrasound examination supplemented with an MRI study revealed fluid collections along the subcutaneous and muscular plane with adjacent subcutaneous edema. A fine needle aspiration cytology (FNAC) obtained tissue sample revealed a necrotizing granulomatous inflammation of likely mycobacterial origin. She was started on an antituberculous regimen consisting of rifampicin (450 mg/day), ethambutol (800 mg/day), and additional clarithromycin (1000 mg/day) to cover possible atypical mycobacteria.
Five months after starting this regimen, she started noticing “blurring and haziness” in both eyes. She consulted an ophthalmologist who noted normal visual acuities bilaterally (6/6), normal appearing anterior segments and fundi. Her color vision, as tested on Ishihara plates, was found to be normal as well. As a precautionary measure, her ethambutol was discontinued. Her symptoms persisted and she sought a second opinion.
On examination, her visual acuity was 6/12(R) and 6/12 (L). Her anterior segments and fundi were normal appearing as were her pupillary reactions. She underwent baseline perimetry (central 30-2, SITA-fast), which revealed central bitemporal hemianopia that respected the vertical midline, consistent with ethambutol toxicity (Figure ).
Ethambutol treatment was discontinued and she was advised to undergo a regular follow up with her primary physician. At last follow-up, a month later, she was visually asymptomatic and her visual acuities were 6/6 bilaterally. She declined further field testing. |
pmc-6559693-1 | We present a 62-year-old male patient, who presented with a few months of left-sided, episodic, blood-stained nipple discharge, occurring spontaneously and without warning. The discharge had the appearance of ‘frank blood’. He had not noticed any other changes to the breast or nipple and had no history of trauma. His previous history included a mild inflammatory arthritis for which he no longer required medication and a microprolactinoma, diagnosed 13 years previously, for which he required testosterone supplementation due to hypogonadotropic hypogonadism, but no other treatment. At the time of the presentation with blood stained nipple discharge, prolactin levels were within normal ranges as were other hormone assays related to his pituitary function. Cabergoline had been discontinued four years prior to presentation. There was no family history of breast cancer, he did not smoke or take alcohol in excess.
Clinical assessment found no visible or palpable abnormality in the breast disc but demonstrated the bloody discharge. Ultrasonography demonstrated subareolar ducts but no focal mass. Mammography was normal on the right but indeterminate on the left with a 16-mm asymmetry in the 9-o-clock position within the retroareolar tissue and with associated flecks of benign appearing calcification (Figure ). Cytology of a smear of discharge showed plentiful red blood cells and histiocytes with no epithelial cells present. As duct excision was planned, core biopsy was not performed.
The case was discussed in a multi-disciplinary team meeting and a left total duct excision was recommended. This was performed under general anaesthetic, with an anterior shave of tissue taken from behind the nipple. Pathological findings were unusual in the context of a male patient, showing a few scattered benign intraductal papillomas measuring up to 2 mm (Figure ). Immunohistochemistry showed heterogenous positivity with cytokeratin (CK) 5/6. No atypia was noted. The patient made an uneventful recovery with no further reported nipple discharge and preservation of his nipple and chest wall symmetry. No surveillance is planned. |
pmc-6559694-1 | A 52-year-old gentleman presented with generalized headache, blurring of vision and unsteady gait for one-year duration. He described his headache was throbbing in nature and progressed to be persistent throughout the day. There was no aura and no preceding history of seizure. He also started to have unsteady gait, followed by blurring of vision especially at downgaze.
Otherwise, he had no known underlying medical illness. He denied of any history of head trauma or fall. There was no memory loss or personality changes. He was recently diagnosed to have ischemic heart disease via stress test.
At presentation, he was alert and conscious with stable vital signs. Visual acuity was 6/6 on both eyes. Optic nerve function tests were normal with no relative apparent pupillary defect. The anterior and posterior segment examination was unremarkable. Surprisingly, both optic disc appeared normal with cup-disc ratio of 0.3, and no signs of papilloedema or optic nerve atrophy seen. Extraocular muscles movement were full in all directions. The only positive finding was the confrontational test revealed a left lower homonymous quadrantanopia. Systemic review and neurological examination were normal.
He underwent computed tomography (CT) scan and whereby he was noted to have a large solitary tumour located at the parasagittal area of occipital region suggestive of parasagittal meningioma (Figure ). Magnetic resonance imaging (MRI) showed similar findings (Figure ). He was then referred to neurosurgical team and tumour excision was done. Post operatively, he recovered fully with no sequalae, but his visual field remained the same. Histopathological examination of the tumour excised was confirmed to be transitional meningioma.
Surveillance MRI after one year of post-surgery revealed a residual tumour at the right occipital area with another new tumour growth at the left occipital area. He was then subjected to radiotherapy treatment. However, a second craniotomy with excision of tumour surgery was performed at the second year of follow-up after radiotherapy failed to shrink the tumour. Prior to his second surgery, his visual field started to deteriorate whereby he was unable to gauge the downgoing staircases (Figure ).
During his ophthalmological follow-up, his visual acuity was still good with 6/7.5 over both eyes. Humphrey visual field demonstrated a bilateral altitudinal visual field defect which was denser at the left inferior quadrant. Fundus examination had no sign of optic atrophy. Currently, the patient is under ophthalmology regular follow-up and on-going visual rehabilitation therapy. |
pmc-6559696-1 | A 21-year-old Saudi male with no previous medical history presented to the emergency department with chest pain that was stabbing in nature. The chest pain was located in the central and left regions of the chest with no radiation. The pain was aggravated by speech and breathing and there were no relieving factors. The pain was of sudden onset preceded by smoking at 2:00 am. The patient rated the pain as 5/10 on a 11-point numerical pain rating scale, which then evolved to 10/10. The patient did not have fever, shortness of breath (SOB), loss of consciousness (LOC), diaphoresis, trauma or previous similar presentation. There were no other associated symptoms.
On examination, the patient was alert and oriented with no acute distress. His vital signs revealed a blood pressure of 104/64 mmHg, heart rate of 105/min, respiratory rate of 20/min, temperature of 36.9C, and he was saturating 100% on room air. A respiratory examination showed tachypnea. The patient had crepitation on palpation and a crunch sound (Hamman’s sign) was heard on auscultation. A cardiovascular examination was unremarkable except for tachycardia. A gastrointestinal examination showed a soft, non-tender and non-distended abdomen. His musculoskeletal examination results were within normal limits and the integumentary system had no acute disease. His neurologic examination was unremarkable.
There were no significant findings in his lab results, as he had a white cell count of 12.13 count/L, a hemoglobin of 166 g/L, and a platelet count of 168 count/L. His cardiac enzymes showed CK 239 U/L and troponin T 0.007 Ug/L. His liver function tests, kidney function tests, venous blood gas result, and anion gap were all within the normal range. An electrocardiogram (ECG) was ordered upon presentation to the emergency department (ED) (Figure ).
Posteroanterior and lateral chest X-rays were obtained to confirm the diagnosis and pneumomediastinum was identified (Figures -).
The patient was kept overnight for observation, with repeat labs ordered the following day. He had a white blood count of 8.58 count/L, hemoglobin of 152 g/L, and a platelet count of 154 count/L. The patient was discharged home with acetaminophen for pain. A follow-up visit after three weeks and a CT chest with contrast before follow-up was planned. However, the patient was lost to follow-up. |
pmc-6559700-1 | A 42-year-old Caucasian female with past medical history significant for type 2 diabetes mellitus with gastroparesis, asthma, hypertension, and coronary artery disease presented to the emergency room (ER) with complaints of acute onset right-sided back pain in association with lower abdominal pain and dysuria ongoing for the last one week. She also reported having nonbloody, watery diarrhea for the last one month and multiple episodes of nonbloody, nonbilious vomiting over the same time. She denied any fevers. In the ER, patient was noted to be markedly hypertensive with a blood pressure of 207/148 mmHg on admission. She was afebrile and oxygen saturation was 100% at room air. The patient was tachypneic with a respiratory rate of 26 breaths/minute. Right costovertebral angle tenderness as well as lower abdominal tenderness was noted. She reported good compliance to her home medications which included lisinopril 40 mg daily and metformin 1000 mg twice daily.
Initial laboratory results showed high anion gap metabolic acidosis with an arterial blood gas showing a pH of 6.7 (normal range: 7.35-7.45), partial pressure of carbon dioxide (PaCO2) of 16.2 mmHg (normal range: 35.0-45.0 mmHg), and bicarbonate levels were reported as less than 2 mEq/L (normal range: 22-28 mEq/L). Anion gap was reported as more than 50 mmol/L. Her creatinine was elevated at 7.45 mg/dL with a BUN 54 mg/dL. The patient did not have a known history of any kidney impairment. Her blood glucose levels were 96 mg/dL, serum osmolality was 311 mOsm/kg, and lactic acid was elevated at 24.2 mmol/L. Blood alcohol and salicylate levels were normal. Creatinine kinase was 160 units/L, within a normal range for our facility. Given elevated blood pressure at presentation and acute back pain, computed tomography (CT) angiography of chest, abdomen, and pelvis for possible dissection was immediately obtained, inspite of the impaired renal function. No significant abnormality on chest, abdominal, and pelvic imaging was reported. The patient was noted to have a white cell count of 18,000/mm³ with 63% neutrophils; hemoglobin on presentation was 15.1 g/dL with an unknown baseline and a platelet count of 497,000/mm³. Urine drug screen was negative.
Once patient received intravenous morphine (single dose of 4 mg) for pain control, her blood pressure dropped to 104/68 mmHg. She received two liters of lactated Ringer's while in the ER. She continued to remain tachypneic with a respiratory rate of 30 breaths/minute. Nephrology was consulted; sodium bicarbonate infusion was started. She was transferred to the ICU where decision to proceed with emergent hemodialysis was made. Blood, urine, and sputum cultures were obtained. The patient was empirically started on vancomycin and piperacillin/tazobactam. As the patient became more hypotensive, inotropic support with norepinephrine infusion was started. Dialysis was initiated and the patient underwent a single session without ultrafiltration via a temporary right internal jugular vein dialysis catheter. She denied any use of nonsteroidal anti-inflammatory drugs (NSAIDs). As per nephrology, etiology of acute kidney injury was felt to be prerenal in setting of volume depletion due to reported vomiting and diarrhea and poor oral intake. Her severe metabolic acidosis with high anion gap was felt to be secondary to lactic acidosis due to metformin toxicity in setting of acute renal failure and hemodialysis was expected to clear the metformin.
After a single session of hemodialysis, her metabolic acidosis resolved. By the time of discharge from the hospital, her creatinine had recovered to 1.13 mg/dL with a bicarbonate level of 26 mEq/L. Her white cell counts normalized and her hemoglobin was subsequently noted to be stable at 9.6 g/dL. She became hemodynamically stable, no longer requiring inotropic support. Metformin levels were checked; this was a laboratory test sent out to another facility and hence results were not available immediately; these were later reported to be as high as 14 mcg/mL with the therapeutic range being 1-2 mcg/mL. Antibiotics were discontinued as blood and urine cultures remained negative. She was transferred out of the ICU and was subsequently discharged home in stable condition. |
pmc-6559999-1 | A 62 years old man had been referred to our outpatient clinic because of recently diagnosed Lynch syndrome due to an MSH2 mutation. His family history was negative for any kind of cancer. He had been treated with curative intent for pancreatic cancer four years ago. The cancer was located in the pancreatic tail and histology showed a poorly differentiated adenocarcinoma of the pancreaticobiliary type, 6 centimetres in size, that extended into the spleen. The tumour could be radically resected; there were no positive lymph nodes. Two years later, he underwent a left-sided nephrectomy because of a low grade (grade I) urothelial cell carcinoma of the pyelum of the left kidney. Both malignancies showed loss of expression of MSH2, and subsequent genetic testing revealed a germ line mutation in the MSH2 gene (c.2090G>A p.Cys697Tyr in exon 13). In a functional test, this missense mutation shows mismatch repair deficiency and is therefore classified as a pathogenic mutation []. At his index colonoscopy, a small but suspect lesion was found in the ascending colon. There was a slight ulceration of the surface of a 7 × 7 mm Paris Is lesion and careful inspection using a Fujinon® Slim zoom video colonoscope (Eluxeo 700 series; 135 × maximum magnification) showed a Kudo Vn pit pattern, suggestive of an early invasive cancer (Fig. a, b). The colonoscopy was aborted and the different therapeutic options, as well as the pros and cons of each option, were discussed with the patient and his son. Besides the possibility of a segmental colectomy or subtotal colectomy, we also discussed the option of removing the lesion by eFTR. The patient consented with the option of endoscopic en bloc removal of the lesion and a colonoscopy under propofol sedation was scheduled to remove the lesion endoscopically. This procedure was carried out as follows: first the margins of the lesion were marked with a marking probe. Then the colonoscope was withdrawn and the Full-Thickness Resection Device (FTRD, Ovesco®) was mounted on the colonoscope. The colonoscope was re-inserted into the caecum and an FTRD® Grasper was used to draw the lesion into the cap of the eFTR system. When all circumferential markings were visible inside the cap, the over-the-scope clip (OTSC) was released and immediately afterwards the tissue within the OTSC was resected using the pre-mounted snare within the cap and the pure cut setting of the Erbe® coagulation system. The endoscope was withdrawn with the specimen in the cap and the specimen was subsequently pinned on a cork board for optimal pathological evaluation. After re-introducing the endoscope a nice full-thickness wound was seen with the OTSC in good position (Fig. c). Pathological examination showed a pT1 moderate to well-differentiated adenocarcinoma of the ascending colon with invasion into the submucosa, Kikuchi level sm1, with an invasive component of 0.3 cm, no lymphovascular invasion and a free resection margin of at least 2 mm (Fig. a H&E, Fig. b desmin immunohistochemistry). There was grade I tumour budding and loss of MSH2 staining. After discussion in the multidisciplinary team and shared decision making with the patient, we agreed not to opt for additional surgical resection, but for close follow-up by regular colonoscopy. Colonoscopy 12 months after the procedure showed no sign of residual or recurrent cancer and a CT scan, that was carried out in the follow-up of his urothelial call carcinoma, showed no sign of distant metastases 12 months after the endoscopic resection. |
pmc-6560255-1 | A 62-year-old male patient presented to our emergency service with complaints of palpitation and shortness of breath of 2 hours’ duration. The patient’s relatives reported that he had no known diseases. His blood pressure was 84/56 mm Hg, and he was in a confused state. Cardiac and pulmonary auscultations revealed third heart sounds and bilateral fine crackles in the basal area of the lungs. An electrocardiogram (ECG) revealed VT with right bundle branch block and a ventricular rate of 188 bpm. The analysis of the ECG showed a superior axis. The use of direct current cardioversion restored the sinus rhythm () and improved the patient’s blood pressure and hemodynamic state. Transthoracic echocardiography showed that the LV ejection fraction was 40% and that there was a large echolucent space (4.6 cm × 3.7 cm in diameter) on the posterobasal portion of the LV. The LV wall motion was normal, with the exception of the LVA segment. The wall thickness of the aneurysm sac was similar to the normal thickness of the LV wall. Laboratory analysis showed a slight elevation in creatine kinase-myocardial band (23 IU/L) and troponin I (0.12 ng/mL). Coronary angiography was performed via the femoral approach, and it demonstrated patent coronary arteries with no thrombus, dissection, or coronary anomaly. However, cardiac ventriculogram confirmed that the position of the aneurysm was on a posterobasal segment ().
The patient was diagnosed with an idiopathic LVA and treated with an angiotensin-converting enzyme inhibitor, a beta-blocker, and an aldosterone-receptor blocker. Because the VT reoccurred during hospitalization, intravenous (IV) amiodarone was administered. Moreover, an IV bolus dose of magnesium sulfate (up to 3 gr) was given. Despite the treatment with IV amiodarone and magnesium sulfate, the patient had numerous recurrent VT episodes. However, when IV lidocaine was added to the current therapy, the frequency of the VT episodes slightly decreased. Because the patient’s hemodynamic state was deteriorating during some of the VT episodes, direct current cardioversion was conducted several times. An electrophysiological study was performed using 3D mapping with the EnSite Precision cardiac mapping system (St. Jude Medical), and it revealed that the VT was associated with scar formation and the tachycardia cycle length was 390 ms. Nonetheless, radiofrequency ablation did not terminate the VT. Upon consensus with a cardiovascular surgeon’s team, urgent surgery was performed due to the resistant VT episodes. The patient underwent cardiac surgery, during which the idiopathic LVA was removed and repaired with a Dacron graft. The patient’s clinical course was uneventful. Because the patient had no known diseases, we investigated the immunologic and infective causes associated with the LVA such as sarcoidosis, Chagas disease, and syphilis; all the results were, however, negative. The patient was discharged on the 11th day after the operation. At the time of this report, we have been following up the patient for almost 1 year; he has not experienced palpitations or associated symptoms during this period. Finally, the patient underwent a 72-hour Holter monitoring, which showed no non-sustained or sustained VT episodes. |
pmc-6560259-1 | A 37-year-old woman was admitted to the emergency department with a severe chest pain of 30 minutes’ duration. Her chest pain was retrosternal with no radiation and persisted continuously throughout the admission time. She described the pain as heaviness in her chest. The pain had no relation to exertion and was not relieved with rest. Additionally, it was neither positional nor pleuritic. There were no other accompanying symptoms. In her past medical history, she had an episode of cardiac arrest 3 months earlier, following an episode of a chest pain similar to her current pain. On that occasion, cardiopulmonary resuscitation was successful, coronary angiography was normal, and an ICD was implanted. She had no history of any previous medical disease, allergy, atherosclerosis risk factors, or smoking, and nor did she consume any drugs. She had a low socioeconomic status. During her physical examination, the patient was agitated and diaphoretic. She had a blood pressure of 80/50 mmHg, a heart rate of 70 bpm, an elevated jugular venous pulse, and normal breath sounds. No murmur was heard on heart auscultation, and the radial pulses were narrow and weak. Her electrocardiography revealed a normal sinus rhythm with an ST-segment elevation in the inferior leads, leads V3–V5, and leads V3R–V5R, along with an ST-segment depression in leads I and aVL ().
During the patient’s initial monitoring in the cardiopulmonary resuscitation unit in the emergency department, her systolic blood pressure and heart rate dropped to 50 mmHg and 45 bpm, respectively. Bedside echocardiography showed a left ventricular ejection fraction of 20%, with no pericardial effusion or mechanical complication. Intravenous atropine (0.5 mg) along with intravenous saline was administered. Due to profound hemodynamic instability, the patient was immediately transferred to the cardiac catheterization unit, where urgent coronary angiography revealed diffuse and severe stenoses in the entire coronary artery tree (). The left coronary artery was selected with an extra backup (EBU) guiding catheter and after the administration of 7500 units of intravenous heparin, a 0.014-inch floppy guide wire was inserted in the left anterior descending (LAD) artery. Next, 100 μg of intracoronary nitroglycerine was injected through the catheter. Control images illustrated near-normal left coronary arteries ().
The right coronary artery (RCA) was intubated with a right Judkins guiding catheter, and images were obtained. An intracoronary injection of 25 μg of nitroglycerine was performed in the next step. In the control images of the right coronary artery (RCA) the coronary lumen was near normal. The patient’s hemodynamics improved dramatically following the intracoronary nitroglycerine injection, and her chest pain vanished suddenly and completely.
Left ventriculography revealed a good left ventricular size and systolic function without regional wall-motion abnormalities (). The patient was transferred to the coronary care unit. Her cardiac troponin I level was reported to be 15 ng/L. Oral diltiazem (30 mg q.i.d.) and oral nitroglycerin (6.4 mg t.i.d.) were administrated. The patient had no episodes of recurrent angina or arrhythmias during hospitalization. On the second day following admission, echocardiography was performed and it showed a left ventricular ejection fraction of 45% with no regional wall-motion abnormalities. The patient was discharged 7 days later and on her evaluation a month subsequently, she had no symptoms or complications and an analysis of her ICD revealed no episode of arrhythmias. |
pmc-6560261-1 | A 32-year-old woman was referred to Sina Hospital, affiliated to Tehran University of Medical Sciences, with abdominal pain. The patient had a small bowel resection 10 years previously for bowel stenosis due to obstruction.
A bruit was heard on the abdominal auscultation. The laboratory findings were normal. Computed tomography showed ectasia in the superior mesenteric vein secondary to an AVF.
A 7-F guiding catheter (Cordis) was placed at the origin of the superior mesenteric artery via the right femoral artery. Then, the catheter was advanced into the superior mesenteric artery. Angiography was performed. There was a large fistula between the superior mesenteric artery and the superior mesenteric vein (). The superior mesenteric vein was aneurysmal.
We decided to perform coil embolization (Cook) at the fistula site. Therefore, we inflated a 5-mm balloon catheter (Ev3, EverCross OTW balloon catheter) before the fistula to prevent coil migration with a high blood flow. After the balloon inflation, we deployed one 8-mm and two 7-mm coils at the fistula site. The final angiography showed successful embolization with no visualization of the fistula or the aneurysmal vein (). |
pmc-6560311-1 | A 50-year-old man with a large metastatic lesion of a primary rhabdomyosarcoma in the left flank region was treated. He had first been diagnosed with a rhabdomyosarcoma in February 2016 with a primary 12 localization in the left gluteus muscle. The patient received surgery, postoperative high dose rate brachytherapy (25 Gy in 5 fractions) and adjuvant chemotherapy. In September 2016 a restaging Positron emission tomography–computed tomography (PET-CT) imaging revealed two metastatic lesions, both in the thorax. The first lesion, located in the lung, was surgically removed and histologically confirmed. The second one, located in the para-aortic space, was treated with stereotactic radiotherapy (total delivered dose 40 Gy in 5 fractions with linear accelerator through volumetric modulated arc technique, VMAT). In May 2017 the patient developed a local recurrence (left gluteus) and underwent re-resection. In August 2017 a contrast enhanced total body CT scan showed a large tumor mass within the contest of the paravertebral muscles in the left flank measuring 7 × 6 × 10 cm (Fig. ). A new course of radiotherapy up to a total dose of 50.4 Gy in 28 fractions was prescribed with concurrent chemotherapy to limit the tumor mass growth. |
pmc-6560317-1 | A 50-year-old male presented at the General Surgery Polyclinic due to increased complaints of swelling and intermittent pain in the neck which had been ongoing for 6 years. On the neck ultrasound imaging, heterogeneous nodules were observed in the parenchyma of 27 × 19 mm in the right lobe and 20 × 16 mm in the left lobe and central anechoic cystic nodules 40 × 18 mm at the isthmus level extending towards the lumen. Thyroid function tests were normal and the patient was diagnosed with multinodular goitre. The patient had no comorbid disease and after premedication was admitted to the operating room for elective surgery. Monitorization was applied on the operating table: TA: 130/85 mmHg, pulse: 75 bpm, SpO2: 99%. Sedation was administered by 2 mg midazolam, then anaesthesia induction was made with 2-3 mg/kg propofol, 100 mcg fentanyl, and 0.6 mg/kg rocuronium. After mask ventilation for 3-5 mins, the patient was intubated with no problems. No hemodynamic or respiratory problems were experienced in the intraoperative period. The surgery lasted 1 hr and 45 mins, after which the patient was awakened with no problems and was transferred to the postoperative anaesthesia care unit (PACU). When the patient was fully awake, he was experiencing chest pain and complained that dentures were not in place in his mouth, so a posterior-anterior pulmonary radiograph was taken and a standing direct abdominal radiograph. The dentures were observed in the stomach (). In the history taken from the patient, it was seen that when going to the operating room, partial fixed dentures were in place, and he stated they were in his mouth until reaching the operating room. The emergency gastroenterologist was consulted, and the patient was evaluated but as he had already eaten food, endoscopy procedures were postponed until the following day. In the upper gastrointestinal endoscopy applied the following day, despite having passed the ligament of Treitz, the dentures could not be visualized. On the standing direct abdominal radiograph, the dentures were seen to be in the jejunum (). The abdominal examination was comfortable for the patient, so it was decided to continue medical follow-up. A standing direct abdominal radiograph was taken daily (), and on the radiograph taken on the 5th day, the dentures could not be seen (). The patient was questioned. The dentures had been expelled during bowel evacuation, but the patient did not recall anything other than a slight pain during evacuation. |
pmc-6560322-1 | Our patient is a 74-year-old man with a history of rheumatoid arthritis (on prednisone), left below the knee amputation (BKA), coronary artery bypass graft (CABG) with a saphenous vein graft to the right coronary artery (SVG to RCA), aortic valve replacement (AVR) with a bioprosthetic valve, and mitral valve replacement (MVR) with a bioprosthetic valve who presented with fever, chills, and generalized weakness after a prolonged course of vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia.
The patient was previously admitted for left foot MRSA osteomyelitis. During that hospitalization, the patient had a myocardial infarction. Source control obtained with BKA of the left leg and five days later subsequently underwent CABG (SVG to RCA), AVR for severe aortic stenosis (AS), and MVR for severe mitral regurgitation (MR). The patient was discharged with a six-week course of vancomycin; however, vancomycin course was extended due to BKA wound that required skin graft surgery. Eighty-eight days after cardiac surgery, the patient was readmitted for MRSA bacteremia attributed to cellulitis of the BKA stump vs. endocarditis. Transthoracic echocardiogram (TTE) at that time was negative for PVE. Patient was treated with a six-week course of vancomycin, and BKA stump cellulitis subsequently resolved. Five days after completing antibiotics, the patient presented with MRSA bacteremia, which progressed to VISA bacteremia with a vancomycin minimum inhibitory concentration (MIC) of 4 μg/mL (). The patient was started on daptomycin, ceftaroline, and rifampin for VISA bacteremia. TEE showed aortic root thickening suggestive of abscess with associated structural defect, a mobile 2.4 cm × 1.9 cm echodensity projecting into the right atrium (RA) (), and left to right shunting ().
The patient subsequently underwent cardiac surgery for redo AVR with a bovine pericardial tissue valve, patch repair of aorta to right atrial fistula with a bovine pericardial patching material from both the left ventricular side and right atrial side, and tricuspid valve repair with a ring. Postsurgery TTE demonstrated a normal left ventricle size and systolic function, a normal right ventricle size and function, a bioprosthetic valve in aortic position (mean gradient 20 mmHg and peak gradient 45 mmHg) and no aortic regurgitation, and an annuloplasty ring indicative of tricuspid valve repair. |
pmc-6560324-1 | We present a case of a 44-year-old female patient diagnosed in 2006 with a bifocal invasive ductal breast cancer, HER-2 positive, who underwent mastectomy, chemotherapy, and radiotherapy. The patient was in remission and was under tamoxifen for five years. Twelve years after the initial diagnosis, she developed debilitating dorsal pain, and an MR of the spine was performed.
The study revealed signs of diffuse medullary metastatic disease, assuming a sleeve-like appearance in the dorsal segment (), filling the perimedullary subdural space, most significantly at the T2-T3 level, and molding the posterior medulla (Figures and ). Additionally, leptomeningeal metastatic spread was also observed as disperse small nodular foci, sticking to the spinal cord and the dorsal roots (Figures and ). There were no signs of intramedullary metastatic spread or signs of cerebrospinal fluid (CSF) blockage. Both the leptomeningeal and the dural components of the disease depicted homogenous uptake of gadolinium. Besides the above-described lesions, there was evidence of bone deposits in the right pedicle of T4 and the vertebral body of T7 (). No signs of brain or intramedullary metastatic disease were found.
Given the described findings and symptoms, radiotherapy (RT) treatment (30Gy) was delivered, being successful in the reduction of the volume of the metastatic sleeve at the thoracic level. As a consequence there was a partial improvement in the symptoms and reduction of the analgesic drug dose for eight months now. The patient is currently under surveillance and is also being consulted in a pain management unit. Hormonotherapy, consisting of anastrozole, an aromatase inhibitor, was also prescribed. |
pmc-6560332-1 | A 34-year-old man presented with high-grade fever with chills and rigors and left-sided pleuritic type chest pain associated with a lump in the anterior chest wall. He was a patient with stage 5 chronic kidney disease and was on regular hemodialysis through an arteriovenous fistula during the past one year. He was awaiting kidney transplantation.
On examination, he was febrile with a temperature of 38.7°C. There were multiple enlarged tender axillary lymph nodes on the left side. The lymph nodes were around 0.5 cm and mobile and deep seated. He was dyspneic, breath sounds were reduced in the left lower zone of the lung with few crepitations. There was a tender lump (5 × 5 cm) on the left anterior chest wall. Other system examinations were found to be normal.
