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pmc-6426556-1 | A 48-year-old Hispanic female with no significant medical history presented to the clinic with a two-year history of multiple medical complaints, including occasional low-grade fevers, intermittent chills, night sweats, recurrent episodes of left eye pain with redness, pleuritic chest pains, intermittent abdominal pain, diffuse myalgias and achiness on the left side of her face, fatigue, hair loss, and unintentional weight loss of 30 pounds. A review of systems revealed insomnia and a pruritic rash on her right hand and right foot that began two days prior to presentation.
The patient denied recent travel, oral/nasal ulcers, joint swelling, morning stiffness, Raynaud’s, photosensitivity, malar rash, or sicca symptoms. A recent short course of oral glucocorticoids helped with her pleuritic pain. She had a history of eight miscarriages and mentioned that past workup had been negative for antiphospholipid syndrome. Multiple specialists had evaluated her over the past two years without a clear unifying diagnosis. The patient denied a family history of malignancy, connective tissue disease, or any autoimmune disorder.
Her physical exam revealed a temperature of 98.8°F, blood pressure of 136/94, and heart rate of 110. The recent range in temperatures from outpatient encounters was within the range of 98.8-99.9°F. The patient was in no acute distress and appeared well-nourished. No oral or nasal lesions were appreciated, and her oropharynx was clear. Her left eye appeared injected and her neck was without adenopathy or thyromegaly. The cardiopulmonary exam was unremarkable. Diffuse tenderness was noted on the left metacarpophalangeal joints, wrist, elbow, and shoulder but the range of motion was normal and no deformities or joint swelling was noted. The skin exam revealed a dry patch of 5-centimeter diameter on the dorsum of the right foot without swelling. No Raynaud’s, telangiectasias, or skin ulcers were noted.
Recent cardiac testing revealed a negative stress test and echocardiogram, showing a small pericardial effusion with normal ventricular function. Recent labs were remarkable for an elevated erythrocyte sedimentation rate (ESR) of 106 mm/h, an elevated C-reactive protein (CRP) of 112 mg/L and a rheumatoid factor of 24 IU/ml. Anti-cyclic citrullinated peptide and antinuclear antibody panel, including antibodies for double-stranded deoxyribonucleic acid (DNA), Scl-70, Smith, RNP, SS-A, and SS-B were negative. Levels of complement C3 and C4, ferritin, creatine kinase, and serum protein electrophoresis were noted within normal range. Erythrocyte sedimentation rate (ESR) and CRP levels normalized with a course of oral steroids but subsequently increased after cessation of therapy.
The patient was referred to ophthalmology and diagnosed with left eye scleritis that resolved with steroid eye drops. The patient was evaluated by oncology and infectious disease and thought not to have an underlying malignancy or infection. Considering the constellation of symptoms, the patient was then evaluated for a periodic fever syndrome. Genetic testing ultimately revealed and confirmed the diagnosis of TRAPS. The patient was then started on treatment with an interleukin-one (IL-one) antagonist canakinumab, resulting in significant improvement of myalgias, achiness, fatigue, chills, and hair loss. Within eight weeks of initiating therapy, she reported great relief of her symptomatic burden with the resolution of chest pain, rashes, scleritis, and fevers. Her ESR and CRP both normalized. Notably, the patient's 26-year-old nephew had experienced similar symptoms since childhood, including migratory myalgias, cyclical chills, and night sweats. The identification and successful treatment of our patient's disease led to genetic testing, confirmation and successful treatment of her nephew with the IL-one inhibitor canakinumab. |
pmc-6426565-1 | A 22-year-old male patient presented with episodes of intermittent lower abdominal pain, burning micturition, and an abdominal lump in the lumbar region to the right of midline lasting for three months. The lump moved on inspiration and measured approximately 3.7 cm x 2.6 cm. The results of the patient’s renal function tests were within the reference range. An abdominal ultrasound (US) revealed a calculus measuring approximately 2 cm x 1.8 cm in the renal pelvis with obstructive features in the form of mild hydronephrosis on the right side. We did not see his left kidney in the left renal fossa. However, we noted a second kidney on the right side fused to the lower pole of the right kidney. Non-contrast computed tomography (CT) of the abdomen confirmed the US findings (Figure ).
On administration of intravenous non-ionic contrast agent, we noted a single ureter draining the collecting system of both the kidneys and terminally opening ipsilaterally into the urinary bladder (Figure ).
However, the left ureter was absent. We noted a subtle thickening of the urinary bladder wall. The fused kidneys were supplied by two renal arteries originating from the left internal iliac artery. A three-dimensional volume-rendering technique revealed a single renal vein draining the fused renal parenchyma into the inferior vena cava (Figure ) and a single ureter draining the crossed fused kidneys into the urinary bladder on the same side (Figure ).
We saw no associated congenital skeletal abnormalities. However, the patient is under follow-up as such cases may show malignant transformation. |
pmc-6426569-1 | A 76-year-old Caucasian woman with a past medical history of hypertension, hypercholesterolemia, and tobacco use presented with a three-week history of progressively worsening left-sided incomplete ptosis. This was accompanied by discomfort in the occipital and upper cervical region. She denied vision changes and eye pain. Her pupils were equal, round, and reactive to light and accommodation, and she displayed no other focal neurological deficits on physical exam. Brain magnetic resonance imaging (MRI) and MRA performed prior to the acute presentation of symptoms showed a 4 mm ipsilateral left PCOM aneurysm. Cerebral DSA performed on admission confirmed a fetal left PCOM with a broad-necked, smooth-walled 4 mm unruptured aneurysm at its origin (Figure ).
Given her recent symptom onset and clinical worsening, the decision was made to perform a left craniotomy with clipping of the aneurysm. Intraoperatively, the non-aneurysmal portion of the left fetal PCOM was found to be compressing the left oculomotor nerve laterally, thus microvascular decompression was performed with a felt pledget, similar to the approach taken in a case of trigeminal neuralgia (Figure ).
The patient tolerated the surgery well and was discharged to rehab after an uneventful postoperative course. On clinical follow-up, her ONP had completely resolved. |
pmc-6426639-1 | A 76-year-old female presented with episodes of headache and double vision for over one month. Eight months prior to her current presentation, she developed abdominal pain and was found to have a large mediastinal mass with splenic lesions. A biopsy revealed large B cell non-Hodgkin’s lymphoma. Her lactate dehydrogenase at the time of diagnosis was 565 U/L. The patient received six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) followed by radiotherapy to the spleen. Her treatment had concluded two months prior to her current presentation. A whole body fludeoxyglucose positron emission tomography scan showed significant resolution of the mass with no uptake in the spleen. Her past medical history included transitional carcinoma of the bladder for which she had treatment. Examination revealed a reduced level of consciousness with right-sided fifth and sixth cranial nerve palsies.
Laboratory tests showed severe hyponatremia (serum sodium = 116 mmol/l), low serum osmolality (232 mOsm/kg), inappropriately raised urine osmolality (546 mOsm/kg), and raised urine sodium (54 mmol/L) suggestive of SIADH. A magnetic resonance imaging (MRI) scan of her head revealed abnormal T2 signal changes but no meningeal disease (Figures -). Magnetic resonance angiogram (MRA) of the head and carotids showed no evidence of stroke or dissection.
A lumbar puncture for cerebrospinal fluid examination was performed to identify spread from the previously resolved lymphoma and this revealed predominant lymphocytosis with raised protein (2.70 g/L). Further cytological examination revealed atypical lymphoid cells with predominant CD10+ B cells in keeping with the invasion of CNS by lymphoma (Table , Figure ).
The patient was managed with dexamethasone, 8 mg twice daily, and fluid restricted to 1 L/24 hrs initially, then to 750 mls/24 hrs for the next four days. On the fifth day, a titrating dose of demeclocycline, 150 mg once daily to 150 mg three times daily, was added with no effect. The hyponatremia responded to a single dose of tolvaptan, 15 mg (increasing to 129 mmol/L within eight hours) and reached normal limits by Day 13 (Figure ). After a specialist opinion, a palliative approach was taken as the patient had declined further treatment with methotrexate. The patient was kept comfortable in her last days of life and passed away peacefully. |
pmc-6426764-1 | Patient is a 43-year-old woman with KRAS mutated (G12V) metastatic mucinous adenocarcinoma who was first diagnosed at age 36 with widespread peritoneal disease. She subsequently underwent a debulking surgery followed by 4 cycles of FOLFOX-based chemotherapy, and then further debulking and hyperthermic chemotherapy (HIPEC) instillation. She completed a further 8 cycles of palliative FOLFOX with disease control for approximately 9 months. When her disease subsequently progressed, she was treated with FOLFIRI plus bevacizumab but suffered severe diarrhea requiring cessation of 5-FU at the time. After suffering a pulmonary embolism, irinotecan plus bevacizumab were stopped and the patient was treated with another round of cytoreductive surgery plus mitomycin-C based HIPEC.
Her disease remained stable for a subsequent 2 years until progression was noted on a PET-CT scan at which point she was started on zFOLFIRI. The patient stayed on therapy despite requiring a dose reduction for approximately 9 months after which time her scan showed stable disease. The decision was then made to treat her dominant pelvic mass with palliative XRT and she subsequently went onto maintenance capecitabine with the addition of bevacizumab for 17 months. Upon disease progression at that time, zFOLFIRI was restarted with stable disease for an additional 8 months with a continued response at the time of data censorship. The CEA trends observed in this patient showed reduction during both zFOLFIRI treatment periods (). |
pmc-6426764-2 | A 56-year-old man was diagnosed with KRAS G12C mutated stage IIIB rectosigmoid adenocarcinoma. Post-resection he was treated with adjuvant FOLFOX. 1.5 years later his disease recurred in the lungs and after a metastatectomy he was treated palliatively with FOLFIRI and bevacizumab for 11 months. At the point of disease progression, he was started on zFOLFIRI which he took for about 2 months. However, due to personal issues, the patient was lost to follow-up for roughly 3 months.
When he again presented to our clinic to reinitiate therapy, restaging scans taken at that time showed stable disease and he resumed treatment without issue. He remained on therapy for an additional 10 months after which he was lost to follow-up. His most recent restaging scans prior to him leaving our clinic showed ongoing disease stability. |
pmc-6426764-3 | A 42-year-old man was diagnosed with KRAS wild-type and BRAF D594N mutated stage III rectal carcinoma. He was started on capecitabine, oxaliplatin, and radiation and subsequently underwent an abdominal perineal resection followed by adjuvant capecitabine and oxaliplatin (XELOX) chemotherapy. After 1 year, the patient recurred with disease in the lungs, liver, and lymph nodes. He was started on a phase II trial of FOLFOX, bevacizumab and hydroxychloroquine but stopped after 6 months due to an oxaliplatin reaction and was treated with maintenance 5-FU plus bevacizumab and hydroxychloroquine.
His disease remained stable for approximately 18 months until he developed progressive disease in the lungs and liver, both of which were resected. However, his disease recurred in the liver, lungs, and retroperitoneum 4 months later and he was started on cetuximab, irinotecan, and ramucirumab on a separate clinical trial but disease unfortunately progressed after 2 months. He was then treated with trifluridine-tipiracil for roughly 1 year after which his disease progressed and he was started on zFOLFIRI. He had a grade 3 small bowel obstruction but once this resolved was able to stay on zFOLFIRI for 8 months prior to progression of disease. The patient survived for another 13.8 months from the time of initiation of zFOLFIRI. |
pmc-6426764-4 | A 44-year-old woman was diagnosed with sigmoid colonic adenocarcinoma with mesenteric adenopathy on CT scan, hemicolectomy revealed a stage IIIB tumor (T3N1M0) that was moderately differentiated. Post-resection, the patient was treated with adjuvant FOLFOX for 6 months and entered surveillance. Three years later her CEA began to rise with CT scan revealing new bilateral ovarian metastases which were biopsy proven as metastatic colonic adenocarcinoma. Analysis at that time was significant for a tumor BRAF V600E mutation. She was then treated with FOLFIRI for 4 cycles initially with bevacizumab, however due to delayed wound healing bevacizumab was held.
Restaging scans after 4 cycles showed progression of disease and therefore she was treated for 4 months with FOLFIRI and cetuximab, however her disease then continued to grow. Given her BRAF V600E mutation, she was treated with vemurafenib, irinotecan, and cetuximab (VIC) () with disease control for 6 months. She was then treated with dabrafenib, trametinib, and panitumumab (DTP) due data showing effectiveness of this combination in these patients (), however she progressed after 3 months. Given that she had never progressed on bevacizumab, she restarted FOLFIRI and bevacizumab which controlled disease for an additional 3 months. At time of progression, she was consented to zFOLFIRI. Despite grade 1 diarrhea, nausea, and vomiting she has tolerated therapy well and has ongoing stable disease at >4 months into treatment at time of censorship. |
pmc-6426764-5 | A 68-year-old man was first diagnosed with metastatic KRAS wild-type rectal cancer at the age of 65 and was treated with FOLFOX plus bevacizumab for 5 months and upon progression was treated with FOLFIRI plus cetuximab for a subsequent 8 months. He then underwent a resection of liver metastases and received radiation to the pelvic region for pain control. He then was continued on maintenance 5-fluorouracil plus capecitabine-based chemotherapy for 5 months after which time his cancer progressed and a liquid biopsy at that time revealed a KRAS Q61H mutation which was felt to be acquired from prior therapy with cetuximab. He was therefore consented to FOLFIRI plus bevacizumab. After 5 months of treatment on this regimen his cancer again progressed and he was consented to zFOLFIRI. On the zFOLFIRI regimen, the patient's disease initially regressed in the liver and then remained stable on multiple scans, allowing the patient to remain on treatment for 14 months with an ongoing response at time of data censorship. |
pmc-6426764-6 | A 52-year-old woman was diagnosed with stage IV KRAS G12C mutated rectosigmoid colonic adenocarcinoma involving the liver and was started on treatment with capecitabine, oxaliplatin, and bevacizumab. She was treated for 6 months with treatment response and subsequently underwent a liver-directed metastatectomy followed by resection of the primary tumor via a low anterior resection. She was then started on FOLFIRI plus bevacizumab after imaging showed progression of disease in the liver on which she was maintained for 4 months. At the time of disease progression, she was started on zFOLFIRI which showed a partial response in the liver. The patient was ultimately able to stay on this treatment for 18 months before imaging showed progression of her liver disease requiring cessation of this line of therapy. The patient ultimately expired 30 months after starting treatment with zFOLFIRI. |
pmc-6426986-1 | In November 2018, a six-year-old neutered male European shorthair cat, suffering from chronic conjunctivitis of the right eye, was referred to its local veterinary clinic in Deutschlandsberg, Austria (coordinates, 46° 48′ 58″ N, 15° 12′ 54″ E) (Fig. ). According to anamnestic data, first signs of ocular disease appeared 4–5 weeks before the cat was brought to the clinic. Ophthalmological examination revealed unilateral serous ocular discharge, conjunctival hyperemia, and mild conjunctival edema. Additionally, a thread-like motile worm was noticed under the nictitating membrane of the right eye. No other ocular abnormalities were detected. The parasite was retrieved using a forceps, placed in a tube with saline solution and sent to the Institute of Parasitology, University of Veterinary Medicine Vienna for morphological and molecular identification.
After removing the parasite, the cat was orally treated with milbemycin oxime 2 mg/kg and praziquantel 5 mg/kg (Milbemax®, Novartis Animal Health, France). In addition, tobramycin 3 mg/ml and dexamethasone 1 mg/ml eye drops (Tobradex®, Alcon Ophthalmika, Austria) were administrated twice a day in a 7-day treatment course. At a follow-up 2 weeks after the treatment, complete resolution of clinical signs was observed and no parasites were detected.
The nematode was identified as a female of T. callipaeda based on the specific morphological features (e.g., striated cuticula, hexagonal oral opening, vulva located anteriorly to the esophageal-intestinal junction, uterus filled with larvated eggs) (Otranto et al. ). Species identity was further confirmed by PCR amplification and sequencing of the cytochrome c oxidase subunit 1 (cox1) gene (Otranto et al. ). Nucleotide sequences derived from the adult nematode displayed 100% identity to the cox1 sequences of T. callipaeda haplotype-1 (GenBank® accession no. AM042549), which is the only haplotype circulating among animals and humans in Europe. |
pmc-6427215-1 | A 15-month-old white Caucasian girl with a negative personal medical clinical history was seen by her family pediatrician for the appearance of petechiae on the soft palate during the last 24 h. As she had been vaccinated with the measles-mumps-rubella (MMR) vaccine 12 days before and had presented a mild episode of febrile diarrhea 8 days beforehand, immune thrombocytopenic purpura (ITP) was suspected. However, a platelet count was immediately performed and excluded this diagnosis (171,000 platelets/mmc3). No drug was prescribed, and the decision was made to wait and see the evolution of the disease. The patient was moderately febrile during the following two days, with a maximum ear temperature of 38.3 °C. The fever disappeared on the third day, whereas the hemorrhagic rash progressively increased and extended to the skin in different parts of the body. The diameter of hemorrhagic lesions varied from few millimeters to several centimeters ().
Hospitalization was decided. At admission, the patient’s general condition was good, but a rash characterized by petechial-hemorrhagic lesions with sharp merges of varying sizes localized to the limbs, face and auricles associated with a strong oedematous component was evidenced ().
Moreover, on the second day of hospitalization, bilateral oedema of the metacarpophalangeal joints with joint pain appeared. The articular manifestations were responsive to analgesic therapy with paracetamol and resolved spontaneously in a week.