Approximately four months prior to the aforedescribed admission, he was investigated previously for fever, poor appetite, and loss of weight lasting for one-month duration. Clinical examination had revealed crepitation in the left lower lung base. Investigations done during that previous admission had revealed normal full blood count, erythrocyte sedimentation rate (ESR) of 93 mm in 1st hour, and C-reactive protein at 23 mg/dl. Chest X-ray had shown evidence of left lower upper and lower lobe patchy opacities. He had been treated with IV co-amoxiclav 1.2 g three times daily empirically. As a further evaluation, contrast-enhanced computed tomography (CECT) of the chest was performed, which had revealed poorly defined small nodules and tree-in-bud opacities in the left lower lobe with focal consolidation in the apical segment of the left upper lobe in keeping with chronic lung infection. A small well-defined enhancing subpleural nodule with speculated margin in the posterior segment of the left lobe and few hilar and pretracheal enlarged lymph nodes were also seen. The Mantoux test had been 20 mm. Sputum direct smear for acid-fast bacilli (AFB) and culture had been negative. A tentative diagnosis of tuberculous infection had been done, and he was started on antituberculous therapy (ATT), namely, rifampicin, ethambutol, pyrazinamide, and isoniazid. After two weeks of ATT, the patient had developed Stevens–Johnson syndrome (SJS), and ATT was discontinued. His symptoms had improved with prednisolone 60 mg daily with tapering over the next preceding month, but ATT was not recommenced due to uncertainty of the diagnosis, because by that time, patient's symptoms had been resolved, and the sputum for tuberculosis (TB) culture was reported as negative.
Investigations done during the latter admission revealed white cell count of 10,000 with neutrophils of 89%, lymphocytes of 10%, eosinophils of 0.2%, hemoglobin at 7.2 g/dl, mean corpuscular volume of 93 fl, and platelets 278 × 103. The erythrocyte sedimentation rate (ESR) was 101 mm in the first hour, and C-reactive protein was 311 mg/dl. Chest radiograph showed left lower zone effusion with consolidation (see ). Considering the history and the high inflammatory markers with X-ray changes, a possible diagnosis of left lower lobe pneumonia with parapneumonic effusion was considered. Initially, he was treated with IV co-amoxiclav 1.2 g three times daily. Sputum for gram stain, acid-fast bacilli, was found to be negative. Sputum for pyogenic culture also did not isolate any organism after 72 hours of incubation. Ultrasound-guided aspiration of the pleural fluid was carried out and aspirated purulent blood-stained fluid. Lymph node fine needle aspiration or biopsy was not considered for several reasons. First, as it was situated on the left axilla, where the patient had his fistula made for the hemodialysis. Second is that the lymph nodes were found to be too small for sampling. Third was since they were deep seated, and it was difficult to gain access, and lastly, because of the possibility of arriving at a diagnosis by evaluating the effusion where access is easily gained.
The aspirate was analyzed with gram stain and AFB stain, which were negative. Pyogenic culture of the aspirate remained sterile after 72 hours. Full report of the aspirated fluid revealed 90% polymorphs and 10% lymphocytes. Lactate dehydrogenase (LDH) was 12,738 IU/l. Adenosine deaminase level (ADA) was 431 μ/l. Because of the high inflammatory markers and the neutrophil predominance, he was treated with intravenous (IV) meropenem 500 mg twice daily and with IV clindamycin 500 mg twice daily for two weeks. But since the ADA was very high, with relation to the past history, underlying tuberculosis infection was also considered. Therefore, aspirate fluid was sent for TB culture. While awaiting TB culture, subsequent CECT revealed empyema necessitans with destruction of the left side anterior upper rib associated with left pleural and mediastinal lymphadenopathy with the most probable infection of tuberculosis (see Figures and ).
The patient was referred to the thoracic surgical team, and they carried out incision and drainage of the lump since the effusion was minimal by that time with the drainage and the treatments. Abscess wall histology did not reveal caseating granulomas. The abscess fluid culture isolated 19 colonies of Mycobacterium tuberculosis organism after one month of incubation; hence, tuberculous empyema necessitans was confirmed. |
pmc-6560389-1 | A 57 year old Caucasian man with a blank past medical history presented at the eye clinic in 2016 with a history of a unilateral swollen eyelid and red right eye. His medical complaints started during a 10-day trip to South Africa, two days after visiting False Bay. Initially, the patient was treated in South Africa by a local general practitioner with oral azithromycin 500 mg for 3 days together with topical dexamethasone/tobramycin eye drops. After an initial improvement, 14 days later conjunctivitis symptoms flared up severely when skiing in Switzerland. Upon return to his home country, the patient consulted the eye clinic. |
pmc-6560718-1 | A 48-year-old male, who had no past medical or traumatic history and no family history of cerebral artery dissections, suddenly felt a severe, throbbing headache on the right side and came to our clinic on the fourth day following onset. MRI examinations showed a tiny dissection-like finding (pearl and string sign-like) on his right proximal segment (tonsillomedullar segment) of posterior inferior cerebellar artery (PICA) (Fig. a). No intramural hematoma, double lumen finding or intimal flap were observed, but PICA dissection (PICAD) could not be ruled out, and the patient was therefore carefully observed, with continuous monitoring of blood pressure, heart rate and other vital signs; also, he was hydrated sufficiently and given analgesic anti-inflammatory agents. MRA on the seventh day revealed that there was an association between the change in shape and volume of the PICA and the time elapsed, strongly suggesting PICAD (Fig. b). The other MRI sequences showed no infarctions or hemorrhages (Fig. d, e. Conventional angiography was not performed because the PICA could be observed by serial high-resolution MRI examinations and angiography was not considered necessary in this case. The inner and outer diameters of the dissected PICA were measured by MRI T1-weighted high-resolution vessel wall imaging (HRVWI) (Fig. f) and T2-weighted HRVWI (basi-parallel anatomical scanning (BPAS); Fig. ), respectively. The severity of the headache was assessed by Numerical Rating Scale (NRS) every day. Two weeks after the onset of headache, the diameter of the dissected vessel grew to the maximum size (Fig. a), though the patient’s headache improved markedly on the eighth day (Fig. ). At that time, surgical or endovascular treatment to prevent subarachnoid hemorrhage was recommended; however, the patient, who had been relieved of severe headache, desired to continue conservative therapy. Four weeks after the onset, the dissection finding on MIP images began to improve. Eight weeks after the onset, his PICA looked almost normal on MIP and T1-weighted HRVWI, though the outer diameter was still bulging on a T2-weighted HRVWI (BPAS). Finally, four months after the onset, the outer diameter was observed to be almost normal in size and shape (Fig. ). The patient has resumed activities, such as marathon racing, again. |
pmc-6560759-1 | A 25-year-old male, from China, born to unrelated parents was presented to the First People’s Hospital of Huizhou city, China. The clinical manifestations were spastic gait disturbance and vision loss (Table ). He was suffering from mild gait difficulties by the age of 5 years; the ambulation was unstable, and he could fall easily. The vision loss was reported at the age of 8 years, while the cognitive development was normal. He was born at full term by uncomplicated delivery. The neurological examination of the patient revealed ocular motility disorders, horizontal nystagmus, absence of the left pupillary light reflex, pes cavus, spastic paraparesis on lower limbs, exaggerated bilateral patellar tendon reflexes, ankle clonus, and positive Babinski sign, while no detectable defect was found in the finger-to-nose test, sensory function. The laboratory biochemical studies of full blood count, liver function, plasma electrolytes, thyroid function, vitamin B-12 and folate, sex hormone, autoantibody profile and syphilis serology exhibited typical levels. Cerebrospinal fluid tests revealed increased protein (1186 mg/L); the normal value was 140–450 mg/L. The GALC enzymatic activity [] detected by Bio-Tek FLx 800 fluorescent analyzer in leukocytes was decreased (3.9 nmol/mg/17 h); the normal value was 18–75 nmol/mg/17 h protein.
The described findings gave reason to perform molecular analysis of the GALC gene. The direct sequencing of the GALC gene (Reference mRNA sequence: NM_000153) in this patient identified a novel missense mutation (c.865G > C: p. G289R) in exon 8 along with a known missense mutation [] (c.136G > T: p. D46Y) in exon 1 (Figs. and ). The former mutation was heterozygous in the mother, while the latter was heterozygous in the father.
Brain MRI revealed a high-intensity signal in the left central gyrus cortex by fluid-attenuated inversion recovery (FLAIR) as well as T2-weighted images, while a decreased signal in the T1-weighted images and high-intensity lesions in the bilateral corticospinal tracts were detected (Fig. ). Cervical spine and thoracic spine MRI showed mild atrophy of the spinal cord (Fig. ). Moreover, electromyography indicated peripheral nerve demyelination, and both visual evoked potentials (VEP) and brainstem auditory evoked potential (BAEP) were normal. |
pmc-6560767-1 | A 58-year-old white woman, weighing 55 kg and with a body mass index of 23, was admitted to our hospital suffering from general weakness, coughing with purulent sputum, fever, and nausea. She presented in a stable general condition, except for schizophrenia with mild cognitive impairment. Prior to admission, she received clozapine (250 mg/day) for schizophrenia. She had no other relevant diagnoses and interventions in her past medical history. She lived in an assisted living facility and was employed in a protected workplace program. She was able to take care of herself and was able to perform daily tasks on her own (for example, grocery shopping). She has no direct relatives and was raised in a children’s home. On admission, she was awake with a Glasgow Coma Scale (GCS) of 15 and was temporal, local, and autopsychic oriented. She showed no neurological deficiency. She was hemodynamically stable with heart rate of 100 beats per minute (bpm), blood pressure of 99/70 mmHg, respiratory rate of 14/minute, and body temperature of 38.9 °C. She had signs of mild dyspnea, coughing, and wheezing at auscultation. Her abdomen was soft without tenderness on palpation. Bowel sounds were equally present. An influenza screening test was negative. Urinary and blood cultures showed no bacterial infection. Blood samples on admission showed an elevated C-reactive protein (CRP) of 39 mg/L, leukocytes of 9.9 g/L, and a lactate level of 2.1 mmol/L. Creatinine clearance, liver function, electrolytes, and counted blood cells were all within normal ranges. With a tobacco smoking history of 40 pack-years, she was now treated for exacerbated chronic obstructive pulmonary disease and antibiotic therapy with intravenously administered amoxicillin/clavulanic acid (1.2 g three times a day). Prednisone (50 mg/day) was also started. Two days after admission, she suffered acute vomiting and presented a diffuse pressure-resistant and distended abdomen. Abdominal computed tomography showed a volvulus in the small intestine, 20 cm from the ileocecal valve, confirming the indication for emergency laparotomy (Fig. ).
After surgery, she arrived in the ICU under sedation with propofol (80 mg/hour) and fentanyl (0.05 mg/hour), decreased bowel sounds, and normal cardiopulmonary parameters. Initially, she received 0.5 mg haloperidol as prophylaxis for delirium. She was continuously administered noradrenaline (0.34 μg/kg per minute) to maintain circulation and Ringer’s acetate for volume support. We treated her respiratory infection with piperacillin/tazobactam (13.5 g/day). For volume support, she received 5000 ml Ringer’s acetate during the first 24 hours. Her urinary output was supported with furosemide (35 mg) over the first 24 hours. In addition, she received anticoagulation with dalteparin (5000 IU).
The initial period was uneventful. Although ventilator weaning was intended for our patient and sedation was reduced, she remained dependent on positive end-expiratory pressure and extubating was not possible. Under volume therapy and a positive fluid balance of 4 liters the next morning, noradrenaline could be partially reduced and maintained at 0.25 μg/kg per minute. Her first post-surgery blood check at 5 p.m. showed a CRP of 179 mg/L, leukocyte count of 17 × 109/L, hemoglobin at 81 g/L, creatinine at 118 μmol/L, and serum lactate at 1.5 mmol/L. She was slightly agitated and received a total 4.5 mg haloperidol over 24 hours for delirium treatment.
In the morning, we included her in a study and routinely measured her microcirculation. The microcirculatory measurement revealed an almost absent MCF (Fig. , see also Supplementary content – Additional file : Video S1, Impaired sublingual microcirculation of the described case, in comparison with Additional file : Video S2, intact microcirculation of a member of the study team). In addition, offline analysis showed an MFI of far below normal (2.6 is the accepted threshold) for all three recordings. Even in the recording with the most perfused vessels (Table ), less than 25% of the vessels were perfused (PPV).
Except for the altered microcirculation, circulatory and laboratory parameters showed no clear indication for a deterioration of the medical situation. Post-surgical CRP and leukocytes were expected to be high. Infrared blood oxygen saturation (SpO2) inconsistently showed low values between 50 and 90% by a fingertip detector. We initially interpreted this to be a malfunction due to a cold periphery.
Because of the normal hemodynamic measurements, we chose an expectant strategy and increased intravenous fluid administration. Arterial blood gas analysis showed only moderate rise of lactate levels from 1.5 to 3 mmol/L (Table ). A laboratory examination 80 minutes later indicated a rapid deterioration of the situation with a lactate level of 5.4 mmol/L and a decreased hemoglobin level of 59 g/L (36.6 mmol/L).
Transfusion of 2 units of packed cells was initiated, and an arterial blood gas sample was drawn after 30 minutes. Transthoracic ultrasound showed a hyperdynamic, underfilled left ventricle, and abdominal ultrasound gave no further information. She underwent an immediate surgical re-evaluation.
The laparotomy showed a dilated and visually ischemic descending colon down to the sigmoid. The previous ileocecal anastomosis was still intact and the ileum was vital. The entire colon was removed, and an ileostomy was implanted in her abdominal wall. A third look surgery a few days later showed an intact and vital remaining bowel. Postoperative microcirculation and blood samples returned to normal, and she recovered slowly without further complications from her severe condition. She could be discharged from our hospital 4 weeks after admission and returned to her domestic environment. In the follow-up consultation after 6 months at our hospital she refused a retrocession of the stoma. She managed the daily care of the ileostomy by herself and felt comfortable with it. Except for the permanent ileostomy, she did not have any residual symptoms from the incident and integrated herself in the daytime routine. No further consultation was planned. |
pmc-6560775-1 | A 66-year-old Japanese man complained of increasing muscle stiffness of the four extremities and difficulty in relaxing his grip, which had been present from early childhood. His parents were consanguineous and his family had no neuromuscular disease (Fig. a). In his youth, mild muscle weakness and muscular hypertrophy had developed. Later in his life, gait disturbance due to muscle stiffness, severe in the starting period and relieved on continuation of walking, developed. The patient was diagnosed as having myotonia congenita at the age of 22 without any complications (Fig. b). He was treated with acetazolamide and phenytoin with relief of the symptoms. In spite of the symptoms, his daily activities were almost normal including working as a gardener, except that his myotonic symptoms got worse at low temperatures. There was no paralytic event during the entire disease course. At the age of 62, his muscular symptoms worsened on discontinuation of phenytoin due to membranous nephropathy, so he was admitted to our hospital. On admission, he had a Hercules-like appearance with hypertrophy of the limbs and axial muscles including the pectoralis major muscles. Physical examination revealed eye closure myotonia, percussion myotonia and grip myotonia. The myotonia improved with muscle exercise or repeated effort, the so-called “warm-up phenomenon”, and was aggravated by exposure to cold. Ocular movement was restricted in every direction with relief on repetition. Dysphagia and dysarthria were also present only when he was exposed to cold. Muscle manual testing was normal at ordinary temperatures.
The other neurologic findings were all normal. There had been no paralytic event or systemic abnormality. Laboratory examination showed an increased level of serum creatine kinase, 388 U/l (normal value < 279 U/l), which decreased with rest in hospital. Electrocardiography, ultrasound cardiography and chest X-raying were normal. Needle electromyography of the left biceps brachii muscle and quadriceps femoris muscle showed myotonic discharges (Additional file ). T1-weighted images of Cranial MRI revealed hypertrophy of all extraocular muscles (Fig. c). His myotonic symptoms improved since the start of administration of mexiletine (300 mg/day).
Genetic analysis: Whole-exome sequencing revealed a heterozygous mutation of the SCN4A gene (c.2065 C > T, p.Leu689Phe). However, we found no mutation of the CLCN1 gene. Then, we confirmed the SCN4A mutation by direct sequencing (Fig. d). Mutation analysis showed no mutation of the DMPK or ZNF9/CNBP gene.
A muscle biopsy was performed on the right biceps brachii muscle, followed by light microscopy and routine electron microscopy. On HE staining, variation in diameter of muscle fibers including hypertrophy (over 100 μm, about a half of muscle fibers) and atrophy was observed (Fig. a, Additional files and ). Internal nuclei, chained nuclei (Fig. ), fiber splitting (Fig. c), pyknotic nuclear clumps (Fig. d), endomysial fibrosis and mild fatty replacement were observed in all areas. Sarcoplasmic masses were absent. On modified Gomori trichrome staining (mGT), ragged-red fibers could not be observed but fibers exhibiting slight marginal hyperstaining were observed (Fig. e). NADH-TR staining showed disorganized intermyofibrillar networks including a moth-eaten appearance and lobulated fibers (Fig. f). Myosin ATPase staining showed reduction of type 2B fibers and predominancy of type 2A fibers (Fig. g). On electron microscopy, atrophic fibers exhibiting Z-streaming were observed (Additional file ). Tubular aggregates were absent in all examinations. |
pmc-6560823-1 | A 59-year-old man was diagnosed in July 2014 with a rectal tumor and associated solitary lung metastasis, cT3N1bM1a. He was treated with Folfox-Bevacizumab during 2 months, followed by radiochemotherapy: 25 × 1,8 Gy in combination with oxaliplatin and 5FU. In December 2014, he underwent a total mesorectal excision (TME) together with a video-assisted thoracoscopic resection (VATS) of the lung lesion. The final pathological stage was ypT3N0M1 adenocarcinoma of the rectum and the patient underwent further treatment with Folfox-bevacizumab until the end of March.
In May 2015, at the time of planned restoration of bowel continuity, a relapse was noted in the liver and a resection of segment 4B was performed.
In November 2015, new liver lesions and a peripancreatic mass were found and for the first time a slight elevation of carcinoembryonic antigen (CEA) - 5 μg/L - was noted. Two months after initiation of Folfiri-Bevacizumab, progressive disease (PD) was found on CT scan (with growth of the peripancreatic mass and liver metastases and occurrence of an aortocaval lymph node). The CEA level had risen to 26 μg/L.
In the meantime, molecular analysis was performed and the tumor proved to be KRAS-NRAS wild type (WT), BRAF mutant with a specific mutation, c.1781A > G (p.(Asp594Gly)) in exon 15 (Next Generation Sequencing (Massively parallel targeted re-sequencing Somatic 1 Multiplicom MASTR assay). Immunohistochemical staining showed no loss of expression of mismatch repair proteins, suggesting microsatellite stability (Antibodies used: Clone ES05 (Novocastra) for MLH1, Clone 6219–1129 (Roche) for MSH2, Clone EP49 (DAKO) for MSH6 and Clone A16–4 (Roche) for PMS2).
Therapy with Folfox-Cetuximab was not successful: there was further progression after 2 months of treatment with occurrence of new liver metastases and a further growth of the peripancreatic lesion and aortocaval lymph nodule. CEA increased to 51 μg/L.
In March 2016, Regorafenib was started at a dose of 160 mg/day (21 days on, 7 days off) while at the same time treatment of the liver metastases with selective internal radiation therapy (SIRT) with Yttrium-90 in combination with stereotactic beam radiation therapy (SBRT) for the para-aortic lymph nodes was planned. Because of a hand-foot skin reaction, treatment with topical corticosteroids and keratolytics was started and a dose modification was made to regorafenib 120 mg/d after 1 treatment cycle. In June 2016, when the treatment with Regorafenib was interrupted in order to proceed to radiotherapy, the CEA level had already dropped to 11 μg/L. SBRT of the para-aortic lymph nodes was administered at a dose of 3 × 8 Gy. CEA was 6 μg/L before selective treatment with Yttrium-90 in the right liver lobe. The patient suffered from bulbitis post radioembolization. In July 2016 a complete remission (CR) was seen in the liver – also in the left liver lobe, which had not been treated with Yttrium-90. CEA had dropped to 5 μg/L.
Regorafenib was stopped in September 2016 after 6 months of treatment.
Re-evaluation at the end of January 2017 showed new lymph nodes in the periampullary region and a rise in CEA level to 12 μg/L. Regorafenib was re-initiated at a dose of 120 mg/d, 3 weeks on, 1 week off. The hand-foot skin reaction was more severe, leading to a personalised treatment schedule - 10 days on/7 days off - in order to increase patient tolerability. Treatment with Regorafenib resulted in normalization of CEA (2 μg/L) and response on CT-scan (Fig. ) and therapy was stopped in August 2017.
In February 2018, the patient consulted with complaints suggesting gastric outlet obstruction. Endoscopy revealed bulbitis. Chronic inflammation post radioembolization was suspected, but tumor cells were found in the biopsies. CEA had risen to 19 μg/L. A palliative Billroth II resection was performed and tumoral deposits were found both in the duodenum and the antrum.
Regorafenib was reintroduced in April 2018 at a dose of 120 mg/d using the same schedule as in 2017. Re-evaluation in July 2018 showed new adenopathies and a further increase in CEA to 43 μg/L. Shortly thereafter the patient developed jaundice because of biliary obstruction due to a lesion in the liver hilum. Biliary stenting was not possible, but the lesion responded very well to radiotherapy (5 × 4 Gy), resulting in an amelioration of the jaundice. The patient declined further interventions.
Overall, treatment with Regorafenib with therapeutic breaks resulted in clinical response, both biochemically and radiologically. Disease control was possible during more than 24 months in this patient with a rare BRAF mutation. A timeline highlighting the most important disease characteristics, the disease evolution and the therapeutic interventions can be found in Fig. . |
pmc-6560852-1 | We reported the case of a 61-year-old male who suffered an extrusion of intercostals nerve with 1–6 left rib fractures among which ribs 3 and 4 were long comminuted fractures (see Fig. a). It was proposed to perform open reduction and internal fixation surgery on ribs 3–6. In view of long segment comminuted fractures of ribs 3 and 4 at a relatively high position, with pectoral muscle covering in front and scapula covering in the rear, reduction and fixation of this two-rib fracture was the key to a successful surgery.
A preoperative CT thin slice scan was used to reconstruct the 3D model according to the scanning results, and the models of ribs 3 and 4 were prepared using 3D printing (Fig. b). The 3D printed model of each fracture segment of the two ribs was adhered and reconstructed respectively (Fig. c). The two-rib titanium alloy frame locking plate was respectively shaped according to the reconstructed model (Fig. d).
The patient was treated with general anesthesia, right lateral position, and a 8-cm incision was made under the lower edge of the 4th rib. The skin and the subcutaneous tissue were separated layer by layer, revealing the anterior latissimus dorsi and musculus serratus anterior. A tunnel-type operating space was made by disconnecting from the back of the pectoralis major and the pectoralis minor to the rear of the scapula along the of surface 3rd and 4th ribs. Under the assistance of endoscope, the titanium alloy rib locking plate, which was shaped before surgery, was placed on the 3rd rib’s surface, and was well fitted with the non-fractured end of the 3rd rib front and rear. The long-angled clamp temporarily affixed the metal internal fixation plate to the rib, and used the Matrix RIB: MIPO system to drill holes. Then, two screws were inserted into both ends and locked, thus the metal internal fixation plate was firmly affixed. A plurality of small fracture segments in the middle were respectively drilled and fixed onto the locking plate. The 4th rib was fixed in the same way. The chest wall was well shaped after surgery (Fig. e). |
pmc-6560852-2 | The second case was a 57-year-old male with multiple fractures of the left ribs, including 4 and 5 costal cartilage and rib 6 anterior costal arch fractures (Fig. a). Because this part was cartilage, including part of the costal arch, and the ribs were not in regular shape, the fixation firmness of costal cartilage was not as good as that of common bone. Therefore, it was proposed that the inner end of the locking plate should be affixed to the sternum and the outer end to the rib bone.
The preoperative CT thin slice scan was used to reconstruct the 3D model according to the scanning results, and the fractured end of the rib fractures were adjusted and restored using software (Fig. b). The 3 and 4 rib models were prepared using 3D printing, and the titanium alloy rib locking plate was prefabricated accordingly (Fig. c, d).
During the operation, the 5th rib oblique incision was taken as the center of the rib fracture according to CT and palpation of fracture end, separated layer by layer. Attention should be paid to the protection of the muscular layer, and the muscle fiber was split to expose the broken end of the rib for drilling, without excessive dissection. Then the inner end of the 4th and 5th ribs were affixed to the sternum, and the distal end was affixed to the rib bone part, and the two ends of the middle cartilage were respectively affixed by 1 or 2 screws. The costal arch can only be affixed by drilling into the costal cartilage due to anatomical limitations. Chest wall was well formed after operation (Fig. e, f). |
pmc-6560852-3 | A 64-year-old female was admitted to our hospital because of traffic accident with 2–11 left rib fractures where 2–6 contained the costal cartilage multiple fractures involving the costal arch (Fig. a). Because the No.3 patient was a female, the operation should not only consider minimally invasive, but also need to protect breast tissue adequately. Moreover, considering the stability of the fixator, the medial side of the locking plate was fixed in the body of the sternum, and then the sternum and armpit were treated with tunneling open reduction and internal fixation.
A preoperative CT thin slice scan was used to reconstruct the 3D model according to the scanning results, and the models of ribs 3–5 were prepared using 3D printing (Fig. b). The titanium alloy frame locking plate was re-shaped according to the reconstructed model.
Intraoperatively, a vertical incision (4 cm long) was performed on the body part of the sternum in the patient, which was free to the bone surface. An 8-cm vertical incision below the armpit was separated layer by layer. Attention should be paid to protect the muscular layer, and the muscle gap or the muscle fiber was split to expose the broken end of the rib, avoiding traversing muscle tissue. Next, the surface of the rib loose tissue was split to the side of the sternum, merging with the chest incision. Then, the broken ends of each rib were slightly split, and the broken ends of each fracture were gently repositioned. Corresponding pre-shaping locking plates were placed in each rib (Fig. c). The proximal sternum was drilled and fixed with two screws; the other end was fixed on the distal bone part of the fracture line with two screws; and the middle cartilage was fixed with 1 to 2 screws at each end. The surgery was completed successfully. |
pmc-6560911-1 | A 65-year-old female with a body mass index of 29 presented with a 7-month history of left shoulder pain and weakness. Physical exam and diagnostic imaging were consistent with a symptomatic full thickness rotator cuff tear of the supraspinatus and a partial tear of the subscapularis tendon (Fig. ). She was indicated for an elective arthroscopic surgical repair. She was otherwise healthy with her only medical comorbidity consisting of hyperlipidemia. She had no prior surgical history including no prior shoulder procedures.
Anesthesia evaluation on the day of surgery was performed and her neck was recorded as “unremarkable.” She was assigned an American Society of Anesthesiologists (ASA) score of 2. On the day of surgery, she was easily intubated with an endotracheal tube in the supine position and then placed in the standard lateral decubitus position for arthroscopic shoulder surgery. Exam under anesthesia was performed followed by a diagnostic shoulder arthroscopy. Normal saline was fed into a Stryker CrossFlow® Integrated Arthroscopy Pump (Stryker Endoscopy, San Jose, CA, USA) set at 25 mmHg initially. Epinephrine was not added to the irrigation fluid. Shortly after beginning the case, the arthroscopic fluid pressure was raised to 35 mmHg to aid in visualization where it remained for the duration of the case. No lavage cycles were utilized. Standard posterior, anterosuperior and anteroinferior portals were placed as well as a lateral working portal. She was found to have a type 1 superior labrum anterior to posterior (SLAP) tear, degenerative changes in the anterior, inferior and posterior labrum, a subscapularis tear in the upper one third which was retracted medially, and a complete supraspinatus tear. A biceps tenotomy was performed followed by rotator cuff repair of the subscapularis and supraspinatus tears utilizing suture anchors. Bone quality was remarkably poor with pull-out of multiple suture anchors during the rotator cuff repair adding to surgical complexity and time. Total operative time was 3 h and 53 min. Upon completion of the case and removal of the surgical drapes, significant unilateral face and neck swelling was noted on the side of the operative shoulder (the non-gravity dependent side). Upon consultation with the anesthesia providers the decision was made to obtain a computed tomography (CT) scan for visualization of the soft tissues surrounding the airway, with a plan to leave the patient intubated overnight. The CT demonstrated diffuse soft tissue edema in the subcutaneous tissues of the neck, chest and face. The airway was deviated at the level of the trachea due to the paratracheal edema. There was no focal collection or extravasated contrast indicative of a hematoma or vascular injury (Fig. ).
The patient was monitored overnight in the Intensive Care Unit (ICU). After resolution of the edema, she met standard ICU extubation criteria, and was extubated on the morning of postoperative day one. Postoperatively, the patient has done well without any airway or pulmonary complications, complete resolution of preoperative symptoms, and return to baseline shoulder function (Fig. ). |
pmc-6560963-1 | Case 1: a 38-year old female patient, diagnosed with HIV infection in 2008, presented with complaints of intermittent high grade fever associated with chills and rigor for one month to a local hospital. This was associated with loss of appetite and generalized weakness. She was transfused two units of packed RBC. She was receiving an antiretroviral regimen consisting of tenofovir, lamivudine and efavirenz. Her CD4 count was 85/μl and the viral load was 56, 670 copies/μl. With a diagnosis of virological failure, she was shifted to an atazanavir/ritonavir based regimen. She was referred to us with persistent fever. On examination, she was febrile with a pulse rate of 120/min and a respiratory rate of 25/min. She had icterus and her jugular venous pressure was elevated. Chest examination revealed decreased bilateral breath sounds and bi-basal crepitations. On abdominal examination hepatosplenomegaly was present. The baseline laboratory evaluation revealed pancytopenia and hyperbilirubinemia (Hemoglobin- 5.9 gm/dl, total leucocyte count- 1500/cu.mm, platelet count- 18,000/cu.mm and bilirubin- 3.3gm/dl). Peripheral smear showed dimorphic hypochromic anemia with a corrected reticulocyte count of 1%. Vitamin B12 and folic acid levels were normal. Lactate dehydrogenase (LDH) levels were elevated (1154 U/l). Blood culture was sterile for bacteria, fungi and non-tubercular mycobacteria. Contrast enhanced computed tomography (CECT) scan of chest and abdomen revealed hepatosplenomegaly (liver-16.8 cm, spleen-13.4cm) and multiple enlarged non-necrotic lymph nodes in mesentery, para-aortic and inguinal region. A whole body Fluorodeoxy glucose positron emission tomography (FDGPET) scan revealed hypermetabolic bilateral supraclavicular, internal mammary lymph nodes and abdominal lymph nodes. There was avid uptake in liver, spleen and bone marrow also. The biopsy from supraclavicular lymph node showed reactive hyperplasia. Staining for acid fast bacilli, GeneXpert and Mycobacterial growth indicator tube (MGIT) culture for Mycobacterium tuberculosis were negative. A bone marrow biopsy was done which showed 60-70% cellularity. It was negative for geneXpert and Cytomegalovirus (CMV) polymerase chain reaction (PCR) assay. Also, pp65 antigen detection test in blood for CMV and rk39-antibody test for visceral leishmaniasis was negative. With a presumptive diagnosis of tuberculosis, modified anti-tubercular therapy (ATT) (levofloxacin, ethambutol and amikacin) was started as the patient had elevated bilirubin level. There was no response even after one month of ATT. Introduction of rifampicin and isoniazid was attempted but the bilirubin levels rose to 9.5g/dl. Clarithromycin was empirically added to cover for Mycobacterium avium complex (MAC) infection. On further investigations, she was found to have a triglyceride levels of 435 mg/dl, fibrinogen levels of 500 mg/dl, ferritin levels of >2000 ng/ml and decreased NK cell activity. With a diagnosis of Haemophagocytic lymphohistiocytosis (HLH), dexamethasone at a dose of 16 mg per day was started. The fever and pancytopenia improved in a week's time (Hemoglobin- 7.4gm/dl, total leucocyte count- 5300/cu.mm, platelet count- 50,000/cu.mm). The patient was doing well but she started getting dyspneic fifteen days after the initiation of steroids. Chest X-ray revealed consolidation in the right middle lobe. With a diagnosis of hospital acquired pneumonia, she was started on cefoperazone sulbactam, but she succumbed to her illness after two days. |
pmc-6560963-2 | Case 2: a 46-year old male patient on tenofovir, lamivudine and efavirenz, presented with intermittent low grade fever for the last four months. This was associated with night sweats, loss of appetite and loss of weight of around five kilograms. He also complained of decrease in urine output and generalized swelling of the body. On general examination, he was febrile and was found to have enlarged right axillary lymph node (1cm x 1cm). On systemic examination, he had ascites and a palpable spleen (8 cm below the left costal margin). Fundus examination was normal. On laboratory investigations, he was found to have pancytopenia, deranged liver function and kidney function tests (Hemoglobin- 7.4g/dl, total leucocyte count-1200/mcl, platelet count-20000/mcl, aspartate transaminase/alanine transaminase-209/117 U/l and urea/creatinine- 78/1.7 mg/dl). His baseline CD4 was 221/μl and the most recent CD4 was 158/μl. Non contrast computed tomography of abdomen revealed multiple enlarged retroperitoneal lymph nodes with the largest measuring 47 x 22 mm. Lymph node biopsy could not be performed due to deranged coagulation parameters. Blood and urine cultures were sterile. Peripheral smear showed normocytic normochromic anemia. Vitamin B12 levels were normal but the folate levels were low (2.2ng/ml). Serum LDH levels were elevated (834 IU/l). Immunochromatography for rk39 antibody was negative. Ascitic fluid analysis revealed a protein of 1.9 g/dl, albumin of 0.9 g/dl, total leucocyte counts of 380/mcl (Lymphocytes 90%, Neutrophils 10%), serum-ascitic albumin gradient of 1.1g/dl and adenosine deaminase levels of 40 IU/l. Ascitic fluid cultures were sterile. With a presumptive diagnosis of disseminated tuberculosis, he was started on ATT. His ferritin levels were elevated (>2000 ng/ml) and triglyceride levels were also high (324 mg/dl). A presumptive diagnosis of HLH was made. A lymph node biopsy was performed after correction of coagulation abnormalities to identify the primary pathology. However, he succumbed to his illness before the results of biopsy were available. The biopsy was suggestive of Hodgkin's lymphoma. |
pmc-6561511-1 | The patient is a 62-year-old man with a history of non-small cell lung cancer status post chemoradiation, chronic obstructive pulmonary disease (COPD), right tongue squamous cell carcinoma status post right partial glossectomy and neck dissection followed by chemoradiation, who had been admitted to an outside hospital for possible pneumonia. Upon admission, he was found to have pancytopenia with white blood cell (WBC) 2600, hematocrit 36.6%, platelet count 62,000, and absolute neutrophil count (ANC) 598. As the ANC continued to downtrend, oncology saw the patient and commented that the "pancytopenia is likely from transient myelosuppression from pneumonia”. He was released from the hospital five days later with antibiotics.
Nine days later, he saw his primary care physician (PCP) for hospital follow-up who wrote:
"His white count went as low as 1600 on his recent hospitalization, but had increased bands and metamyelocytes and was thought to have some transient marrow suppression secondary to infection or medications…They also advised him to follow up with outside infectious disease and hematology, although I see little need for this."
Routine blood work a few days later revealed worsening pancytopenia. He was advised to go to the emergency room and was admitted to the hospital. The day following admission, flow cytometry was sent due to high suspicion of leukemia. A week later, almost three and a half weeks after this initial presentation of pancytopenia, with ANCs reaching as low as 280, results confirmed diagnosis of AML and chemotherapy was initiated. The patient began to decline rapidly and was transferred to the medical intensive care unit (MICU). There, he experienced respiratory failure that required intubation. A few days later, the decision to hold chemotherapy was made. The patient became anuric and ultimately developed vancomycin-resistant Enterococcus (VRE) bacteremia. After discussing his prognosis with his wife, the decision was made to extubate and treat with comfort care. The patient died less than a month later. |
pmc-6561512-1 | An 84-year-old male resident of a nursing home facility of Hispanic descent was brought to our emergency department (ED) for respiratory distress and altered mental status. He was intubated promptly on arrival to the ED. His past medical history was significant for intracranial aneurysm with bleeding following VP shunt placement, ischemic stroke with aphasia and paraplegia, and percutaneous endoscopic gastrostomy (PEG) tube placement. His vital signs and clinical laboratory results are presented in Table .
The clinical picture was suggestive of septic shock. We ordered a sepsis workup including two sets of blood cultures and urine culture. The patient was treated with aggressive intravenous fluid hydration and broad-spectrum antibiotics (vancomycin and meropenem).
A non-contrast computed tomography (CT) of the chest, abdomen, and pelvis revealed bibasilar pulmonary atelectasis without focal infiltrate and the presence of a right-sided VP shunt catheter traversing the right neck, the right chest, and the right abdominal wall; the tip of the catheter was located within the gastric lumen and had likely entered through the PEG tube insertion site (Figures -). The PEG tube was outside the gastric lumen, terminating in the abdominal wall that was evidenced in the repeat CT scan confirmed that patient had abdominal wall cellulitis and localized abscesses around the PEG tube insertion site (Figure ). Medical records from another facility confirmed previously normal positioning of the PEG tube and normal intraperitoneal positioning of VP shunt catheter one year prior.
Given the malposition of the VP shunt inside the gastric lumen, we suspected VP shunt infection or meningitis/encephalitis and subsequently lumbar puncture was performed; the results of the cerebrospinal fluid (CSF) analysis were unremarkable. Blood cultures and urine culture results were negative.
The wound culture was positive for Proteus mirabilis sensitive to carbapenems and piperacillin/tazobactam. We debrided the abdominal wall and drained the abscess. Intravenous antibiotic coverage was continued according to the sensitivity testing, and patient received intravenous meropenem for a total of 10 days with good clinical outcome.
Esophagogastroduodenoscopy revealed a small lumen catheter, likely the VP shunt, entering into the gastric lumen proximal to the incisura angularis; this was identified as the previous PEG tube insertion site (Figure ). The catheter tip was found in the fundus of the stomach. We also noted frank purulent drainage from the PEG insertion site (Figure ).
Once stabilized, the patient was transferred to a higher center of care for neurosurgical evaluation with proper positioning and removal of the VP shunt. The patient underwent shunt catheter removal from the stomach lumen followed by repositioning of the PEG tube. The neurosurgery team decided against reinsertion of the VP shunt.
The patient was followed up at six months from the time of discharge, and his PEG tube was functional and also he didn't develop worsening of hydrocephalus. |
pmc-6561513-1 | A 14-year-old Chinese boy presented with a complaint of progressive worsening vision in both eyes for two years. The patient had been aware of poor vision since childhood, and there had recently been further deterioration. His mother noticed that he had poor eye contact since the age of four months. Both parents consulted an ophthalmologist once when the patient was nine years old. They were informed of poor visual prognosis, and declined ophthalmology follow-up since then.
Past medical history revealed that the patient developed lethargy and severe vomiting three years earlier, and underwent a thorough systemic examination and work-up. Ocular examination at that time confirmed bilateral optic atrophy and pigmentary retinal changes. Abdomen ultrasonography showed small bilateral renal cysts and coarse liver texture. No liver cysts were observed. He was diagnosed with end-stage renal failure, anemia, and hypertension. He was started on continuous cycling peritoneal dialysis. Subsequently, the chromosomal studies confirmed 46XY. The diagnosed was revised. His clinical manifestation was consistent with Senior-Loken syndrome. The patient’s general condition was stable and he was compliant with treatment.
On examination, the patient was a small build teenager with a height of 140 cm and a weight of 33.8 kg. His blood pressure was in the normal range on medication. There was no evidence of abnormal sexual development or spinal deformity.
The visual acuity was counting fingers at one foot in both eyes. He had nystagmus bilaterally. Slit lamp examination showed moderate nucleus sclerosis in both eyes. Funduscopy revealed bilateral pale optic discs, hypopigmentation at the mid-periphery of the retina, and sclerosis with attenuated vessels at all quadrants of the retina (Figures -).
In the left fundus, there were telangiectatic vessels at the periphery, retinal hemorrhages, and subretinal exudates with a shallow exudative retinal detachment (Figure ).
Fundus fluorescence angiography was deferred in view of his renal condition. Optical coherence tomography revealed foveal atrophy in the right eye. However, the images were poor in both eyes due to nystagmus.
The patient underwent one session of laser photocoagulation under general anesthesia in the left eye. The condition persisted, and an external drainage of the subretinal fluid was performed one month later. His best-corrected visual acuity was hand movement, and the retina appeared flat. The collection of subretinal fluid resolved after the procedure.
The patient was monitored closely during post-operative periods. The visual acuity in both eyes at one year postoperatively remained hand movement. Both retinae were flat. |
pmc-6561524-1 | A 55-year-old female with a history of renal cell carcinoma of the left kidney metastatic to the bony pelvis, lungs, mediastinum, and spleen presented to the emergency department with shortness of breath, pleuritic chest pain, and left scapular pain. She presented to the same emergency department one week prior with pleuritic chest pain but was discharged home after pulmonary embolism was ruled out.
She was diagnosed with renal cell carcinoma of the left kidney five years prior after presenting with gross hematuria. At that time, she underwent left radical nephrectomy. One year later, she developed a metastatic lesion in the bony pelvis for which she underwent radiation therapy. She as treated with pazopanib for two years with stable disease but stopped due to gastro-intestinal toxicity. Therapy was switched to nivolumab, which was discontinued after six months due to grade four pancreatitis and grade two rash. Eight months prior to her current presentation, she underwent radiation treatment to metastatic lesions in the left pubic symphysis and spleen. The patient initiated therapy with cabozantinib, a tyrosine-kinase-inhibitor used to treat renal cell carcinoma, three months prior to her current presentation.
On physical examination, she was wheezing in all lung fields and hypoxemic requiring supplemental oxygen. She had prior 12-pack-year smoking history but no formal diagnosis of chronic obstructive pulmonary disease (COPD). A chest x-ray revealed a small left pleural effusion and left basilar atelectasis. Laboratory workup, including complete blood count, renal and hepatic panels, and troponin, was unremarkable. An electrocardiogram (ECG) revealed sinus tachycardia without signs of ischemia. CT was not repeated due to her negative CT angiogram one-week prior. Given radicular and left scapular pain, an MRI of the spine was done, which revealed no pathologic metastases in the thoracic or lumbar spine but did reveal a new sacral lesion. Given her progressive stridor, she underwent laryngoscopy, which revealed a normal upper airway. A bronchoscopy showed significant trachea-bronchomalacia and thick purulent secretions in the left upper lobe, lingula, and right upper lobe.
Two days after admission, repeat chest X-ray revealed near complete opacification of left lung and large pleural effusion, a remarkably different radiograph from admission (Figure ).
Subsequent CT chest revealed a large left pleural effusion with partial loculation as well as partial atelectasis of the left upper lobe and complete atelectasis of the left lower lobe. A right perihilar metastasis and perisplenic metastases were reported. The study was negative for pulmonary thromboembolism.
Thoracentesis revealed cloudy straw colored exudative effusion. A four French pigtail catheter was placed. Approximately 400 milliliters of yellow-green fluid was immediately drained. Pleural fluid studies revealed a white blood cell count of 33,000/μL (97% neutrophils), pH of 6.44, LDH of 4760 U/L, and an amylase of 394 U/L. She was started on vancomycin, cefepime, and metronidazole for presumed empyema. Pleural fluid cultures showed heavy growth of lactobacillus species, heavy growth of anaerobic gram negative cocci, and moderate growth of Candida krusei. Antimicrobial therapy was subsequently narrowed to ertapenem and anidulafungin. Given lack of improvement and continued significant chest tube output over the following week, further CT imaging was obtained, revealing a gastro-pleural fistula (via the left diaphragm and superior posterolateral stomach) with associated complex pleural effusion containing contrast material and gas (Figure ). This process abutted the known splenic metastases.
An esophagogastroduodenoscopy (EGD) revealed a 1.5-cm fistula in the posterolateral stomach that opened to the pleural space (Figure ).
Endoscopic suturing was attempted to close the fistula with limited success (partial closure noted on imaging, with methylene blue dye taken via mouth visualized in the chest tube drainage catheter on water seal; Figure ).
For complete closure, the authors attempted a novel approach utilizing a venting gastrostomy tube and chest tube to water seal to facilitate closure of the fistula over the ensuing six weeks. Enteral feeding via jejunostomy tube to aid closure of the fistula was employed. The patient was continued on ertapenem and anidulafungin. She was also initiated on a proton pump inhibitor. She was discharged to a rehabilitation facility with plans to repeat imaging and methylene blue swallow in six weeks.
Unfortunately, CT scans after six weeks showed that the fistula remained patent. A second attempt was made at endoscopic closure, which was again unsuccessful. One month later, during a hospitalization for electrolyte abnormalities, the patient decided to pursue elective surgical repair of the fistula in hopes of regaining the ability to resume normal oral intake. Four months after her initial presentation, she underwent laparoscopic surgery for fistula repair. The surgeon visualized extensive radiation fibrosis involving the stomach, spleen and retro-peritoneum. Given these findings and to avoid splenic bleeding, they pursued a conservative surgery whereby they stapled the stomach to ligate the gastro-pleural fistula anatomically. This approach is novel and was successful in our patient. A fluoroscopic upper GI series with oral contrast three days after surgery demonstrated no leakage of contrast outside of the GI tract or into the pleural space, and CT five days after surgery revealed no evidence of communication between the stomach and pleural space (Figure ).
She tolerated an oral diet. Gastrostomy tube, jejunostomy tube, and chest tube were removed without complication. |
pmc-6561525-1 | In August 2018, a 69-year-old Asian male presented to the emergency department for five days of subjective fever with chills and generalized weakness. Three days before presentation, he had been prescribed a course of amoxicillin-clavulanic acid for possible pneumonia. His past medical history was remarkable for right upper lobe lung cancer that is currently in remission after being treated with lobectomy in 2012 and adjuvant chemotherapy completed five years ago, hypertension controlled with daily atenolol 25 mg, hepatitis B carrier on daily tenofovir 300 mg, nephrolithiasis status post lithotripsy, chronic kidney disease, and benign prostatic hyperplasia. A recent outpatient chest X-ray showed postoperative changes of the right lung, pulmonary fibrosis, and borderline enlarged lower mediastinal lymph nodes adjacent to the distal esophagus (Figure ). His outpatient blood tests were significant for transaminitis and platelet count of 42 k/μL. The patient denied any recent travel history or tick bites but stated that he had a golfing trip in Westchester, New York until one day before feeling sick. His social history was only remarkable for drinking alcohol. He quitted smoking for two months and denied any illicit drug use.
In the emergency department, he was febrile (temperature of 39.7°C), tachycardic (77 - 122 bpm), tachypneic (15 - 26 breath per minutes) and hypotensive (85/39 mmHg - 118/69 mmHg). His blood pressure was responsive to 3 liters of the normal saline bolus. He was awake and oriented. His physical examination was unremarkable except for bilateral mild yellow tint conjunctiva. His blood tests showed anemia (Hgb 8.7 g/dL; Hct 26.4%), neutropenia (WBC 4.71 K/μL), thrombocytopenia (platelet 37 K/μL) and low haptoglobin (<10 mg/dL). Our patient received one dose of intravenous (IV) piperacillin-tazobactam for presumed sepsis.
Three blood cultures were collected and they later showed no bacterial growth. Urinalysis detected few bacteria, moderate blood, urine protein of 30 mg/dL and urine urobilinogen of 4.0. His liver function tests showed elevation in total bilirubin of 3.5 mg/dL with direct bilirubin of 1.6 mg/dL and indirect bilirubin of 1.9 mg/dL, and lactate dehydrogenase of 636 U/L. His serum chemistry results were remarkable for serum sodium of 131 mmol/L, serum carbon dioxide of 17 mmol/L, blood urea nitrogen of 29.0 mg/dL, and serum creatinine of 1.39 mg/dL. Immunological tests including C3, C4, myeloperoxidase Ab, protease 3 Ab, and ANA were not significant except that the C3 level was 55 mg/dL.
A blood smear showed slight anisocytosis, moderate poikilocytosis, moderate Burr cell, and few polychromasia, but no schistocytes. It also revealed 25% of atypical lymphocytes with some toxic granulation and possible parasites in RBCs (Figure ). Imaging studies were remarkable for mild splenomegaly (Figure ) and left renal cyst (Figure ).
Empirical treatment for parasitic infection to cover babesiosis and Lyme disease was started with Clindamycin 600 mg PO q8h, quinine 650 mg PO q8h, and doxycycline 100 mg PO BID as there was a strong concern for a parasitic infection as noted on the peripheral smear. Lyme IgG and IgM Western blot serology, Anaplasma Qualitative Real-time PCR and Babesia DNA Real-time PCR were performed to confirm the diagnosis and only the Babesia test came back as positive. Our patient responded well to the treatment regimen, and his hemoglobin and platelet count were 9.1 g/dL and 158 k/μL, respectively, at the time of hospital discharge. Oral Clindamycin, quinine, and doxycycline were continued to complete a 10-day course. |
pmc-6561526-1 | A 30-year-old female with a past medical history of gastric bypass and chronic pain syndrome presented to the emergency department with mental confusion and fever. Initial lab results showed thrombocytopenia with a platelet count of 80,000 and anemia with hemoglobin of 4.2 g/dl. A preliminary diagnosis of TTP was made, and the patient was admitted to the hospital for further management. Peripheral smear did not show any schistocytes. The patient subsequently developed worsening vivid visual hallucinations. Cefepime and vancomycin were empirically started for meningitis but the patient did not improve. Lumbar puncture was within normal limits. The patient’s condition worsened, and she became hypotensive with the development of DIC. Hypoxic respiratory failure ensued and the patient was intubated. Chest X-ray showed diffuse pulmonary opacities and MRI was positive for leptomeningeal enhancement consistent with meningitis or inflammatory changes (Figure ). Typhus serologies came back positive and doxycycline was initiated, which led to rapid and complete resolution of symptoms, and the patient recovered. |
pmc-6561527-1 | A 60-year-old morbidly obese, white female was admitted to the floor with one week of worsening shortness of breath, right upper quadrant (RUQ) pain, nausea, emesis, and a fever. General surgery was consulted after a large, fluctuant and erythematous mass was visualized on the RUQ abdominal wall. The patient noted a history of severe cholecystitis the year prior that was managed by a percutaneous cholecystostomy drain. After the drain was removed, she was lost to follow up. Initial laboratory evaluation revealed: leukocytosis with 91% neutrophils (white blood cell count 14,800, reference range 3500 - 10300 mm3), international normalized ratio of 2.51 (reference range 0.90-1.10), alkaline phosphatase of 162 (reference range 20-130 U/L); lactic acid, aspartate aminotransferase, and alanine aminotransferase were within normal limits. A computed tomography (CT) scan of the abdomen revealed a 14 cm x 5 cm abdominal wall fluid and air collection suspicious for an abscess in the RUQ as seen in Figures -.
Incision and drainage (I&D) of the abscess were performed with a cruciate incision over the indurated RUQ of the abdomen as seen in Figure . One hundred and fifty milliliters of the purulent material was irrigated via pulsed lavage with normal saline. Intraoperative wound cultures revealed Escherichia coli along with Bacteroides fragilis, which were treated with ertapenem. The patient continued to improve with daily packing changes until day seven post operation, when she was noted to have yellow-green discharge draining from the wound site and increasing tenderness with packing changes. Figure demonstrates the wound and discharge appearance. There was a concern that the fluid was bile rather than an infection due to the location and size of the initial abscess. A hepatobiliary iminodiacetic acid scan was performed but failed to demonstrate a biliary fistula tract. A second CT scan with oral contrast was ordered and after further review, it was noted that her gallbladder was severely contracted and located near the abscess site, which supported the idea of a CCF. This study was compared with a prior CT taken after percutaneous cholecystostomy tube placement in 2016. It was noted that the current abscess site was located near the drain placement site. Due to worsening drainage from the wound and the probable fistula formation, a robotic-assisted cholecystectomy with intraoperative cholangiogram was performed.
Once inside the abdomen, dense adhesions were visualized in the RUQ of the peritoneal cavity along with a laterally adhered, contracted gallbladder. Two hours of adhesiolysis was performed due to the numerous dense adhesions in the RUQ. An intraoperative cholangiogram confirms the suspected anatomy and demonstrated mild distension of the common bile duct. The gallbladder was removed and sent for histopathological examination. It was 6.7 cm x 3.0 cm x 2.2 cm in size with associated cholelithiasis and chronic inflammatory changes. Postoperatively the patient remained stable throughout her course and received daily packing changes, ertapenem, and eventual negative pressure wound therapy placement. The patient was discharged on day 5 post-operation with subsided drainage, early granulation tissue, and improving wound erythema as seen in Figure . The patient was sent home with negative pressure wound therapy, education material, and an emphasis on the physician follow-up. |
pmc-6561613-1 | We present the clinical case of a 29-year-old male patient treated at the Instituto Nacional de Cancerología of Colombia with a diagnosis of chronic myelogenous leukemia (CML) in high-risk chronic phase since February 2010. He started treatment with imatinib at a dose of 400 mg, obtaining a hematological response in the second month but not achieving a cytogenetic response in the 18th month. At that time, the patient continued treatment in another institution. It was possible to elucidate that the patient had a change of his treatment to dasatinib in March 2013 with the previous verification of the lack of cytogenetic response documenting a level of BCR-ABL transcription of 6.3%, period after which the patient, unfortunately, lasted eight months without treatment due to assurance problems. In September 2016, a BCR-ABL transcription level of 58% was documented, without a real knowledge about how much time he had taken dasatinib continuously at the moment of BCR/ABL evaluation; then, nilotinib treatment was begun.
The patient was readmitted to our institution in March 2017 and we diagnosed a progression to blast crisis of myeloid origin with a bone marrow study that documented 72% of blasts with karyotype without the growth of metaphases, being also very striking, the concomitant infiltrative cutaneous involvement, bone lesions of lytic type and hypercalcemia that required the use of zoledronic acid as an oncological emergency (Figure ).
At the end of the induction with 7 + 3 (seven days of cytarabine and three days of idarubicin) chemotherapy associated with bosutinib for 14 days and after several infectious complications, including invasive fungal infection and bacteremia due to Enterococcus faecium, as well as symptomatic hypocalcemia because of bisphosphonates, it was documented a percentage of blasts by flow cytometry of 29% in bone marrow and the existence of 46% of cells with basophilic versus mast cell characteristics on day 28 at the end of induction (Figures , ).
A basophilic transformation was suspected versus aggressive systemic mastocytosis with a clonal, non-mastocytic hematological disorder (Figures , ). Levels of serum tryptase and mutation D816V C KIT were requested, which were not reported. Treatment with CLAG-M (Cladribine, Cytarabine [Arabinosylcytosine-araC], granulocyte colony-stimulating factor [G-CSF], Mitoxantrone) was proposed, however, the patient died early in hyperleukocytosis and severe thrombocytopenia with central nervous system bleeding (Figure ). |
pmc-6562339-1 | A 64-years old male patient was diagnosed with stage IVB poorly differentiated NSCLC favoring adenocarcinoma of the right upper lobe with several bone lesions (cT4N2M1c). His medical history included a cerebrovascular accident and ischemic heart disease with subacute myocardial infarction in 2003. His chronic medication included acetylsalicylate acid 100 mg once daily (OD) and simvastatin 40 mg 0D, both since 2003. Regarding the tumor no driver mutation was identified by next-generation sequencing analysis. The Programmed Death Ligand-1 (PD-L1) expression level was assessed by immunohistochemistry using a monoclonal antibody to PD-L1 (clone 22C3, Dako) and a Benchmark Ultra (Roche) automated scope with subsequent evaluation by a certified pathologist, revealing 100% staining of a section including at least 100 evaluable tumor cells. Hence, pembrolizumab 200 mg every 3 weeks was started. Ten days after the first dose the patient was admitted to the hospital due to severe myalgia in both lower limbs with severe functional loss. Biochemistry showed creatine kinase (CK) of 1265 IU/L (upper limit of normal (ULN) = 190) and myoglobin of 2361 μg/L (ULN = 72) with normal renal function. Autoimmune serology showed a normal anti-nuclear factor (ANF) titer (1/80) without any characterization (especially for primary immune-mediated myositis with no anti-JO1, PL-7, PL-12, EJ, SRP, Mi-2, MDA-5, HMGCoA reductase) and anti-neutrophil cytoplasmic antibodies (ANCA) with a high titer of anti-PR3 (178 U/mL, ULN = 2); the infectious serology was negative. The statin was taken for several years prior to these symptoms and CK level before the start of the anti-PD-1 was normal. The electroneuromyography before corticoids showed proximal myopathy of moderate intensity without signs of necrosis. The quadriceps biopsy before corticotherapy was normal. He was treated with analgesics, intravenous fluids, and high-dose methylprednisolone (1 mg/kg/day) with favorable evolution. The diagnosis of immune-mediated myositis associated to granulomatosis with polyangiitis (GPA), former Wegener's disease, was established. The anti-PD-1 remained discontinued. Eight months after an initial partial response (PR) to pembrolizumab, progressive disease was noted and second-line doublet chemotherapy was started after antalgic irradiation of a metastatic pelvic mass. Subsequently, PR was noted. A year after the initial presentation of myositis the patient's condition worsened due to dyspnea and arthritis. Evaluation showed a new left-sided pleural effusion and a new lung consolidation. Based on a strong inflammatory syndrome (C-reactive protein (CRP) 116 mg/dL) and a neutrophilic exudate without evidence for empyema the patient was treated with amoxicilline-clavulanate for 14 days. In total, three pleural fluid cultures remained sterile. Due to persistence of the effusion and lack of clinical improvement a pleuroscopy was performed. The fluid appeared unclear and a few non-specific lesions were biopsied on the parietal pleura. They revealed a subacute pleuritis without tumor infiltration, granuloma or vasculitis. The arthritis was symmetrical and located in the wrists, metacarpophalangeal (MCP) joints and knees, without any evidence for infection or crystal-associated disease. A few days later, skin lesions appeared on the MCP and knees (). Biopsy there showed a neutrophilic vasculitis, as can be seen in cutaneous forms of GPA () (). The new lung consolidation was biopsied and showed only necrosis with no specific features of GPA-related lung involvement. Along with this clinical deterioration the autoimmune serology showed a rise in anti-PR3 titer (352.1 U/mL). The CRP dropped dramatically after initiation of corticoids (methylprednisolone at 1 mg/kg/day) along with clear clinical improvement. Recent clinical and radiological evaluation showed that the patient was in good overall condition with no signs of oncological progression despite discontinuation of the chemotherapy. We noted a progression-free survival (PFS) of 10 months after the second line chemotherapy and an overall survival (OS) of 18 months. |
pmc-6562483-1 | A 15-year-old female with no significant past medical history presented after being struck in the face by a ball while playing water polo. The patient felt pain in her jaw, which was the chief complaint when she presented to the emergency department. Upon neurological assessment, the patient complained of midline tenderness from the skull base to midline cervical spine over C3; denied headaches, changes in vision, speech or swallowing, extremity weakness or paresthesias. A maxillofacial computed tomography (CT) scan did not show evidence of an acute facial fracture. However, the CT scan did reveal a radiolucent, ovoid-shaped lytic lesion arising in the left lateral mass of C1, between the anterior tubercle and the transverse process. Magnetic resonance imaging (MRI) studies further confirmed an enhancing osseous lesion at the left lateral mass of C1, with cortical breach and extension into the left lateral atlantodental joint space (). Of note, three years prior, patient had a CT cervical spine which, upon retrospective review, demonstrated a similar but much smaller lesion.