Blood counts, hepatic and renal function, C-reactive protein, coagulation, antineutrophil cytoplasmic autoantibodies, serology for Epstein Barr virus, cytomegalovirus, Rubella, Herpesvirus, parvovirus B19, fractions C3 and C4 of the complement, pharyngeal swab, blood culture, urinalysis, factor V leiden, D-dimer, erythrocyte sedimentation rate and peripheral blood smear were collected. The blood and serological tests showed an increase in C-reactive protein concentration (3.58 mg/dL) in the absence of leukocytosis and with a normal platelet count (180,000/mm3). The examination of the peripheral smear showed the presence of some large mononuclear elements with hyperbasophile cytoplasm. No alterations in platelet morphology were evidenced. Ultrasound examination of the abdomen and the urinary tract excluded visceral involvement. To avoid an invasive procedure in a child with an already well-defined diagnosis, cutaneous biopsy was avoided, given the good general condition of the patient.
The skin manifestations progressively diminished and disappeared spontaneously within 3 weeks, leaving no sequelae.
Management of the case was approved by the Ethics Committee of Santa Maria Hospital, Terni, Italy (2018-PED-01). The patient’s parents provided their written informed consent for the management of their child and the publication of the case report (including the Figures). |
pmc-6427864-1 | A 35-year-old Han Chinese male football player presented with abnormal ECGs for 8 years without any evident subjective discomfort. The patient recently complained about slight exertional dyspnea with reduced sport/physical tolerance and was admitted to our hospital. This patient had been employed as a professional football player from the age of 10 years and had been a physical education teacher from the age of 26 years. He was a longtime local resident and never went to any affected areas (areas with high prevalence of infectious diseases). He reported being formerly healthy without any medical histories or current comorbidities, and he reported taking no medications. He has smoked 20 cigarettes per day for 7 years and consumed alcohol for 10 years at 100 to 250 g per day. His parents were healthy, and his family history was unremarkable. His physical examination revealed no abnormal findings. His body temperature was 36.5 °C, blood pressure was 121/73 mmHg, respiratory rate was 18 breaths/min, pulse was 69/min, heart rate was 70 beats/min, and reflexes were normal. He had no pathology reflex, and his body mass index was 22.81 kg/m2. Laboratory evaluation revealed slightly elevated cardiac troponin T level of 0.017 ng/ml, N-terminal probrain natriuretic peptide level of 291.80 pg/ml, and C-reactive protein level of 0.40 mg/L. The patient’s blood lipid levels, liver function, and renal function were within the normal range with glutamic oxaloacetic transaminase level of 23 U/L, glutamic-pyruvic transaminase level of 31 U/L, alkaline phosphatase level of 84 U/L, total protein level of 67.9 g/L, albumin level of 41 g/L, globulin level of 26.9 g/L, total cholesterol level of 4.01 mmol/L, triglyceride level of 1.42 mmol/L, high-density lipoprotein level of 1.08 mmol/L, low-density lipoprotein level of 2.14 mmol/L, uric acid level of 353 μmol/L, epidermal growth factor receptor level of 105.48 ml/min/1.73 m2; serum K+ level of 4.05 mmol/L, serum Ca2+ level of 2.16 mmol/L, serum Mg2+ level of 0.88 mmol/L, and serum Na+ level of 141 mmol/L. The results of routine blood test and urinalysis were negative, thyroid function was normal, and microorganisms were not detected. Chest radiography showed an apparently normal morphology of the heart and lungs (Fig. ). ECGs revealed progressively deepened and widened Q waves on the II, III, and avF leads and contiguous TWIs on the I and avL leads (Fig. , Table ). Echocardiography revealed an increasingly thickened interventricular septum from 10 mm to 13 mm, an enlarged left atrium and ventricle, and a reduced left ventricular ejection fraction from 73% to 63% (Fig. ). Coronary angiography (CAG) was performed and showed no distinct stenosis. Emission computed tomography (ECT) revealed mild myocardial ischemia of the left ventricular inferior wall (Fig. ). All of these clinical tests supported the diagnosis of HCM, which became gradually evident with time. For further identification, we proposed other examination techniques for this patient, including cardiac magnetic resonance imaging (CMRI) to better evaluate the left ventricular wall thickness and to identify potential areas of myocardial fibrosis, Holter monitor recordings and an exercise test to evaluate possible “dynamic” changes of repolarization abnormalities, as well as genetic testing. However, the patient refused all of these suggestions and was discharged. In the subsequent follow-up visits at 1 month, 3 months, and 6 months after discharge, the patient showed poor compliance and was eventually lost to follow-up. |
pmc-6427873-1 | An 83-year-old Japanese man underwent PCI for a proximal stenosis in his left circumflex artery through a 7-Fr sheath from his right CFA. We used an EXOSEAL VCD for hemostasis after we confirmed no calcification at the puncture site of the CFA. We performed the plug implantation according to the manufacturer’s instructions without any complications. However, we could not achieve complete hemostasis just with this procedure. Therefore, we added manual compression for 10 minutes in total, and we finally completed hemostasis. The next day, he complained of short distance intermittent claudication.
His past medical history was significant for hypertension, chronic kidney disease, paroxysmal atrial fibrillation, and silent myocardial ischemia. His regular medications were dual-antiplatelet therapy of aspirin (100 mg) + prasugrel (3.75 mg), and an oral factor Xa inhibitor (apixaban, 2.5 mg twice daily). There was no family history. He was a farmer. He did not smoke tobacco and he was a social drinker. His physical examination revealed an absence of a right popliteal pulse. His right lower extremity was pallid and perishing cold without ulceration. There was no motor and sensory loss. His blood pressure was 170/75 mmHg, pulse rate was 70 beats/minute, oxygen saturation was 98%, and body temperature was 36.5 °C. The laboratory examination findings were as follows: serum creatinine 1.28 mg/dL, creatine phosphokinase (CPK) 1236 U/L, aspartate aminotransferase (AST) 45 U/L, alanine aminotransferase (ALT) 25 U/L, lactate dehydrogenase (LDH) 229 U/L, C-reactive protein 0.7 mg/dL, white blood cell count 4.63 × 103/μL, red blood cell count 11.6 × 106/μL, and platelet count 176 × 103/μL. His blood culture was negative.
A chest X-ray demonstrated no abnormal findings. Electrocardiography showed normal sinus rhythm and complete left bundle branch block. On echocardiography, the left ventricular ejection fraction was 42% and diffuse motion abnormality in his left ventricle was observed. His ankle-brachial pressure index could not be measured on his right leg. Doppler ultrasound demonstrated no stenosis or occlusion in the visible area of his right CFA and superficial femoral artery (SFA). However, in his right POP-A, the acceleration time was prolonged up to 125 msec, and the blood flow pattern was monophasic. Therefore, severe stenosis or occlusion in the distal SFA was suspected, and we performed an emergency angiography.
The angiography showed no significant stenosis from the right common iliac artery to the CFA. However, a subtotal occlusion at the proximal site of POP-A was observed, and we moved on to endovascular treatment (EVT) using a 6-Fr guiding sheath via his left CFA. First, we pressed his POP-A by a cuff at 200 mmHg for the purpose of avoiding a distal embolization due to further treatment. We performed manual aspiration using a 6-Fr guiding catheter, but no embolus was aspirated and we could not recanalize the artery. Next, we passed a 0.014-inch guidewire with the support of intravascular ultrasound (IVUS). IVUS imaging demonstrated a smooth-surfaced high-density homogenous structure that was suspected to be polyglycolic acid fiber plug material of the EXOSEAL VCD (Fig. ). We tried embolectomy by pulling an ordinary 5.0 × 20-mm inflated balloon catheter back from the POP-A into the 6-Fr guiding catheter in the SFA, similar to using a Fogarty balloon catheter. However, the embolus was too large to be collected into the 6-Fr guiding catheter. Therefore, we decided to seal the material on the arterial wall with a stent. To avoid stenting the POP-A, we pulled the embolus up to the proximal SFA and compressed it on the arterial wall by 5.0 × 20-mm balloon catheter inflation for 30 seconds (Fig. ). We confirmed that the embolus was attached to the arterial wall of the proximal SFA by angiography and IVUS. Then, we deployed a 7.0 × 60-mm self-expandable nitinol SMART (Cordis, CA, USA) stent to seal the embolus (Fig. ). Final angiography demonstrated a favorable blood flow in our patient’s right lower extremity (Fig. ). After the procedure, the value of his ankle-brachial index (ABI) was normalized and his symptoms completely disappeared. Angiography conducted 11 months postoperatively demonstrated no significant restenosis in the stent of his right CFA. Doppler ultrasound performed 18 months postoperatively showed no stenosis or occlusion in his right CFA and SFA. His postoperative course was uneventful in an 18-month follow-up study. |
pmc-6427890-1 | A 45-year-old man was admitted for a progressively worsening headache over 2 weeks. He denied history of recent head trauma or anticoagulation and antiplatelet medication. General and neurologic examinations were not remarkable on admission. Routine laboratory investigations including coagulation profiles and platelet function were within normal limits. Head computed tomography (CT) on admission revealed an isodense CSDH on the right hemisphere with mild midline shift (Fig. a). A CT angiography (CTA) was performed to rule out any intracranial vascular malformation. A DAVF was noticed at the transverse sinus with dilated cortical venous drainage (Fig. b). So, a digital subtraction angiography (DSA) of the external carotid artery and DAVF embolization was planned.
No anomaly was noticed during selective angiography of the internal carotid and vertebral arteries and the left external carotid artery. Selective angiography of the right external carotid artery showed that the DAVF was located at the transverse sinus and fed by posterior branch of the middle meningeal artery (MMA), the occipital artery, and the posterior meningeal artery and drained to the occipital cortical veins with venous ectasia (Fig. a-b). The DAVF was classified as type IV according to the Cognard classification. The embolization was performed via the MMA. The Headway duo catheter was used and accessed to the DAVF, and Onyx was injected until the shunt disappeared (Fig. c-d). The patient experienced an uneventful recovery. His CSDH gradually resolved in 1 month (Fig. ). No neurologic deficit was noticed.
A PubMed search of published studies written in English and Chinese was conducted on June 30th, 2017. The following key words were used in relevant combinations: dural arteriovenous fistula, dural arteriovenous malformation, subdural hematoma, subdural haematoma, subdural hemorrhage, and subdural haemorrhage. The reference lists of the identified articles were also manually searched for additional studies. Studies of which full text could not be obtained or those without sufficient individualized description of the isolated SDH cases mixed in larger case series were excluded.
Finally, 13 articles containing 14 patients were identified [–]. In all 15 patients (9 females, 60%) including 1 case in our institution were included for the final interpretation (Table ). The inflicted patients were aged from 27 to 82 years (55.5 ± 8.6).Of note, 12 (80%) of the 15 patients were aged between 40 and 60 years of age, and 8 (53.3%) patients were between 50 and 60 years. Sides of the DAVF or SDH were obtained in 13 patients with 9 (69.2%) located at the left side and 4 at the right side. The intracranial locations of DAVF were anterior fossa (2), middle fossa (2), frontal region (2), parietal region (3), temporal region (2), and occipital region (2). The types of SDH were CSDH (7/15), acute SDH (ASDH) (7/15), and undefined SDH (1/15). Of the 12 patients feeding artery could be identified, MMA was the commonest feeding artery (8/12, 66.7%). Multiple feeding arteries were identified in 3 (25%) patients. The causes of DAVF were only defined in 3 patients (2 iatrogenic and 1 traumatic), with the rest undefined or not mentioned. Cognard classifications (Table ) of the DAVF were reported or deduced from the reports in 12 patients, with type I, type III, and type IV in 7, 2, and 3 patients respectively. The treatment strategies included hematoma evacuation (2/15), CSDH drainage and DAVF embolization (5/15), craniotomy and DAVF resection (3/15), DAVF embolization and hematoma evacuation (1/15), DAVF embolization (2/15), and not applicable or not mentioned (2/15). Of the 12 patients with direct description of outcome, 7 (58.3%) patients were neurological intact, 3 (25%) patients with neurological deficits, and 2 (16.7%) died. |
pmc-6427899-1 | A 30-year-old female patient, without comorbidities, who regularly used cocaine and marijuana, started to have lower-limb edema, which showed a progressive and ascending evolution, affecting the face a few days later, associated with an isolated febrile episode and oligoanuria. Initial laboratory examinations showed Hb of 9.44 g/dL; Ht of 26.8%; MCV of 93 fL; MCH of 30.7 pg; leukocytes 10,700mm3 (segmented 7597, eosinophils 428, lymphocytes 1926, monocytes 749); platelets 284,000mm3; Cr 14 mg / dL; Ur 225 mg / dL; Na + 135 mEq /L; K + 6 .5mEq / L; Serology for HIV, hepatitis B and C negative (Table ).
Urinalysis showed pH: 5.0; UD: 1015, Proteins: +++ / 4; Leukocytes: +/− 4; Hemoglobin: +++ / 4. Sedimentoscopy: numerous red blood cells, numerous leukocytes, rare epithelial cells; presence of coarse granular cylinders; moderate bacteriuria; 24-h Proteinuria: 2161 mg (Volume: 400 mL / 24 h).
The presence of proteinase-3 31 IU/ml (Reference Value: reagent if > 3 IU/ml), cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) was verified: reactive 1:80, with renal biopsy (Figs. , and ) compatible with rapidly progressive glomerulonephritis (RPGN), while immunofluorescence showed granular deposits in the capillary loops of C3c (one cross) and fibrinogen (one cross). The patient was hospitalized and submitted to pulse therapy with methylprednisolone 1 g / day for 3 days and cyclophosphamide IV. Her evolution showed no recovery of renal function, she abandoned treatment and remained in dialysis treatment. The diagnosis was pauci-immune ANCA-related RPGN. |
pmc-6427899-2 | A 34-year-old female patient, with difficult-to-control hypertension and a frequent user of cocaine, showed generalized sudden edema together with diffuse and progressive pruritus associated with oliguria, fever, nausea, and vomiting. The initial laboratory tests showed Hb of 6.6 g / dL; Ht of 19.6%; MCV: 91.1%; MCH of 30.6pg; RDW: 13.6%; Leukocytes: 9914mm3; platelets: 79150mm3; Reticulocytes 3.39%; LDH 2702 IU/L; TB 0.65 mg/dL; DB 0.21 mg /dL; IB: 0.44 mg /dL; Creatinine 13.3mg / dL; Urea 227 mg / dL; K+ 4.7 mEq /L; APTT 0.89 s; INR 0.87; CPK 128 u /L; C3 114 mg / dL; C4 26 mg / dL; Serology for HIV, hepatitis B and C negative. Urinalysis: pH: 5.0; UD: 1010, Proteins: ++ / 4; Leukocytes: ++ / 4; Hemoglobin: ++ / 4. Sedimentoscopy: RBC (zero), Leukocytes (15 / field) (Table ). At the physical examination she had BP of 160/110 mmHg and the fundus examination showed flame-shaped hemorrhages, with pathological AV crossing and tortuosity without other alterations. Schistocyte screening was positive, with negative direct Coombs test, and negative serologies for hepatitis B, C and HIV, as well as negative anti-double-stranded DNA, Anti-SSA and Anti-SSB. The renal biopsy was compatible with thrombotic microangiopathy, associated with moderate interstitial fibrosis and acute tubular necrosis (Figs. and ). The patient persisted with BP peaks and received optimized antihypertensive medication, being discharged without renal function recovery, with persistence of the need for dialysis therapy at discharge. The diagnosis was Thrombotic Microangiopathy (TMA) secondary to cocaine use. |
pmc-6427899-3 | A 25-year-old male patient, without comorbidities, who had been a cocaine user for 5 years had a sudden onset of generalized disabling myalgia (especially in the lower limbs) associated with recent frontotemporal headache, palpitation, dizziness, and a non-measured febrile episode; the patient had used cocaine at the night before symptom onset. The physical examination showed hemorrhagic suffusion, blood pressure of 180/110 mmHg and tachycardia of 110 bpm. The patient was initially treated in another unit, which did not have logistics to dose myoglobin, and also no records regarding the initial value of CPK. Initial laboratory examinations from our hospital admission until 5 days after the admission showed Serology for HIV, hepatitis B and C negative; Creatinine of 13.8 mg/dL; Urea of 259 mg / dL (Table ), and urgent hemodialysis was performed. CPK was 1731 U/L. During the hospitalization, the patient showed progressive improvement of both hemorrhagic suffusion and elevated BP. He showed improved diuresis and recovery of renal function in 13 days during hospitalization, and dialysis therapy was suspended. The final probable diagnosis was AKI secondary to cocaine-induced rhabdomyolysis. |
pmc-6428359-1 | A 70-year-old male with past medical history of psoriasis, diabetes mellitus, and hypertension, presented to the emergency department with diffuse, sharp, abdominal pain of four days duration. Physical exam was remarkable only for diffuse tenderness to palpation of abdomen, and mild abdominal distention. Laboratory data showed white blood cells (WBC) of 13.4 K/MCL (Normal 4–10 K/MCL), lipase 18 U/L (Normal 0–160 U/L). Colonoscopy performed two years ago was unremarkable. Computed tomography (CT) abdomen/pelvis showed intermediate grade small bowel obstruction, without evidence of any mass (Figure ). Exploratory laparoscopy with ileal mass resection was performed. Upon gross examination of resected segment, a necrotic mass measuring 4.8 cm x 3.9 cm x 3.8 cm was visualized. Specimen pathology showed high-grade medullary carcinoma of the ileum with angiolymphatic invasion (Figure ). The carcinoma invaded through the muscularis propia into the periileal adipose tissue (Figure ). The tumor stage was pT3N0M0. Immunohistochemistry was positive for epithelial membrane antigen (EMA), and pancytokeratin. Ki-67 index was 80%. CDX-2, CD56 synaptophysin, and chromogranin were negative. The patient was treated with local excision and radiation therapy and instructed on appropriate follow-up. On follow-up, the patient was noted to be free of disease without any adjuvant therapy one year later. |
pmc-6428360-1 | A 56-year-old male presented to the emergency department (ED) with significant substernal chest pain starting 30 minutes prior to arrival. The patient was immediately brought back to an exam room after an electrocardiogram (ECG) was performed and was seen by a provider within 10 minutes of registration (Figure ).
The initial ECG revealed atrial fibrillation with a rapid ventricular response, rate of 147, with minimal ST depression within the lateral leads but was without apparent ST-segment elevation. On initial assessment, the patient had point-of-care labs immediately drawn (a basic metabolic panel and troponin), and a chest X-ray performed to evaluate for a possible aortic dissection which revealed no gross abnormalities (Figure ).
With a non-diagnostic chest X-ray alternative diagnoses were pursued. The ultrasound fellow in the department was consulted for an immediate cardiac ultrasound for evaluation of right heart strain secondary to pulmonary embolism. During the bedside cardiac ultrasound, the patient experienced ventricular fibrillation (Video ), and CPR was immediately started.
The ACLS algorithm was followed for pulseless ventricular fibrillation, and the patient received multiple rounds of epinephrine, 450 mg of amiodarone (300 mg and then 150 mg), and three conventional defibrillations with increasing joules at 150 J, 200 J, and 200 J (the departmental defibrillators are biphasic and have a maximum output of 200 J). The patient continued with ventricular fibrillation throughout the ACLS algorithm, and the decision was made to attempt DSD. The patient had a second set of pads applied in the anterior-posterior orientation in addition to the conventional right upper chest and left lateral chest with successful conversion of the ventricular fibrillation. The patient was additionally given Lidocaine, 100 mg, due to a wide-complex tachycardia and apparent non-responsiveness to the previously given amiodarone (Figure ). An improvement was noted after the use of Lidocaine, and a Lidocaine drip was started.
Once the patient was stabilized, he was taken for computed tomography (CT) imaging to further evaluate for the possibility of a pulmonary embolism. In the CT room, he developed bradycardia and subsequently lost his pulse. CPR was again started, the patient was given atropine, and return of spontaneous circulation (ROSC) was achieved shortly after. The CT scan did not reveal any evidence of aortic dissection or pulmonary embolism and a repeat ECG was performed which showed a persistent wide complex tachycardia with no obvious ST-segment changes. Due to the morphology of the QRS complexes and length of resuscitation time from initial arrest (nearing 90 minutes), tissue plasminogen activator (tPA) was used as a thrombolytic for what was presumed to be a large vessel occlusion myocardial infarction. Hundred milligram of tPA was administered (50 mg as a bolus and 50 mg as a drip given over 60 minutes) with an apparent reperfusion rhythm followed by a "normal" appearing sinus tachycardia. Another ECG was repeated which revealed sinus tachycardia, at a rate of 114, now with ST-segment elevations present in aVR, V1, V2, V3, and V4 with depressions in leads II, III, and aVF (Figure ).
Given the patient's persistent elevations despite thrombolytic therapy, interventional cardiology was consulted, and the patient was transferred to a tertiary care facility for cardiac catheterization revealing a thrombotic occlusion in the proximal left anterior descending coronary artery.
After transfer to the tertiary care facility for cardiac catheterization, the patient developed cardiogenic shock. The patient was started on ionotropic medications with no improvement, and he was placed on venous-arterial extracorporeal membrane oxygenation (ECMO) therapy (~20 hours after his cardiac arrest). Before initiation of ECMO, the patient was awake, alert, and following simple commands (although still intubated). Unfortunately, despite ECMO support, his cardiac function did not improve, and the patient was not a candidate for cardiac transplantation. Seventeen days after the patient's initial presentation to the ED, the family decided to withdraw care. The patient was extubated, had ECMO discontinued, and time of death was documented shortly after. |
pmc-6428361-1 | A 53-year-old man sought treatment at the department of oral medicine and radiology at Sri Ramachandra University in Chennai, India, for a painful and progressive swelling involving the right mandibular region for four days. It was associated with a toothache on the right lower jaw. The pain in the tooth was dull, continuous, and aggravated on taking hot or cold beverages. The swelling was small when he initially noticed it and gradually increased to the presenting size. The patient had visited a private dentist a day before, where an orthopantomogram was taken, and he was advised to undergo extraction after a course of antibiotics and non-steroidal anti-inflammatory drugs. His medical history was noncontributory. Extra orally, a single, well-defined swelling was evident in the right lower jaw region, with signs of inflammation. The swelling was 4 cm x 5 cm, warm, tender, soft, compressible, and not fluctuant. Intraoral examination revealed dental caries in 47, with gross destruction of the crown and mucobuccal fold obliteration in relation to 47. A provisional diagnosis of dental caries in 47, with a dentoalveolar abscess, was promptly made. The previous orthopantomogram revealed radiolucency in 47 with gross destruction of the crown associated with radiolucency around the roots (Figure ). No other associated pathologies were evident. The patient was advised to continue the same medication for four more days. Four days later, the patient reported with painless swelling, which had reduced in size to 3 cm x 4 cm involving the same site. The swelling was nontender, soft, and compressible; it was not fluctuant, pulsatile, or fixed to the skin and underlying bone. The results of the transillumination screening were negative.
Given that the patient was asymptomatic, we extracted tooth 47 while he was under local anesthesia. The postoperative period was uneventful. When the patient was evaluated one week later, the asymptomatic swelling remained the same size (Figure ).
There was no cervical lymphadenopathy and, intraorally, the mucosa was normal and moist (Figure ). The mouth opening was 4.2 cm inter incisally. The patient could vaguely recollect the presence of a painless small lump for one year, which was brought to his notice by his family members. The patient did not experience pain at any time, nor was there any change in the size of the swelling before and after eating.
Considering the history of painless swelling lasting one year that was well-defined, soft, nontender, with no intraoral manifestation, a lipoma of the right submandibular region was suspected. Fine needle aspiration cytology was performed under ultrasound guidance. Ultrasonography revealed a well-circumscribed hyperechoic mass measuring 3.2 cm x 2.7 cm separated from the right submandibular gland (Figure ).
The smear showed mature fibro-adipose tissue, which would be consistent with a lipoma (Figure ).
Surgical removal of the lesion was done by the submandibular gland approach under general anesthesia. The excised mass showed mature adipocytes, a few capillaries, and fibro-collagenous tissue. The physical features were again consistent with a lipoma (Figure ). |
pmc-6428731-1 | Patient II.1 () is a 17-years-old male child affected by non-immune hydrops fetalis and congenital lymphatic dysplasia. During pregnancy, a fetal pleural effusion (32 weeks) was observed. The proband was born at 38 weeks by cesarean section. Birth parameters showed a low Apgar score (5/8) with breathing difficulties treated by continuous positive airway pressure, axial hypotonia, peripheral edema, hydrocele, hypoglycemia, and normal auxologic parameters (weight 3.650 Kg; length 53 cm; and head circumference 36 cm). The hemogram resulted normal for age, and total hyperbilirubinemia was observed (13.2 mg/dL) treated by phototherapy. During childhood, a hydrocelectomy (2-years-old) and a scrotum reduction surgery (14-years-old) were performed. At 14 years, a lower limb lymphoscintigraphy was executed, showing distinctive changes of a severe bilateral lymphovascular disease. Particularly, the patient highlighted poor asymmetrical uptake of tracer in the groin at 45 min (almost in the right limb) with evidence of rerouting in the scrotum at 2 h. At 15 years, a thoracentesis was performed to reduce the excess of fluid because of respiratory failure due to restrictive lung disease. The cytological analyses highlighted the presence of chylous fluid. After 1 week the chylous edema was re-observed at X-ray. Due to the worsening of respiratory disease at 16 years, magnetic resonance imaging was performed. The analysis showed an impairment of the chylothoraces and reoccurrence of the hydrocele (). Currently, the proband presents a progressive worsening of the respiratory function.
The other family members are healthy expect for the mother of the proband (I.2) that showed an iron deficiency anemia due to imbalanced diet supplies negative for hemoglobinopathies.
We performed WES on the proband and the parents, highlighting the presence of two variants within PIEZO1 gene: the nucleotide substitution c.6165-7G>A in the intron 42–43, annotated in 1000 Genomes database (rs141011459) with a minor allele frequency (MAF) = 0.0004; the novel nucleotide deletion c.5725delA that results in the frameshift variant p.Arg1909Glufs∗12 (). According to the recessive pattern of inheritance, the proband showed a compound heterozygous genotype. Indeed, the father, I.1, carried the variant c.6165-7G>A, while the mother, I.2, carried the variant c.5725delA. We also extended the analysis to additional unaffected subjects: the patient’s brother, II.2, carried the variant c.6165-7G>A, while the sister, II.3, carried the variant c.5725delA.
To evaluate the possible effect of the frameshift variant on mRNA processing, we sequenced the PIEZO1 cDNA of the proband. Amplification of the specific exon region, encompassing the mutation, of PIEZO1 cDNA highlighted the selective expression of the wild-type allele, while the c.5725delA allele was not expressed, demonstrating its decay (). Human Splicing Finder web-tool predicted for the splicing variant c.6165-7G>A the creation of a new “branch point motif,” and two exon splicing enhancer (ESE) motifs for SRp40 protein. High sensitivity analysis of the exon regions encompassing the intronic variant (exons 42–44), using the Agilent 4200 TapeStation system (), demonstrated that the proband and the father expressed about the 4 and 36%, respectively, of PIEZO1 cDNA compared to the control ().
To further evaluate the role of PIEZO1 variants, we assessed gene expression in all the family members, as well as in a subset of healthy controls (HCs). A significant decrease of PIEZO1 expression in the proband compared to those revealed in the HCs was observed, and a minor decrease (about 50%) of mRNA levels in both parents was detected compared to HCs (). Nevertheless, immunoblot analysis on RBCs membranes highlighted a marked decrease of PIEZO1 protein in the proband compared to the HCs expression with about 30% of expression (). The parents showed also a decrease of PIEZO1 level with 47 and 65% of PIEZO1 expression for mother and father, respectively. Additionally, we evaluated the expression of other RBC membrane proteins, including Band 3 and Stomatin, altered in hereditary spherocytosis (HS) and overhydrated hereditary stomatocytosis (OHS). Proband showed a similar amount of both proteins compared to the HCs ().
The ektacytometry analysis was performed for the proband and his parents. As shown in , the proband (II.1) exhibited an ektacytometry curve with right shift compared to the curve obtained from the HCs, indicating overhydration of the erythrocytes. The mother (I.2) showed a right shift of the osmolarity curve similar to those observed in the proband. Conversely, the osmolarity curve of the father I.1 was in the range of the controls with a slight right shift of the curve compared to both the proband II.1 and the subject I.2.
We measured extracellular and intracellular potassium levels in fresh blood samples from all family members, and HCs. The proband (II:1) and his mother (I.2) showed a decrease of potassium content compared to the HC, while the father (I.1) showed intracellular [K+] comparable to HC (). The analysis of K+ plasmatic levels showed increased levels in the proband and his parents compared to the HC.
The hemogram showed a slight reduction of the Hb content with normal MCV and decreased MCH and MCHC values (). The RDW resulted increased while the reticulocytes count was normal (). Accurate analysis of the peripheral blood (PB) smear of the proband revealed marked anisopoikolocytosis, hypocromia, several spherocytes, some stomatocytes, some mushroom-shaped RBCs, several RBCs fragmentation and debris (). |
pmc-6428736-1 | Our first patient was a 57-year-old female who presented to our outpatient department with complaints of persistent numbness over the lateral side of her palm and poor grip strength of her right hand after undergoing carpal tunnel release at another clinic 2 years previously. Physical examination revealed atrophy of the right thenar muscle and positive Tinel's sign and Phalen's test. X-ray revealed a solitary calcified nodule sized 1.3 × 0.8 × 1.0 cm3 at the volar side of the capitate–hamate region (). Both T1- and T2-weighted magnetic resonance imaging revealed lower focal intensity of the nodular lesion without obvious contrast enhancement (). A nodular lesion mimicking CTS was diagnosed, and the patient subsequently underwent tumor excision. Intraoperative findings revealed a solitary, whitish, well-margined nodule with easily crumbled content. |
pmc-6428736-2 | Our second patient was a 52-year-old female with a history of medically controlled type II diabetes mellitus for 5 years. She reported numbness in her first, second, and third fingers with decreased grip strength of her right hand since 10 months ago. Physical examination revealed right hand thenar muscle atrophy and Tinel's sign and positive Phalen's test. She received a local injection of lidocaine at the clinic; however, her numbness did not improve as expected. Ultrasound was used as the initial imaging modality; the median nerve was scanned by the upper limbs nerve tracking protocol (). The patient was made to lie on the bed in the supine position and was asked to maintain forearm supination. The ultrasound transducer was placed at middle of the patient's forearm, a position where the median nerve travels between the flexor digitorum superficialis and profundus tendons. Next, the transducer was moved to the distal area, where the median nerve passed from below the flexor retinaculum and tendons. The palmar cutaneous branch of median nerve (PCMN), which emerged from the radial aspect of the median nerve and circled around the upper border of the median nerve to reach the antebrachial fascia, was traced; PCMN passed through the antebrachial fascia and entered the ulnar side of the flexor carpi radialis tendon (). A hyperechoic ovoid lesion with posterior shadowing between the median nerve and capitate, which led to compression of the median nerve, was noted (). X-ray also revealed one radiopaque nodule sized size of 0.6 × 0.6 × 1.3 cm3 in front of the capitate (). The patient was then referred to our outpatient department. Electromyography (EMG)/nerve conduction velocity (NCV) testing revealed moderate demyelination of the median nerve in the right hand. Resection biopsy and transverse carpal ligament release were performed; the intraoperative findings revealed a solitary, whitish, well-margined nodule over the carpal tunnel (). Postoperative sonography revealed no compression of the median nerve by foreign bodies (). The pathological findings of both patients indicate a grayish, calcified nodule. Both patients reported immediate improvements in their symptoms after surgery. |
pmc-6428745-1 | An 81-year old man was admitted at 7:00 a.m. to our hospital due to wake up symptoms of right-sided hemiparesis and dysarthria. Timepoint of last known well was stated for the eve of (22:00 p.m.). The patient reported to had woken up at 4 o'clock in the morning noticing a paresis of the right leg, but had fallen asleep again. At 6:30 a.m. he had woken up again with right-sided hemiparesis and dysarthria, whereupon the emergency medical services had been called (see for a graphical presentation of the time course). Clinical examination at admission revealed a moderate right-sided sensomotoric hemisyndrome with dysarthria and inconsistent signs of neglect [National Institutes of Health Stroke Scale (NIHSS) = 6 points]. Following the house-intern standard operating procedure the patient was admitted and clinically evaluated outside of the imaging room. As a matter of routine, the results of this emergency evaluation determine the subsequent procedure, especially the choice of imaging modality.
Due to permanent atrial fibrillation the patient was taking dabigatran 150 mg twice per day. Last intake was reported distinctly for the eve of, i.e., ~12 h prior to admission.
Based on the assured intake of dabigatran ~12 h ago and the reasonable suspicion of an acute cerebrovascular event, i.e., either cerebral ischemia or intracerebral hemorrhage, idarucizumab 2 × 2.5 g was applied immediately upon neurological examination at admission, prior to cerebral imaging as well as prior to proven (by laboratory testing, i.e., TT) anticoagulation. Due to unknown time of symptom onset and mild to moderate symptoms of acute cerebrovascular event we decided to perform primary MRI (according to the house-intern standard operating procedure, and with respect to the WAKE-UP trial (). MRI-DWI sequences revealed an acute ischemia in the area of the left anterior choroidal artery without correspondent hyperintensity on the FLAIR-sequences (see ). No occlusion of any cerebral artery was shown in MRI. After MRI and completed application of idarucizumab a new blood sample was taken, and intravenous thrombolysis with 90 mg alteplase was started immediately, resulting in a door-to-needle time of 50 min. During ongoing application of intravenous thrombolysis, the result of second TT (of blood sample taken directly upon completion of idarucizumab application) was examined. Since TT revealed normalized here (TTpost Idarucizumab = 18.3 s, TTinitial = 61.7 s), application of rtPA was proceeded to the full dose of 90 mg (equivalent 0.9 mg/kg body weight). Follow up CT on the next day revealed a small demarcated ischemia in the corona radiata (see ), corresponding to the aforementioned diffusion-restricted area, without intracranial hemorrhage. Dabigatran was restarted in the evening of day 4 (i.e., 108 h upon thrombolysis). The patient was discharged on day 26 with mildly ameliorated hemiparesis (NIHSS = 4 points). |
pmc-6429541-1 | A 75-years-old man was admitted due to respiratory failure (day 0). The patient had history of colonic and prostatic cancer 11 and 7 years earlier, respectively, both successfully treated without recurrence. He also had a history of hypertension, alcoholism, smoking and chronic obstructive pulmonary disease. During his transfer to the hospital in ambulance, he was given intravenous infusion of furosemide. Upon arrival his physical exam was significant for fever, cough, tachypnoea and tachycardia He was admitted to the intensive care unit (ICU), requiring mechanical ventilation. Laboratory was remarkable for a white blood cell count of 10.5/mm3, C-reactive protein, lactate dehydrogenase and lactic acid were increased. An initial lung CT angiography showed bilateral ground glass pulmonary infiltrate without evidence of pulmonary embolism. With presumptive diagnosis of community acquired pneumonia, bronchoalveolar lavage (BAL) and BCs were done (Bactec aerobic medium; BD Diagnostic Instrument Systems; Bactec 9240). Fungal and bacterial stains and cultures from BAL were negative, and Galactomannan (PlateliaTM Aspergillus Ag) OD index was 0,45. Patient was started on piperacillin-tazobactam, vancomycin and hydrocortisone, and become afebrile at 24 hs.
On day 4, BCs were negative, thus vancomycin was discontinued. On day 6, after a short period of stabilization, he became hypotensive requiring inotropic assistance. Three BCs (1 from peripheral vein and 2 from CVC) were taken. A transthoracic echocardiogram didn't show valvular lesions.