Differential diagnoses underlying this vertebral cortical erosion included those of infectious etiology, as well as oncologic lesions, such as giant cell tumor of bone, aneurysmal bone cyst, osteoblastoma, osteosarcoma or even Langerhans histiocytosis (LCH). Oncology recommended that the cervical spine lesion be biopsied for tissue diagnosis. Due to the unusual location of the lesion and risk of locally aggressive pathology, or possible tumor seeding along the biopsy track, interventional radiology was unable to perform a CT guided needle biopsy. It was therefore decided that the patient would require open neurosurgical biopsy for diagnosis.
Due to the anterior and lateral location of the vertebral lesion, an anterior transoral approach to the C1 lesion was performed, in order to obtain a sufficient amount of the contrast enhancing component of the mass for pathologic diagnosis. The transoral approach was performed in a multidisciplinary fashion, during which the otolaryngology team used direct visualization, as well as stereotactic navigation, to expose the C1 anterior tubercle on the left side. Once exposure was completed, neurosurgery team utilized a matchstick burr to then drill the anterior outer cortex of C1. Multiple specimens from the fibrous tumor were taken, with curettes and pituitary forceps.
The sampled tissue did not show features of osteoblastoma or osteosarcoma, nor were there features of LCH or signs of infection. In the sampled region, the lesion consisted of a proliferation of nondescript stromal cells with intermixed multinucleated giant cells, and occasional clusters of foamy histiocytes (). Special testing for giant cell tumor of bone (G34W staining) was negative, as was fluorescence in situ hybridization (FISH) testing for Ubiquitin Specific Peptidase 6 (USP6), making a primary form of aneurysmal bone cyst unlikely. However, due to the aggressive nature of the patient’s osteolytic lesion and the significant risk for atlantoaxial instability associated with its location, it was decided to start the patient on Denosumab. Denosumab is an osteoclast inhibiting pharmaceutical agent, which was administered to the patient in order to stabilize and consolidate the lesion. Samples of the patient’s lesion were also sent out to a nationally recognized expert bone pathologist, whose findings were most consistent with benign giant cell rich lesion with histiocytes.
The patient was re-assessed three months postoperatively and MRI studies revealed that there was no interval decrease in the size of the tumor. In fact, there was a slight progression of the lesion anteriorly, despite treatment with Denosumab. After presenting the patient’s case at our institution’s multidisciplinary tumor board, it was decided to offer the patient a gross total resection of the offending lesion. This would inherently lead to significant atlantoaxial instability, therefore a posterior occiput to cervical three instrumented fusion was also warranted.
The transoral approach was performed in a multidisciplinary fashion, during which the otolaryngology team used direct visualization as well as stereotactic navigation, to expose the cervical vertebrae through the posterior pharynx. Fibrous tumor was identified and dissected until superior, inferior, and lateral margins of tumor resection were confirmed grossly, with fluoroscopy, and neuronavigation. Additional C1 anterior tubercle eccentric towards the right side was also taken, to include a normal bony margin. A small rim of tumor adherent to the vertebral artery was left behind. After the otolaryngology team closed the posterior pharynx, the patient was carefully turned prone, maintaining spinal precautions. Base of the occiput to cervical three was then exposed. C2 pedicle screws were placed. C3 lateral mass screws were placed. An occipital plate was sized. Screws into the occiput were placed. Fluoroscopy confirmed excellent position and spinal alignment. There were no post-operative complications and the patient was discharged home in good condition. Pathologic examination of the resected material at this time showed complete disappearance of the giant cells, due to Denosumab therapy, with the remaining lesional tissue resembling benign fibrous histiocytoma (). Post-operative imaging studies revealed a stable posterior cervical spine construct, along with minimal rim-enhancement along the vertebral artery, as expected (). At a three-week follow up visit in clinic, the patient’s incisions were healing well, she was neurologically intact, tolerating regular diet, and was eager to return to school. |
pmc-6562613-1 | The patient presented with hypovolemic shock due to the rupture of HB when he was 6 years old. The initial stage was Pretreatment Tumor Extent (PRETEXT) II (V0, P0, E0, F0, R1, C0, N0, M0) []. He underwent right hepatic artery embolization and chemotherapy consisting of cisplatin (80 mg/m2) and tetrahydropyranyl adriamycin (THP-ADR) (30 mg/m2) followed by right lobectomy based on the protocol described in Japanese Study Group for Pediatric Liver Tumor (JPLT)-1 []. The initial histological analysis revealed HB without features of hepatocellular carcinoma. Two adjuvant cycles of the same regimen were added postoperatively. However, as the HB recurred in the remnant of the liver a year later (at 7 years of age), the patient underwent partial resection followed by an additional 4 cycles of the same regimen.
Unfortunately, the tumor recurred in the remaining lobe of the liver, so partial resection was performed again when he was 8 years old. Postoperatively, 4 cycles of the C5V regimen (cisplatin (90 mg/m2), 5-fluorouracil (600 mg/m2) and vincristine (1.5 mg/m2)) were provided. At 9 years of age, magnetic resonance imaging (MRI) revealed the recurrence of HB in the liver, so the patient was referred to our center and underwent living donor liver transplantation (LDLTx) as a rescue treatment. Irinotecan (CPT-11) was selected as an adjuvant therapy after LDLTx. The details of his treatment course and AFP values are shown in . A histological analysis revealed wholly epithelial-type (fetal subtype) HB, intrahepatic metastasis(im)(+), s0, vp1, vv0, va0, b0 and sm(−). The postoperative course was uneventful, and the patient was discharged after a month.
His AFP remained within normal range for 45 months after the first LDLTx and then began to rise without any precedent events when he was 14 years old. MRI showed nodules in the transplanted liver, which prompted us to perform exploratory laparotomy. The pathological findings of metastatic lesion in the liver were HB, which consistent with the original histology at the time of the first LDLTx (A,B). Elastica van Gieson (EVG) stain of the specimen is also shown, indicating the HB surrounded by elastic fiber of portal veins (C). Intraoperatively, we found peritoneal nodules other than metastatic lesions in the liver that turned out to be metastatic HBs (D,E).
We then planned to perform ICG navigation surgery to achieve complete eradication of the disseminated HBs several days later. The study was approved by the institutional ethical review board of Keio University School of Medicine (approval No. 20160226). ICG (0.5 mg/kg) was given 72 h prior to the operation to minimize the background uptake by the normal hepatocytes. A Photodynamic Eye system® (PDE®; Hamamatsu Photonics, Hamamatsu, Japan) was used to visualize the lesions taking up ICG in near-infrared mode. While the exact locations of the disseminated HBs were not clearly identified in white-light mode (A,C), the corresponding view in near-infrared mode (B,D) showed well-demarcated nodules in the parietal peritoneum and mesocolon adjacent to the transplanted liver, all of which were successfully excised.
All specimens that were visualized by PDE® were histologically positive for HB tissues. Thereafter, meticulous examination of the entire abdominal cavity by PDE® was performed, which revealed no other metastatic lesions besides the aforementioned area in the right upper quadrant. However, the transplanted liver graft was infiltrated with diffuse metastatic HBs. After a two-month interval, another laparotomy utilizing ICG navigation (0.5 mg/kg of ICG was administered three days before laparotomy) was performed to explore whether or not there were any residual disseminated HBs. Although numerous uptakes of ICG in the transplanted liver were noted, we confirmed the complete absence of any extrahepatic lesions in the abdomen.
In a multidisciplinary conference, we discussed whether or not, provided the all detectable extrahepatic metastases were brought under control, re-transplantation is rational from an oncological perspective and is the only curative option. In Japan, since the number of deceased donor transplantations is limited (50–60 liver transplantations from deceased donors per year), a second LDLTx was considered. The patient and the family were well informed of the risk of recurrence even after a second LDLTx but remained willing to proceed. The institutional review board approved the second LDLTx.
Prior to the second LDLTx, CPT-11 (20 mg/m2) was administered to delay the growth of the tumor cells. The AFP value decreased from 439 ng/ml to 297 ng/ml after 2 cycles of CPT-11. The second LDLTx was performed when the patient was 14 years old, which was 62 months after the first LDLTx. Again, 0.5 mg/kg of ICG was administered intravenously three days prior to the second LDLTx. Fortunately, no extrahepatic tumor was observed at the time of the second LDLTx, although multiple instances of the uptake of ICG in the explanted liver were visualized by PDE® (A,B). Of note, the hepatectomy of the donor was delayed until it was confirmed that no new extahepatic metastases were seen by PDE®. The ICG-positive lesions in the liver were compatible with HBs pathologically. Postoperatively, an additional two cycles of CPT-11 were provided. The patient has been recurrence-free for 30 months since the second LDLTx, with the value of AFP being within the normal limit (). |
pmc-6562692-1 | A 13-year-old Italian female patient (Patient 1) was infected from the mother at birth. She has been in follow-up at our outpatient clinic from 2014. She was diagnosed to be infected by HCV in 2007, at the age of three years. For this reason, she was admitted to another hospital and was discharged with diagnosis of hepatic steatosis, obesity, and chronic hepatitis by HCV. At baseline, she presented an infection with HCV genotype 4. Interferon-based treatment has not been prescribed for toxicity constrains. From 2012 to 2017, a rapid progression of liver fibrosis at liver elastometry was observed (liver stiffness worsened from 4KPa in 2012 to 8KPa in 2017), so we decided to treat her with DAAs. |
pmc-6562692-2 | A 16-year-old Syrian female patient (Patient 2) who arrived in Italy in 2015. She was born from a positive HCV mother and received several blood transfusions for severe anemia. She came to observation in 2015. She was also affected by cerebral palsy, cryoglobulinemia, skin lesions at her hand and feet, and moderate fibrosis at transient elastography (10.1 KPa). Also for this patient, DAAs treatment was indicated. |
pmc-6563334-1 | A 79-year-old Caucasian male, with a past medical history of atrial fibrillation on warfarin and metoprolol, and coronary artery disease on atorvastatin with previous coronary artery bypass grafting and placement of a dual-function pacemaker/ implantable cardioverter defibrillator (ICD), was on a motor boat in a remote location. The patient’s boat went over a wake of a larger boat passing by. He bounced off his seat in a vertical direction and subsequently landed on his tailbone. After the high impact fall, he complained of both immediate lower back and diffuse abdominal pain but did not seek out urgent medical help.
Two days after the initial incident, he started to become pale and diaphoretic; additionally, his ICD delivered three shocks over a 30-min period. He presented via ambulance service to a local community hospital in hemorrhagic shock with a blood pressure of 63/22 and heart rate of 118 beats/min. A primary survey was pertinently positive for hemodynamic instability and diffuse abdominal and lower thoracic spine tenderness.
He was resuscitated with 1 L of normal saline leading to an improvement of his pressure to 106/88. Initial laboratory investigations included a hemoglobin of 95 g/L, lactate of 6.1 mmol/L, creatinine of 129, and a supratherapeutic INR of 8.8. An initial non-contrast CT abdomen and pelvis showed moderate hemoperitoneum with sentinel clot in the left upper quadrant and pericolic gutter, as well as the area adjacent to the posterior wall of the stomach. An additional finding of a severely comminuted, minimally displaced burst fracture of the T10 vertebral body was noted (). Further interventions included INR reversal with 3 mg of Vitamin K and 3000 units of prothrombin complex concentrate, and administration of 2 units of packed red blood cells and 2 L of normal saline. Based on clinical severity, the patient was transferred to the trauma service at a tertiary-care Level 1 trauma center.
Primary survey revealed a protected airway, spontaneous and bilateral air entry, and hemodynamic stability with a blood pressure of 100/60 and a heart rate of 88 beats/min. His abdomen continued to be mildly distended and tender without peritoneal signs, however the patient reported it had improved since his original presentation to the local hospital. Repeat laboratory investigations revealed a stable hemoglobin of 94 g/L, and correction of his INR to 1.2. Given his stable condition, he underwent a CT RIPIT (Rapid Imaging Protocol in Trauma) [] and CT angiogram (CTA) of the abdomen and pelvis. His imaging revealed pseudoaneurysms of the left gastric artery measuring up to 6 mm with another 9 mm rounded area of increased attenuation along the lesser curve of the stomach (, ). No extravasation was seen. Decision was made to monitor the patient closely with serial abdominal exams and repeat imaging in 72 h, or sooner if the patient exhibited any signs of deterioration.
Over the next 72 h, the patient’s vital signs and abdominal exams, improved and his hematological profile remained stable. Given the patient’s CHADS score of 2, it was decided to hold therapeutic anticoagulation until the patient’s bleeding risk decreased, however deep venous thrombosis prophylaxis was initiated. A repeat CTA was performed to follow the evolution of the two pseudoaneurysms. The imaging study revealed unchanged pseudoaneurysms but noted the distal aspect of the left gastric artery was attenuated in keeping with a focal dissection and intramural thrombus. Secondary to the dissection, the patient was started on 81 mg of aspirin daily. Over the next few days the patient continued to improve clinically, and was discharged home. The patient lived outside of the local area, and arrangements for close follow up were made. |
pmc-6563345-1 | A 69-year-old male patient, with a three months history of abdominal pain asthenia and macroscopic hematuria, was admitted to the outpatient clinic. Abdominal CT revealed an 8 cm left renal growth suggestive of neoplasia, with the involvement of the tail of the pancreas, tumor thrombus in the left renal vein and multiple left para-aortic adenopathies (). A biopsy was performed and showed to be inconclusive regarding the possibility of renal cell carcinoma. Radical left nephrectomy with distal pancreatectomy and splenectomy was proposed.
The procedure (Video 1 in Supplementary data) started with an extensive Cattel-Braasch Maneuver, allowing exposure of the inferior vena cava and the aorta, and thus isolation of the left renal vessels. The tail of the pancreas and spleen were freed, and a no-touch approach [] was adopted to minimize the spread of tumor cells with proximal splenic vein ligation. Caudal splenopancreatectomy was performed with section of the pancreas with a GIA 80 (vascular load), followed by proximal ligation and section of the splenic artery and what was thought to be the left renal artery (). The junction of the left renal vein with the vena cava was opened, and the tumor thrombus was resected, followed by caval suture. The renal vessels were, at this point, presumably controlled. The nephrectomy was continued with the release of the kidney and para-aortic lymphadenectomy, during which only the stump of the left renal vein could be identified, lacking the previously ligated renal artery stump. The renal artery was located inside the mass of lymph node tissue in the left para-aortic space, and the stump belonged to the superior mesenteric artery, ligated flush with the aorta. There was no arterial pulse in the mesentery confirming the injury. After removing the specimen, the distal stump of the superior mesenteric artery was exposed, and a repair with a terminoterminal anastomosis was performed from the proximal stump of the splenic artery (). The viability of the gut was assessed by palpation of an arterial pulse in the superior mesenteric artery.
The postoperative period went uneventfully. Histological examination showed a renal sarcomatoid carcinoma pT4N1M0G3. Control imaging at three months showed permeability of the celiac trunk and the superior mesenteric artery (). |
pmc-6563357-1 | A 38-year-old Caucasian man presented to the emergency department of our hospital with a 3-week history of dysarthria and facial weakness on the left side. A few weeks before symptom onset, he had undergone surgery for carpal tunnel syndrome on the right side. Apart from increasing fatigue and continuous weight gain of almost 20 kg over the last 2 years, his medical and family history was unremarkable. His clinical examination revealed a mild lower motor neuron facial palsy on the left, uvular deviation to the left with preserved gag reflex, tongue deviation to the left, lingual dysarthria, and xerosis. His pupils and eye movements were normal, his power and sensation for all qualities including vibration sense were preserved, his reflexes were present symmetrically, and he had no ataxia. Facial fullness and edematous extremities were noted. His mucous membranes were unremarkable, but his skin was dry. His vital parameters were normal apart from an increased body mass index (31.6 kg/m2) and hypothermic tympanic temperature of 35.6 °C (blood pressure 127/79 mmHg, heart rate 70 beats/min).
His blood test results on admission showed elevated serum creatinine of 151 μmol/L (glomerular filtration rate 47 ml/min/1.7 CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration equation]) and increased creatinine phosphokinase (CK) activity (1243 U/L). Results of brain magnetic resonance imaging (MRI) and renal ultrasound were unremarkable. Cerebrospinal fluid (CSF) analysis revealed a normal cell count but increased protein levels of 758 mg/L and a CSF/serum albumin ratio of 10.5 × 10− 3/L (reference range < 6.7) without signs of intrathecal immunoglobulin production or oligoclonal bands. Results of serological testing were unremarkable. MRI of the brain did not show any pathologic lesions or contrast enhancement, especially within the cranial nerves. Multiple cranial neuropathy was presumed, and the patient was admitted to the department of neurology.
On the following day, routinely performed thyroid function tests detected markedly elevated levels of thyroid-stimulating hormone (TSH) (292.2 mIU/L), low free thyroxine levels (1.1 pmol/L), and free triiodothyronine levels below the limit of detection (< 0.4 pmol/L). A diagnosis of overt hypothyroidism was made, and levothyroxine therapy in a dose of 100 μg/d (1.0 μg/kg body weight, 1.3 μg per ideal body weight) was started after hypocortisolism was excluded. Ultrasound revealed a small thyroid gland (4.8 ml) with an inhomogeneous pattern but without signs of focal lesions. Further diagnostic workup showed a markedly reduced basal metabolic rate on indirect calorimetry (1380 kcal/d, reference 1950 kcal/d) and elevated antibodies against thyroid peroxidase (495 IU/mL, reference range < 34 IU/mL). When the patient was discharged 1 week after admission, his symptoms were unimproved. Six weeks later, the patient was seen in our outpatient clinic and reported a substantial improvement of speech quality and general well-being. On clinical examination, no residual pathologic signs were observed. The patient’s levothyroxine dosage was eventually increased to 150 μg/d, and his levels of TSH and free T4 normalized (Table ). At the following visit, 5 months after initiation of levothyroxine substitution, the patient’s facial features had changed substantially, and all his neurologic symptoms had completely resolved. A loss of 2 kg body weight was noted. The remainder of his physical examination was unremarkable. Laboratory analysis showed normal levels of thyroid hormones and TSH as well as normal creatinine phosphokinase and kidney parameters. Increased total and low-density cholesterol levels at initial presentation also had normalized at the 5-month follow-up visit. |
pmc-6563362-1 | A 50-year-old woman presenting with subacute onset of memory loss and behavioral changes lasting for one month was admitted to our hospital on July 9, 2018. On examination, she was confused and apathetic, disoriented to time and space with impaired memory and executive dysfunction, slurred speech with partly comprehensive aphasia, and urinary and fecal incontinence when she was admitted to our hospital. She was poorly collaborative in Mini-Mental State Examination (MMSE). No localized symptoms or signs were observed.
Two years ago, this patient presented at age 48 with right ptosis. She was diagnosed with MG based on positive AChR Ab (titre > 20 nmol/L) and a neostigmine test, as well as a decrement of 15% in low frequency (3 Hz) repetitive nerve stimulation on orbicularis oculi muscles, trapeziuses and deltoid muscles. A computerized tomography (CT) chest showed a thymoma (3.1 cm × 1.9 cm), which was resected on August 22, 2016 (Fig. a). Histological examination showed WHO type B2: Kpan(+++), CK19(+++), CD30(+++), CD20(−), CD3(−), CD5(+), TdT(+), and Ki67(+, 90%). Whole-body bone scans by emission computed tomography were normal. Space-occupying lesions were not found in the liver, kidneys or subclavian area investigated with B-ultrasound. For the next two years, the patient’s symptoms were well-controlled with pyridostigmine treatment.
Routine serum analyses were within the normal range, including thyroid hormones and associated antibodies, anti-nuclear antibody, and anti-dsDNA. Polymerase chain reaction (PCR) for herpes simplex virus, cytomegalovirus, influenza virus, enterovirus, and measles virus in serum were also negative. Cell count, protein, glucose and chloride were normal in the cerebrospinal fluid (CSF). CSF and serum were negative for oligoclonal bands. Antibodies against cell surface or synaptic proteins were assessed in serum and CSF obtained before immunotherapy using transfected HEK-293 cells by the indirect immunofluorescence method (Kindstar Global, Wu Han, China) showed high levels of serum (1:1000) and CSF (1:32) antibodies against the AMPAR GluR2 (AMPAR2, Fig. b and d). A wide range of abnormalities in 6–8 Hz low to middle slow waves was found by electroencephalographs (EEGs). Brain magnetic resonance images (MRI) identified high-intensity signals on fluid-attenuated inversion recovery (Flair) in both the medial temporal lobe and hippocampus on June 25, 2018 (Fig. ). Antibodies against α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) GluR1, N-methyl-D-aspartate receptor, GABA B type receptor, leucine-rich glioma inactivated protein 1 (LGI1) and Caspr2 were negative. The chest CT was normal without thymoma recurrence after thymectomy on July 11, 2018 (Fig. b). Ultrasounds of the liver, pancreas, spleen, kidney, bladder, ovary and uterus, as well as serological tumor markers, were also normal and did not reveal a neoplasm. Anti-AMPAR2 encephalitis was thus diagnosed. Intravenous methylprednisolone (1 g/day for 3 days and 500 mg/day for 3 days) followed by oral prednisolone (1 mg/kg/day) was administered with slow tapering. The patient’s symptoms did not have significant remission, and azathioprine (50 mg twice a day) was applied when she was discharged on July 20, 2018. A neuropsychological exam showed memory deficit, calculative and comprehensive dysfunction, lack of motivation and social emotion and urinary incontinence.
The patient had voluntary urinary control, and the initial MRI lesions resolved in 16 days (July 11, 2018). The patient only had mild long-time memory deficits and a good recovery with an MMSE score of 24 at follow-up on September 13, 2018. |
pmc-6563401-1 | An 86-year-old male with no significant past medical history was admitted to the hospital with a history of prolonged high fever unto 104°F. Workup for infection was unremarkable. He did not have leukocytosis, white blood cell count was 5.2/mm3, and chest X-ray, computed tomography (CT) scan of abdomen, and transthoracic echocardiogram were unremarkable. Blood culture and urine culture showed no growth, and flu screen was negative. Since the patient had elevated D-dimer, Doppler ultrasound was ordered with the suspicion of thrombus, which could explain the fever but it showed no evidence of deep vein thrombosis. His ferritin level was elevated at 725 ng/mL (reference range: 26-388 ng/mL), hemoglobin 12.0 g/dL, erythrocyte sedimentation rate (ESR) was 66 mm/h (ref: <20 mm/h), and C-reactive protein (CRP) 55.9 mg/L (ref: <8 mg/L). He was found to have a positive ANA speckled pattern 250, but additional laboratory findings including ANA specificity, rheumatoid factor, and ANCA were found to be negative. During the hospital course, he started having episodes of confusion and there was suspicion of meningoencephalitis. Physical examination was not indicative for meningitis with negative meningeal signs, and lumbar puncture was done, which was unremarkable for viral and bacterial pathogens. Rapid plasma reagin, hepatitis panel, QuantiFERON, mono spot, HIV test, and paraneoplastic panel tests were negative.
Malignancy was ruled out with normal CT scan of chest, abdomen, and pelvis and magnetic resonance imaging of brain. Bone marrow biopsy showed changes suspicious for myelodysplastic syndrome with single lineage dysplasia (refractory anemia), but he did not have neutropenia or leucopenia. There was low suspicion of GCA initially as he denied typical symptoms of GCA such as headache, jaw pain/claudication, stiffness in the shoulder joints, or visual disturbances. With no explanation for the findings of fever, he was started on prednisone 60 mg for presumed GCA after which his condition markedly improved and fever was resolved. He had temporal artery biopsy of both sides, of which biopsy of the right side showed mild to moderate intimal hyperplasia, partial disruption of internal elastic lamina with fibrosis, and minimal lymphocytic and histolytic infiltrates, which was consistent with GCA (). |
pmc-6563654-1 | The female infant was born to healthy non-consanguineous parents (25-year-old father, and 22-year-old mother) after an uncomplicated first pregnancy and 40 weeks of gestation. A Cesarean section was performed due to a failed vaginal delivery, but the Apgar score until 15 min after birth and birth weight was normal (3,300 g). The patient was intubated after developing progressive tachypnea, moaning, and severe hypoglycemia (0.9 mmol/L). The patient developed hyperbilirubinemia that was unresponsive to phototherapy, but the parents took the baby home, for home care at the age of 9 days.
At the age of 1.4 months, the patient was admitted to a provincial hospital for jaundice, vomiting, afebrile seizures, and pneumonia. The lowest blood glucose level during the hospital stay was 1.4 mmol/L. The serum cortisol levels were extremely low (13.8–29.3 nmol/L, normal range 138–690 nmol/L) while adrenocorticotropic hormone levels were slightly lower or normal (6.0–18.5 pg/ml, normal range 6.4–40 pg/ml). A cortisol deficiency was diagnosed, but parents refused hormone replacement therapy. The patient was discharged after the pneumonia was resolved and blood glucose levels were stabilized.
At the age of 3.2 months, the patient was presented to our hospital for cholestasis without obvious symptoms of hypoglycemia, infection, alacrima, or achalasia. Repeated morning serum cortisol levels were extremely low (8.8–10.6 nmol/L, normal range 138–690 nmol/L), while ACTH was extremely elevated (1656.9–1911.8 pg/ml, normal range 6.4–40 pg/ml). Upon physical examination, significant jaundice, skin hyperpigmentation and slight hepatosplenomegaly (liver 2–2.5 cm below the right costal margin, and 2.5 cm below the xiphoid process; spleen 1.5–2.0 cm below the left costal margin) were observed. Slight dysmorphic features such as a transverse palmar crease in the right hand, a prominent forehead, hypertelorism (inner canthal distance greater than the palpebral fissure length) were noted. The palmar crease, and the changes in skin pigmentation are presented in . Written informed consent was obtained from the parents for the publication of this case report and related images. Changes in body weight/length, complete blood count, procalcitonin, serum biochemistry, blood coagulation, and endocrine profiles throughout the disease course are provided in .
Genetic screening for abnormalities related to congenital adrenal hyperplasia (list of 44 genes are provided in ), and multiplex ligation-dependent probe amplification (MLPA) analysis of the CYP21A2 gene were performed by a commercial genetic testing company (Customized target capture sequencing, ). The result showed compound heterozygous variants in the melanocortin 2 receptor (MC2R) gene, but the result of the CYP21A2 gene MLPA analysis was negative for hot-spot mutations and copy number variants (). We conducted protein modeling with SWISS-model () using the most similar structure (5jtb.1.A, Adenosine receptor A2a), and polar contacts of wild-type and mutated amino acid residues were compared with Pymol software (). The c.433C>T/p.R145C was reported in the dbSNP152 (), and gnomAD (), but not in the 1000 Genome Database () and Exome Variant Server (). The c.712C>T/p.H238Y variant was not reported in the dbSNP152, gnomAD, 1000 Genome Database, and Exome Variant Server. The c.433C>T/p.R145C variant of maternal origin caused the change of arginine (polar, basic) at the amino acid position of 145 to cysteine (non-polar, neutral). R145 is a relatively conserved amino acid residue, and five out of eight in-silico prediction tools () predicted this variant as pathogenic. This is a known disease-causing variant (HGMD CM116421, rs139218324), and reported to be associated with FGD1 in an adopted Chinese girl (). Protein modeling showed no effect of R145C residue change on polar contact with V149. The c.712C>T/p.H238Y variant of paternal origin caused the change of amino acid residue histidine (polar, basic) at the position of 238 to tyrosine (polar, neutral). H238 is a strictly conserved residue, and all eight in-silico prediction tools predicted this variant as pathogenic (). Protein modeling showed that the H238Y mutation changed polar contact of the amino acid residue in the position of 238 with adjacent residues, and polar contact with N261 in the transmembrane domain (TMD) 7 was lost. Confirmation with Sanger sequencing, conservation status of amino acid residue that have been affected, protein modeling results, and in-silico pathogenicity prediction results for both MC2R variants are provided in and .