On day 8 abdominal laparoscopy was done due to ascites. Ascitic fluid culture was negative. During the procedure a liver biopsy was done, later showing cirrhosis.
On day 9 the pair of BCs taken at day 6 showed a positive growth index. Direct microscopy showed hyaline, ovoid to elliptical yeasts (). A new set of BCs were drawn in order to confirm that finding. On day 13, yeasts were found on all BCs samples from days 6 and 9. The patient denied outdoor activity or recent traveling. No skin lesions were found on physical exam, and the portal of entry remained unclear. After 3 days, subcultures on Sabouraud agar showed slow-growing colonies, initially with smooth glossy mucous appearance, that over time became velvety olivaceous black ( A, B). Microscopy revealed pigmented septate branched hyphae with annelidic conidiogenesis, and ellipsoidal conidia of different sizes with a thin wall, forming aggregates (). The isolate was identified as Exophiala spp. MALDI-TOF (Bruker Daltonics) identified the colonies as E. dermatitidis with a 1.689 score. Patient was diagnosed of CLASBI due to non-Candida fungus according to CDC definition. Anidulafungin was started and CVC was removed. The strain was submitted to the national mycology reference center (“Departamento de Micología, Instituto Nacional de Enfermedades Infecciosas Dr. Carlos G. Malbrán”), for further for molecular identification. Sequence data of the rDNA ITS regions of the D1-D2 of the large (28S) ribosomal subunit of the isolate resulted in 98.6% similarity to E. dermatitidis. Antifungal susceptibility testing was performed according the methodology recommended by the CLSI, document M38-A2 (2008), revealing a MIC (μg/mL) for amphotericin B, anidulafungin, and caspofungin of 0.125, 0,008 and 0,008 respectively.
Neither renal ultrasound nor ophthalmologic examination, reveal evidence of disseminated fungal infection. Standard histological stains for fungi were requested on liver histological sample with negative results. Histological diagnosis of cirrhosis was done.
BCs done on day 16 were negative. On day 18 the patient died due to haemoptysis and supraventricular tachycardia.
Due to described outbreaks of Exophiala spp. caused by medication contamination, audit and surveillance of the practices of preparation and administration of intravenous medication was made. No irregularities were found. ICU drug preparation surfaces were cultured in search for fungi, which were negative for Exophiala spp. Surveillance for secondary cases in ICU patients was conducted by incubated all BCs in a prolonged manner (14 days) during a period of 3 months from the index case. No other patient presented E. dermatitidis fungemia. |
pmc-6429545-1 | A 46 years old woman was referred to our facility for surgical therapy of an enlarging metastatic gastrointestinal stromal tumour involving the liver. This is on the background of partial gastrectomy for a “benign” tumour in Germany in 1994, which was believed to be the primary. Staging computed tomography scan revealed a grossly enlarged right hepatic lobe secondary to multiple metastases. Two lesions measured 23 cm × 18 cm (oblique axial dimension) and 23 cm × 25 cm × 24 cm (anteroposterior dimension), respectively. The huge tumour led to compression of IVC, right portal and hepatic veins (). The patient’s laboratory studies were within normal except for anaemia (Hb 100). She received neoadjuvant therapy of imatinib, to which the tumour responded with significant size shrinkage.
She proceeded to undergo an extended right liver resection using cardiopulmonary bypass (CPB) and autotransfusion with intraoperative cell salvage (ICS). Induction of anaesthesia was uncomplicated, followed by placement of lines and a transoesophageal echocardiogram (TOE) probe. On rotational thromboelastometry (ROTEM), maximal clot firmness on FIBTEM was indicative of low fibrinogen (A5 value at 4 mm; A10 value at 4 mm; A20 value at 5 mm). Intraoperatively, a massive tumour of right liver lobe (17 kg) was discovered (). The TOE during early dissection phase was consistent with severe IVC compression and pressure overload on RA/RV suggesting that CPB – instead of veno-venous extracorporeal membrane oxygenation – was necessary to complete the surgery. She was heparinised (20,000 U) to reach activated coagulation time (ACT) of 602 before establishment of CPB. During tumour resection, large volume of fluid and blood products [6 U of packed red blood cells (PRBC), 6 U of fresh frozen plasma (FFP)] was infused to replace intra-abdominal losses. Bleeding from liver edges was controlled adequately with local haemostatic agent (Floseal, Baxter, US). High dose vasopressor support was instituted soon after commencing CPB and early resection – initially with noradrenaline (8 mg/100 ml at 10–50 ml/h) and then vasopressin (2.4 units/h). Eventually, the liver tumour was successfully resected and delivered.
The rates of noradrenaline and vasopressin were running at 50–75 ml/h (16 mg/100 ml) and 6 units/h towards the end of CPB, respectively. Steroids were given and, at this time, there was adequate flow on CPB with no evidence of clot. The patient was then weaned from CBP with good cardiac function. CPB time was 2 h 15 min. A total of 300 mg protamine sulphate was administered for heparin reversal prior to decannulation. Even though her coagulation profile including ACT and ROTEM was acceptable, the haemorrhage was refractory to protamine and blood components. She continued to demand a relatively high dose of vasopressors, although the demand was decreasing over time. Total blood products consumed at that stage were 18 U PRBC, 17 U FFP, 17 U of cryoprecipitate apheresis (equivalent to 34 U of cryoprecipitate derived from whole blood), 3 U pooled platelets and 2500 U prothrombinex. A joint decision among the surgeon, anaesthetist and haematologist was made to administer rFVIIa (90 ) of rFVIIa (NovoSeven, Novo Nordisk, Denmark) approximately 1-h post-CPB in an attempt to arrest the bleeding. The pH was 6.808 and temperature was 35.3 °C at time of administration.
Ten minutes following administration of rFVIIa, the patient became haemodynamically unstable secondary to right ventricular failure and went into cardiac arrest. Intraoperative TOE demonstrated extensive thrombi within the right atrium, right ventricle and bilateral pulmonary arteries (). Heparin was readministered to achieve an ACT of >999 s, CPB was emergently resumed and internal cardiac massage was performed. Right atriotomy and pulmonary atriotomy were attempted successfully to evacuate the aforementioned thrombi. Despite the clearance of right atrium, repeat TOE showed formation of thrombus in left ventricle and aortic arch. There was also noticeable intra-coronary venous thrombosis. The prothrombotic state resulted in eventual propagation of clot into venous drainage line of CPB machine and no flow could be established due to the blocked venous cannulae (SVC and IVC).The treatment was ultimately withdrawn and the patient died soon on the table. Following this event, Therapeutic Goods Aministration (TGA) was notified of the suspected adverse drug reaction. |
pmc-6429616-1 | A 34-year-old man was diagnosed with multiple sclerosis (MS) 13 years ago. He was initially treated with intravenous steroid therapy and thereafter underwent the following drug therapy: Interferon beta 1a (two years), glatimer acetate (one year), natalizumab (three years), fingolimod (two years), and ocrelizumab (one year). The patient also received stem-cell infusions on two separate occasions. During the same period the patient underwent 10 MRI scans, where Gd was used as a contrast medium: MRI showed numerous hyperintense surfaces (data not shown). Recently, the patient spontaneously interrupted therapy and decided to undergo the EDTA chelation test. Due to the patient’s inability to walk, he presented in a bath chair; he also had difficulty speaking. Results regarding toxic metal levels in the urine sample can be seen in .
Notably, Gd values were found to be at levels considered unacceptable for humans. Lower amounts of the toxic metals Al, Cd, and Pb were also found. How did this patient accumulate so much Gd? Was he unable to eliminate it? Some subjects reveal the inability to detoxify themselves owing to low levels of glutathione or enzymes that help remove ROS. Was the Gd that accumulated in the patient’s brain responsible for symptom exacerbation? Was the immunosuppressant therapy associated with Gd administration the cause of the rapid deterioration of the young patient’s condition? This important result might suggest the assessment of not only renal function in patients that undergo MRI as a clinical determinant of subacute Gd toxicity. |
pmc-6429616-2 | A woman was diagnosed with MS when she was 39 years old. She was treated with intravenous steroid therapy, followed by interferon beta 1a therapy for one year. The patient decided to interrupt immunosuppressant therapy owing to intolerance. She underwent chelation testing that showed Gd, Cd, and Pb intoxication, as shown in . The patient showed significant tiredness, fine motor skills disturbance in the hands, and reduced foot sensitivity.
The patient had previously undergone only two diagnostic MRI examinations with Gd, yet this toxic metal was the most present among those found. The patient decided to undergo chelation therapy, whose beneficial effects were evident as MS symptoms disappeared. Chelation therapy was initially carried out on a weekly basis, which, after 12 months, was modified to two applications per month. However, Gd levels decreased very slowly, as shown in , which highlights toxic metal levels in urine samples after one year of EDTA chelation therapy.
Gadolinium levels fell only after two further years of chelation treatment, as shown in .
During therapy, all MS symptoms progressively disappeared, and the patient appeared to be in a good state of general health (EDSS = 4 before the beginning of chelation therapy; EDSS = 0 three years after). She observed correct diet avoiding glucose, took glutathione daily (250 mg, Oximix 7+ Driatec, Italy) and 15 drops of the antioxidant deutrosulfazyme three times a day (Cellfood, Eurodream, La Spezia, Italy). The patient is now well and undergoes chelation therapy twice a year. |
pmc-6429708-1 | The patient was a 3.5-year-old girl, a product of consanguineous first-degree cousin marriage, who was born at the gestational age of 38 weeks after a normal and uncomplicated pregnancy. She was in good health after delivery with a good APGAR score. Her weight, length and head circumference were 2500 g, 45 cm and 33 cm, respectively. Weight and length were below the 3rd percentile, whereas head circumference was slightly above the 15th percentile according to the national child growth curve. Failure to thrive and proportional microcephaly continued until one year of age but development was good. She presented with jaundice at the age of one year. Laboratory tests showed decreased WBC count (3000/mm3, reference range for age: 5000–15,500/mm3) with 64% neutrophil and decreased hemoglobin levels (11 g/dL, reference range for age: 12–14 g/dL). Furthermore, lab results revealed an MCV of 88.7 fL, platelet count of 261,000, ESR of 2 mm/h, reticulocyte count of 5.1%, a positive direct Coomb’s test, negative indirect Coomb’s test. Moreover, ACLA, ANA, ds-DNA, C3, C4, ANCA were within normal range. Osmotic fragility test was negative. Hb electrophoresis showed Hb-A1 of 91.8%, Hb-F of 5.7%, and Hb-A2 of 2.5%. Viral marker tests revealed negative cytomegalovirus (CMV) PCR and parvovirus antibody. The patient was referred to a hemato-oncologist with a diagnosis of AIHA and was subsequently treated with prednisolone. The patient’s parents did not mention any history of hospitalization or outpatient visits due to infectious disorders. Furthermore, according to her flow-cytometry results, low level of CD19+ and the very high level of CD56+ cells were detected. (Table ). The immunophenotyping test were performed at the age of 2.5 years.
As the patient was a result of a consanguineous marriage, a thorough family history was taken from her parents. Both her parents were in good health. The other sibling was a boy who presented with jaundice and anemia at the age of three months. He then presented with recurrent infections and passed away at the age of three years due to pneumonia. Serum PCR for CMV was positive in the deceased individual. No further clinical and laboratory data were available.
To evaluate the patient for the underlying genetic disorder, whole-exome sequencing was carried out on the DNA extracted from the proband’s peripheral blood sample. Whole Exome Sequencing (WES) was performed on Illumina NextSeq500 instrument. The sequencing results were subsequently analyzed using different bioinformatics tools and databases such as BWA aligner, GATK and ANNOVAR. Whole exome sequencing details of coverage and number of reads are provided in Table . It was found that the patient had a stop-gain mutation in NHEJ1 gene (NM_024782.2:c.532C > A). Sanger sequencing subsequently confirmed that the patient was homozygous and both parents were heterozygous for the mutation (Fig. ).
On follow-up, the patient had growth and development retardation with her length/height, head circumference and weight being below the 3rd percentile corrected for the age. Except for axillary lymphadenitis following BCG vaccination, the patient had had full vaccination including BCG, HepB, polio, MMR and DTP without any complications. On the last follow-up at the age of three years, the patient’s height and weight were 86 cm and 9.1 kg, respectively—both below the 3rd percentile corrected for the age. However, she has not had any evidence of immunodeficiency, despite living a normal life without any special precautions to preserve the patient’s health. |
pmc-6429714-1 | A 79 years old male with multiple comorbidities including hypertension, valvular heart disease, diabetes mellitus and stage 4 chronic kidney disease with a baseline creatinine of more than 300 μmol/L presented with bilateral symptomatic large renal stones for which he underwent staged stone treatment. Prior to presentation to our hospital, he had bilateral double J stent (DJS) insertion and left extracorporeal shockwave lithotripsy followed by FURS and laser stone fragmentation of the left renal stones. Subsequently, he sought medical advice in our facility. Non-contrast CT scan showed multiple bilateral renal stones. In the left kidney, there were 3 stones distributed to middle and lower pole calyces with a stone burden of approximately 3.0 cm as measured using the CT scan. In the right kidney there were also three stones, two in middle calyces and one in the pelvis with a total stone burden of 3.2 cm. After stopping the aspirin for seven days, he underwent simultaneous bilateral FURS and holmium laser lithotripsy and insertion of bilateral DJS under general anesthesia with endotracheal intubation. The surgical procedure took 125 min (65 min for the left side followed by 60 min for the right one) and the procedure was similar in both sides. Following insertion of a hydrophilic tip guidewire (Sensor, 0.038 in), a ureteral access sheath (Inner diameter: 12 Fr, Length: 55 cm) was inserted and the tip was located approximated at the level of ureteropelvic junction. Karl Storz flexible ureterorenoscope (8.5 Fr) was used. During the procedure the normal saline was allowed to run from the bag (approximately 80 cm above the level of the patient pelvis without a pump) and the outflow of saline from around the scope was observed throughout the procedure. Laser energy between 1.0–1.2 joules with a frequency ranging between 8 and 12 Hz (short pulses) were used in both sides. 4200 and 4066 pulses were used in the left and right sides respectively. He was discharged home in a good condition the next day with almost clear urine. Four days later, he reported back to the emergency department with severe suprapubic pain and gross hematuria which required continuous bladder irrigation with a three-way catheter. His hemoglobin dropped dramatically from 121 to 84 g/dl requiring an initial transfusion of two units of packed red blood cells. CT scan showed left-sided subcapsular, perinephric and retroperitoneal hematoma (Fig. ), bladder clots and complete dislodgement of the left DJS. Cystoscopy revealed bleeding from the left ureteric orifice. Evacuation of clots and change of the DJS were performed. Postoperatively, he continued to have hematuria which was initially treated conservatively with bladder irrigation. His Hb dropped again from 113 to 85 g/dl and in view of the ongoing hematuria he required an additional five units of packed red blood cells. In view of the impaired renal functions, the patient was initially reluctant to have angiogram but ultimately it was performed and showed pseudoaneurysms in two small branches of the left main renal artery with extravasation of the contrast outside the renal parenchyma (Fig. ). Both branches were then selectively embolized using 3x2mm microcoils. As results, the hematuria ceased and he was discharged home two days later. On follow-up, his creatinine remained similar to the pre-operative values and in view of the patient comorbidities and of what happened during this procedure; he decided not to go for another procedures for the residual stones. |
pmc-6429764-1 | A 56-year-old female was referred to our department from another facility in the patient’s area for a rapidly progressing tumor in the gallbladder and liver area. The patient reported several-month right upper quadrant pain and 4-kg weight loss over the past year. There was no laboratory sign of obstructive jaundice at the day of admission. Preoperative CT and MR scan (Figs. and ) of the liver was performed, and the patient was diagnosed with a tumor in the gallbladder area with a relatively massive infiltration of the S5 and S6 liver segments and extensive regions of necrosis. Given the potentially resectable lesion according to preoperative imaging, exploratory laparotomy was indicated to attempt radical resection. During the exploration, a voluminous tumor was found attached to the peritoneum. Intraoperative ultrasound was performed and revealed a tumor originating from the gallbladder bed area and reaching up to the area of the hepatic hilum and extensive involvement of the hepatoduodenal ligament by the tumor through the lymph nodes. The tumor was classified as inoperable due to this finding. But during the exploration, however, a rupture of the fragile tumor occurred with massive eruption of the necrotic mass and the gallbladder content into the abdominal cavity, accompanied by bleeding of the liver parenchyma. We decided that the condition could only be managed by attempting modified resection. We performed cholecystectomy and non-anatomical resection of hepatic segments S5 and S6 and partial resection of S4 without lymphadenectomy as a debulking operation (Fig. ). The course of hospitalization was uncomplicated, and the patient was discharged to home care on postoperative day 9. Histologically, the tumor was confirmed as MINEN of gallbladder (Figs. , , and ), and its non-neuroendocrine component had the character of moderately differentiated tubular gall bladder adenocarcinoma, while the neuroendocrine component had the appearance of small cell carcinoma and was dominant, accounting for more than 65% of the viable tumor. The neuroendocrine component contained extensive necrosis, with mitotic index 64/10 HPF and a proliferation index of 70% (Fig. ). It was therefore obvious that the prognosis and the subsequent biological behavior would be influenced in particular by the neuroendocrine carcinoma component. Six weeks after the discharge, the patient underwent a follow-up CT scan prior to the initiation of systemic therapy, which revealed a large recurrence of the disease at the resection surface of the liver accompanied by hilar lymphadenopathy. The patient was started on systemic therapy with etoposide and carboplatin in combination with somatostatin analogues with very good radiological effect. We use this regimen as a standard in patients with MINEN of gastrointestinal tract with dominant neuroendocrine component, even with no somatostatin receptors staining available. Now the patient is almost a year after being diagnosed with a tumor, after completion of 6 cycles of adjuvant chemotherapy (carboplatin + etoposide) in combination with biological therapy, the long-acting somatostatin analogues. The patient is in good clinical condition, and while a recently performed PET/MRI scan revealed a hepatic lesion and hilar lymphadenopathy in full regression, there was a spread of small peritoneal and pleural metastases, with a solitary metastasis in Th9. The condition was evaluated as disease progression stage according to RECIST criteria, the patient remains in the follow-up care, and it is now 13 months after surgery (Figs. , , and ). |
pmc-6429769-1 | A 33-year-old married Sri Lankan woman presented with an episode of sudden onset of dark-colored urine with the background history of self-ingestion of 15 mothballs 2 days prior. This was an impulsive attempt after a quarrel with her husband. She denied co-ingestion of other substances including pharmaceuticals.