Extensive etiologic evaluations from birth until the last follow-up (4.9 months) are provided in . After ruling out other causes of hypoglycemia, cholestasis, and adrenal deficiency, a diagnosis of FGD1 was made. Oral hydrocortisone was started at a dose of 30 mg/m2 body surface area (divided into three doses) at the age of 3.4 months. Cholestasis was resolved at 4.9 months, skin hyperpigmentation was improved, and no further episodes of hypoglycemia occurred. Morning serum cortisol levels 1 h after hydrocortisone intake was normal, while ACTH levels returned to near normal levels. However, parents decided to stop the medication at the age of 7.4-months, and serum cortisol/ACTH levels returned to extreme levels at the age of 8.1-months (). |
pmc-6563758-1 | A 4-year-old girl (weight, 18 kg) with no medical history presented with 3 days of fever, 2 days of rash, and conjunctivitis. Physical examination revealed bilateral cervical lymphadenopathy and swelling of limb extremities. Chest and cardiac examination results were unremarkable. Laboratory test showed that the white blood cell (WBC) count was 12.50 × 109/L, neutrophils ratio (NE%) was 70.8%, platelet count (PLT) was 121 × 109/L, and C-reactive protein (CRP) was 127 mg/L. Erythrocyte sedimentation rate (ESR) was 90 mm. Serum albumin (ALB) and sodium were 38.17 g/L and 129 mmol/L, respectively. Troponin I was 0.07. Brain natriuretic peptide (BNP) was 147.03 pg/ml. Echocardiography on day 1 was normal (shortening fraction: 35%; ejection fraction: 66%). Diameters of the left and right coronary arteries were 0.24 and 0.20 cm (Z score, 2.0). Hence, she was suspected of having KD, and on day 2 of admission, before we could treat her with IVIG, she showed signs of shock, including increase in heart speed, cool extremities, oliguria, tachypnea, and hypotension (70/33 mmHg) requiring mechanical ventilation. She was immediately transferred to the intensive care unit. Electrocardiography (ECG) showed sinus tachycardia with alternation of T wave on leads II, III, and avF (). Chest X-ray showed bilateral lung field exudation and cardiomegaly. Arterial blood gas showed a lactate of 4.9 mmol/L. The urine output of the patient was < 0.5 ml/kg/h. She urgently received continuous renal replacement therapy (CRRT) in CVVHDF mode and therapy for septic shock. Echocardiography showed a depression of systolic function (EF 35%) with dilation of left ventricular end diastolic dimension (LVDd 3.7 cm) and severe tricuspid valve regurgitation (TR; ). Cardiac index (CI) was 1.7 L/min/m2. Despite 0.6 μg/kg/min of both epinephrine and norepinephrine, her blood pressure couldn't be maintained (range, 57–69/31–40 mmHg). BNP was >15,000.00 pg/ml, and troponin I was 0.55. Laboratory findings and clinical features concluded the diagnosis of cardiogenic shock resulting from KDSS. Four hours later, she was placed onto central VA ECMO via neck cannulation.
A 15-Fr cannula (Medtronic or Edward's Lifesciences, Irvine, CA, USA) was placed in the right atrium and a 12-Fr cannula (Medtronic or Edward's Lifesciences, Irvine, CA, USA) was placed in the right common carotid aorta (). The fraction of inspiration O2 (FiO2) was 1.0, blood flow was 0.8 L/min, and gas sweep flow was 1.0 L/min. Treatment with 2 days of IVIG (1 g/kg per day) and 5 days of intravenous methylprednisolone (2 mg/kg per day) were initiated right away. A mean blood pressure level of 50–60 mmHg was maintained by the initial flows of ECMO, and the serum lactate was normalized within 8 h. After 2 days of IVIG, her body temperature still fluctuated, and she was considered to be IVIG-resistant; she received plasma exchange (PE) for 6 h to reduce the inflammatory and immune reaction. Aspirin was maintained for 3 days at a dose of 30 mg/kg, and then at a dose of 5 mg/kg since. Fever settled on day 6.
The cardiac function of the patient recovered promptly on ECMO, and blood flow was reduced to 0.18 L/min and gas sweep flow was 0.3 L/min after 76 h, which meets the standard of separation of ECMO. showed the X-ray post-ECMO. The patient's vital signs tended to be stable during ECMO, with proper blood pressure, adequate urine output, and resolution of heart failure (EF 46% at day 2 ECMO and EF 54% at day 3 ECMO). Bilateral blood culture detected no infections spreading through the bloodstream. shows laboratory findings pre- and post-ECMO. On day 9, the mechanical ventilation was separated and she was discharged on day 22. Follow-up within 3 months demonstrated that the cardiac and vascular functions were in the normal range (EF 65%, coronary arteries; Z score, 2.0). |
pmc-6563780-1 | Case 1: A 25-year-old male with Duchenne muscular dystrophy and baseline respiratory function as per Table , using nocturnal NIV and mouthpiece intermittent positive pressure ventilation (MIPPV) presented to the emergency department with right-sided chest pain and dyspnoea. The evening prior to onset of symptoms, he reported using MIPPV for 10 h. He then completed five cycles of MI-E (pressures +50 cm of water (cmH2O) for insufflation, −47 cmH2O for exsufflation) to clear excess saliva. He went to bed on NIV via total face mask (settings per Table ) and upon waking four hours later, noticed sharp right-sided chest pain. The patient completed another five cycles of MI-E; however, this worsened his symptoms, prompting emergency department presentation.
On presentation, the patient was tachypnoeic with a respiratory rate of 36 breaths/min. All other vital signs, including pulse oximetry were within normal limits. Initial arterial blood gases were unremarkable. Chest radiograph performed in the emergency department revealed a large right-sided pneumothorax (Fig. ) and a pigtail intercostal catheter (ICC) was inserted and placed on −10 cmH2O suction. Repeat chest radiograph two hours later demonstrated poor re-expansion of the right lung. The suction was increased to −20 cmH2O, resulting in good re-expansion on subsequent imaging. The patient used NIV on usual settings continuously throughout this period. The ICC was removed on the third day of admission and the patient was discharged on day five with advice to cease all MI-E until clinical review in two weeks.
The MI-E pressures were decreased to +25 cmH2O insufflation and −40 cmH2O exsufflation by a physiotherapist at this review, with instructions to use sparingly for cough augmentation or saliva clearance only. Pharmacological modalities of saliva management were recommended; however, the patient had no success with these previously.
Unfortunately, this patient represented on three occasions (total of four presentations) with right-sided pneumothorax in the following six months. Bedside chemical pleurodesis was conducted on two occasions (iodine and alcohol/iodine, respectively), both failing to prevent recurrence. The patient was discharged home with a long-term pleural catheter after the fourth admission, which was removed two months later. The patient continues to use MI-E sparingly and has had no subsequent recurrence. |
pmc-6563780-2 | Case 2: A 71-year-old male with motor neurone disease presented with a 36-h history of worsening dyspnoea that began immediately after LVR therapy. This patient did not use LVR routinely, instead using as required for cough augmentation. He noted a sharp, sudden onset of central chest pain following LVR, but attributed this to musculoskeletal stretching of his thoracic cage. He described mild “shallow breathing” that worsened over the next two nights (despite using nocturnal NIV with usual settings; Table ) and subsequently presented to the emergency department. Chest radiograph revealed a large right-sided pneumothorax; the apex of the right lung projected over the inferior margin of the sixth rib, with no mediastinal displacement. An ICC was inserted, with resolution of the pneumothorax and removal of the ICC occurring on the fourth day of admission. There was no recurrence with resumption of use of NIV. He was discharged with advice to cease LVR. |
pmc-6565551-1 | The index patient was a 34-year old female referred to the bariatric clinic by the general practitioner on her own request to treat her morbid obesity. She was born with a normal birth weight but large head circumference for which she never had a diagnostic analysis. At the age of five, her body weight was already significantly higher compared to her peers. No specific life events could explain her obesity. Cognitive development was normal and she followed normal education. She underwent treatment for recurrent nasal polyps. Her mother also had a large head size and suffered from morbid obesity as well. She was diagnosed with thyroid cancer and died from a pulmonary embolism after placement of an Adjustable Gastric Band. A maternal aunt was diagnosed with breast cancer before the age of 50 and the maternal grandmother died from breast cancer at young age. The younger sister of the index patient was overweight and was reported to also have a large head size (Figure ).
Since childhood, the index patient followed several different coaching programs to change her eating behavior and exercise pattern to induce weight loss. She lost weight several times but was never able to maintain her weight loss. At the time of the intake procedure at the bariatric clinic, her height was 1.69 m (SD −0.2) and weight 164 kg (SD +6.8), resulting in a Body Mass Index (BMI) of 57.6 kg/m2 and a predominant abdominal obesity. Head size was not measured at that time since this is not part of bariatric screening procedures. Biochemical analysis of the blood revealed no abnormalities, and excluded endocrine hormonal disorders such as hypothyroidism. The fasting glucose level was 5.9 mM.
The combination of early onset morbid obesity resulted in suspicion of a genetic cause of her obesity. She was offered diagnostic genetic analysis of 52 obesity–associated genes to identify a possible underlying genetic obesity cause.
The patient was eligible for bariatric surgery and underwent a sleeve gastrectomy without complications (performed in 2014 using a standardized fashion). At 1, 2 and 3 years after surgery, she achieved a percentage Total Body Weight Loss of 39.4, 48.8 and 44.9, respectively. This resulted in a current BMI of 30.1 kg/m2. This was within the range of the results which were observed in a control group of 18 female patients, with a negative obesity genetic test result. These female patients were matched for age and BMI and achieved a percentage Total Body Weight Loss (TBWL) of 30.3 after 1 year, 31 after 2 years and 30 after 3 years of follow-up.
A few months after surgery, the result of the obesity gene panel analysis was returned and showed heterozygosity for a known pathogenic mutation in the PTEN gene (): c.202T>C p.(Tyr68His). This mutation has been described previously in patients with PTEN Hamartoma Tumor Syndrome (PTEN HTS) (Marsh et al., ). No other pathogenic mutations were shown in the remaining 50 obesity–associated genes (Table ). At the genetic clinic, a head circumference of 63 cm (+5SD) and pedigree analysis (family history of multiple tumors) further supported the molecular diagnosis of PTEN HTS.
According to the PTEN HTS guidelines, patients with pathogenic PTEN mutations are advised to visit the outpatient clinic for familial tumors, for lifelong surveillance of tumors that are associated with the PTEN mutations (Dutch Guidelines, ; Eng, ). Our patient underwent additional biochemical laboratory- and ultrasound screening to exclude thyroid gland carcinoma. Besides a few benign nodules on the ultrasound, no abnormalities could be determined. A yearly follow-up ultrasound of her thyroid gland and yearly serum thyroid stimulating hormone analysis was advised. Screening for breast, endometrium and colorectal cancer, also revealed no anomalies. |
pmc-6565561-1 | A 12-year-old boy (Ⅱ1) (Figure a) presented with multiple lesions on the face, neck, elbows, wrists, limbs, knees, inguinal region, hands, and feet for 12 years. At one month of age, he developed symmetrical erythematous on the hands and feet, and progressive thickening of the palms and soles. By age 8 years, hyperkeratotic plaques appeared, affecting the face, neck, elbows, wrists, limbs, knees, inguinal region, hands, and feet. Lesions tend to became worse in summer and to improve in winter. Hair and teeth were not affected. Cutaneous examination showed fixed, finely scaly, symmetrical erythematous keratotic erythema, plaques on the face (Figure b), neck, elbows, wrists, limbs, knees (Figure c), inguinal region (Figure d), hands, and feet. The plaques were thicker on the elbows and there was a well-defined, brownish-colored hyperpigmentation halo on the inguinal region. His parents were not consanguineous. His parents and brother did not show any erythrokeratodermia variabilis related abnormality. |
pmc-6565561-2 | A 7-year-old girl (Ⅱ1) (Figure e) presented with multiple lesions on the hands, feet, wrists, and ankles for 6 years. She had erythematous on the hands and feet at the age of 10 months. She then developed symmetrical erythematous on the hands and feet, as well as progressive keratotic erythema, plaques on the dorsal hands, dorsal feet, wrists, and ankles. Lesions tend to become worse in summer and to improve in winter. Hair and teeth are not affected. Her parents were not consanguineous. Cutaneous examination showed fixed, finely, symmetrical erythematous, plaques on the hands (Figure f,g), feet (Figure h), wrists, and ankles. Her parents did not show any similar abnormality. |
pmc-6565817-1 | A 69-year-old male patient was admitted to our department with a diagnosis of three aortic aneurysms. His history included severe chronic obstructive pulmonary disease and hypertension. The aneurysms consisted of aortic arch saccular aneurysm with a protruding diameter of 25 mm, descending aortic aneurysm with a protruding diameter of 18 mm, and abdominal aortic aneurysm with a diameter of 36 mm. Of these, saccular aneurysm of the aortic arch required prompt treatment. We performed TEVAR using Najuta (Kawasumi, Tokyo, Japan) for this specific aneurysm and the operation was successful. After the operation, the patient complained of mild abdominal pain but on examination, there was no abdominal tenderness and the blood test showed no acidosis or abnormality. On the fourth post-operative day, patient suddenly complained of strong abdominal pain. Enhanced CT showed SMA embolism about 52 mm in length from the ileocolic artery bifurcation. As the distal side of the stent graft was placed to stick the thrombus of the aorta, it was thought that the embolus may have been liberated from this point (Fig. ). We diagnosed SMA embolism and emergently performed revascularization with intervention radiology (IVR).
The operation initiated with the patient in the supine position. A 6-French (Fr) guiding sheath was inserted into the right femoral artery. Subsequently, a 4-Fr shepherd hook catheter was placed in the SMA, and then the 0.035-inch guidewire was left in the SMA, and the shepherd hook catheter was changed to a 4-Fr straight catheter. Using this catheter as a foundation, the guiding sheath was placed into the SMA. The contrast injection as well as the CT image showed that the SMA was occluded from the ileocolic artery bifurcation. However, the 0.014-inch guidewire and 4-Fr catheter easily passed the occlusion lesion. Following them, the guiding sheath was placed close to the central side of the occlusion lesion. While moving the catheter, negative pressure was applied from the sheath to perform thrombus aspiration. This procedure was repeated several times, and small white materials and red thrombus were detected in the aspirated blood. After several aspiration, although some thrombus reduction was observed and the flow of the jejunal branch improved, thrombus still remained much and migrated to the central side. Judging that there was a limit to aspiration alone, we placed a 4 mm × 40 mm RIVAL (Bard, Covington, USA) into the occlusion area and PTA was carried out by inflating a balloon slowly. After PTA, the patient’s abdominal pain improved, and the thrombus grew smaller but remained. We injected urokinase solution (60 000 unit) into the artery, leaving the sheath and finishing the operation at once. Next day, further reduction of the thrombus was seen by contrast injection and additional PTA was performed using 4 mm × 40 mm Angiosculpt (PHILIPS, Amsterdam, Netherlands). After PTA, successful revascularization was achieved in almost all branches (Fig. ). At this point, surgery was completed.
Patient resumed oral feeding on the first day after operation, and TEVAR using Zenith alpha (Cook, Bloomington, USA) for descending aortic aneurysm was performed on the 28th day. The patient was discharged by Day 59 post-surgery with no complication, and there was no recurrence of abdominal symptoms or findings suggestive of intestinal ischemia throughout the course. The white material collected intraoperatively was found to be cholesterol crystals as a result of the pathological test (Fig. ). |
pmc-6566138-1 | A 60-year-old woman had noted obstinate constipation. One month later, she developed weakness in the lower limbs and bilateral paresthesia below the chest. One month later, she was admitted to our hospital because of a girdle sensation in the right region of the abdomen and progressive severe weakness in the lower limbs. She showed sensory impairment of all modalities below Th6 dermatomes on the right and below Th8 dermatomes on the left. Deep tendon reflexes were absent in the right upper and lower limbs. Bilateral Babinski reflexes were observed, and cranial nerve examination identified no abnormalities. There was no bladder dysfunction.
Serum anti-aquaporin 4, anti-myelin oligodendrocyte glycoprotein, anti-glycolipid (GM1, GM2, GM3, GD1a, GD1b, GD3, GT1b, GQ1b, galactocerebroside), and anti-neurofascin155 antibodies were all negative. Serum anti-lactosylceramide antibody (IgG) was positive, while serum anti-glucoceramide antibody and cerebrospinal fluid (CSF) anti-lactosylceramide antibody (IgG) were equivocal. CSF analysis revealed pleocytosis (35 cells/μL, 100% mononuclear) and an elevation of total protein (83 mg/dL). Myelin basic protein level was high (818 pg/mL) and the IgG index was upregulated (1.54). OCB were positive. Gadolinium-enhanced magnetic resonance imaging (MRI) demonstrated multiple foci of abnormal signal intensities in the medulla and spinal cord (). Neither ovoid lesions nor Dawson's fingers were observed.
A nerve conduction study (NCS) revealed reduced compound muscle action potential (CMAP) amplitudes in the bilateral peroneal nerves (right and left: 0.8 and 0.9 mV, respectively). Conduction block was observed in the right tibial nerve (distal and proximal CMAPs: 10.7 and 1.9 mV, respectively; ). Distal motor latency (DML) was prolonged in the right peroneal nerve (6.0 ms). A sensory nerve action potential was not evoked in the left sural nerve. In addition, the F wave was absent in the bilateral peroneal nerves (). The peripheral nerve involvement was asymmetric and resembled multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, which is a subtype of chronic inflammatory demyelinating polyradiculoneuropathy. Short-latency somatosensory evoked potentials (SSEPs) and visual evoked potentials were normal (, ).
Upon treatment with methylprednisolone pulse therapy (1,000 mg/day for 3 days, two times), RCF was observed in NCS (, ); however, the patient's muscle strength in the right upper limb was weakened on day 8 post-admission. Post-contrast-enhanced spinal MRI demonstrated abnormal enhanced lesions at the C3 to C4 level (). SSEPs revealed that the right central conduction time (N19–P35) was normal, but prolonged from 20.4 (in the first SSEP) to 23.9 ms (normal values: < 28.3 ms), and right N13 and N20 negative peaks were not observed (, ). Selective plasma exchange (1.25 plasma volume exchange with 5% albumin replacement fluid; selective plasma exchange procedures were performed twice a week for 2 weeks) and additional methylprednisolone pulse therapy only improved muscle strength in the right upper limb.
After the first total plasma exchange (1.25 plasma volume exchange with fresh frozen plasma replacement fluid; total plasma exchange procedures were performed twice a week for 1 week), muscle strength in the right upper limb and lower extremities improved and the patient could walk with a walker on day 28 post-admission. CSF analysis revealed improved cell count (17 cells/μL), total protein levels (75 mg/dL), and IgG index (0.70). Because MRI showed that abnormal enhanced lesions remained in the medullary cone and cauda equina (), the patient started a regimen of oral prednisolone (PSL; 20 mg/day; 0.5 mg/kg/day) after the second plasma exchange, on day 35 post-admission, and she was discharged on day 40 post-admission (). Her daily dose of PSL was tapered off, decreasing by 5 mg/week, and was finally suspended on day 68 post-admission
After PSL was discontinued, the patient had progressive muscle weakness in the lower limbs and was readmitted at day 51 post-discharge. At the time of readmission, she needed to use a wheelchair. NCS revealed prolonged DML and decreased motor nerve conduction velocity (MCV) in the right tibial and peroneal nerves (DML of right tibial nerve and right peroneal nerve: 6.8 and 6.6 ms, respectively; MCV of right tibial nerve and right peroneal nerve: 32 and 35 m/s, respectively; ). MCV was also decreased in the left tibial nerve (36 m/s). Amplitudes of sensory nerve action potentials were not recordable in the bilateral sural nerves (). CSF analysis showed elevated cell counts (31 cells/μL) and total protein levels (77 mg/dL). Gadolinium-enhanced MRI demonstrated multiple foci of abnormal signal intensity from the epiconus to the cauda equina ().
Following treatment with methylprednisolone pulse therapy (1,000 mg/day for 3 days, two times), muscle strength in both lower limbs improved, NCS was normalized (), and abnormal signal intensities were decreased on the follow-up MRI (, ). Oral PSL (40 mg/day; 1 mg/kg/day) was initiated after high-dose methylprednisolone pulse therapy (). Because she could walk with a walker and her CSF analyses were improved, she was discharged on day 19 post-readmission.
The daily dose of PSL was tapered off to 20 mg/day (0.5 mg/kg/day) by decreasing the dosage by 5 mg/month. At the time of publication, the patient remains in remission and NCS results (in both median, ulnar, tibial, peroneal, and sural nerves) have remained normal with the aid of low-dose PSL treatment (20 mg/day; 0.5 mg/kg/day) for 7 months so far (). |
pmc-6566482-1 | A 78-year-old female Chicagoland native with a history of a left ankle fracture treated with open reduction and internal fixation in 1990 presented to her local orthopedic surgeon with chronic pain and underwent a left total ankle replacement in November 2016. She did well post-operatively until approximately one month later when she developed wound dehiscence. Superficial wound cultures were negative and after progression on 18 days of amoxicillin/clavulanic acid (875–125 mg) twice-daily, she underwent removal of the hardware, placement of a Palacos® (Heraeus Medical, Hanau, Germany) cement spacer mixed with 1 g of vancomycin and 1.2 g of tobramycin per 40 g of cement, anterior tibial tendon and extensor hallucis longus tendon removal, and left free vastus lateralis flap with a split-thickness skin graft to the open wound site. Operative cultures were negative and she received 6 weeks of empiric intravenous vancomycin 1 g every 8 h and ceftriaxone 2 g every 24 h, then oral ciprofloxacin 500 mg twice-daily and sulfamethoxazole/trimethoprim 800–160 mg twice-daily for an additional three weeks. The wound closed around March 2017; however, 15 months later in June 2018 she presented to plastic surgery clinic with a 1 cm wound dehiscence. She was otherwise well, living at home, and ambulating without any recent travel or hospital exposures except for wound care and outpatient follow up appointments at her local facility. She underwent a deep wound debridement, closure with flap advancement and allograft superficial peroneal nerve reconstruction. Operative findings included fibrinous tissue with the appearance of biofilm. The spacer was not removed as it did not appear involved. Deep wound cultures obtained from this procedure were plated on Blood, Chocolate and MacConkey agar and grew Candida auris in pure culture in moderate amounts after 2 days on Blood and MacConkey agar plates. Identification was confirmed via 18S rRNA sequencing using the ITS1/ITS4 primer sets and D1/D2 DNA sequencing along with combined phenotypic characterization. Candida auris identification was obtained through matching ITS sequences with previously established signatures in the GenBank database. Antifungal susceptibility testing was performed using Sensititre™ YeastOne™ YO3IVD AST Plate (Thermo Scientific™, West Sussex, UK) and minimum inhibitory concentration (MIC) values (in µg/mL) were: fluconazole: 2, micafungin: 0.06, caspofungin: 0.125, 5-fluorocytosine: <0.125, itraconazole: 0.125, voriconazole: <0.03, and amphotericin B: 0.5. The patient was started on oral fluconazole 400 mg daily. Two weeks later, her wound showed increasing erythema and a new area of purulent drainage. Daily fluconazole dose was increased to 600 mg, and she was admitted for surgical intervention. On admission, she was afebrile and hemodynamically stable. A complete blood count and a comprehensive metabolic panel were normal. Given a lack of systemic symptoms, blood cultures were not obtained. She underwent antibiotic spacer removal, debridement of the remaining extensor tendons, partial excision of necrotic distal tibia and talus bones, and placement of a moulded spacer composed of 40 g Palacos® cement mixed with 100 mg of heat-stable powdered amphotericin B deoxycholate (Fungizone). Operative cultures were negative. Postoperatively, she received intravenous micafungin 100 mg daily for 2 weeks followed by oral fluconazole 400 mg daily. The wound has healed and she has regained mobility without any assistive device. She recently noticed onset of hair loss, presumably due to prolonged use of fluconazole. The patient has completed six months of fluconazole 400 mg daily with plans to continue this for at least a year followed by a lower dose, if tolerated. |
pmc-6566896-1 | An 83-year-old male with a 40 pack-year smoking status and no relevant medical history was admitted to our hospital presenting exertional dyspnea for two weeks. He also complained about his right upper back pain and unintentional weight loss. On admission, his performance status, according to the Eastern Cooperative Oncology Group, was 3, and his vital signs were normal and physical examination was remarkable for decreased breath sounds on the right side of the chest. Contrast computed tomography (CT) scan showed right contrast-enhanced pleural thickness with massive pleural effusion (A,B). 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed high FDG uptake in the thickened right pleura and mediastinal and cervical lymph nodes (C,D). He was suspected of having malignant mesothelioma and received CT-guided pleuropulmonary biopsy. Pathological diagnosis based on microscopic and immunohistochemical findings was poorly differentiated non-small-cell carcinoma with sarcomatoid differentiation (E,F). The clinical stage as per the 8th edition AJCC/TNM was T4N3M1c (stage IVB). Molecular studies detected no ALK rearrangement and EGFR mutation. Immunostaining with anti-PD-L1 revealed high PD-L1 expression; a tumor proportion score (TPS) after the manual evaluation was reported as 65%.
The patient was treated with ICI Pembrolizumab (200 mg per course/body). At day 8, his white blood cell count increased up to 36,300/μL. His respiratory status was initially improved but his condition gradually got worse. At day 15, chest CT revealed increased circumferential thickness of right pleura and increased amount of pleural effusion. His status was considered as progressive disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria and the next administration of Pembrolizumab was postponed. The patient passed away at day 28 due to multiple organ failure. Postmortem CT showed lobular consolidation in both lungs (G,H). Autopsy revealed medullary variegated hemorrhagic–necrotic cancer encasing the whole right lung, suggesting the pseudomesotheliomatous lung cancer, with metastasis to lymph nodes, adrenal glands, and vertebral column. |
pmc-6566896-2 | An 86-year-old male, who had 60 pack-year smoking status and no relevant medical history, was admitted to our hospital presenting hematochezia. His performance status was 3 and his vital signs and physical exam were unremarkable. CT detected a mass lesion in S6 of the right lung (A,B). FDG-PET scan showed high tracer uptake in the right hilar region and in the liver (C,D), suggesting local progression and systemic metastasis. Transbronchial biopsy revealed poorly differentiated squamous cell carcinoma positive for TTF-1 and negative for p40. The patient was diagnosed as squamous cell carcinoma (cT2aN0M0, stage IB) and underwent lobectomy of the right lower lobe with mediastinal lymph node dissection. Histopathological examination of the surgical specimen showed spindle cells and giant cells (E,F), which was consistent with pleomorphic carcinoma with no evidence of lymph node metastasis (pT3N0M0, stage IIB). The tumor was negative for ALK rearrangements, and EGFR and ROS-1 mutations. No adjuvant chemotherapy was administered.
Three months after the surgery, PET-CT revealed local recurrence and systemic metastases at the follow-up visit. Additional immunostaining of the surgical tumor specimen showed high PD-L1 expression with 90% TPS after manual evaluation, and therefore the patient was treated with Pembrolizumab (200 mg/body). During the treatment, his white blood cell count elevated up to 61,100/μL on day 3. He passed away on day 9 due to respiratory failure. Postmortem CT showed the right bronchial invasion of the tumor causing the collapse of the right lung and the massive right pleural effusion (G,H). An autopsy revealed the local recurrence of the carcinoma involving the hilar area of the right upper lobe. The cancer spread to the right adrenal, liver, and paraaortic abdominal lymph nodes. |
pmc-6567292-1 | A 39-year-old man was referred to our clinic due to infertility. His height and weight were 175 cm and 82 kg, respectively. The patient left school when he was in the third grade of primary school because of learning issues. He was unable to read and write properly, and had deficits in intellectual ability like reasoning or problem solving. Currently, the patient was working as a cleaner in a factory. He was noted to have mild ID.