There was no significant complaint other than malaise and mild epigastric pain. She did not have features suggestive of urinary tract infection. Her past medical history, including history of hereditary hemolytic anemias, was unremarkable. She was not on any routine medications. Examination revealed severe pallor with lemon tinge icterus. Abdominal examination was normal, and other systemic examination was unremarkable.
Her clinical test revealed severe normochromic normocytic anemia with a hemoglobin level of 5.9 g/dL and a reticulocyte index of 2.36 with indirect hyperbilirubinemia. Her blood picture featured normochromic normocytic red cells with reduced count, blister cells, bite cells, and red cell fragments suggestive of intravascular hemolysis (Fig. ). Other investigations, including arterial blood gas are shown in Tables and . As she had normal oxygen saturation and partial pressure, plasma methemoglobin levels were not measured.
She was hydrated adequately with monitoring of urinary output as well as serum creatinine. During hospital stay, she was transfused with two packs of red cell concentrate. Over a week, the hemoglobin levels increased and hemolysis settled. She never went into acute kidney injury. A review after 4 weeks revealed a hemoglobin level of 12.1 g/dL and she was symptom free. |
pmc-6429833-1 | A 59-year-old Lebanese woman was started on the FOLFIRINOX chemotherapy protocol for metastatic pancreatic adenocarcinoma with irinotecan (180 mg/m2), 5-FU (2400 mg/m2), leucovorin (400 mg/m2), and oxaliplatin (85 mg/m2). She presented to the hospital 1 week after her first cycle with weight loss and decreased oral intake owing to odynophagia. She was diagnosed with grade 4 mucositis and was started on fluconazole and later acyclovir. Owing to very poor oral intake, total parenteral nutrition with electrolyte correction was necessary until the patient was able to better tolerate food. At presentation to the hospital, she also reported three or four episodes of watery bowel movements per day. All stool study results were negative, so she was considered to have grade 1 chemotherapy-induced diarrhea and was started on loperamide. On the second day of hospitalization, the patient developed febrile neutropenia, so piperacillin and tazobactam were initiated along with vancomycin. Subcutaneous filgrastim was administered daily for 9 days and then twice daily for 3 days until the neutropenia subsided. During her stay, the patient also developed a drop in hemoglobin and platelet count, as well as an erythematous rash over the trunk with desquamation of the skin under the breasts. Owing to the severe side effects, FOLFIRINOX was discontinued despite a decrease in tumor marker, and the protocol was changed to gemcitabine and nanoparticle albumin-bound paclitaxel with a good initial response to treatment. With most regimens for the treatment of advanced pancreatic cancer including 5-FU, its oral prodrug capecitabine, irinotecan, or oxaliplatin, and because of the severe reaction the patient experienced, we decided to test the patient for DPD and uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) deficiency. UGT1A1 deficiency is associated with Gilbert’s syndrome and increases the toxicity of irinotecan. Those two tests would help us determine which of the two drugs was the culprit and guide us to use either or both drugs in a reduced dose. The functional activity of the DPD enzyme was not measured, but the DPYD gene was analyzed by next-generation sequencing of both DNA strands of the entire coding region and highly conserved exon-intron splice junctions. The patient was found to have three different variations of the DPYD gene as follows: heterozygous pathogenic variant DPYD*2A (splice site variant 1905+1G>A, also called IVS14+1), heterozygous deficiency-associated variant c.1601G>A (p.Ser534Asn) [, ], and heterozygous deficiency-associated variant c.2194G>A (p.Val732Ile) (Table ) [, ]. All three variations are proposed to cause a reduced activity of the DPYD enzyme. The phase of the three variants (cis or trans) could not be determined, because both parents were not available. The patient also had UGT1A1 deficiency and hence Gilbert’s syndrome. |
pmc-6430302-1 | A 78-year-old male patient with coronary artery disease status post coronary stent placement was found to have a lung nodule on the chest radiograph at that time. The patient underwent a computed tomography (CT) scan, and bronchoscopy, and was found to have a 9 mm fatty endobronchial lesion in the bronchus intermedius above the middle lobe with 2 cm extraluminal fatty lesion into the right hilum. An endobronchial ultrasound with biopsy of the mass was performed, which showed benign bronchial epithelial cells. Since endobronchial resection of the mass would lead to a large defect in the right bronchus intermedius, the decision was made to perform robotic-assisted resection of the lesion (Video ).
We used the Da Vinci Xi robot to perform resection of the endobronchial lesion and hilar mass with right lower lobe superior segmentectomy to remove the lesion. The patient had a “five on a dice” port placement for the operation [, ]. First, we performed the right lower lobe superior segmentectomy to obtain adequate exposure of the hilar mass. We mobilized the superior segmental branch of pulmonary artery and superior segmental branch of the right lower lobe going to the inferior pulmonary vein and divided them with the vascular robot stapler. We divided the superior segmental branch of right lower lobe bronchus with the robot blue load stapler. We used indocyanine green angiography to define the borders of the superior segment of the right lower lobe, which was divided using the robot blue load stapler. This provided access to the hilar fatty tumor, which allowed for removal of the hilar mass and subsequent resection of endobronchial lesion with scissors. The frozen section on both lesions was negative for malignancy. We confirmed complete resection with intraoperative bronchoscopy that also showed a large opening in the airway.
In order to reconstruct the airway, we placed two 3-0 vicryl stay sutures at the proximal and distal ends of the airway and placed the suture through the posterior ports to pull the airway posteriorly away from the main pulmonary artery. We closed the opening with 4-0 PDS (polydioxanone) in an interrupted fashion eight times. This provided good closure of the opening. We performed a bronchoscopy that showed no abnormalities and the air leak test demonstrated no appreciable air leaks.
The patient went home on postoperative day 3 without any complications. The final pathology report was lipomatous hamartoma. |
pmc-6430305-1 | A 40-year-old male with a past medical history of hypertension and a family history of premature myocardial infarctions (MIs) in a number of first-degree relatives came to the emergency department (ED) with chest pain of two hours’ duration. The patient described it as sudden onset retrosternal pressure which was constant, non-progressive, 10/10, non-radiating, and without any aggravating or alleviating factors. Symptoms started at rest and were associated with mild shortness of breath, left arm heaviness, vomiting, and a syncopal episode. The patient reported that his mother experienced myocardial infarction at 38 years of age and two of his maternal uncles and three first cousins died of myocardial infarction in their 40s. Enroute to the ED, the patient received aspirin (162 mg) and sublingual nitroglycerin with minimal improvement. Vital signs were remarkable for a heart rate of 55 beats/minute and normal blood pressure, respiratory rate, and oxygen saturation. Physical examination revealed normal heart sounds and clear lungs.
The initial electrocardiogram (ECG) showed sinus bradycardia with a first-degree atrioventricular (AV) block but without any ST-T wave changes. The initial troponin-T was negative and a total creatine kinase (CK) was 248. The patient received Plavix (600 mg), atorvastatin (80 mg), morphine for pain, and nitroglycerin and heparin infusions for presumed unstable angina. Beta-blocker was not given due to bradycardia. A subsequent ECG four hours later showed prominent Q-waves in the inferior leads and the troponin-T and CK rose to 0.2 and 624, respectively. Interventional Cardiology was consulted and the patient was taken to the catheterization lab for further management of the non-ST elevation myocardial infarction (NSTEMI). The coronary vessels on initial angiography were large and ectatic with visibly swirling blood flow (Figures -). There was a 100% thrombotic occlusion of the first obtuse marginal (OM1) artery and a 60% thrombotic occlusion of the left circumflex artery (Figure ). There was a 20% stenosis of the mid-left anterior descending (mid-LAD) artery and right coronary artery (RCA) as well. The culprit lesions in OM1 and circumflex arteries were treated with balloon angioplasty and with multiple rounds of manual thrombectomy yielding red thrombi (Figure ). Interestingly, the post-intervention antegrade flow by Thrombolysis in Myocardial Infarction (TIMI) grade decreased in both vessels (TIMI 1), possibly due to the distal migration of the thrombi (Figure ).
The patient received eptifibatide (180 mcg/kg double bolus) immediately before the initiation of PCI, followed by a continuous infusion of 2 mcg/kg/minute. The infusion was continued for 18 hours after which the patient was started on ticagrelor, 90 mg orally twice a day (maintenance dose), and continued on daily aspirin, high-intensity statin, a beta blocker, and Coumadin bridged with heparin. Echocardiography done on the following day showed basal lateral and basal-mid inferolateral wall akinesis and an estimated ejection fraction of 55.0%. Owing to a personal and family history of premature MI, the patient underwent extensive rheumatologic workup which included complement levels (C3 and C4), anti-myeloperoxidase antibody, anti-proteinase-3 antibody, anti-dsDNA-antibody, and anti-Smith antibody, but all results were unremarkable. Interestingly, the patient had an elevated antinuclear antibody (ANA) and a low positive Scl-70 antibody titer, but a final diagnosis of scleroderma or any other connective tissue disorder was not entertained given the absence of suggestive clinical signs and symptoms. The hypercoagulability workup was kept limited to JAK2 kinase mutation analysis, Factor-V Leiden, and prothrombin gene mutational analysis as the patient had received anticoagulants, as well as antithrombotics, in the acute setting. The patient also underwent MRA (magnetic resonance angiography) of the whole body which failed to show any aneurysmal dilation of vasculature elsewhere. The hospital course remained uneventful and the patient was discharged on aspirin, ticagrelor, and Coumadin after achieving therapeutic INR (international normalized ratio). During the one year follow-up period, the Coumadin was switched to rivaroxaban, ticagrelor was stopped after six months, and the patient was continued on guideline-directed medical therapy (GDMT) for coronary artery disease (CAD) with favorable outcomes. The patient has been playing full-court basketball games without any further complaints or hospitalization. |
pmc-6430306-1 | A 54-year-old woman with past medical history of systemic sclerosis presented with fatigue, muscle cramps and progressive dysphagia. She was initially diagnosed with systemic sclerosis after presenting with hypertension and scleroderma renal crisis. She denied any dryness of eyes or mouth at that time. She also had diffuse cutaneous thickening, esophageal dysmotility and Raynaud’s phenomenon. Her renal function was normal, i.e., blood urea nitrogen (BUN) of 13 mg/dL (10–20 mg/dL), serum creatinine (Cr) of 0.7 mg/dL (0.6–1 mg/dL). Anti-SSA antibody was negative at the time of initial diagnosis. After the initial episode of scleroderma renal crisis, the patient was on maintenance mycophenolate for worsening skin disease, which ultimately was tapered off due to poor response. Her hypertension was well controlled (systolic blood pressure (BP) 80–100 mmHg and diastolic BP 50–60 mmHg) on a calcium channel blocker and angiotensin converting enzyme inhibitor.
New onset hypokalemia and hypotension were noted eight years into the course of her disease, necessitating cessation of her anti-hypertensives. Her serum electrolytes and renal function tests were as follows: BUN 11 mg/dL (10–20 mg/dL), Cr 0.87 mg/dL (0.6–1 mg/dL), sodium 132 mmoL/L (136–146 mmoL/L), potassium 2.6 mmoL/L (3.6–5.1 mmoL/L), chloride 85 mmol/L (98–107 mmol/L), bicarbonate 35 mmoL/L (23–31 mmoL/L), calcium 9.4 mg/dL (8.4–10.3 mg/dL) and magnesium 1.2 mg/dL (1.6–2.6 mg/dL). Urine electrolyte levels were as follows: urine sodium 61 mmoL/L, urine potassium 184 mmol/L, urine calcium 3.7 mg/dL (spot urine calcium/creatinine ratio: 0.054), and urine magnesium 10 mg/dL (fractional excretion of magnesium: 13.7%). Urine diuretic screening test was negative. The clinical and laboratory findings were attributed to acquired Gitelman syndrome, and the patient responded well to the initiation of spironolactone, potassium and magnesium supplements. At the peak of her electrolyte losses, the patient required approximately 200–250 mEq potassium chloride and a total of 300 mg of elemental magnesium in divided doses. Her electrolytes were stabilized with ongoing supplementation and a diet rich in potassium and magnesium. |
pmc-6430307-1 | A 63-year-old female was admitted to the emergency department with a complaint of palpitation, which had started a few hours ago. Her 12-lead ECG was suggestive of atrial fibrillation (AF; Figure ).
The patient’s medical history included oral anticoagulation therapy for recurrent episodes of AF and topiramate due to essential tremor strictly confined to the arms. After intravenous administration of amiodarone, the new 12-lead ECG was compatible with atrial flutter with cycle length 240 ms and 4:1 atrioventricular response (Figure ).
Notably, flutter waves were present in both limb and precordial leads. To evaluate the underlying heart rhythm, two-dimensional transthoracic echocardiography (2D TTE) was performed. Measurement of transmitral flow using pulsed-wave Doppler revealed a diastolic pattern with normal atrial rhythm (Figure ). |
pmc-6430308-1 | A 70-year-old female patient was admitted with epigastric pain and bloating. Abdominal ultrasonography revealed a 6 x 5 cm sized, well-confined cystic lesion without a solid component in the pancreatic tail. There was no pancreatitis history in her anamnesis. The patient was prescribed an upper abdomen magnetic resonance imaging (MRI) scan which showed a cystic lesion with calcified walls in the pancreatic tail along with a 6 x 3 cm hypointense corpus lesion which was invading the splenic vein, at the same time it was showing less contrast uptake when compared to normal pancreatic tissue (Figure ).
CA 19-9 value was elevated at 1012 IU/ml. The positron emission tomography-computed tomography (PET-CT) scan showed a focally increased fluorodeoxyglucose (FDG) metabolization in the pancreas body with maximum standardized uptake value (SUVmax) of 11.8 without the involvement of the cystic lesion localized in the pancreatic tail. After meticulous evaluation of the tail lesion, it was concluded to be a Type V hydatid cyst without the opportunity of ruling out cystic pancreatic lesions. After the necessary preoperative assessment, the patient was operated on and had a subtotal pancreatectomy with a splenectomy via the left subcostal incision. The pathology report stated that the solid mass was an intermediate grade ductal pancreatic adenocarcinoma with clear surgical margin (Figure ).
The cystic lesion was interpreted as an Echinococcus granulosus cyst with all the pathological features present like germinal layer and protoscoleces (Figures -).