On physical examination, the patient had no dysmorphic features. He was married for 8 years; he and his wife were not consanguineous. His parents had two children and the family history of the patient was remarkable for a deceased brother at the age of 15 years, who had also ID (
). Since there was no history of spontaneous pregnancy during his marriage, the patient was considered to represent a case of primary infertility who had also mild ID. Sperm analysis showed complete azoospermia.
In vitro fertilization was performed four times by testicular sperm extraction without success. Luteinizing hormone, follicular stimulating hormone and testosterone levels were compatible with hypergonadotropic hypogonadism (
). Y micro-deletion analysis demonstrated that AZFa, AZFb and AZFc regions on the Y chromosome were intact. After conventional cytogenetic analysis, we performed array conventional cytogenetic technique (aCGH). Karyotype analysis could not be performed for the parents or the patient’s brother, since they were not alive.
Conventional cytogenetic technique: Peripheral blood lymphocytes were used for a 72-hour culture. Chromosome analysis was performed on phyto-haemagglutinin-induced peripheral blood lymphocytes. Metaphase plaques were analyzed using the GTG banding method at almost 500–550 band resolution.
aCGH: An Agilent SurePrint G3 CGH+SNP Microarray Kit (4x180K) was used for genetic analysis of the patient. Microarray data were analyzed using Feature Extraction and Agilent Cytogenomics v4.0.3.12 software. Log ratios between -0.5 – 0.5 and variations with less than 5 consecutive probes were excluded. Genomic positions were based on GRCh37/hg19
Homo sapiens assembly.
Conventional cytogenetic analysis revealed that the patient had an insertional translocation: 46, XY, inv ins(18;2)(q11.2;q13q22) (
). Array CGH did not show any deletion or duplication (
). |
pmc-6567373-1 | Case 1: Based on the clinical assessment of the subject (male, 69 years old) was not at risk of a fall, but 2 prospective falls occurred. As shown in , he showed high instability in ML direction during the QS, 7MW and postural transitions (QS3, 7MW4 and CST3 were above the 75th percentile). This may corroborate the idea that ML stability is crucial to prevent falls in community-dwelling older adults [,]. |
pmc-6567373-2 | Case 2: The older adult (female, 81 years old) had all the health-related measures within their reference values, but she had poor strength (low HAND and PWR). The weakness is reflected in poor ability to maintain the static balance: High “ML Postural Reaction Time and Jerkiness” (QS3) and “AP Postural Control Impairment” (QS4), confirming the findings reported elsewhere []. She showed also high “Gait Jerkiness” (7MW3) and poor ability to perform the CST test: high “Dynamic Postural Impairment” (CST1), “Stand-to-Sit Jerkiness” (CST4) and “AP Stand-to-Sit Weakness” (CST5). |
pmc-6567373-3 | Case 3: The older adult (male, 86 years old) had all the health-related measures within their reference values, except for the gait speed, which was below 1 m/s. This cut-off point has been related to the risk of adverse health outcomes and disabilities [,]. Indeed, the Radar Plots show that his capacities to maintain static balance are not compromised, but he had difficulties while walking (high “Walking Impairment”, 7MW1, “ML Gait Instability”, 7MW4, and “Gait Variability”, 7MW5) and while performing postural transitions (high “Dynamic Postural Impairment”, CST1 and “Stand-to-Sit Jerkiness”, CST4, and “AP Stand-to-Sit Weakness”, CST5). |
pmc-6567432-1 | A 58-year-old Japanese man with a 17-year history of type 2 diabetes mellitus was admitted to our hospital because of diabetic gangrene of his left lower limb. This case has been briefly described previously []. A transfemoral amputation was performed due to widespread infection, and blood culture showed Staphylococcus haemolyticus sepsis. Therefore, the following antibiotics were administered before and after the amputation: minocycline 100 mg/day intravenously for one week and orally for two weeks; ceftriaxone 1 g/day intravenously for 11 days; vancomycin 1 g/day intravenously for one week; and clindamycin 1800 mg/day intravenously for one week. The doses of the antibiotics were decreased because his renal function was severely impaired (serum creatinine level, 5.02 mg/dL).
After acute-phase treatment was finished, he continued to be hospitalized for rehabilitation with an artificial leg. About four months after the admission, a hard mass at the insulin injection sites in the left lower abdomen was discovered by chance. He had almost always injected insulin at those sites before admission, but he mainly injected insulin at other sites in the abdomen after admission. At the time that the mass was discovered, he had no fever and no pain, and the laboratory tests showed no signs of inflammation (white blood cell count, 7.30 × 103/μL; serum C-reactive protein level, 0.01 mg/dL). In addition, no abnormal findings of the surface skin of the mass were observed. When skin incision biopsy of the mass was performed, necrotic tissue was seen around the mass. Therefore, a drainage tube was put into the necrotic tissue for two days, an empirical oral antibiotic was administered for four days, and the wound healed in two weeks. |
pmc-6567560-1 | A 29-year-old woman (II-11) was referred to the Genetic Outpatient Clinic for consultation in the 12th week of her fifth pregnancy with a diagnosis of generalised hydrops foetalis.
In anamnesis, the child - a boy from her fourth pregnancy, born prematurely using Caesarean section at 36 weeks of gestation, with an Apgar score of 7, birth weight 2600 g (> 50th centile), length 47 cm (> 50 centile), occipotofrontal head circumference 34 cm (> 10 centile), had numerous birth defects. They were as follows: heart defects, i.e. ventricular septal defect (VSD) and atrial septal defect II (ASD II); central nervous system (CNS) defects, i.e. lack of the cerebellar vermis and slight enlargement of the lateral ventricles; eyeball defects, i.e. defects of the eyelids and eyeballs, and lenticular staphyloma diagnosed in the left eye.
An orofacial cleft, hearing loss, and limb defects were also present. Among the dysmorphic features observed in the child were: synophrys, eyelids defect, wide nose root, anteverted nostrils, large maxilla, small retracted mandible, dysmorphic auricles.
The child died at 8 months of age due to a complex heart defect with pulmonary hypertension and circulatory insufficiency.
Medical records were obtained after the child’s death, and the previously begun genetic diagnostics was completed only after the diagnosis of congenital defects of the foetus in the subsequent pregnancy (III-22), using earlier sampled material from the child (III-21). The remaining three older children showed no signs of disease.
The mother had a sister with a clinically diagnosed Down syndrome (II-14) and other six healthy siblings who had healthy children. The information about the clinical diagnosis of Down syndrome in the sister was obtained while collecting the interview from the mother before performing prenatal tests. However, the family did not agree to carry out genetic diagnosis in the patient. Therefore, the final diagnosis is unknown.
In the family of the child’s father (II-10), no congenital defects or disabilities were found (Fig. ).
In the ultrasound examination done in the fifth pregnancy, the foetal CRL (Crown–Rump Length) value at 12 weeks was 50 mm and NT (Nuchal Translucency) was 8 mm, while in a biochemical examination MoM for PAPP-A was 0.47, and MoM for BHCG was 1.49.
Nuchal translucency [NT] is an ultrasound marker used in non-invasive prenatal screening to assess the risk of foetal aneuploidy in the first trimester of pregnancy. It arises due to the accumulation of fluid around the neck of the foetus. In the examined case, in the foetus the NT was 8 mm (> 95th centile) with enlargement of the skin edema up to the sacral and pericranial regions. The basic mechanism of formation of non-immune hydrops foetalis - (NIHF) are imbalances between the production and absorption of interstitial fluids. Generalized swelling may be a consequence of increased venous pressure in the course of foetal failure, the presence of abnormal structures in the chest, increased capillary permeability, impaired lymphatic flow or reduced plasma oncotic pressure.
A combination of nuchal translucency with the maternal serum PAPP-A and B-hCG has a detection rate of approximately 90% for trisomies 21,18 and 13 with a 5% false positive rate.
Because of the abnormal presentation of the foetus in ultrasound examination and an elevated risk of aneuploidy shown in at 15 weeks of pregnancy, the mother decided to undergo amniocentesis with amniocytes genetic tests.
In the ultrasound examination at 18 weeks of pregnancy, intrauterine growth restriction (IUGR) of 2 weeks was found. Furthermore, abnormal foetal head contour, with agenesis of the corpus callosum, enlargement of the lateral ventricle anterior horns and hypoplasia of the cerebellar vermis, were diagnosed. The nuchal fold thickness (NF) of 8.5 mm with numerous cysts was found. Abnormal facial profile with retrognathy, hypertelorism and anteverted nostrils was also noted. The palatopharyngeal arch had an extended angle with preserved continuity (Fig. ). In the spine, important shortening of the sacrocaudal section, and in the limbs shortening of all long bones by approximately 2 weeks in relation to other dimensions of foetal biometry and its age, were observed. Hands with a normal number of fingers and bilateral clinodactyly of the fifth finger were found. Moreover, subaortic ventricular septal defect (VSD), double outlet right ventricle (DORV) and pericardial effusion were observed.
The parents (II - 10 and II-11) were informed about the unfavourable prognosis due to severe brain abnormalities and other foetal defects, high probability of its death in utero or shortly after birth, and if surviving, severe intellectual disability. Therefore, the parents elected a termination of the pregnancy. |
pmc-6567598-1 | A 48-year-old, para 5, postmenopausal black African woman who was human immunodeficiency virus (HIV)-negative presented to our casualty department with a 5-year history of progressive abdominal swelling. Five years prior to presenting, which was 1 year before she reached menopause, she had noticed that her abdomen was gradually distending. Her symptoms were associated with constipation, feeling of incomplete rectal emptying, early satiety, vomiting, and urinary frequency and urgency. She did not have any chronic illnesses and had a negative personal and family history of ovarian, uterine, bowel, and breast cancers. She was not receiving any medication prior to this presentation. She had delivered five children by cesarean section, and they were all alive and well. She lived in a rural area and was a subsistence farmer. She did not smoke and did not drink alcohol.
She had ascitic taps three times in 1 week at a district hospital before referral to a higher-level hospital because of recurrent reaccumulation of ascites. A transabdominal ultrasound scan (USS) showed generalized ascites with a thick fluid with septa, as well as bilateral mild hydroureter and hydronephrosis. Again, the ascites was drained twice. One month later, she underwent computed tomography (CT), which showed a large predominantly cystic lesion that occupied almost the entire abdominal and pelvic cavities, which were distended, causing a marked mass effect on surrounding organs and bowel. The lesion had areas of internal septation predominantly on the right flank with no features of metastatic disease. Tumor markers measured during this admission are shown in Table .
The patient was referred to a tertiary hospital but only went 5 years later. Upon admission, she had marked temporal wasting, with bilateral pitting lower limb edema extending to her sacrum. She had a normal breast examination. Her blood pressure was elevated at 167/93 mmHg, with tachycardia of 150 beats/min. Her body temperature was 36.8 °C. She had equal air entry bilaterally, and her cardiorespiratory and neurological systems were normal. She had a lower midline scar with massive abdominal distention that was nontender and had a positive fluid thrill test result (Fig. ).
Results of investigations showed microcytic anemia with hemoglobin of 9.9 g/dl, white blood cell count of 7 × 103/μl, and platelet count of 250 × 103/μl. She had normal urea and electrolytes and hypoalbuminemia of 21 g/L, with results of the rest of her liver function tests being normal. Urinalysis did not show abnormalities.
Her case was discussed by a multidisciplinary team (MDT) that included gynecological oncologists, radiation oncologists, general surgeons, anesthetists, and nursing staff. The MDT considered the risks of death following hemodynamic instability and bleeding as well as the postoperative risks of deep vein thrombosis, pulmonary embolism, difficulty weaning off the ventilator, and death. The conclusion of the meeting was to take the patient for staging laparotomy despite these risks.
Preoperatively, the patient and her relatives were counseled on the possible complications. The patient received a transfusion with 2 Units (U) of packed cells (PCs). The team also contemplated drainage of the mass preoperatively but was unable to secure appropriate drains to drain the thick green fluid from the mass.
At laparotomy, through a right paramedian incision, a huge abdominopelvic mass was found filling the whole abdomen and pelvis. The liver, spleen, and hemidiaphragms looked normal. The mass was shelled out by blunt dissection (Fig. ). The mass burst during mobilization, however, with rapid drainage of dark-colored fluid and decompression 50 min into the surgery. Subsequently, the mass was stripped off the anterior abdominal wall and completely excised. A total abdominal hysterectomy was done. The anterior abdominal wall was noted to have very deficient layers. Estimated blood loss was 450 ml. Anesthetically, the patient was unstable, particularly after the rapid decompression. She received a massive transfusion of 7 U of PCs, 6 U of fresh frozen plasma, and 4 L of gelafundin with 7 L of Ringer’s lactate. The surgery lasted about 3 hr. The patient was admitted to the intensive care unit (ICU) for cardiopulmonary support.
The patient was critically ill in the ICU. On the day of admission, she had a cardiac arrest and was successfully resuscitated. She required inotropic support and ventilation. By day 5, she had developed hepatosplenomegaly, uremia, and an increased international normalized ratio. She was leaking serous fluid from the suture line, with darkening of the previously stretched skin of the anterior abdominal wall. She remained anemic with thrombocytopenia. She received a further 6 U of PCs. She was kept on albumin and given high-protein energy feeds by the dietitian in view of her hypoalbuminemia and malnutrition. By day 6, she was noted to have disseminated intravascular coagulopathy. She was given vitamin K. A pneumothorax was noted, and the cardiothoracic surgeon inserted a chest drain. She was also noted to have aspiration pneumonia following a self-extubation on the same day. By day 10, she was noted to have multiple organ failure with oliguria, falling level of consciousness, aspiration pneumonia, a gangrenous abdominal wall (Fig. ), and coagulopathy.
She required inotropic support and ventilation. She died on day 10 after surgery. The pathology report showed a partial cystic lesion with benign epithelia of mucin-secreting columnar cells, no evidence of stromal invasion, no stratification, and no atypia and intraluminal mucin (Fig. ). The cyst walls were necrotic with fibrinopurulent exudate. Normal ectocervical and endocervical mucosa was observed. The endometrium was inactive, and there was evidence of an anterior fibroid. This confirmed the diagnosis of benign mucinous cystadenoma. Figure illustrates the sequence of events. |
pmc-6567614-1 | A 49-year-old Japanese woman was presented with chronic hepatitis due to HCV genotype 2 infection. She had a psychiatric history of mild innate anxiety but was not medicated. She was prescribed subcutaneous injection of PEG-IFNα-2a at a dose of 180 μg per week to treat chronic hepatitis. After initiation of therapy, a low-grade fever and mild general fatigue were observed. Psychiatric symptoms such as enervation, palpitations, an episode of hyperventilation, and consciousness disturbances with myotonia appeared after the third injection of PEG-IFNα-2a. It was impossible to decide if the symptoms were IFN-related or due to a somatization disorder elicited by anxiety, but the IFN therapy was discontinued and followed by administration of etizolam and paroxetine hydrochloride hydrate treatment by psychiatrists. Although the symptoms gradually improved, it took 3 months for the patient to completely recover (Fig. ); the anti-anxiety medications were continued for a prolonged period. While waiting for approval of DAA therapy, the patient was administered liver supporting therapies: oral ursodeoxycholic acid and glycyrrhizinate. Upon approval, the patient was administrated with IFN-free sofosbuvir and ribavirin combination therapy. She was 57 years at this time point and 8 years had elapsed since the PEG-IFN therapy. The patient remained diagnosed with chronic hepatitis, as she showed a low score of 2.50 in the fibrosis-4 index [] and aspartate aminotransferase-to-platelet ratio index [] was 0.731. Unexpectedly, psychiatric symptoms similar to those observed with IFN and consciousness disturbance attacks appeared 4 days after treatment initiation. Initially, psychiatrists attributed the symptoms to epileptic seizures, and sodium valproate was administrated. However, her symptoms did not improve, and the patient was admitted for further observation and treatment.
Physical examination was unremarkable. The liver and spleen were not palpable, and her bowel sounds were normal. Anemia and jaundice were not seen in palpebral conjunctiva or bulbar conjunctiva. Flapping tremor and leg edema were absent. Abnormal neurological finding were not detected. The patient denied alcohol and/or drug abuse. Upon admission, the patient was administrated etizolam and paroxetine for anxiety disorder, ursodeoxycholic acid and glycyrrhizinate for chronic hepatitis, and metoprolol and enalapril for chronic heart failure after a surgical operation for endocardial cushion defect. Other than a mild increase in serum aspartate and alanine aminotransferase levels due to sodium valproate administration, no abnormal laboratory findings, including ammonium or glycemic levels that might induce consciousness disturbances, were found (Table ). There was no evidence for HBV and HIV co-infection. Furthermore, the patient’s electroencephalogram and brain magnetic resonance imaging findings were normal (Fig. a-c). These results indicated no evidence of infection or hepatic or drug-induced encephalopathy. In addition, the patient had stable vital signs and communicated well even during the psychiatric attacks unless prompted about hepatitis related topics (which would not have been the case if she was suffering from epileptic seizures). Based on the clinical picture, psychiatrists confirmed a diagnosis of somatization disorder induced by anxiety from antiviral therapy. Sodium valproate, sofosbuvir, and ribavirin were discontinued, and her symptoms gradually disappeared after 3 months. Anti-anxiety medication was continued for treatment of the somatization disorder; the patient continued to receive liver supporting therapies because of a mild increase in serum aspartate and alanine aminotransferase levels; interruption of antiviral therapy showed no clearance of HCV. With the combination of mental health support from psychiatrists, we are planning to retry an alternate DAA regimen without ribavirin. |
pmc-6567639-1 | A 78-year-old woman underwent curative open right hemicolectomy for ascending colon cancer. Pathological diagnosis was well-differentiated tubular adenocarcinoma with K-RAS mutation, T4a, N0, stage IIB []. Twenty-six months after the operation, PM was detected and CRS (CC-0) and HIPEC were performed 6 months after adjuvant chemotherapy. Her PCI score was 17/39. After surgery, she developed a surgical site infection and wound dehiscence. She was followed-up without adjuvant chemotherapy. Fifteen months after CRS and HIPEC, liver metastases to segments 2 and 5 were detected (Fig. ) and systemic chemotherapy (IRIS + bevacizumab, 12 cycles) was initiated because the patient refused surgical treatment. Systemic chemotherapy was continued for 12 months, until discontinuation due to malaise and dizziness. Twenty-two months later, the liver tumor increased in size and dilatation of the peripheral bile duct of the tumor in segment 2 was observed. The patient accepted surgical treatment at that time, and she underwent left hemihepatectomy and partial resection of liver segment 5. Operative time was 4 h and 29 min, and her total blood loss was 530 mL. Broadwide adhesion around the liver was identified and we carefully dissected adhering organs, which included the diaphragm, stomach, duodenum, jejunum, and colon (Fig. ). It took 2 h and 34 min from the time of the skin incision to the initiation of liver transection. A small amount of chylous ascites were found in the abdomen during the surgery. The postoperative course was uneventful, except for the chylous ascites from the abdominal drain, which gradually subsided after implementation of a fat-restricted diet and diuretics. No recurrence was detected in the absence of adjuvant chemotherapy for 12 months after hepatectomy. |
pmc-6567639-2 | A 57-year-old woman underwent curative laparoscopic ileocecal resection for cecum cancer. Pathological diagnosis was moderately differentiated tubular adenocarcinoma without K-RAS mutation, T3 N1, stage IIIB []. Twelve months after the operation, PM and bilateral ovarian metastases were detected and CRS (CC-0) and HIPEC were performed 5 months after adjuvant chemotherapy. The PCI score was 5/39. The postoperative course was uneventful, and she was followed-up without adjuvant chemotherapy. Five months after CRS and HIPEC, liver metastasis to segment 6 was detected (Fig. ) and systemic chemotherapy (FOLFOX + bevacizumab) was performed. After 5 cycles of chemotherapy over a period of 4 months, the size of the liver metastasis had decreased and no other metastasis or dissemination was detected. Surgical treatment was indicated and posterior sectionectomy of the liver [] was performed. Operative time was 2 h and 30 min, and her total blood loss was 233 mL. Adhesion of the liver surface to the diaphragm and stomach was found, although it was relatively loose. It took 56 min from the time of the skin incision to the initiation of liver transection. The postoperative course was uneventful, and no recurrence was detected in the absence of adjuvant chemotherapy for 5 months after hepatectomy. |
pmc-6567639-3 | A 38-year-old man underwent Hartmann’s operation for the perforation of the sigmoid colon. Sigmoid colon cancer with PM was detected, and bilateral and diffuse CRLM were also diagnosed during the operation. Pathological diagnosis was moderately differentiated tubular adenocarcinoma without K-RAS mutation, T4a N2, M1c, stage IVC []. FOLFOX + bevacizumab was performed for 10 cycles and discontinued because of drug-induced pneumonitis. After the second-line chemotherapy using 5-FU + leucovorin (LV) was performed for 10 cycles, complete remission of liver metastases was achieved. CRS (CC-0) and HIPEC were performed 13 months after the primary tumor resection. The PCI score was 2/39. The postoperative course was uneventful. Adjuvant chemotherapy using 5-FU + LV + bevacizumab was performed because the risk of recurrence was high. After 8 cycles of adjuvant chemotherapy, recurrence of liver metastases in segments 2, 3, 5, and 8 was newly detected (Fig. ). Six months after CRS and HIPEC, he underwent left lateral liver sectionectomy [] and partial resection of liver segments 5 and 8. Operative time was 5 h and 35 min, and his total blood loss was 250 mL. The surface of the liver tightly adhered to the abdominal wall, diaphragm, stomach, duodenum, and colon, and we dissected them carefully without damage to other organs. It took 1 h and 37 min from the time of skin incision to the initiation of liver transection. Two months after the hepatectomy, metastases to the liver and lymph nodes were detected. Systemic chemotherapy was performed, but the cancer progressed gradually. The patient died 16 months after hepatectomy.
The clinical courses of the three cases are summarized in Fig. . |
pmc-6567645-1 | A 46-year-old male patient, a native of district Gorakhpur, Uttar Pradesh state, India, in October 2017 presented to us with complaints of a painless progressive swelling in the left side of the abdomen with abdominal distension for the last 8 years. The swelling was not associated with any symptom therefore the patient did not seek any medical attention for the same; however, for the last 2 years, the swelling has increased considerably as per the patient and causes dragging discomfort. It was not associated with any bladder or bowel complaints or any other systemic symptoms like fever, weight loss, or loss of appetite. Apart from dragging discomfort, there was no history of anorexia, paroxysmal hypertension, tachycardia, headache, perspiration, or palpitations. The socioeconomic status was lower middle (class III) as per modified Kuppuswamy scale [], and the patient was a farmer by profession. On abdominal examination, there was a large, firm swelling of size around 20 × 15 cm occupying the left upper and lower quadrant (Fig. ). It was non-tender and dull on percussion. The scrotum and testis were normal and there was no pedal edema or lymphadenopathy. A provisional clinical diagnosis of pseudo-pancreatic cyst was made.
Blood and laboratory investigations were within normal limits. Abdominal contrast-enhanced computed tomography was suggestive of a thin-walled hypodense cystic mass of size 25.7 × 15 × 14.3 cm in the left side of the abdomen extending from the lesser sac till the left iliac fossa. The lesion was compressing the body and tail of the pancreas. It was also displacing the head of the pancreas, stomach, first and second parts of the duodenum, small bowel loops, abdominal aorta, and superior mesenteric vessels to the right side. It was compressing the left ureter causing mild hydro-ureteronephrosis. The head of the pancreas was mildly bulky but there was no focal lesion and no evidence of free fluid or lymph nodes in the abdomen suggesting a possible diagnosis of cystic pancreatic lymphangioma (Fig. a, b). Twenty-four-hour urinary metanephrines were also done to rule out a cystic retroperitoneal paraganglioma and the test was negative. The diagnostic aspiration of cyst fluid (done in December 2017) revealed a total cell count of 85 cells/mm3 with 60% lymphocytes and 40% neutrophils whereas glucose was 45 mg/dl, protein 4.5 g/L, and amylase 24 U/L. The culture of cyst fluid was sterile and malignant cytology was negative.
The patient posed to us a diagnostic dilemma and we were unable to reach a definite diagnosis even after extensive investigations. The patient was planned for exploration with a probable diagnosis of pancreatic pseudocyst or lymphangioma. The patient was operated on February 2018, on exploration, and there was a cystic mass of size 25 × 15 × 15 cm (Fig. ), which was present in the retroperitoneum pushing the small and large bowel loops anteriorly and to the right. The ureter and gonadal vessels were compressed posteriorly by the mass. Cranially, it was pushing the stomach and pancreas to the right, but there was no obvious connection with the pancreas. There were no obvious dilated lymphatics in the retroperitoneum.
Histopathology of the cyst revealed a unilocular cyst with walls composed of fibro-collagenous tissue lined by flattened epithelium and focal areas of calcification along with a few fragments of microfilaria (Fig. ). The features were suggestive of a lymphatic cyst of filarial origin. The postoperative recovery of the patient was uneventful and was given diethylcarbamazine therapy (100 mg t.i.d. for 3 weeks). Further, filariasis immunochromatographic test (ICT) by Alere™ BinaxNOW® Filariasis kit for Wucheria bancrofti was positive. Ultrasound of the scrotum, groin, and lower extremity was reviewed again for possible adult worm and, however, was negative. The patient was doing fine up to 8 months of follow-up. |
pmc-6567902-1 | We present the case of a 71-year-old self-employed, non-smoking German female patient scheduled to undergo a right TKA. Relevant past medical history included type 2 diabetes mellitus treated with insulin (HbA1c 43 mmol/mol), BMI of 35.5 kg/m2 (176 cm/ 110 kg), arterial hypertension (usual value 140/60 mmHg via right arm) and restless leg syndrome. Important self-medications were metformin, valsartan, hydrochlorothiazide, nebivolol, aspirin, lercanidipine hydrochloride, levodopa and benserazide hydrochloride. The patient’s history included a TKA on the right side in 2000, a traumatic dislocation in 2011 and a revision arthroplasty in 2012 due to instability. These operations were performed under general anaesthesia without complications.
In February 2018, the patient presented to our orthopaedic outpatient department because of increasing pain in the right knee joint. Examinations showed implant loosening and Staphylococcus epidermidis infection. Therefore, the patient was scheduled for a two-stage revision with implant removal and antibiotic-loaded spacer implantation. Antibiotic therapy was deliberately withheld in view of the patient’s stable, non-septic clinical parameters and to better evaluate potential antibiotic sensitivities following surgical removal of the infected prosthesis. For pain management, she received a prescription for celecoxib and metamizole per os (PO), as well as subcutaneous antithrombotic prophylaxis with enoxaparin sodium. The patient was advised to follow the rest/ice/compression/elevation (RICE) protocol during the time until surgery.
In the premedication visit, the patient was classified as ASA III (according to the American Society of Anaesthesiologists) with a metabolic equivalent of ≥4. An electrocardiogram (ECG) and current lab values (erythrocytes 7.0 mmol/l; Hb 7.0 mmol/l; Hk 0.32 l/l; CRP 5.7 mg/l; all others were without abnormalities) had already been determined. The patient showed no signs of cardiopulmonary decompensation such as dyspnoea, oedema or auscultatory abnormalities at the time. On the day of surgery, 5 mg oxazepam PO and the patient’s usual medication, except metformin, valsartan and hydrochlorothiazide, were administered. The patient was informed that she could eat until 6 h before surgery and drink clear liquids until 2 h before surgery. The procedure was performed under general anaesthesia with endotracheal intubation. The initial vital parameters were a blood pressure (BP) of 160/80 mmHg and a heart rate (HR) of 65 bpm. Anaesthesia induction was performed under standard monitoring (non-invasive BP, HR and pulse oximetry) in the following order: propofol (180 mg) intravenous (IV), sufentanil (20 μg) IV and rocuronium (50 mg) IV. Sevoflurane (target value of minimal alveolar concentration of 0.8–0.9) and sufentanil (10 μg as a single IV bolus at the incision site) were used to maintain anaesthesia.
Furthermore, 1 g of tranexamic acid IV and balanced electrolyte solution (2 l of Jonosteril, which includes sodium chloride, sodium acetate trihydrate, potassium acetate, magnesium acetate tetrahydrate, calcium acetate) was given during the entire surgery. After anaesthesia induction, BP was 95/55 mmHg, and BP measurement was performed every 3 minand documented every 5 min. Because of a fall in blood pressure, the patient received norepinephrine (20 ml/h at 3 μg/min via IV perfusion) for 20 min to increase the mean arterial pressure to 65 mmHg. This regimen was performed directly after anaesthesia induction and was stopped at when the mean arterial pressure reached 65 mmHg, which occurred after 28 min (after the initial surgical incision). Thereafter, the patient was stable without catecholamines.
After incision and preparation of the knee, the surgeon observed pronounced synovitis and intramedullary femoral and tibial periprosthetic infected membranes. A smear was collected, and the patient received cefuroxime at 1.5 g IV. During the tibial component removal, spontaneously resolving episodes of asystole were observed on 3-lead-ECG. The asystole events were observed twice over a maximum of 2 s and depended on the surgical manipulation. Before any intervention, the events ended spontaneously with complete removal, and no haemodynamic changes were observed. Because of the short action and no haemodynamic changes, as well as the observation of stable blood pressure, we checked the 3-lead-ECG to exclude an artefact due to the manipulation and the high sensibility of the derivation. The operation proceeded without abnormalities until 45 min after incision, and the surgeon began the intramedullary reaming. This procedure led to a seven-second asystole again and was associated with a fast fall in BP (42/18 mmHg), oxygen saturation (68%) and end-tidal CO2 (21 mmHg). We informed the surgeon and interrupted the intervention. Epinephrine was prepared but not injected because at the same time, the asystole vanished. There was a complete recovery of haemodynamic parameters (92/56 mmHg; 98%; 42 mmHg). The heart rate was 52 bpm. The patient received 0.5 mg of atropine IV to prevent reproducible asystole for the rest of the procedure. Catecholamines were not necessary because of increased BP. Other reasons for asystole were checked, without any indication of a reversible cause. It is possible that the manipulations (reaming) led to pain with a vasovagal reaction, but around these events, the patient had no signs of pain, such as hypertension or tachycardia. From the advent of asystole until the end of the surgery, the depth of anaesthesia was monitored by the bispectral index (BIS), with no evidence of low anaesthesia (BIS score of 42) after the last event. According to our standard operation procedure, BIS was not indicated for this surgery, but we wanted to ensure an adequate depth of anaesthesia while minimising sevoflurane anaesthetic administration due to the patient’s comorbidities until the end of operation.
Extubating was performed without any problems. The patient received metamizole (1 g) at the end of surgery to prevent postoperative pain. In the recovery room, the patient first received a 12-channel ECG, which was without any abnormalities. Laboratory tests and blood gas analysis (troponin, BNP, CK-MB, D-Dimers, electrolytes) were performed to exclude ischaemia, embolic events, infarction or changes in electrolytes as the reason for asystole. We performed a case conference with our cardiologists. The subsequent transthoracic echocardiography was also without any abnormalities according to the age of our patient. Non-invasive cardiovascular investigations, such as repeated 12-channel-ECG, 24-h Holter monitoring and ultrasound of extracranial vessels, were performed. These investigations revealed minor supraventricular ectopic activity but were otherwise unremarkable. The cardiologist assumed that the patient had a vagal reaction when bone manipulations were performed by the surgeon and advised atropine IV (without recommendation of a dose) for the following operations.
Six weeks later, the patient underwent scheduled spacer removal and TKA. The patient received atropine IV (1 mg) after induction of anaesthesia to reach a higher HR and underwent invasive BP measurement and BIS monitoring. As the surgeon manipulated the medullary cavity, the patient developed a self-limiting episode of bradycardia (40 bpm) lasting only 3 s. No other events were recorded during surgery or hospital stay. |
pmc-6568211-1 | A 2-year-old girl (patient A) presented to the emergency department with a 24-h history of lethargy, fever and abdominal pain. One week previously, she had suffered from a mild gastroentritis-like illness but had recovered fully. She was a dichorionic-diamniotic twin born at 33 weeks, was previously well and fully vaccinated according to the UK schedule, including neonatal BCG. There was no family history of immunodeficiency ().
On admission, she had a distended abdomen, tachycardia, pyrexia (39°C) and raised inflammatory markers; she was admitted and treated as suspected appendicitis. At laparotomy, frank pus was found in the abdomen but the appendix appeared grossly normal. A diagnosis of spontaneous bacterial peritonitis was made. Blood cultures from admission grew serotype 10A S. pneumoniae, a strain not contained within the 13-valent pneumococcal conjugate vaccine administered to children in the UK.
Routine investigation of pediatric invasive pneumococcal disease in our center is based on the protocol described by Gashinard et al. (). The patient's results are summarized in and . The beta-2 peak on serum electrophoresis was absent, commensurate with low C3 (). Significantly reduced activity of both the classical and alternative complement pathways was noted and subsequent investigation demonstrated completely absent CFI and reduced levels of complement factors B and H indicative of consumption.
The clinical diagnosis was confirmed by Sanger sequencing of CFI (NM_000204.4) in the proband, which revealed compound heterozygous variants (c.129C>A; p.Cys43* and c.559C>T; p.Arg187*, ) predicting protein truncation within the factor I membrane attack complex (FIMAC) domain and scavenger receptor cysteine rich domain, respectively (). The p.Cys43* variant has not previously been reported, however the p.Arg187* variant has been identified in two individuals with complete CFI deficiency, on each occasion in trans with a frameshifting allele (). The p.Arg187* variant has an allele frequency of 0.00001415 with no homozygote identified in gnomAD.
The patient remains well at 5 years and 4 months of age, and has had no further invasive bacterial infections following initiation of prophylactic antibiotics. Vaccination against encapsulated bacteria including H. influenzae type b, pneumococcus and meningococcus were optimized with good responses (). Complement levels and function in the proband's twin were normal, excluding complete CFI deficiency, however he was found to be heterozygous for the 129C>A variant. |
pmc-6568211-2 | A 32 year old lady (patient B) presented to the emergency department with a 3 day history of gradual onset frontal headache, blurred vision and slurred speech, followed by several tonic-clonic seizures in short succession, deteriorating into coma. Her family reported preceding upper respiratory tract infection symptoms. She was admitted and treated as presumed meningoencephalitis. MRI neuroimaging showed diffuse, confluent cerebral and cerebellar white matter high signal changes, oedema, and mass effect without DWI change (). She had suffered three similar presentations in the past; a severe episode aged 10 and two milder episodes at the ages of 12 and 18. Her sister had died of fulminant haemorrhagic leukencephalopathy at the age of 16 (). The family had not been investigated further.
CSF sampling showed an inflammatory picture (WCC 322, 55% polymorphs), but no bacterial or viral pathogens were detected by routine culture or PCR. C3 was borderline low and acute phase proteins remained normal during her illness. There was no improvement following treatment with empirical antibiotics and antivirals but a slow recovery ensued following pulsed methylprednisolone, with no residual neurological though very mild cognitive deficit. Whole genome sequencing (WGS) was undertaken in the proband and the proband's unaffected mother to achieve a unifying diagnosis. Filtering of all the variants identified by WGS based on quality metrics, deleteriousness, inheritance pattern and biological function led to a short list of 5 genes that were investigated further (, ). Of these, the CFI gene was the only gene to show the expected compound heterozygosity.
WGS revealed two heterozygous variants in CFI (c.191C>T; p.P64L and c.262C>A; p.Q88K) lying within the CFI FIMAC domain (). Although paternal DNA was not available, Illumina read-level information was used to confirm the variants lay in trans (). The CADD score for the p.P64L variant is 33.00, SIFT predicted the variant to be damaging and PolyPhen2 predicted the variant to be probably damaging with an allele frequency of 0.0002335; no homozygotes were identified in gnomAD. P64 is highly conserved across taxa (). Previous reports have associated the p.P64L variant with atypical haemolytic uraemic syndrome () and age related macular degeneration (). The p.Q88K variant has not been reported previously. Although the CADD score for p.Q88K was only 7.34 and SIFT predicted the variant to be tolerated, Polyphen2 predicted the variant to be possibly damaging. Q88 is also highly conserved across taxa ().
To further assess the pathogenicity of these variants, mutation Cutoff Scanning Matrix (mCSM) analysis was performed (), an approach that predicts the effects of amino acid variation on protein stability by estimating free energy changes (). Using the CFI crystal structure solved to 2.7 Å (), mCSM analysis predicted a destabilizing effect of both the p.P64L and p.Q88K variants with ΔΔG of −0.715 and −0.844 kcal/mol, respectively. Three-dimensional modeling of the protein structure of CFI in complex with C3b shows the close topological relationship between the P64 and Q88 residues of CFI and the V1658 residue of C3b (). Furthermore, the G71 residue, mutations of which have also been associated with neurological presentations of CFI deficiency (), lies on a side chain between these two mutations .
Consistent with these in silico prediction, factor I levels were measured in the proband and found to be undetectable. Commensurate reductions in functional activity of the classical and alternative pathway were also identified () confirming the genomic diagnosis. DNA from the deceased sibling was not available for testing. Heterozygous variants in three other immunologically relevant genes were identified by WGS in Patient B: C6, PTPRC and CD74 (). The heterozygous variant in C6 illustrates the challenges of interpreting variants based exclusively on bioinformatic predictive scores. Although the CADD score for this variant is 15.1, serum concentrations of the terminal complement complex are elevated in patient B, the assembly of which could not occur without functioning C6. Furthermore, deficiencies in the terminal complement cascade are associated with meningococcal infections, which were not a feature in the clinical presentation. The heterozygous variant identified in PTPRC is unlikely to be clinically relevant given PTPRC variants are associated with severe combined immunodeficiency and the variant was also identified in the healthy mother. The heterozygous variant in CD74 has CADD score of 34; CD74 encodes the class II invariant chain that facilitates peptide loading within the endoplasmic reticulum. Immunodeficiency associated with CD74 variants have not been described. |
pmc-6570691-1 | We report here the case of a 60-year old Caucasian woman who died from amyotrophic lateral sclerosis. She donated her body to the anatomical department giving informed consent for using her body for scientific and educational purposes prior to death []. At admission a 30 cm scar was found at the left lateral thigh, and another 10 cm transversal collar scar. No further medical data are available. Her corpse was preserved using an arterial injection of a formaldehyde–phenol solution and immersed in phenolic acid in water for 3 months [].
The corpse was used for a surgical-anatomical study on the superficial and subfascial vascularity of the gluteal region. When dissecting the right side and detaching the gluteus maximus muscle to display the gluteal arteries and veins no piriformis muscle could be found.
The greater sciatic foramen is properly formed by the greater sciatic notch, the sacrotuberal and the sacrospinal ligaments. Only neurovascular structures pass, a common gluteal artery (replacing the superior gluteal artery), a superior gluteal vein, the sciatic nerve, an inferior gluteal vein, a (bipartite) pudendal nerve and the internal pudendal vessels. In other words, the piriformis muscle is missing as well as the inferior gluteal artery. Both, a vessel resembling the ‘descending branch of the inferior gluteal artery’ and the artery to the sciatic nerve originate from the common gluteal artery. Furthermore, at the lesser sciatic foramen, a quite large gemellus superior muscle accompanies the obturator internus muscle, whereas the gemellus inferior muscle is also missing (Fig. ).
The left side shows no variations; the piriformis muscle exists. |
pmc-6570831-1 | A 9-month old boy presented at a hospital in a south western state of Nigeria, with a swollen left upper arm adjoining the chest, low-grade continuous fever (38.1 °C), frequent passage of loose watery stool and persistent cries for more than 3 h. Child had been immunized about 24 h earlier. The mother reported that the symptoms were observed 2 h after the child was vaccinated with the measles vaccine at a private hospital. The child was one of three children reported to have been vaccinated with measles vaccine at a private hospital during the immunization clinic session.
On examination, he was mildly pale, febrile and anicteric. He was moderately dehydrated; mildly dyspnoeic with normal heart sound, heart rate of 148 beats/ min, breath sound was vesicular and respiratory rate of 54 cycles per minute. He was well nourished as the weight was appropriate for age. There was extensive swelling with skin discolouration (hyperemia) involving the entire left upper arm, sparing the distal third of the forearm and hand. There was also swelling of the upper part of the anterior chest wall. The swelling was firm and mildly tender. There was no history of adverse reaction to immunization or any form allergic reaction.
A day after admitting the child, extensive erythema of the left upper arm and anterior area of the chest was observed with extensive scalded skin lesion involving the deltoid area, the upper chest wall and arm (Fig. ). Desquamation of the affected areas was observed presenting like severely burned skin from a hot liquid. There was darkening and hardening of the skin over the affected area on the arm with eventual severe necrosis up to a depth of about 5 mm thereafter (Figs. and ). A diagnosis of severe necrotizing fasciitis was made.
Radical debridement of necrotic tissues was carried out under general anaesthesia. Child was also transfused with blood. Daily dressing of the wound was done and antibiotics administered were intravenous metronidazole (20 mg/ kg/ day in 3 divided doses) and ceftazidime (100 mg/ kg/ day in 3 divided doses). Child was referred to University College Hospital, Ibadan, a teaching hospital in a neighbouring state where skin grafting was performed. Presently, child have recovered and he is fully healthy.
A causality assessment was conducted by the state AEFI committee using the detailed AEFI investigation forms using WHO AEFI causality assessment methodology [, ].Visits were made to the private hospital where the child was reported to have received the vaccine. The routine immunization focal person in the facility was interviewed. Assessment of available cold chain devices for vaccine storage was also carried out. The knowledge and skills of health workers in vaccine handling, management and administration were assessed [–]. In addition, the caregivers of two other children immunized during the session were recalled and interviewed. The case of interest was the first child to be vaccinated with measles vaccine during the immunization clinic while the second child, a 9 months old female who received vaccination from the same measles vial had fever and abscess formation at the site of immunization only however, the third child who was also vaccinated during the immunization clinic was healthy and without symptoms. The third child was found to be vaccinated with measles vaccine from a newly reconstituted measles vaccine vial different from the measles vaccine vial used for the other two children on the day of the immunization clinic. Incision and drainage procedure was carried out for the second child with wound dressing conducted for two weeks who thereafter recovered fully.
The findings from the investigation indicated that a programmatic error may have been responsible for the reactions.We found that two children were vaccinated with a measles vaccine that have been reconstituted for a period of > 6 h. The measles vaccine administered to these children was reconstituted 7 days ago and used during the previous immunization clinic with the left-over stored in a refrigerator within the hospital. This was due to poor knowledge and skill in vaccine management and administration among health workers who administered the vaccine. Other key issues identified includes poor documentation of vaccination activities using the recommended data management tools resulting in difficulty to tracked other children vaccinated with other vaccines for further investigation and poor vaccine storage system at the private hospital as the hospital lacks the recommended Solar Direct Drive (SDD) refrigerator for proper vaccine storage. Also, effort to retrieve the samples of the left-over doses of the vaccine in the opened vials for laboratory investigation proved abortive as the used/empty vial of the vaccine was said to have been discarded by the health workers immediately after the immunization clinic. Furthermore, blood samples collected from the child with NF by the attending physician during the preliminary case management at a local hospital for microbiological culture investigation shows contamination of culture plate as samples were not properly stored during the culture process due to lack of the required facility to perform the test at the hospital. |
pmc-6570874-1 | A 49-year-old woman was admitted because of fever and abdominal pain. She had chronic renal failure caused by type 2 diabetes mellitus and initiated continuous ambulatory PD (CAPD) one year ago, with a conventional twin-bag system and no automated cycler device. Although her body fluids and solute levels were well controlled, she developed recurrent infections with Staphylococcus caprae at the catheter exit site, leading to chronic subcutaneous tunnel infection with abscess around the catheter (Fig. a). Subsequently, she underwent subcutaneous pathway diversion two months ago. When admitted to the hospital, she had a body temperature of 38.6 °C, pulse rate of 98 beats/minute, and blood pressure of 118/73 mmHg. Her entire abdomen was tender, with apparent rebound tenderness. The catheter exit site showed no signs of infection. Her laboratory data revealed that a white blood cell (WBC) count of 8950/μL, with 85.1% neutrophils, and C-reactive protein level of 9.43 mg/dL. Her dialysis effluent appeared cloudy, and the WBC count in the effluent was 3870/μL (76% polymorphonuclear cells). Considering these results, she was diagnosed as having CAPD-associated peritonitis.
Initially, the peritonitis was suspected to be because of the recurrent subcutaneous tunnel infection caused by S. caprae, as it occurred relatively soon after the subcutaneous pathway diversion. However, an abdominal computed tomography scan revealed no findings of recurrent subcutaneous abscess (Fig. b). After sampling the effluent in blood culture bottles and sterile plastic tubes for bacterial culture, she received empiric antibiotic therapy with continuous intraperitoneal ceftazidime that was mixed in the dialysate bags (125 mg/L of dialysate). Her fever and abdominal pain immediately ameliorated, and the WBC count in the effluent normalized in five days. The causative bacteria for the peritonitis were not identified by culture testing. However, mass spectrometry (MALDI Biotyper, Bruker Daltonics, Germany) for bacterial identification successfully detected C. canimorsus in a tiny colony in solid culture medium inoculated from samples collected in sterile plastic tubes (Fig. ). The patient had four cats in her house, and the room for bag exchange was not sequestered from these cats. Additionally, she frequently slept with the cats on the bed, although the catheter had never been damaged by cat bite or scratch. She was thoroughly advised not to allow the cats in her bedroom and in the room for bag exchange. |
pmc-6570886-1 | Five month old boy born to second degree consanguineous parents was brought for evaluation of global developmental delay since birth, and remittent fever, recurrent seizures and vomiting since three months of age. The pregnancy had been unplanned. Though the antenatal period was uncomplicated child had a low birth weight- 2.2 kg (<− 3SD) and had evidence of symmetrical intrauterine growth retardation (OFC - 33 cm/ <5th centile, length – 46 cm/ (− 2) - (− 3) SD). He had recurrent vomiting since two months of age associated with poor weight gain. The clinical course was complicated with recurrent seizures since three months and the child had developmental regression with poor visual fixation and loss of social smile. He had remittent fever for several months with repeatedly negative septic screen following which a central cause for irregularities in thermoregulation was suspected. Later in the clinical course, he developed marked dystonia and dyskinetic movements suggesting extrapyramidal nervous system involvement. His elder sibling who had developmental regression and epileptic encephalopathy, died at 1 ½ years of age following aspiration pneumonia whilst being evaluated for a neuro-metabolic disorder.
Clinical examination at five months revealed severe growth retardation: weight – 5 kg (<−3SD), length – 59 cm (<−3SD), OFC- 39 cm (<5th centile). He had four limb spasticity and exaggerated reflexes. Electroencephalography revealed encephalopathy. Brain MRI showed multiple areas of increased T2 signal intensity with diffusion restriction involving brain stem, basal ganglia and white matter tracts and suggested widespread demyelination. Urine FeCl3 test was positive for phenylketonuria. Plasma amino acid profile revealed elevated Phenylalanine – 1245.71 μM (range 25–120 μM). Plasma Phenylalanine/ Tyrosine ratio was 21.87 (range 0.4–2.2). Blood Neopterin levels were very low – 0.01 nmol/g Hb (range: 0.19–2.93 nmol/g Hb, Haemoglobin – 9.8 g/dl) and Biopterin were not detectable (range: 0.08–1.20 nmol/g Hb, Haemoglobin – 9.8 g/dl). Dihydro Pteridine reductase activity was normal – 2 mU/mg Hb (range - > 1.1 mU/mg Hb). Plasma acylcarnitine profile and screening for other metabolic disorders were negative. Genetic studies were not performed due to lack of facilities and as the biochemical tests were sufficient enough to make the diagnosis of GTPCH 1 deficiency (Figs. , and ).
Child was commenced on Phenylalanine restricted diet with supplementation of other essential amino acids by special formula milk. Micronutrients were also supplemented. Breast feeding was continued and complementary feeds were commenced with a carbohydrate rich and phenylalanine restricted diet. L-Dopa was commenced after detection of BH4 deficiency and Tetrahydrobiopterin and 5-hydroxytryptophan were requested as they were not available. Multidisciplinary care was arranged with involvement of paediatrician, nutritionist, metabolic specialist, neurologist and geneticist. Since parents wished for a third child they were offered genetic counseling. Plasma Phenylalanine levels were monitored monthly to assess biochemical improvement. Plasma Phenylalanine level and Phenylalanine/ Tyrosine ratio at 9 months were 18.6 μM and 0.35 respectively. |
pmc-6570917-1 | A 49-year-old woman presented with a 3-month history of repeated ptosis of both eyelids and oral ulcers and erosions. Physical examinations revealed scattered ulcers and erosions in the mouth (Fig. ). Laboratory examinations showed that CA 125 was elevated (51.6 U/ml), while other tumor markers, including CA199, 153, CEA, and AFP, were normal. Autoimmune antibodies, including anti-CENP-B antibody, ANCA, anti-AchR antibody, and ANA, were all positive.
The patient was first diagnosed with an oral aphthous ulcer and ocular myopathy myasthenia gravis. She was treated with gentamycin and dexamethasone spray inhalation to improve her oral lesions and pyridostigmine to cure muscle weakness. However, the oral ulcers improved slightly and the myasthenia gravis persisted. An abdominal ultrasound showed a hypoechoic mass in the left adrenal gland. A further CT examination showed a 6 × 5 cm, well-defined round solid mass with central necrosis in the pancreatic tail. There was no calcification detected in the mass. The solid part of the mass had slight enhancement in the arterial phase with many serpentine feeding arteries, moderate enhancement with a draining vein around the tumor in the portal venous phase and persistent enhancement in the delayed phase (Fig. a-e). The fundus of the stomach was compressed by the mass. The boundary between the mass and the splenic artery and vein was not clear, and swollen lymph nodes were not observed in the posterior peritoneum. The mass was initially considered to be a neuroendocrine tumor in the pancreatic tail.
At the same time, the patient’s symptoms worsened. She could not swallow, and she felt severe pain in her mouth. She also developed a cough and expectoration. A chest CT revealed infection in the lower lobes of both lungs. Streptococcus was detected from a throat swab. Levofloxacin was administered to fight the infection, methylprednisolone to fight the inflammation, and thalidomide to alleviate the vascular inflammatory reaction in addition to pyridostigmine and immunomodulatory therapy. However, 3 days later, the patient progressed to severe dyspnea, wheezing and difficulty with expectoration. Emergency intubation and mechanical ventilation were administered. Aspergillus was detected after bronchoalveolar lavage. Immunoglobin and voriconazole were given. Four days later, the symptoms resolved and the intubation was detached. Most of the infections in the lungs were resolved according to a chest CT. The pain in the mouth was also alleviated.
After a multidisciplinary discussion, the patient’s tentative diagnosis was paraneoplastic pemphigus and the myasthenia symptoms caused by the pancreatic tumor. Myasthenia gravis, in turn, led to the patient’s inability to excrete sputum. If the pancreatic tumor could not be removed, the symptoms would not completely remit, and the symptoms due to myasthenia gravis would also continue to aggravate, finally leading to the occlusion of the respiratory tract. Therefore, the patient was transferred to general surgery. During the surgery, a 4 × 5 cm dark-red tumor with medium texture and clear boundaries was detected in the pancreatic tail (Fig. ). The tumor was close to the splenic artery and vein, and the spleen was normal. Postoperative pathology confirmed the tumor was a follicular dendritic cell sarcoma with immunohistochemistry showing CD21(+), CD23(+), CD138(+), SMA(+), Des(+), CD117(−), DOG-1(−), S-100(−), CD34(−), CK(−), EBER and EBV(−)(Fig. a-c).
The patient continued to be treated with antifungal and anti-infection therapy. Twelve days after surgery, the patient developed sudden heart palpitation, discomfort and difficulty in breathing. Mechanical ventilation was again administered. However, the patient died of inability to excrete sputum and occlusion of the respiratory tract. |
pmc-6570926-1 | On December 11, 2017, a 22-year-old Chinese unmarried male patient reported a history of male-male oral sex during high school. In June 2017, he underwent a peri-anal abscess operation at another hospital. No other history of anal sex, surgery, blood transfusion, dust exposure, or recent bird or poultry exposure was reported. Repeated coughing began more than a month prior, with a small amount of white sputum. He simultaneously began to experience shortness of breath after light activities, which was gradually aggravated. Two days before admission, the patient had a low fever, followed by no fever with cold and chills, and significantly aggravated dyspnoea, and he could not tolerate fast walking. An examination upon admission showed a white blood cell count of 6.9 × 109/l, a neutrophil ratio of 83.8%, a lymphocyte ratio of 10.2%, a serum lactic dehydrogenase (LDH) level of 363 u/l, and a high-sensitivity C-reactive protein level of 77.00 mg/l. Arterial blood gas analysis showed a partial pressure of oxygen (PO2) of 62 mmHg, pressure of carbon dioxide (PCO2) of 33 mmHg and a pH of 7.43 without oxygen. An enzyme-linked immunosorbent assay (ELISA) was negative for HIV, and the results of other tests showed negative results for cytomegalovirus IgM antibody, positive results for cytomegalovirus IgG antibody, a CD4+ T-cell absolute value of 7.70/μl, a CD8+ T-cell value of 296.29/μl, a (1–3)-β-D-glucan level of 283 pg/ml, negative galactomannan and cryptococcal latex agglutination tests, an IgG level of 16.10 g/l, an IgM level of 1.36 g/l, an IgA level of 4.02 g/l, and an IgE level of 192.0 IU/ml. White Candida albicans growth was observed twice on sputum smear microscopy, and the sputum culture showed C. albicans growth once. Chest computed tomography (CT) showed diffuse ground glass-like lesions in both lungs (Fig. ). The patient was initially treated with piperacillin tazobactam sodium injection + azithromycin injection + fluconazole injection + methylprednisolone injection, and his cough and shortness of breath improved slightly. PJP was suspected, and alveolar lavage was performed. The cellular proportions in the bronchoalveolar lavage fluid (BALF) were 62% phagocytic cells, 6% neutrophils, 30% lymphocytes, and 2% eosinophils. The centrifugal precipitate smear of the lavage fluid was stained with Wright’s stain and hexamine silver, and P. jirovecii cysts were observed under a light microscope (Fig. ). PJP was diagnosed, and the treatment was changed to sulfamethoxazole and trimethoprim (SMZ-TMP) + clindamycin injection + methylprednisolone injection to treat the PJP. Serum HIV antibody retests were performed using latex agglutination tests and western blotting; however, neither test detected the antibody (Fig. ). Two weeks after receiving anti-P. jirovecii treatment, the patient’s symptoms were mostly relieved, and chest CT revealed that the lung disease was mostly absorbed (Fig. ). Although the HIV antibody test results were negative or undetermined in three repeated examinations, because the patient was colonised with P. jirovecii and he was young and had low CD4+ T-cell levels, HIV infection could not be ruled out, and plasma HIV RNA testing was performed. Surprisingly, the results showed that the patient’s viral load was 32,4000 cp/ml, and the retest result also showed a high load of 17,5000 cp/ml; thus, HIV infection was confirmed. After the diagnosis, highly active antiretroviral therapy (HAART) was started with Dolutegravir + Truvada (FTC + TDF). After being hospitalised and observed for 1 week, the patient was discharged. At the time of discharge, the patient had no positive symptoms or signs other than a few scattered rashes on his body. |
pmc-6570927-1 | A 74-year-old woman with type 2 diabetes mellitus was admitted to our hospital for management of poorly-controlled diabetes. Diabetes, diagnosed at age 49 years, was treated with insulin injections. She was taking insulin glargine 14 units, insulin aspart 24 units, sitagliptin 50 mg and metformin 500 mg, daily, for treatment of hyperglycemia before the first admission. She was also administered antihypertensive, lipid-lowering and antiulcer medications (nifedipine 40 mg, trichlormethiazide 1 mg, rosuvastatin 2.5 mg and famotidine 20 mg per day). She had undergone cataract and pelvic fracture surgeries at 63 and 71 years of age, respectively. She had no history of diabetic ketoacidosis, diabetic coma, severe hypoglycemic episodes, impaired renal function, hepatic dysfunction or central nervous system manifestations, including chorea, before the first admission. She had no history of either smoking or habitual alcohol consumption.
This patient’s clinical course is presented in Fig. . No physical, including neurological, abnormalities were found. Glycosylated haemoglobin (HbA1c) and the serum glucose level on admission were 11.1% and 213 mg/dL, respectively. Intensive treatment with insulin injections was thus necessary. After several days, her glycemic control improved. The patient showed symptoms of hypoglycemia, such as palpitations and cold sweats, from a few days to 1 day before the first attack of hemichorea. Hypoglycemia was managed with glucose ingestion. The last symptomatic hypoglycemic episode during hospitalization appeared 1 day prior to the first hemichorea attack. Continuous glucose monitoring (CGM) was performed for daily evaluation of glycemic control, and the lowest serum glucose level measured during CGM was 49 mg/dl.