The distance between the cyst wall and carcinoma's lateral border was 19 mm without any histological evidence of any relationship between the lesions. After appropriate recovery, the patient was discharged on postoperative day 11. The patient was referred to medical oncology. |
pmc-6430309-1 | A 55-year-old Caucasian male with a history of HIV diagnosed in 1996, whose cluster differentiation 4 (CD4) count was 245 cells per microliter and HIV-ribonucleic acid (RNA) was less than 75 copies per milliliter, presented to the emergency department with the primary complaint of two weeks of weakness and multiple falls. The patient’s comorbid conditions were significant for hypertension (HTN), hyperlipidemia (HLD), anemia, hypogonadism, pancreatitis, peripheral neuropathy, and chronic pain (managed with opiate medication and not with any nonsteroidal anti-inflammatory drugs (NSAIDs)). He denied any other complaints. The physical examination was significant for facial ecchymoses. The laboratory examination yielded an elevated creatinine at 2.8 mg/dL. The patient had no history of previous kidney disease and had been followed regularly by his primary care physician. Potential nephrotoxic home medications, including Atripla and lisinopril, were stopped at the time of presentation and the patient underwent full workup for new acute kidney injury (AKI). Of note, the patient had been on lisinopril for a number of years; however, he had begun therapy with Atripla approximately 170 days prior to this presentation. The initial workup yielded no results. The patient was discharged home but returned multiple times with sequelae of worsening creatinine and ultimately developed the nephrotic syndrome. Further workup of Fanconi syndrome also proved negative. Ultimately, a renal biopsy was performed, which helped in establishing the patient’s diagnosis as MN (Figures -). The patient was managed conservatively with steroids only, to which his renal function responded minimally but stabilized. The patient was further followed up as an outpatient with a nephrologist. |
pmc-6430716-1 | A 6 years old male patient with HFM referred to our institution for TMJ and mandibular reconstruction. The patient was free from any other medical conditions. Family history revealed that no other family member had similar condition. |
pmc-6430718-1 | A 34-year-old female presented with abdominal distension and severe back pain for one year duration, during which she had been diagnosed and treated as a case of irritable bowel syndrome. She also reported weight loss and constipation. Her past medical history was negative. |
pmc-6430731-1 | An 80-year-old male patient was referred to the abdominal surgery department due to incarcerated ventral hernia and ileus. In the past he was operated due to perforated gastric ulcer. He also had arterial hypertension, chronic pulmonary obstructive disease and pulmonary hypertension, a history of smoking, he suffered an ishemic stroke in the past. He was urgently operated on the same day. Segmental resection of small bowel with end-to-end anastomosis was performed and the hernia defect was closed with direct sutures, without prosthetic mesh because the bowel was resected. There were no surgical or other complications after surgery and he was discharged from hospital after 8 days. 5 days later he was admitted to the hospital again due to early recurrence of ventral hernia. The content in hernia sac could however be reduced back to his abdomen. Laboratory findings showed leucocytosis and elevated C-reactive protein (CRP - 148 mg/l). Intestinal winding with a thickened wall up to 5 mm was found at the location of the ventral hernia by ultrasound examination. The patient underwent a second surgery 22 days after the first surgery due to obstructive ileus, which was seen on the abdominal computed tomography (CT) a day earlier. Due to additional diseases and disorders (ischemic stroke and insertion of stent in his left internal carotid artery in 2011, arterial hypertension, asthma, pulmonary fibrosis and hypertension, which were not properly treated, because the patient did not follow the prescribed treatment) the anaesthesiologist decided for the spinal anaesthesia, because the general anaesthesia would be to risky. The surgery was performed by an abdominal surgeon with 5 years experiences as a specialist and he performed more than 30 Rives-Stoppa ventral hernia repairs. The skin incision was made along the previous skin incision. In the subcutaneous tissue the small intestine was tightly adhered on to the skin. We managed to release it but unfortunately, a segment of the small intestine was damaged during adhesyolisis. Segmental resection of the damaged small bowel with end-to-end anastomosis was performed (). The small intestine was reduced back in to the abdominal cavity. Ventral hernia was repaired according to Rives-Stoppa technique with prosthetic mesh (). Other than postoperative tachycardia there were no reported issues. A couple of hours after the procedure apnoeic episodes appeared followed by unconsciousness. A computed tomographic angiography (CTA) of the brain vascular system was made and it showed a stenotic left vertebral artery (90% stenosis). Because of respiratory insufficiency and haemodynamic instability, the patient was transferred to the intensive care unit. Due to a worsening clinical condition, a CTA of the abdomen was preformed and an occlusion of superior mesenteric artery (SMA) was discovered. Interventional radiologist preformed an embolectomy and thrombus aspiration from the SMA with an insertion of a stent. The patient's condition continued to worsen so the abdominal surgeon decided for a “second look” abdominal exploration. At surgical revision we found a small intestinal and sigmoid colon gangrene. Because of the patients age, several other comorbidities and gangrene of the entire small bowel, the multidisciplinary team (abdominal surgeon, anaesthesiologist, intensivist) decided for conservative treatment. The patient died the day after surgery. |
pmc-6430745-1 | A 75-year-old South-East Asian man presented with exertional chest pain. Risk factors for coronary disease included hypertension, diabetes mellitus, hyperlipidaemia, and family history. High sensitivity Troponin was normal. An electrocardiogram (ECG) showed sinus rhythm with deep T wave inversion in leads I, aVL, V4–V6 (Figure ). Coronary angiography showed diffuse, non-obstructive disease (Figure ). Rubidium-82 positron-emission tomography (PET) imaging demonstrated increased tracer uptake at rest, suggestive of left ventricular (LV) hypertrophy. There was adenosine stress-induced LV cavity dilation with reversible hypoperfusion in a left anterior descending artery territory (Figure A). The global myocardial perfusion reserve (MPR) was reduced at 1.22 ml/g/min (Figure B). In view of the resting ECG abnormality, high tracer uptake at rest and reduced global in the context of non-obstructed coronaries, cardiac magnetic resonance (CMR) imaging (3T Skyra) was performed to exclude a cardiomyopathy. This demonstrated marked regional variability in heart muscle thickness with a maximal wall thickness of 19 mm in the mid inferoseptum (Figure A). Left ventricular ejection fraction was supranormal (82%) with apical systolic cavity obliteration (see on-line Video A). Although there was only minimal late gadolinium enhancement seen involving the superior right ventricular insertion point (image not shown), native T1 was elevated at 1276 ms consistent with diffuse fibrosis (mid septum, normal range 1052 ± 23 ms; Figure B). Adenosine stress imaging demonstrated a circumferential epicardial-endocardial signal intensity gradient, most pronounced in areas of maximal myocardial thickness (Figure C, arrows; on-line Video B). |
pmc-6431024-1 | A 48-year-old Caucasian woman, Eastern Cooperative Oncology Group (ECOG) performance status 1, was diagnosed with locally advanced rectal carcinoma infiltrating the dental line with lymph node metastases. She was diagnosed by computed tomography (CT) (Fig. a) and proctoscopy (no image available) after presenting with problems with defecation, constipation, and tumor-related anemia (see Table for treatment timeline). In fact, painful stenosis prevented endoscopic ultrasound. Significant preexisting diseases were not known, except hypothyroidism or any history of cancer in close family members. She had no occupational noxae. She did not smoke or drink substantial quantities of alcohol. Histological examination of a biopsy specimen of the tumor, which occupied the entire circumference of the rectum, revealed a poorly differentiated adenocarcinoma with a large cell NEC component (Fig. a) confirmed by strong diffuse staining for synaptophysin and CD56 (Fig. b) and comprising > 30% of the tumor in the biopsy material. The result of chromogranin A testing was negative. The patient’s Ki67 index was > 80%. Histology of the NEC component was consistent with grade 3 (G3) NEC of large cell type (Fig. c). More than ten metastases were also detected in both lobes of the liver by CT scan (Fig. b), so the patient’s TNM stage was cT3cN1cM1.
The patient received a regimen of cisplatin (CDDP; 20 mg/m2 on days 1–5, every 4 weeks) in combination with irinotecan (IRI; 50 mg/m2/day on days 1/8/15, every 4 weeks), an agent known for its efficacy in both colorectal cancer and NEC [, ]. In parallel, conventionally fractionated pelvic radiotherapy up to 50.4 Gy (reference point dose, intensity-modulated radiation therapy) was performed with the primary goal of alleviating pain and preventing obstruction by achieving maximum response. Initially, the patient received a red blood cell transfusion and sodium picosulfate against constipation. For antiemetic prophylaxis during all chemotherapy cycles, she received aprepitant (125 mg/day, d1; 80 mg/day, d2–5), ondansetron (16 mg/day), dexamethasone (12 mg/day, d1; 8 mg/day, d2–5), and pantoprazole 40/mg/day and enoxaparin sodium 40 mg/day.
At the end of chemoradiation, the patient experienced rectal pain, which was treated with tramadol (3 × 100 mg/day), and fatigue. Parenteral nutrition was required because of diarrhea (Common toxicity Criteria for Adverse Events version 5.0 [CTC] grade III) and dehydration (CTC grade III). The patient had port-related sepsis (Staphylococcus epidermidis in blood culture), which was successfully treated with vancomycin (2 × 1 g/day, intravenous), and a urinary tract infection (Escherichia coli), which was treated with ciprofloxacin (2 × 400 mg/day, intravenous). She needed red cell blood transfusions for anemia during the first cycle (CTC grade III) (see Table ) and filgrastim 480μg/0.5 ml for 6 days for the treatment of leukopenia (CTC grade IV) at the end of the second cycle of chemotherapy. There were no unexpected events or clinical examination results. A summary of relevant laboratory parameters at baseline and during treatment is provided in Table .
As the CT examination performed immediately after the end of radiotherapy showed only partial remission of the liver metastases (Fig. c), four additional cycles of modified CDDP/IRI (CDDP 20 mg/m2 on days 1–4, every 4 weeks; IRI 50 mg/m2/day on days 1/8/15, every 4 weeks) with prophylactic treatment mentioned above were administered after the end of chemoradiotherapy. No toxicity CTC grade III or IV was observed, but the patient had temporary need of a fentanyl patch for rectal pain treatment. Ultimately, she had ECOG I with no pathologic findings in the physical and neurological examinations.
In light of clinical complete remission of the deep rectal cancer and improvement of rectal stenosis, confirmed by simple proctoscopy with direct visualization, surgical resection was not performed, owing to uncertainty regarding the chances of preserving fecal continence. Complete remission of the liver metastases seen in the CT scan was also achieved after a total of six cycles of CDDP/IRI (Fig. d).
Recurrence of an initial metastasis in segment I was detected after a treatment-free interval of 3 months (Fig. e). Examination of a liver biopsy specimen revealed poorly differentiated NEC (Fig. d). The patient underwent eight new cycles of CDDP/IRI (CDDP 20 mg/m2 d1–3; IRI 60 mg/m2 d1, d8, d15; cycles IV to VIII with 60% of the dose) with the same prophylactic treatment and stereotactic body radiotherapy of the liver metastasis within the first cycle of chemotherapy. The fractionation scheme was 15 × 3 Gy (reference point dose), 60 Gy (equivalent dose in 2-Gy fractions with α/β = 10). During this treatment, there was a port infection (CTC grade III, S. epidermidis) treated with vancomycin (2 × 1 g/day, intravenous), but no other higher-grade toxicity or relevant neurologic or physical findings during hospital stay or outpatient visits, which took place at least once per week.
Treatment resulted in complete remission of the metastasis (Fig. f). Serum neuron-specific enolase, an independent marker of overall survival of NETs (upper limit of normal, 17.49 ng/ml), also decreased in parallel with the treatment cycles (Fig. ).
The patient was followed up by CT scan of the chest and abdomen, as well as MRI of the liver every 6 months, and was tumor-free and symptom-free for 5 years and had no signs of impaired liver function or late toxicity after rectal radiotherapy. Results of all clinical and laboratory investigations remained unremarkable (Table ). The patient’s last follow-up examination was in the autumn of 2018. |
pmc-6431033-1 | The medical history of a 12.5-year-old boy, referred due to pain in the area of the lower left PFM (tooth 36), reported serious health conditions since the first year of life (Fig. ). At the age of 3.5 years, he was diagnosed with ALPS; although all of the findings were indicative of ALPS, there was no history of ALPS in the family and no mutation of the most commonly involved genes (FAS, FASLG) [], as confirmed by genetic analysis. His dental history reported fillings on all second primary molars; however, no inflammatory complications were reported. A dental panoramic tomogram (DPT), obtained when the patient was 6 years old, is presented in Fig. a.
At the age of 12.5 years, a dental clinical examination revealed complete permanent dentition, and both upper central incisors were built up (Fig. b). Reportedly, this treatment was performed by a general dentist as soon as the incisors erupted as they had hypoplastic incisal thirds. Otherwise, the crown morphology was normal. On the cervical halves of the PFMs, poor mineralization of the enamel was identified, which most likely occurred during enamel formation. The remaining tooth crowns appeared intact. Except in the area of the right mandibular PFM, the oral mucosa was of normal coral pink color, size and resilience and showed no inflammatory or other pathologic signs. Swelling was observed buccally in the area of the right PFM (tooth 46), whereas the patient reported constantly present spontaneous pain related to the left PFM (tooth 36). Both mandibular PFMs were sensitive to percussion and did not respond to cold or an electric pulp test. The right one was pathologically mobile. Diagnostic evaluation findings are presented in Fig. . DPT and periapical radiographs revealed profoundly malformed pulp cavities and tooth roots of all four PFMs (Figs. c, d). There was an appreciable peri- and para-apical radiolucency related to tooth 46. In addition, DPT showed the presence of both maxillary third molars but no mandibular third molars.
Based on clinical and radiographic findings, a diagnosis of symptomatic apical periodontitis associated with the necrotic mandibular left PFM and of pulpal necrosis with acute apical abscess for the mandibular right PFM was reached. Due to the very poor prognosis for the endodontic treatment of mandibular PFMs with aberrant root canal morphology, the recommendation of the interdisciplinary team (endodontist, orthodontist and pediatric dentist) was extraction of all four abnormally formed PFMs. This was performed followed by an orthodontic space closure. Prior to any procedures, written informed consent was obtained from the patient and his parents. Extraction resulted in an immediate post-operative resolution of pain, and uneventful healing was observed at the 2-week clinical recheck. No further oral/dental problems have been reported.
Teeth 16 and 36 (Figs. a, b) were fixed with 10% neutral buffered formalin and demineralized with the Shandon TBD-2 Decalcifier (Thermo Fisher Scientific Inc., Waltham, MA, USA) and the mild bone-decalcification solution Osteosoft® (Merck KGaA, Darmstadt, Germany), respectively [, ]. Progression of the demineralization was monitored by dental radiographs (Figs. c, d).
Both decalcified specimens were dehydrated and embedded in paraffin to prepare a series of 5-μm histological sections cut in a mesiodistal direction at 50-μm intervals using a Leica SM 2000R microtome (Leica Biosystems, Nußloch, Germany). The specimens were stained with hematoxylin and eosin (HE), a Masson-Goldner kit (Merck KGaA, Darmstadt, Germany), toluidine blue (pH 7.2) and alcian blue (pH 2.5; Merck KGaA, Darmstadt, Germany). A Nikon Microphot-FXA microscope equipped with a DS-Fi1 camera and NIS-Elements imaging software (NIS Elements D.32; Nikon Instruments Europe B.V., Badhoevedorp, the Netherlands) were used for histological examination. Representative tissue sections were presented using Adobe Creative Cloud.
Examination by light microscopy revealed profoundly folded dentin (especially in the root portion) as well as an unusual tissue filling in the majority of the pulp chamber, comparable to CMD []. Only minor areas of preserved normal pulp were evident (tooth 16; Fig. a, b; tooth 36; Fig. a, b). The course of the dentinal tubules appeared normal only in the occlusal third of the crown (Figs. a, b). The CMD contained connective tissue canals with blood vessels, many of which resembled osteons (Figs. c, f and e, f). The surrounding tissue consisted mainly of globules and interglobular matrix that contained only scarce collagen fibers (Figs. d and g). At the border between the CMD and the occlusal dentin, amorphous tissue resembling tertiary dentin was present (Figs. and c). In areas where the dentinal wall was thinner, there were chondrocyte-like cells (Figs. d, e). The cervical area (where the floor of the dental pulp chamber and furcation should have been) contained cellular cementum and some periodontal ligament tissue. The root canals were obliterated with mineralized structures resembling pulp stones (Figs. g-k) with remnants of normal pulp tissue (Figs. a, b, i, j). Sequential histological sections cut in a mesiodistal direction at 50 μm displayed similar findings.
Tooth 46 was fixed in 10% neutral buffered formalin, rinsed, bisected bucco-palatally and embedded in epoxy resin (Araldite, Ciba-Geigy, East Lansing, MI, USA) with the cut side exposed. After polymerization, the exposed axial cross-section was polished, etched with 37% orthophosphoric acid for 30 s, rinsed with distilled water spray for 30 s, dried with compressed air, dehydrated with 70% ethanol, dried again and sputter-coated with carbon (Vacuum Evaporator, Type JEE-SS; Japan Electron Optics, Tokyo, Japan). Subsequently, the sample was subjected to ultrastructural analysis via SEM (JEOL JSM - 5610, JEOL, Tokyo, Japan) performed in the secondary electron imaging (SEI) and backscattered electron (BSE) modes. Micrographs were recorded at 15 kV and a working distance of 20 mm.
The SEM images revealed a normal structure and thickness of the enamel, areas with normal and abnormal dentin, and an almost completely mineralized pulp chamber (i.e., a CMD). This CMD was composed of brighter and darker areas (Fig. ), referred to as “brighter tissue” and “darker tissue” in the text below, corresponding to globules/interglobular matrix and connective tissue canals with blood vessels, respectively (cf. Figs. and ).
Mineral densities and the elemental composition of four areas were compared: 1) brighter tissue and 2) darker tissue of the abnormal hard tissue located at the site of the pulp chamber (CMD), 3) dentin and 4) enamel.
For mineral density analysis, 10 BSE images of each selected tissue were taken at a magnification of 1500x, 15 kV and a working distance of 20 mm. For enamel, the images were taken approximately in the middle of the whole enamel thickness, on the occlusal and proximal sides, at the occlusal half of the tooth crown. For dentin, images were obtained from normal dentin located on occlusal side between the enamel and pulp chamber area, approximately in the middle of its thickness. For brighter tissue and darker tissue of the CMD, we randomly took images in the area of the CMD in regions where we found typical appearance of brighter and darker tissue. Using the OpenCV library in Python (Windows, Microsoft), for each pixel in an image, the grayscale value in the range of 0 to 255 (black to white) was determined, and the average grayscale value was then computed for each image.
For elemental analysis, five representative images were taken of each of the four tissues, selected in the same manner as described above. Elemental analysis was performed with energy dispersive X-ray spectroscopy-EDXS (500 Digital Processing; IXRF Systems, Houston, TX, USA) at a working distance of 20 mm, an acceleration voltage of 15 kV and a counting time of 80 s. This approach was conducted on the entire surface area of the SEI images under 1500x magnification. For each of the four tissue groups, five images were analyzed, and the values obtained were expressed as the mean ± SD. The results of the EDXS spectra were further evaluated in relation to the carbon-oxygen ratio (C:O) and calcium-phosphorous ratio (Ca:P) as described previously [].
The statistical significance of differences between analyzed tissues was determined by one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test using SPSS 20.0 for Windows (SPSS Inc., Chicago, Ill, USA). A P-value≤0.05 was considered statistically significant.
Mineral density and elemental composition analyses confirmed the similarities between the brighter tissue and enamel, and between the darker tissue and dentin. Figure (a-d) shows representative SEM images of each of the tissues from the crown of the tooth. The mineral density of the darker tissue was comparable to that of the dentin (29.16 ± 0.37 and 29.24 ± 0.16, respectively; P = 0.458), whereas the mineral density of the brighter tissue was lower than that of the enamel (39.64 ± 0.88 and 42.63 ± 0.49, respectively; P = 0.05). Data on the elemental composition are summarized in Table . The darker tissue and brighter tissue displayed elemental compositions that resembled dentin and enamel, respectively. The C:O ratio differed significantly between the pairs of groups (enamel/brighter tissue vs. dentin/darker tissue), whereas the Ca:P ratio was only reduced in the darker tissue (Table ). |
pmc-6431048-1 | A 61-year-old male patient was admitted to our hospital with a prior one-year history of cutaneous hyperpigmentation. Loss of appetite, abdominal distension, constipation, dry skin, less sweat, and insomnia were concomitant symptoms. Ten months prior to admission, his symptoms became severe and were accompanied by symmetrical pitting edema, lower extremity numbness, and weakness in the left lower limbs. Brain MRI showed cerebral infarction, and the patient was treated appropriately. One month later, he was diagnosed with hypothyroidism and Addison’s disease (AD) for severe edema of the lower extremities, unexplained cutaneous pigmentation, and higher ACTH levels (Tables and ). Hydrocortisone 20 mg and Levothyroxine 12.5 μg per day as well as diuretic therapy were administered, and the symptoms mildly improved. After discharge from the hospital, he gradually stopped the diuretic drugs and the doses were adjusted to hydrocortisone 40 mg and Levothyroxine 200 μg per day based on the lab tests. Concomitantly, he experienced pain and numbness in his lower limbs. Since the onset of illness, his general condition was poor. The patient suffered from decreased appetite, poor sleep, weight loss of 15 kg, and hyposthenia (Fig. ).