On the 19th hospital day, sudden involuntary movements involving the left face, shoulder, arm and leg [see Additional file ] were observed. These involuntary movements were exacerbated by stress, but diminished during sleep. No other remarkable neurological abnormalities were noted and there was no muscle weakness in either the upper or the lower limbs. A brain MRI scan was obtained during the involuntary movements. However, no abnormal high-intensity areas on T1-weighted images associated with the involuntary movements were detected in either the putamen or the striatum (Fig. a). In addition, there were no abnormal signal intensity findings in the putamen were on T2-weighted, FLAIR, or diffusion-weighted images. Neither the cerebral nor the carotid artery was stenotic on brain MR angiography imaging and carotid ultrasonography. She had no family history of diseases characterized by involuntary movements, such as Huntington’s disease. In addition, our patient’s thyroid functions were within normal range and serum thyroid autoantibodies were negative. Collagen disease antinuclear antibodies and antiphospholipid antibody were also negative. These data pointed away from Hashimoto encephalopathy or encephalopathy associated with collagen diseases such as antiphospholipid antibody syndrome. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) seemed very unlikely because none of the typical clinical abnormalities associated with this disease (mental disorder, cardiomyopathy, or deafness, etc.) was present. In addition, infection- associated forms of hemichorea, such as Sydenham’s chorea, seemed very unlikely because our case had no history of infectious disease from several months before admission. Furthermore, the last symptomatic hypoglycemic episode had occurred 1 day before the onset of hemichorea, and the clinical course and examinations of our case showed no diagnostic indications of other etiologies of chorea unrelated to hypoglycemia- associated chorea. We thus speculate that the choreiform movements in this case, while not being accompanied by abnormal high- intensity in the contralateral putamen on T1-weighted brain MRI scans, were associated with hypoglycemic episodes.
Administration of dopamine receptor antagonists (tiapride 50 mg and haloperidol 0.75 mg per day, respectively) was initiated. During the first 4 days after the chorea attack, choreic movements occurred frequently and persisted for several hours, but the frequency of such involuntary movements decreased 5 days after the onset. Her involuntary movements showed improvement at 8 days after the onset of hemichorea. She was discharged on a maintenance regimen of dopamine receptor antagonists. A brain MRI scan was obtained 1 month after discharge, and again no remarkable changes were recognizable (Fig. b).
12 months after the first admission, she required readmission due to marked deterioration of glycemic control. Her HbA1c levels ranged from 10.0 to 12.0% during the time between admissions, but she had been free of hemichorea. She received intensive treatment consisting of food intake restriction and an increased insulin dosage, leading to improved glycemic control. No hypoglycemic episodes occurred during the second hospitalization. Follow-up brain MRI showed no remarkable changes (Fig. c). Dopamine receptor antagonists were discontinued before discharge. 1 month later, i.e. 38 days after administration of these medications had been stopped, the left-sided hemichorea recurred. Her serum glucose levels, measured with a self-monitoring device during the few days before the hemichorea re-manifested, had ranged from 187 to 231 mg/dL. The severity of hemichorea at recurrence was milder than that during the first episode. No brain MRI changes associated with hemichorea were detected at the time of recurrence (Fig. d). She resumed taking the dopamine receptor antagonists and the recurrent hemichorea showed immediate improvement. In the 5 years, to date, since restarting the dopamine receptor antagonists she has experienced no further episodes of hemichorea. |
pmc-6570942-1 | A 42-year-old man presented to the emergency room with intermittent diarrhea for over four months and progressive lower extremity edema for three months. He had 5–6 bowel movements per day, with no obvious fever or abdominal discomfort. Progressive pitting edema of the bilateral legs was noticed one month later, accompanied by a decline in exertional tolerance. The patient lost approximately 15 kg over this period of time. A series of echocardiographic examinations had revealed a growing mass in his left atrium of uncertain origin, which grew from 25 × 22 to 60 × 54 mm within 3 months. His previous medical history was remarkable for poorly controlled type 2 diabetes mellitus complicated by diabetic nephropathy, retinopathy and peripheral neuropathy. He also had a five-year history of major depressive disorder without regular treatment. He lived with his mother and sister in the city of Qingdao, Shandong Province, and denied any recent travel history. The patient’s sister reported that he had intermittently consumed raw river fish for as long as 6–7 years before onset of this episode. Due to the mental status of the patient, his medical history was also obtained and confirmed by his mother and sister who lived with him.
On admission, the patient appeared emaciated and anemic. He was afebrile, his blood pressure was 93/67 mmHg, and heart rate 102 bpm. He was moody, disoriented, and slightly hypoxemic with an oxygen saturation of 90% at room air. A grade II diastolic rumbling murmur was heard at the apex. Examination of his lungs and abdomen was otherwise unremarkable. Decreased myodynamia of the bilateral limbs was appreciated, more significant on the left side, with a positive left Babinski sign.
Initial laboratory assessment revealed peripheral eosinophilia (eosinophils 6.64 × 109/L) and anemia (hemoglobin 85 g/L). The level of gamma-glutamyl transpeptidase was elevated at 1093 U/L, and alkaline phosphatase was 666 U/L, with no apparent hyperbilirubinemia (Table ). Serial of electrocardiograms showed paroxysmal atrial fibrillation. A bedside echocardiogram was immediately arranged, and a space-occupying lesion measuring 60 × 54 mm was identified in the left atrium with a slight pericardial effusion (Fig. a). The left ventricular ejection fraction (LVEF) was moderately reduced at the level of 55%. The initial chest CT showed scattered bilateral pulmonary infiltrations and pleural effusion, with a cavity in the right upper lobe. Abdominal CT scan showed intrahepatic bile duct dilatation with no obvious obstruction (Fig. b). A CT scan of the head was also preformed due to recurrent episodes of seizures during hospitalization, and showed low density lesions in bilateral corona radiate.
The initial differential diagnosis included infectious endocarditis, Löffler endocarditis, hypereosinophilic syndrome, parasitic infection and hypersensitive reactions to recent medication. Although no evidence of fungus was identified from qualified sputum samples, sulperazon and caspofungin were initiated empirically based on the CT manifestation and history of uncontrolled diabetes. Supportive care was also initiated. A multi-disciplinary discussion was held, and consensus was achieved regarding the urgency of cardiac surgery, both to alleviate progressive heart failure and to obtain a tissue specimen for diagnostic purposes. The patient underwent the surgery two weeks following admission. Surprisingly, the cardiac mass turned out to be an endocardial hematoma, possibly due to mechanical perforation of the left ventricular posterior wall close to the base of posterior mitral valve (Fig. c). The valves were otherwise intact. Pathological review of the specimen revealed nonspecific inflammation and all pathogenic examinations turned out to be unremarkable.
The surgical findings largely ruled out endocarditis of infectious or autoimmune origin, nor did they reveal any evidence of eosinophilic infiltration. Given the systemic involvement and the dietary habits mentioned by his family, we began to consider the possibility of parasitic infection with systemic involvement. A more detailed history confirmed raw or half-raw consumption of freshwater fish and shrimps, frogs, tadpoles and snake gall bladders nearly every month in recent years as a result of his altered mental status. Further tests were warranted. Multiple stool samples were sent for microscopic examination by direct fecal smear, and various eggs were identified. Eggs of Clonorchis sinensis were first identified (measuring 27-30 μm × 16-18 μm, Fig. d), at a count of 3–5/low-power (LP) field. Clonorchiasis was therefore confirmed, which partially explained the patient’s chronic diarrhea and dilatation of intrahepatic bile ducts. However, this liver fluke rarely causes such widespread organ damage. A few days later, another type of egg smaller than that of C. sinensis was identified, which was morphologically most consistent with that of heterophyid trematodes (measuring 23-26 μm × 13-15 μm, Fig. d). The eggs of Heterophyidae were much fewer in number, and required 10–20 LP field to find one. Moreover, several large-sized eggs were also observed (measuring 100-110 μm × 60-70 μm), consistent with those of the Echinostomatidae family (Fig. e). Approximately five eggs of the Echinostomatidae could be identified per fecal smear. Further evaluations included a contrast-enhanced cerebral magnetic resonance imaging test with angiography, which revealed multiple long T2 densities in the centrum semiovale with no obvious vascular involvement. Lumbar puncture was performed and showed moderately elevated intracranial pressure at 210 mmH2O and a slightly elevated protein level in the cerebral spinal fluid. A colonoscopy was apparently normal, but deposition of C. sinensis eggs was later observed on ileocecal squash slides. Specific PCR band patterns of C. sinensis were later observed in samples of the ileocecal tissues and stool, but not in the sputum or heart tissues. DNA of heterophyid trematodes was not detected from any obtained samples. The primers of PCR were designed according to previous studies (Additional file : Table S1).
Once the diagnosis of triple trematodiases was established, treatment with praziquantel was started. Due to the comprehensive involvement and the concern for hypersensitivity reaction, a reduced oral dose of praziquantel at 25 mg/kg/d was initiated for the first 10 days combined with low-dose dexamethasone. The patient tolerated this regimen well and received the full dose of 75 mg/kg/d for ten days each month for another consecutive two months. His diarrhea gradually resolved with a steady improvement in nutritional status and cardiac function. Continuous surveillance of his stool samples revealed no further trematode eggs since the second month of treatment. Follow-up CT scans showed remission of pulmonary and liver lesions, while enhanced MRI showed absorption of previous abnormal signals in centrum semiovale. |
pmc-6570946-1 | A case of C.X.Z, male aged 39-year old, and farmer by profession was wheeled into our department with severe symptoms of subacute RHF. His spouse narrated that in January,2018, he had experienced mild bilateral swelling of lower limbs (in form of stockings), and was managed on diuretics for about 7 days, after which symptoms disappeared completely. She denied him having had any cardiac surgery, chest radiation, tuberculosis or significant chest trauma. 8 months after initial symptoms, thus in October,2018, he suddenly developed chest pain, which he thought was due to long working hours in the field. On-counter remedies (pain killers) offered temporal relief. After 2-days of progressive chest pain, patient begun experiencing abdominal discomfort and observed swelling of feet after bed. On the 4th day in his illness, he developed shortness, a development that prompted him seek medical attention.
On presentation the patient through his spouse complained of breathing difficulties, abdominal fullness and swelling of lower limbs. She further narrated that, during bed time, shortness of breath worsened upon lying flat. During physical examination, patient exhibited incoherent talk, responded to various questions with same answer repeatedly. Both the neck veins (JVD~ > 15mmH2O) and abdomen were highly distended. Chest auscultation demonstrated a ‘cardiac knock’, and both S1 and S2 were muffled. Abdominal palpation revealed gross ascites. The lower extremities were cold to touch with bilateral pitting edema from knee and below. Prior and post procedure vitals are tabulated in Table..
Diagnosis of localized CP was established using cogent imaging results of comprehensive transthoracic echocardiography (TTE) and computed tomography(CTA). A 4 chamber video clip (Additional file ) of a 2D TTE examination demonstrates dyskinesia of the right ventricle(RV) due to the presence of a thickened (calcified) pericardium(cyst-like) on its anterior wall. Other visible abnormalities include: right atrium enlargement, respirophasic interventricular deviation into left ventricle and shudder, scientifically proven to be due to the differential filling rates of both ventricles in diastole. A comprehensive TTE report (not shown here) demonstrated hepatic vein distension, a patent inferior vena cava (with no respirophasic variation) and ejection fraction(EF) of 50%. The chest radiography appeared normal (Panel A). However, CTA uncovered two adjacent pads of calcification with interposed fluid: panels B and C (Fig. ).Because CP is relatively common in our region,radiology personnel have gained experience in diagnosing CP with occasional application of the Swan-Ganz catheter.
Through standard midline sternotomy, an off-pump partial pericardiectomy was performed from cardiac surgery operation room. Using a combination of cautery, scissors and sharp hooks, we approached the pericardium from the free RV wall (junction with right atrium). After 30 to 40 min into decortication process, we judiciously punctured a plate of calcified tissue overlaying the anterior RV wall with subsequent gush of a ῾milk-like’ fluid(approx.700mls). Fluid decompression led to adjustments of ventriculae pressures and cardiac out-put. The video in (Additional file ) shows the heart beating with less obstruction. Fluid sample results and pericardium tissue pathological report are depicted in (Table ) and (Fig. ) respectively. |
pmc-6570964-1 | A 4-day-old baby girl was referred from a paediatric tertiary care hospital for the genetic evaluation of bilateral asymmetric ectrodactyly. She is the second child of a non-consanguineous couple; a 25-year-old father and 23-year-old mother. The baby was delivered normally at term following an uncomplicated pregnancy. The birth weight was 2.5 kg and there were no post-natal complications. She had ectrodactyly involving three limbs, with the absence of the third digit on the left hand and the second and third digits on the right hand. The right thumb was clinically normal, but the fourth and fifth digits were malformed. The right foot had fixed clubfoot deformity with only 2 toes (Fig. ). There was no facial dysmorphism or facial clefts. Radiographs of the upper limbs showed complete absence of the metacarpal bone and the phalanges of the third digit in the left hand and absent metacarpals and phalanges of two digits on the right hand (Fig. ). During a subsequent evaluation of the proband at the pediatric clinic, right tibial hemimelia was documented in the patient’s medical records by the attending clinician, but the radiological images of the leg were not available for inclusion in this article. Cardiovascular, respiratory and abdominal examination showed no abnormalities. Ultrasonography of the abdomen, brain and bilateral hips were normal.
The mother also had bilateral ectrodactyly involving both hands, with the absence of the third digit on the right hand and two digits on the left hand. She had bi-phalangeal fifth digit on the left hand (Fig. ). She had not previously been investigated for this condition and was otherwise healthy without any remarkable events in the medical and obstetrics history. The first child of the couple who was aged 2 ½ years old at the time of consultation had normal growth and development with no congenital anomalies. There were no other family members or close relatives affected with similar limb deformities or other congenital anomalies.
Peripheral venous blood samples were obtained from the baby and the mother with informed written consent. Genomic DNA was extracted from the blood samples and quantitative polymerase chain reaction (qPCR) was performed to identify rearrangements of the BHLHA9 gene (Chr17:1173858–1,174,565, hg19)(Ref Seq BHLHA9:NM_001164405). The RPPH1 gene (NR_002312) was used as the gene of reference. The qPCR results showed a BHLHA9/RPPH1 ratio of 1.46 in the baby and 1.50 in the mother confirming the BHLHA9 gene duplication. The unaffected sibling was not available for genetic assessment of her BHLHA9 status. Genetic counseling was offered to the family.
At the time of reporting, the baby was 10 months of age. Her body weight was 7.95 kg (25th centile), length was 72 cm (above 50th centile) and head circumference was 44 cm (between 25th and 50th centile). She had age-appropriate developmental milestones. Hearing and visual assessments were normal. Repeat ultrasonography of the brain and the abdomen showed no abnormalities. 2D-echocardiography showed a structurally and functionally normal heart. She is currently being followed up at the pediatric tertiary care hospital and awaiting reconstructive surgery. |
pmc-6570968-1 | An 11-year-old Asian girl presented with headache and skin rash on the left side of her chest that had begun 3 days earlier. She had been diagnosed with varicella when she was 2 years old and therefore had no history of receiving the VZV vaccine. She did not have any episode associated with primary immunodeficiency.
Before the onset of illness, she had been feeling fatigue due to exhaustive preparation for a school gymnastics event over the course of several weeks. She visited the local clinic due to repeated afebrile vomiting and severe headache. On the same day, she was admitted to our hospital with a concern of meningitis.
Upon her admission, physical examination revealed a body temperature of 37.2 °C, respiratory rate of 20 breaths/min, heart rate of 85 beats/min, and normal hemodynamic parameters with blood pressure of 117/68 mmHg. She was noted to have a maculopapular rash evolving into vesicles with erythematous regions on the left side of her chest (Fig. ). Her consciousness was clear, and her deep tendon reflexes were normal; Kernig’s sign was negative, although she had neck stiffness.
A cerebrospinal fluid (CSF) examination revealed normal protein concentration (36 mg/dl), normal glucose level (47 mg/dl; blood glucose level, 92 mg/dl), and lymphocytic pleocytosis (429 lymphocytes/μl). Bacterial culture of CSF yielded no growth. Varicella zoster virus (VZV) deoxyribonucleic acid (DNA) was detected in CSF by polymerase chain reaction (PCR) on day 5. Results of blood examination were within normal ranges, including white blood cells (7180/μl), leukocytes (5220/μl), lymphocytes (1507/μl), monocytes (287/μl), eosinophils (43/μl), and basophils (28/μl). Results of VZV anticomplement immunofluorescence studies revealed values of 19 mg/dl for immunoglobulin G (IgG) and below 1 mg/dl for IgM, which indicates the previous infection and acquisition of humoral immunity against VZV. Moreover, there was no increase in the inflammatory biomarker levels. She had normal levels of quantitative immunoglobulins and lymphocyte markers: IgG 1106 mg/dl (normal range, 870–1700 mg/dl), IgA 71 mg/dl (normal range, 110–410 mg/dl), IgM 132 mg/dl (normal range, 46–260 mg/dl), CD3 71.6% (normal range, 59–88%), CD4 32.1% (normal range, 29–65%), CD8 38.8% (normal range, 13–40%), CD4/CD8 ratio 0.83 (normal range, 0.9–3.2), CD19 12.8% (normal range, 4–26%), and CD56 15.5% (normal range, 2–26%).
She was diagnosed with aseptic meningitis and cutaneous manifestation of herpes zoster despite immunocompetence. Acyclovir (45 mg/kg/day) was administered intravenously for 3 days from admission. Because the symptoms of headache, neck stiffness, and skin rash eventually resolved, treatment was switched to oral valacyclovir (75 mg/kg/day) for another 10 days. Given the favorable evolution of the illness, she was discharged from the hospital on day 8. She had no apparent sequelae or comorbidities at the time of the 6-week follow-up. |
pmc-6570972-1 | A 17-year old boy without significant past medical history presented himself with a 6-month history of back pain in May 2015. Physical examination revealed a huge abdominal mass, and subsequent magnetic resonance imaging verified a giant multifocal tumor with solid and cystic formations filling the space of the retroperitoneum, continuing to the posterior mediastinum and the small pelvis, in transversal diameter measuring 214 × 144 mm. He hadn’t noticed an enlarging mass in the right testicle for several months prior. Consequently, right orchiectomy was performed, and histology revealed mature teratoma. A staging computer tomography (CT) scan confirmed a huge retroperitoneal tumor and revealed also left supraclavicular lymphadenopathy and numerous bilateral lung metastases (Fig. ). Metastatic involvement and high levels of human beta-choriogonadotropin (bHCG) 23,594 IU/L and alpha-fetoprotein (AFP) 2159 mIU/L classified the patient into the intermediate prognostic group based on the International Germ Cell Cancer Collaborative Group classification []. He was treated with 5 cycles of Cyclo-BEP (cyclofosfamide, bleomycin, etoposide, cisplatin) in the Children’s Oncology Hospital with minimal tumor regression and a slow decrease of tumor markers. In that time our institution was consulted, and our head surgeon suggested a few step surgery. However, the patient declined. He was given second line chemotherapy TIP (paclitaxel, ifosfamide and cisplatin), but after one cycle patient decided not to continue. From December 2016 he was followed for 10 months. During this time the disease was stable, there was an almost complete normalization of bHCG and a slightly elevated AFP (21.4 mIU/L) with discrete growing of abdominal tumor mass. Therefore, a diagnosis of growing teratoma syndrome was established. In September 2017, due to clinical deterioration, weight loss, necessity of opioid analgesis to control backache and recurrent acute renal failure after insertion of bilateral nephrostomies, he finally accepted operation.
Patient was admitted 1 week before scheduled surgery for nutritional support, preoperative anesthesiologic evaluation, and isotope renography to evaluate actual renal functions.
Complete tumor resection in the abdomen as well as in the mediastinum was planned, leaving the supraclavicular tumor for subsequent surgery if needed. As isotope renography revealed a functionless right kidney, autotransplantation of the left kidney was planned at the end of the procedure. Patient and family were informed about the probability of losing both kidneys. Together with vascular surgeons we considered performing a two-stage procedure – an extra anatomic bypass (axillo –bifemoral) first, followed by subsequent tumor resection to achieve ischemia-reperfusion time shorter. Based on our previous experiences we decided to perform a one stage procedure while selectively considering the need of the extra anatomic bypass intraoperatively – in regards to the estimated length of the aortal and caval clamping. We planned to perform Y bypass reconstruction of the aorta as well as the inferior caval vein with optional left kidney autotransplantation according to intraoperative finding on the left renal vessels.
After the extensive laparotomy allowing good access, a huge tumor completely filling the abdominal cavity was visible (Fig. ). We found the tumor resectable as it was possible to access the aorta safely just in the level of superior mesenteric artery (SMA). Due to encasing of the left kidney’s vessels by the tumor mass, autotransplantation was not possible. We started with tumor resection, a complete mobilization of liver, small bowel and large bowel was performed yet no infiltration of above-mentioned structures was presented. During mobilization of the duodenum and pancreatic head and body we found infiltration of the third part of the duodenum so segmental resection using stapling devices was performed. Afterwards we encircled the aorta above the renal arteries and below the SMA, and the inferior caval vein (IVC) below the caudate lobe, common iliac arteries and external iliac veins. After medial frenotomy we did mobilization of the mediastinal part of the tumor. As we had very good exposure and complete access to important vessels, we estimated that the time of ischemia-reperfusion will be certainly less than 120 min, so we decided to not use extraanatomic bypass. After administration of Heparin – in the dose of 100 units per kilogram, we put clamps on the aorta, IVC and iliac vessels and we finished the resection of the tumor by separating it from the vertebral columns and psoas muscles (Fig. ). The function of the left kidney was preserved until clamping during the whole resectional part of the procedure, with intraoperative urine output 0.66 ml/kg/hour in average. Subsequently we started reconstruction: we did proximal aortal anastomosis and due to the short segment of the aorta below the celiac trunk, we did reinsertion of the SMA to the prosthesis. During the creating of the distal arterial anastomosis the anesthesiologist reported cardiac arrhythmias with no pulse waves detected. Complete resuscitation using manual direct heart massage and complete pharmacologic support was started. Emergent perioperative blood tests revealed severe hyperkalemia (8.3 mmol/l), severe acidosis (pH 7.05), hyperphosfatemia (2.98 mmol/l) and hypercalcaemia (2.87 mmol/l) due to the administration of calcium chloratum after each blood transfusion - 3 units in total. The serum creatinine level was slightly elevated (135 μmol/l) and serum hemoglobin after substitution was 98 g/l. Even after complete cardiopulmonic resuscitation, administration of natrium bicarbonate, i.v. glucose with insulin, another calcium chloratum with the aim to decrease serum potassium level and after serial electric defibrillations due to ventricular fibrillation, the patient developed asystolia and, after 40 min of complete resuscitation, exitus was stated. After reviewing the clinical case and the evidence, cardiac failure was established as the cause of patient’s death by the pathologist after autopsy.
The final pathology report describes large encapsulated tumor mass mesauring 33x25x13 cm, the mass show grey-brown color, with multifocal cysts with gelatinous and serous material (Fig. ). Histology showed tissue arrangements mimicking organoid morphology, mature glandular tissue of the skin, respiratory tract and gastrointestinal tract: cysts lines by respiratory type of epithelium and intestinal epithelium with goblet cells, surrounded by smooth muscle and adipose tissue and cartilage, intraluminally was found mucoid areas with multinucleated giant cells, without cytologic atypia or necrosis and minimal mitoses, without original structures of lymphoid tissue (Fig. ). It was not provided 12p amplification. Immunohistochemistry: AE+/3+, CD117-, CEA+, PLAP-, HCG-, CD30-, LCA-, CDX2+. The final diagnosis was postchemoterapy lymph node metastases from mature teratoma. |
pmc-6571118-1 | A 62-year-old white man first sought treatment for a subacute subdural hematoma of the left frontal lobe, for which he underwent trepanation. The neurological examinations done with contrast-enhanced MRI showed an elongated collection of hyperintense signals on T2, with peripheral enhancement, measuring 61 × 16 mm in the left frontal lobe, which characterized a subacute subdural hematoma. A solid tumor measuring 4.0 × 2.5 cm, occupying the base of the skull with total invasion of the sphenoid and the cavernous sinuses presenting suprasellar expansion was also observed. The tumor reached the optic chiasm and invaded the nasal area (Fig. a–c). A diagnosis of pituitary macroadenoma was made, but the occurrence of chordoma, metastasis, or cancer of the sphenoid sinus was also suspected.
The patient reported decreased libido and sexual impotence that had started 14 years earlier. He presented with no visual impairment and was a nonprofessional shooting competitor. He had astigmatism; his campimetry result was normal; and he did not complain of headaches.
Two-dimensional color flow Doppler echocardiography revealed a double aortic valve lesion with moderate stenosis, as well as concentric left ventricular hypertrophy with normal global and segmental systolic functions and left ventricular diastolic dysfunction. This pattern did not change throughout treatment.
At diagnosis, the patient had a prolactin level of 14,992 ng/ml (normal value < 17 ng/ml for males), follicle-stimulating hormone 0.5 IU/L (normal value up to 10 IU/L), luteinizing hormone 0.5 IU/L (normal value up to 9 IU/L), total testosterone 260 ng/dl (normal value 240 to 816 ng/ml), cortisol 25 μg/dl at 8 h (normal value 5.4 to 25 μg/dl), and 15 μg/dl at 16 h (normal value 2.4 to 13.6 μg/dl). The normal levels of cortisol secretion were preserved throughout treatment. During follow-up, the patient developed secondary hypothyroidism with thyroid-stimulating hormone (1.7 μIU/ml but free thyroxine 0.83 ng/dl, and replacement with 50 μg of levothyroxine was initiated. The patient’s complete blood count, electrolytes, urea, creatinine, glutamic pyruvic aminotransferase, glutamic oxaloacetic aminotransferase, γ-glutamyl transpeptidase, calcium, and phosphorus were normal during the 17 years of observation.
Cabergoline treatment was initiated 2 months after diagnosis. The prolactin response is shown in Fig. . The prolactin level dropped from 14,922 ng/ml to 1717 ng/ml in the first 2 months of treatment with a 1.0-mg agonist. Nevertheless, the patient’s prolactin level remained high at 840 ng/ml even when taking a higher dose of cabergoline agonist of 3.5 mg per week for 48 months. At 111 months of treatment, quetiapine and mirtazapine were introduced, and the cabergoline was maintained, for treatment of psychotic conditions (see description below), causing a transient increase in prolactin that remained high until the last evaluation, 17 years after treatment was initiated.
After 4 months of cabergoline use, the prolactin level dropped to 646 ng/ml, but the testosterone level remained low (280 ng/dl), and sexual impotence persisted. Testosterone replacement was started, and the patient’s sexual activity normalized.
The patient presented with type 2 diabetes mellitus at first evaluation that was controlled with diet, metformin, and vildagliptin 50 mg. Glycated hemoglobin remained between 6.0% and 7.8% (normal value 4–6%). The patient also had high blood pressure. At the last evaluation, he was using indapamide 1.5 mg, bisoprolol hemifumarate 2.5 mg, amlodipine 5 mg, captopril 50 mg twice daily, and potassium chloride 600 mg twice daily. At age 67, and after 5 years of taking 2.0 mg of cabergoline weekly, the patient’s prolactin level was 1049 ng/ml. The patient underwent coronary angioplasty with stent placement due to unstable and progressive angina.
At age 69 and after 7 years of taking 2.0 mg of cabergoline weekly, the patient had a stroke. A computed tomographic scan showed right temporal intraparenchymal hemorrhage with ventricular flood. After neurosurgical interventions, the patient received phenytoin or carbamazepine for a few months.
One year after this event, he developed psychiatric alterations with persecutory delusion; he claimed that his neighbor was going to attack him. He also presented aggressive behavior with friends and family and demanded to have his firearm, which was used only for firing competitions, given back to him so he could defend himself, a behavior he had not presented previously. Initially, a 25-mg dose of quetiapine four times per day was used to control the psychiatric crisis. The dose was then changed to 100 mg once to three times daily as needed to control psychiatric symptoms; in the latter evaluation, he was taking 100 mg twice daily. Mirtazapine 30 mg every night was used throughout this period. Owing to the psychiatric outburst, the patient was maintained on a lower dose of cabergoline (1.5 mg per week) until the last evaluation.
MRI evaluation of the tumor at 8 months and again at 17 months of taking 1.5 mg of cabergoline weekly showed no changes in tumor characteristics. The patient was lost to follow-up for 3 years; during this time, he used 3.5 mg of cabergoline weekly. MRI evaluation at 41 months of treatment showed partial regression of the adenoma, especially where it invaded the sphenoid sinus, but there was still invasion of the cavernous sinus on both sides but no suprasellar expansion. Figure shows the images obtained in the last evaluations done at 17 years of treatment. Figure a shows a significant decrease in the pituitary adenoma with significant changes in the invasion pattern of the cavernous sinuses and the sphenoid sinus; the optical chiasm was downward. Figure b shows the tumor with heterogeneous contrast uptake and less invasion of the cavernous and sphenoid sinuses than when treatment began. Figure c shows heterogeneous uptake of contrast by the tumor with invasion of the sphenoid sinus and pituitary stalk. Figure d shows cystic degeneration of the tumor, hypersignal of the right temporal lobe, slightly dilated ventricles, and enlargement of the cerebral sinus. |
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.