The patient’s past history showed he was a carrier of hepatitis B virus for 60 years, psoriasis for 40 years with external steroid use, had a 10-year history of type 2 diabetes mellitus controlled by insulin glargine and voglibose, and had hypertension for 2 months. In addition, he was diagnosed with depression two months prior and was treated with flupentixol and melitracen tablets without obvious improvement.
Examination showed T 36.1°C, P 75 bpm, R 16 tpm, BP 140/85 mmHg, H 176 cm, W 62 kg, and BMI 20 kg/m2. The patient had diffuse cutaneous pigmentation of his skin and mucous membranes, especially the areolas and armpits. His superficial lymph nodes were not palpable. He had edema of the eyelids and pitting edema of the upper and lower extremities (Figs. , , , , ). Neurological examination showed grade IV muscle strength in his left lower limbs. His physiological reflexes were normal, and his pathological reflexes were not elicited. His thyroid function and adrenal function were abnormal (Tables and ).
Mild anemia was noted, with HBsAg(+), HBsAb(−), HBeAg(−), HBeAb(+), and HBcAb(+). Rheumatoid factor, anti-nuclear factor, and anti-HIV were negative. Serum electrolytes revealed normal sodium levels. BNP was 2010 ng/L (450–900), and TNI < 0.012 ng/ml (0–0.12). Albumin was 34 g/L (35–55), and fasting blood glucose (FBG) was 5.3–6.5 mmol/L (3.6–5.8). Electroneuromyography disclosed polyneuropathy of the upper and lower extremities. The results of an adrenal CT scan and a head MRI were negative. Abdomen B-ultrasound presented splenomegaly (4.8 × 13.8 cm) and ascites. UCG indicated pericardial effusion with 59% EF. Bone marrow aspirate showed medullary phagocytosis. No M protein was found via serous protein electrophoresis but an immunofixation examination revealed a monoclonal IgAλ peak. The diagnosis POEMS syndrome was made.
The patient was initially treated with a very expensive drug, Revlimid (lenalidomide capsules 25 mg), which is generally used for multiple myeloma (MM) patients. He then underwent autologous stem cell transplantation (ASCT) and experienced significant improvement of his hyperpigmentation and weight loss(Fig. ). Hydrocortisone and Levothyroxine were gradually decreased. His diabetes was also relieved. |
pmc-6431358-1 | A 27-year-old female patient with medical history of reoccurring hematuria led a CT angiography examination of the kidneys, revealing a polycystic kidney with angiomyolipomas. Suspicion on the TSC was made and confirmed with genetic examination revealing a TSC1 mutation in DNA in March 2012. Since then, the patient was started on a mTOR inhibitor therapy (everolimus) with dose adjustments based on blood concentrations during regular check-ups.
Patient with known TSC, polycystic kidneys with bilateral AMLs (), failing renal functions with prehemodialysis values (urea: 18.5 mmol/L; creatinine: 317 μmol/L), lung lymphangiomyomatosis (LAM), and cerebral supratentorial lesions was admitted to our department for pre-kidney-transplant evaluation in October 2012; potential living donor was patients' mother.
During 2013 patient's renal parameters showed a slight decline (urea: 18 mmol/L; creatinine: 395 μmol/L). The patient was hospitalised twice for minor hematuria without the need for blood transfusion and surgical or endovascular intervention.
In May 2014 patient's renal parameters declined severely (urea: 25 mmol/L; creatinine: 457 μmol/L). Due to the deterioration of renal functions, renal transplantation with bilateral nephrectomy was scheduled. Before the procedure patient was put off everolimus therapy in August 2014. However, the potential living donor was contraindicated based on serology results (anti-HBs 433 IU/l). In September 2014 while still off everolimus therapy, the patient was hospitalised for massive hematuria (haemoglobin: 79 g/L) with the need for blood transfusion. Computed tomography angiography revealed symptomatic pseudoaneurysm (PSA) in the right kidney AML. The patient underwent an urgent transarterial embolisation of the PSA feeding vessel in the right kidney's AML (). The procedure was successful. After the procedure, the patient had neither hematuria nor the need for further blood transfusion. Since then, the patient did not have any major hematuria requiring hospitalisation.
Due to the decrease of the renal parameters a native radiocephalic arteriovenous fistula was created for hemodialysis. The patient was put on the “kidney transplant waiting list”. The Czech Republic allocation system does not allow for a priority based on the high risk of bleeding.
In July 2016 the patient was admitted to our center for a cadaverous kidney transplant based on “kidney transplant waiting list” order.
The patient underwent a bilateral nephrectomy combined with renal transperitoneal allotransplantation of the cadaverous kidney graft with a prophylactic appendectomy, and cholecystectomy through midline laparotomy (end-to-side anastomosis of the renal graft's vein- external iliac vein, renal graft's artery-external iliac artery; ureterocystoanastomosis with 24 cm 2,4 French JJ stent) (). The procedure was performed without any complications. Postoperative period was complicated by delayed graft function (urea: 32 mmol/L; creatinine: 797 μmol/L); the patient was anuretic two days after the procedure with good graft's perfusion based on Doppler ultrasonography. This might have been caused by the time in-between the kidney graft harvest and the renal transplantation (21 hours). Grafts' biopsy was indicated, revealing acute tubular necrosis. The patient underwent two hemodialysis cycles. After six days, the patients became uretic again (1980 ml of urine/24 hours); renal functions improved drastically (urea: 26 mmol/L; creatinine: 284 μmol/L). Controlled biopsy showed focal regeneration of the acute tubular necrosis of the graft. The grafts function was repeatedly checked using Doppler's ultrasonography.
The patient was discharged on the 17th postoperative day with good renal graft function (urea: 15 mmol/L; creatinine: 133 μmol/L). The patient was discharged from hospital on immunosuppressive therapy: extended release tacrolimus (daily dose of 17 mg), mycophenolate (720 mg dose twice a day), and prednisone (daily dose of 20 mg). mTOR inhibitors were refrained to avoid potential wound healing complications.
Patients follow-up is currently 23 months with good graft function (urea: 10 mmol/L; creatinine: 106 μmol/L). Immunosuppressive therapy was adjusted to extended release of tacrolimus (daily dose of 4,25 mg), mycophenolate (440 mg dose twice a day), and prednisone (daily dose of 5 mg). |
pmc-6431363-1 | A 66-year-old man had been diagnosed with infectious cervical tuberculosis on C1 and undergone posterior C1-2 screw-plate fixation at a hospital in India one year prior to his visit to our hospital. Although the surgery was successful and his neck pain had improved, his swallowing function had gradually worsened over the nine-month period after the initial surgery, along with loss of reduction. Due to progressive dysphagia and severe weight loss, he was referred to our hospital. His medical history included hypertension and mild diabetes mellitus (HbA1c 6.2% NGSP). He had been given antitubercular treatment since he was diagnosed with infectious cervical tuberculosis at the local hospital.
The patient's height was 165 cm, his weight was 52 kg (BMI 19), and he exhibited normal cognitive function. He had lost 25 kg over 7 months because of difficulty in swallowing, and a nasogastric (NG) tube was placed for tube feeding. Neurological examination of the patient revealed left dominant proximal arm muscle weakness with atrophy, dysesthesia in distal fingers, hyperreflexia throughout with bilateral extensor plantar reflex. Oral examination was remarkable for left tongue atrophy as well as left tongue deviation, which was consistent with unilateral HNP. Routine blood work showed slightly elevated level of C reactive protein (CRP), but the findings were otherwise normal.
Chest X-ray results showed no specific abnormality. Lateral cervical X-ray showed O-C2 angle of 17-degree kyphosis (). Computed tomography (CT) showed an erosive lesion at dens and anterior arch of the atlas (). Magnetic resonance imaging showed a space-occupying lesion in the retropharyngeal space, which presented with heterogeneous signals on both T1- and T2-weighted images (). Further sequential review of previous imaging studies revealed that, contrary to the progression of O-C kyphosis, the lesion had been gradually decreasing in size.
In sum, the patient had two main problems: severe dysphagia and subsequent malnutrition and neck pain. Initially, we assumed that the dysphagia was primarily caused by oropharyngeal stenosis resulting from O-C kyphosis [–]. However, since no findings of the intracranial pathology were observed and the patient exhibited a persistent unilateral HNP and severe swallowing dysfunction, we eventually hypothesized that the dysphagia would have been deteriorated even worse due to the limited tongue movement. In other words, both O-C kyphosis and HNP were related to dysphagia, and it was not possible to draw a clear line by which these two factors were divided regarding the etiology. No conservative treatments had improved these symptoms, and we therefore decided to perform a corrective surgery to restore the swallowing function and to relieve the neck pain.
Posterior O-C3 fusion surgery with iliac bone graft was performed without complications. The O-C kyphosis was corrected to 6-degree lordosis on O-C2 (). Findings of the tissue biopsy from the retropharyngeal mass were negative for infectious etiology. The postoperative course was uneventful. His swallowing function concomitantly with his tongue movement improved in two weeks after the surgery. At the final follow-up visit at five months, bone union was observed, and swallowing function was confirmed without further deterioration. |
pmc-6431373-1 | A 51-year-old Japanese woman was admitted to our hospital for the evaluation of heavy proteinuria, deteriorating renal function, and severe hypertension. She had a medical history of RA at the age of 42 and left vitrectomy for retinal detachment and bilateral femoral head replacement following fracture at the age of 49. Since she had drug allergies to many drugs, various treatments for RA were tried to introduce including methotrexate, infliximab, etanercept, salazosulfapyridine, leflunomide, bucillamine, tacrolimus, abatacept, and/or tocilizumab in addition to prednisolone (PSL) and nonsteroidal anti-inflammatory drugs. She was treated with the dosage of 2 to 3 mg/day of tacrolimus, standard dose for RA in addition to PSL 8 mg/day from the age of 48 for 2 years and 3 months. Clinical course after introduction of tacrolimus is shown in . BP was increased from 120/70 mmHg to 140/80 mmHg 20 months after tacrolimus treatment, trough levels of tacrolimus fell within acceptable ranges between 5 and 10 ng/dL during the course. Proteinuria began to increase from the baseline proteinuria of 0.3 to 0.5 g/g creatinine 24 months after tacrolimus treatment, but serum creatinine level was sustained around 0.8 mg/dL. Tacrolimus and tocilizumab were changed to tofacitinib citrate 27 months after tacrolimus treatment because of uncontrolled arthritis of RA. However, tofacitinib citrate was discontinued 2 months after the treatment because of allergic reaction. Proteinuria was further increased after discontinuation of tacrolimus and tocilizumab, and then severe hypertension 190/100 mmHg and progressive renal dysfunction developed. 40 mg telmisartan/5 mg amlodipine besilate combination tablet was introduced 2 months after tacrolimus discontinuation. Her renal function was further deteriorated to creatinine of 2.63 mg/dL; thus she was admitted to our hospital 3 months after tacrolimus discontinuation.
On admission, body temperature was 36.5°C, height 154.0 cm, weight 44.9 kg, BP 170/102 mmHg, and pulse rate 88/min. Physical examination showed numbness in hands, pain in the elbows, wrists, knees, and metacarpophalangeal (MP) joint of the right thumb finger, swelling of MP joint in the right second finger, and mild pitting edema in bilateral legs but no abdominal bruit. She had no focus of infection and sclerotic skin lesion and no experience of Raynaud's phenomenon. The laboratory data on admission are shown in . Urinary examination showed heavy proteinuria and microscopic hematuria. Urinary low-molecular-weight proteins and urinary N-acetyl-β-D-glucosaminidase were elevated. Blood examination showed anemia, hypoalbuminemia, renal dysfunction, and hypocalcemia. Immunological examination indicated normocomplementemia, normal tests for anti-DNA antibody, anticardiolipin antibody, and myeloperoxidase and proteinase 3-anti-neutrophil cytoplasmic antibodies, but positive tests for RA-associated factors including rheumatoid factor, matrix metalloproteinase-3, and anti-SS-A antibody. Repeated peripheral smears showed no evidence of hemolysis. Serum renin activity and aldosterone concentration were of high value. Her hypocalcemia could be explained by use of denosumab for the treatment of steroid-induced osteoporosis.
The electrocardiogram showed voltage criteria of left ventricular hypertrophy. Chest X-ray showed no apparent cardiomegaly and lung edema. Abdominal ultrasound detected normal shape and size in the kidneys and multiple hemangioma in the liver. Echocardiography revealed ejection fraction 56% Simpson method, ratio of E to e' 22.6, and left ventricular wall thickening. Fundoscopy did not show exudate hemorrhage and papilledema.
With a clinical suspicion of secondary amyloidosis, focal segmental glomerulosclerosis (FSGS), or malignant nephrosclerosis, renal biopsy was performed. A renal biopsy showed 5 glomeruli with adhesive lesions and segmental sclerosis or global sclerosis and 8 glomeruli with ischemic shrinkage of glomerular tufts out of 22 obtained glomeruli (Figures , , and ). Some of the remaining glomeruli showed collapse of capillary tufts (Figures and ), FSGS (), and segmental thickening of capillary walls showing double contour (). There were extensive tubular atrophy and interstitial edema to fibrosis involving 70% of renal parenchyma, accompanied by chronic and acute inflammatory cell infiltration (Figures and ). Distribution of the tubulointerstitial damage was zonal, indicative of ischemic injury following vascular compromise (). The afferent arteriole of the glomerulus was occluded by an organized thrombus, and the arterioles showed concentric intimal hyperplasia forming “onion skin” lesion (). Some of the small arterial and arteriolar lumina were markedly narrowed by thickened fibrous intima (). Of note, some arteriolar walls exhibited circumferential and transmural nodular hyalinosis (Figures and ). An immunofluorescence study showed nonspecific segmental staining of IgM, C1q, and C3 in glomeruli, and IgA and IgM in tubular casts. Electron microscopy revealed swollen glomerular endothelial cells with loss of fenestrations, irregularly thickened lamina rara interna, and foot process effacement involving 30% of podocytes (). No electron dense deposit was identified. Collectively, these histological findings are suggestive of malignant nephrosclerosis and tubulointerstitial damage, represented by subacute/chronic TMA.
Severe hypertension and tacrolimus use were considered to be causes of TMA in our patient. Since tacrolimus had already been withdrawn, we tried to manage blood pressure on an appropriate level. It is reported that hypertension is highly prevalent among patients with RA, and use of anti-inflammatory analgesics and disease-modifying drugs with hypertensive potential, and yet to be determined inflammatory pathways, and genetic factors may synergistically lead to hypertension []. Nonsteroidal anti-inflammatory drugs and tofacitinib citrate [] might have contributed to severe hypertension in our patient. However, it is more likely that her severe hypertension may have been caused by renal parenchymal damage with marked activation of renin-angiotensin-aldosterone system. To control severe hypertension, amlodipine besilate was changed to nifedipine. In addition, methyldopa and also aliskiren to inhibit renin-angiotensin system were introduced, then BP was gradually decreased. After aliskiren was administered, renin activity was reduced from 12 to 0.6 ng/mL/h and aldosterone concentration from 242 to 69.4 pg/mL in one week. Blood pressure and renal function eventually stabilized with gradual reduction of proteinuria. One year after renal biopsy, serum creatinine was 4.03 mg/dL and proteinuria was 1.0 g/g creatinine (). |
pmc-6431376-1 | A 42-year-old Italian woman arrived to our attention for a two-year history of eyelid ptosis, ophthalmoparesis, dysphagia, exercise intolerance, and myalgia. She presented mild hyperCKemia (243U/L). Patient's parents were not consanguineous. She had no family history of neurological disorder. In the past, she has suffered of anxiety disorder. Neurological examination showed mild proximal weakness of lower and upper limbs, weakness of facial muscles, bilateral eyelid ptosis, and ophthalmoparesis. Forearm ischaemic test revealed basal hyperlactacidemia (25 mg/dL, reference value: 4,5-19,8 mg/dl), increased production, and delay in the recovery of lactate. Electromyography showed a myopathic pattern. Echocardiogram was normal but the ergospirometric test showed a functional limitation; spirometry was normal but maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were reduced (MIP=4,1 kPA, n.v. >7,61, MEP 5,17 kPA, n.v. >10,2). Muscle biopsy revealed ragged red and ragged blue fibers and COX negative fibers (). Sequencing of the entire mtDNA from muscle was normal. Long-PCR analysis, in muscle tissue, showed mtDNA multiple deletions (), and next-generation sequencing (NGS) analysis detected two DGOUK compound heterozygous mutations: the known pathogenetic variant c.462T>A (p.Asn154Lys) and a new variant of the donor splice site of intron 5 c.707+2T>G, predicted to alter the splicing on Human Splicing Finder () and thus considered pathogenetic. While we could not test their parents, two asymptomatic siblings harbored the c.707+2T>G pathogenetic variant. Since we could not test the parents, it is possible to assume that the two variants were inherited in an autosomal recessive manner in the patient; however, it is equally possible one arose de novo. |
pmc-6431385-1 | A 61-year-old African American male with medical history of diabetes mellitus presented with worsening exertional dyspnea of 2 weeks. He takes about 5 alcoholic drinks per week and quit tobacco smoking 40 years ago. On examination, he was noted to be bradycardic with heart rate (HR) 47 and hypertensive with blood pressure (BP) 180/80. Electrocardiogram (ECG) showed complete heart block and junctional escape rhythm (). Previous ECGs were noted to show first-degree heart block and mobitz type 1 heart block, at which time he was asymptomatic. Transthoracic echocardiography (TTE) revealed an estimated ejection fraction (EF) of 55–60%, no regional wall motion abnormality (RWMA), mild increase in left ventricular wall thickness in the posterior (13 mm) and septal (13 mm) walls, and mild diastolic flattening with right volume overload. A permanent pacemaker was inserted, the ECG postprocedure showed normal electrical pacemaker rhythm. He was commenced on medications for the new onset systemic hypertension and discharged in stable condition. Of note, chest radiograph done at this admission did not reveal bilateral hilar lymphadenopathy (LAD), and LAD was also not noted on physical examination.
After a year of inadequate follow-up, the patient presented with shortness of breath (SOB) and decreased exercise tolerance (ET). No significant findings were noted on examination, and pacemaker interrogation was normal with no events recorded. Investigations were significant for mildly elevated brain natriuretic peptide- (BNP-) 248, hypoalbuminemia, and new onset normocytic anemia. TTE showed dilated right atrium, moderately reduced systolic function with an estimated EF of 30–35%, mild mitral regurgitation, moderate diffuse hypokinesis with regional variations, and grade 2 diastolic dysfunction e/a ratio of 1.7, impaired relaxation, and moderately elevated left ventricular end diastolic pressure. The patient was managed symptomatically with improvement in symptoms and discharged against medical advice (AMA). The CT angiogram chest and CT abdomen done before discharge to rule out pulmonary embolism and to evaluate an incidental finding of likely liver mass on TTE showed hepatomegaly with liver span of 17.6, innumerable nodules in the liver and spleen, with widespread lymphadenopathy (LAD) including bilateral hilar and mediastinal LAD and patchy peribronchial opacities in both lungs. These findings raised a suspicion for sarcoidosis and/or possible lymphoproliferative disorder.
The patient did not follow-up appropriately, presented six months later with similar symptoms of SOB, and decreased ET that worsened 3 days before presentation. He becomes dyspneic on walking around in his apartment; ET tolerance was previously about 2 blocks. On examination, he was noted to have right posterior cervical and bilateral inguinal lymphadenopathy, bilateral lower extremity edema, abdominal distension, and positive hepatojugular reflux. Investigations were significant for elevated BNP-816, infiltrative pattern on liver panel-elevated alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) with higher values compared to his last admission. TTE showed severely reduced systolic function with an estimated EF of 15–20%, severe diffuse hypokinesis with regional variations, and a severely dyssynergic right ventricle, and ECG showed short runs of native conduction with the left bundle branch block (LBBB) pattern. He was admitted and managed symptomatically for acute decompensated heart failure with systolic dysfunction. Pacemaker interrogation done revealed 88% ventricular pacing, left cardiac catheterization showed nonobstructive coronaries, and an inference of nonischemic cardiomyopathy secondary to possible cardiac sarcoidosis was made. Unfortunately, cardiac magnetic resonance (CMR) could not be done because of the pacemaker. Granulomatous disease workup done showed hypercalcemia, hypercalciuria, very low parathyroid hormone, low 25-hydroxy vitamin D, and bilateral upper lobe changes on chest X-ray. A working diagnosis of multisystemic sarcoidosis was made, and he was started on high-dose prednisone 60 mg and Pneumocystis carinii pneumonia prophylaxis while awaiting liver biopsy result. Whole body gallium-67 scintigraphy () showed increased uptake within the parotid and submandibular glands, inguinal lymph nodes, normal physiologic uptake in the liver, and no abnormal uptake in the chest and abdomen. Cardiac resynchronization therapy defibrillator (CRT-D) was done, and the patient was discharged with cardiology clinic follow-up. Liver biopsy later revealed multinucleated giant cells, noncaseating granuloma, moderate portal inflammation comprising lymphocytes, neutrophils, and plasma cells, and periportal fibrosis consistent with a clinical diagnosis of sarcoidosis. At his last clinic appointment, 6 weeks after discharge, there was significant clinical improvement as patient's symptoms had resolved, and ET improved to 5 blocks. A repeat TTE to evaluate cardiac function was planned for his next clinic appointment. |
pmc-6431388-1 | A 41-year-old male, without regular medical care, initially presented in the outpatient setting with progressive fatigue, weight gain, shortness of breath, and lower extremity edema over the past year. At that time, he was diagnosed with hypothyroidism (TSH 136 uIU/mL) and was started on 50 μcg PO levothyroxine daily. Two days later, he presented to the emergency room with chest pain and worsening shortness of breath. The patient was admitted for further evaluation which included an ischemic workup for coronary artery disease.
A diagnostic cardiac catheterization was performed and the patient was noted to have multivessel obstructive coronary disease with a severely reduced ejection fraction. The patient subsequently underwent stenting of the left anterior descending and left circumflex coronary arteries. However, within 24 hours, the patient developed cardiogenic shock and a second percutaneous intervention was emergently done to address the right coronary artery lesion. Due to patient's condition, an intra-aortic balloon pump (IABP) was utilized and he was transferred to another institution for escalation of care.
Upon arrival to the second institution, vital signs demonstrated a blood pressure of 67/31 mmHg, a heart rate of 68 bpm, an oral temperature of 35.7°C, a respiratory rate of 14, and an oxygen saturation of 99% on 4 L nasal cannula. Evaluation of the patient was significant for altered mental status and signs of systemic hypoperfusion with cold extremities in the lower extremities. The physical exam also was positive for bilateral nonpitting edema in all extremities. Further pertinent positives on the physical exam were notable for thinned hair to the lateral eyebrows, macroglossia, a waxy, yellow appearance to his skin, and an absence of hair on the lower extremities.
Initial laboratory findings included hemoglobin of 7.7 g/dL, platelets of 24 K/μL, and a TSH level of 51.09 uIU/mL with free T4 of 0.26 ng/dL and free T3<1.0 pg/mL. Thyroid peroxidase was also noted to be elevated at 209 IU/mL (normal < 9 IU/mL). An electrocardiogram was obtained which showed diffuse Q waves (). Cardiac monitoring was reviewed which demonstrated low-voltage complexes with an intermittent junctional bradycardia. Bedside echocardiogram revealed severely reduced systolic ejection fraction of 10% with mild to moderate RV dysfunction.
Patient's clinical presentation was consistent with myxedema coma, and the patient was treated with stress-dose steroids and intravenous levothyroxine. Given the refractory cardiogenic shock, the IABP was upgraded to a transcaval Impella 5.0 upon admission. Patient's clinical condition subsequently improved as his lactate cleared from 5.5 mmol/L to 1.1 mmol/L; vasopressors were discontinued; Impella wean commenced over the course of a few days. Unfortunately, his clinical course was complicated with acute ischemia of his right lower extremity on day 6 leading to acute renal failure and sepsis. Ischemia was likely multifactorial with a large 24F venous sheath from the Impella exerting pressure on the femoral artery also containing 5F arterial line; the patient also developed an aortic thrombus further impairing perfusion. Despite emergent revascularization efforts and Impella removal, the muscles were nonviable. Family was informed of the need for an above the knee amputation; however, the family decision was to proceed with comfort care and the patient died on the 8th day of hospitalization. |
pmc-6431389-1 | A 62-year-old woman (body mass: 61.2 kg; height: 1.57 m; body mass index (BMI): 24.8 kg.m−2) was hospitalized in an intensive care unit for ARDS of infectious origin.
Her medical history included autoimmune hypothyroidism, arterial hypertension, and anosmia. She reported no history of smoking. She was retired and practiced regular physical activity: walking, hiking, and using a home stepper. She was only treated by levothyroxine.
The patient was first seen as an outpatient with influenza-like symptoms and was treated with probabilistic antibiotic therapy (amoxicillin then ceftriaxone) for 7 days. The evolution was unfavorable and she was admitted to the pulmonary critical care unit on 5 April 2016 with signs of acute respiratory distress. The chest X-ray on admission showed bilateral alveolar-interstitial syndrome with bilateral lower lobe consolidations (), prompting spiramycin addition to her antibiotic treatment. Following a rapid deterioration in lung function under high-flow oxygen therapy, the patient was intubated (D+1) and transferred to the intensive care unit. The worsening clinical picture prompted antiviral treatment with oseltamivir (75 mg twice daily) in addition to ceftriaxone (2 g) and spiramycin (1.5 million units daily). Repeated samples were taken for bacteriological (i.e., protected brush sampling of mucus plugs, cytobacteriological examination of urine, blood culture, polymerase chain reaction, and antigenuria) and virological (e.g., polymerase chain reaction for influenza) investigations. The patient was treated with norepinephrine up to 0.5 microgramme.kg−1.min−1 for 24 hours because of hemodynamic instability.
Moderate ARDS (partial pressure arterial oxygen/fraction of inspired oxygen ratio = 123 mmHg with positive end-expiratory pressure ≥ 5 cm H2O) with bilateral pneumonitis was diagnosed.
The patient was placed on mechanical ventilation at 6 mL.kg−1 predicted body weight, along with sedation using midazolam and sufentanil and curarization with cisatracurium for 48 hours. The favorable response led to a gradual decrease in sedation and ventilatory weaning at D+10. However, following respiratory distress secondary to laryngeal edema, the patient was reintubated, and systemic corticosteroid therapy (1 mg.kg−1) was initiated. In the absence of bacteriological evidence and given the favorable clinical course, antibiotic therapy was reduced to ceftriaxone alone for 10 days. The definitive extubation (D+13) proceeded without complication. The patient (body mass: 62.0 kg, i.e., BMI: 25.2 kg.m−2) was discharged from the intensive care unit (D+14) after weaning from oxygen. This delay is according to the literature, which recommends between 2 and 3 weeks []. She then received respiratory physical therapy in the after-care and rehabilitation department.
The rehabilitation program comprised physical exercises []. The endurance exercises were performed on a cycle ergometer, treadmill, or stepper. Initially, endurance exercises were executed in sequences of 10 minutes or less, with the goal of reaching 30 minutes per session. The intensity of endurance exercises was prescribed on the effort perception (score of 11-13 on the ratings of perceived exertion scale) []. In addition, muscle strengthening exercises for the upper and lower limbs were proposed, lasting 10-15 minutes per session and using weights, dumbbells, or elastic bands. Each exercise comprised a series of 6-12 repeated movements. A 1-minute recovery period was observed between exercises. Warm-up and stretching exercises were performed, respectively, before and after each session []. Moreover, the patient was encouraged to increase the time spent in daily living activities.
One month after this episode, she experienced dyspnea on exertion with whitish sputum and a 2-kg weight gain despite daily physical activity (30 minutes/day on a stepper). At D+39, a new chest X-ray showed the clear regression of alveolar condensation with some persistent sequelae at both pulmonary bases ().
Three months later, the patient (body mass: 63.0 kg, i.e., BMI: 25.6 kg.m−2) was seen in consultation in the pulmonary department. She had continued daily physical activity with satisfactory tolerance (30 minutes/day of treadmill walking and 15 minutes/day cycling at moderate intensity). Pulmonary function testing (PFT) revealed impaired alveolar-capillary transfer with a carbon monoxide diffusing capacity reduced to 3.93 mmol/(min∗kPa) (60% of the theoretical value). The pulmonary volumes and expiratory flow rates were normal (forced expiratory volume second = 1.84 L, vital capacity = 2.2 L, total lung capacity = 4.49 L; i.e., 102%, 98%, and 109% of the respective theoretical values), with no sign of obstruction (Tiffeneau ratio: 87.1%). Respiratory muscle strength was normal (based on maximal inspiratory and expiratory pressures and the sniff test). The patient covered a satisfactory distance of 542 m (i.e., 109% of the theoretical value) [] in the 6-minute walk test, with significant desaturation (i.e., 8% drop in saturation, with 88% saturation at the end of the test). The cardiopulmonary exercise test indicated normal aerobic fitness with a peak oxygen flow (VO2peak) of 20.4 mL.min−1.kg−1. The exercise intolerance appeared to be ventilatory in nature with low ventilatory reserve (RV = 6.3%), high respiratory quotient (RQ = 1.32), inappropriate hyperventilation (69 L.min−1) with high respiratory equivalents, significant desaturation on exertion, and a high alveolar-arterial gradient (8.1 kPa), consistent with ARDS sequelae. The exercise limitation also appeared to be of metabolic origin, related to overweight. She was advised to continue regular physical activity (at the first ventilatory threshold) at home, where she had a treadmill and an ergocycle.
At the 6-month evaluation, the patient displayed only mild exertional dyspnea, stage 1 of the modified Medical Research Council (mMRC) classification, but her physical activity was limited by pain from a sternal fracture caused by a road accident (August 2016). The chest CT scan confirmed residual bilateral basal consolidations.
At one year, the patient no longer experienced dyspnea. The chest CT scan showed the persistence of a bilateral interstitial syndrome associated with bronchial dilatation and pleural-based consolidations (). PFT had remained stable (carbon monoxide diffusing capacity: 63%) and no other abnormality could be detected. |
pmc-6431390-1 | RC is a 62-year-old male who initially presented with a T3N2M0 midrectal cancer and underwent neoadjuvant chemoradiation four weeks prior to a laparoscopic low anterior resection with diverting loop ileostomy. He completed adjuvant chemotherapy and returned for an elective reversal of his ileostomy nine months postoperative. His preoperative workup included a colonoscopy which revealed exclusion colitis for which he was treated. He also underwent a gastrografin enema and computed tomography (CT) imaging of his abdomen and pelvis with no evidence of recurrence, obstruction, or distant metastases. On CT imaging, the proximal ileum appeared normal, but the distal ileum was not imaged. After his reversal, his postoperative course was complicated by persistent small bowel obstruction, for which he was managed conservatively for two weeks. He subsequently underwent a CT abdomen and pelvis, which was highly suspicious for anastomotic stricture.
On postoperative day 14, the patient underwent a diagnostic laparoscopy showing multiple adhesions around the previous reversal site with normal-appearing dilated proximal and collapsed distal small bowel. There was no localized stricture in the defunctionalized distal ileum. He underwent a resection of the prior reversal site and creation of a new side-to-side primary anastomosis. Despite creation of new anastomosis, his small bowel obstruction continued for additional two weeks. CT imaging and small bowel series were obtained, both modalities showing a narrowing of the ileum distal to the previous anastomosis (Figures and ). On hospital day 27, the patient underwent a final exploratory laparotomy with intraoperative findings of persistent collapsed bowel loops distal to the new anastomosis. The collapsed distal segment was resected, and an ileocolic anastomosis was created. On gross examination, the entire distal ileum was thickened without stricture (Figures and ). The pathology of the distal ileum showed submucosal fibrosis with hyalinization of the lamina propria and atherosclerotic changes in the adjacent vessels. After the second revision, the patient progressed as expected with return of bowel function and tolerance of diet and was later discharged on hospital day 38. Our presented patient continues to do well on the outpatient follow-up. |
pmc-6431392-1 | A 47-year-old man known to have hypothyroidism and hypertension on treatment presented to the gastroenterology clinic complaining of two-year history of abdominal distension that was worse after oral intake especially milk. He had normal bowel motions and denied nausea and vomiting. There was no previous abdominal surgery. On examination, the abdomen was distended with no tenderness. Colonoscopy was done and showed normal rectum, grossly dilated sigmoid with redundant colonic wall, and mild mucosal inflammation. Abdomen computerized tomography showed distended sigmoid colon with collapsed rectum and no obstruction ().
As his symptoms were severe and he already failed conservative management, the patient was referred to general surgery. He underwent laparotomy () and extended hemicolectomy of the affected segment, with colorectal anastomosis. He did well intra- and postoperatively. The pathology unexpectedly showed chronic schistosomiasis in the colonic wall (Figures and ). Upon further evaluation, we found that he lived in the north of Saudi Arabia (Hail) but denied exposure to unclean water or recent travel. His Schistosoma serology titer was high (1 : 1024). Other laboratory findings included slightly elevated direct and total bilirubin (12.3 and 41.5 μmol/L, respectively), normal aminotransferases, erythrocyte sedimentation rate = 11 mm/hour, and C-reactive protein < 3.50 mg/L. He was referred to the infectious disease clinic and was treated with praziquantel. At six-month follow-up, the patient was doing well with resolution of his abdominal symptoms. |
pmc-6431401-1 | A 54-year-old man was admitted with 4-5 days of abdominal pain that began in the left upper quadrant and then migrated subumbilically. The pain was sharp, steady, and of moderate severity. He also described nausea and a low-grade fever. Past medical history included kidney stones and a sigmoid colectomy for diverticulitis 15 years previously. He denied a history of excess alcohol use. His only medication was atenolol 50 mg daily.
On admission, physical examination revealed normal sinus rhythm, normal pulse and blood pressure without postural change, normal temperature, moderate tenderness to palpation in the left supraumbilical and subxiphoid areas without peritonitis, organomegaly, or mass lesion. Stool was negative for occult blood.
Lab results: WBC: 10 x 103/μL, Hgb: 16g/dL, Chemistry 7, liver enzymes, and serum amylase and lipase were within normal limits. Upper GI endoscopy was interpreted as a 5 mm sessile gastric antral polyp with normal gastric mucosa on biopsy. Abdominal CT scan showed mesenteric inflammation surrounding the distal body and proximal antrum of the stomach and adjacent low-density thickening of the stomach wall, measuring up to 18 mm in thickness. He was treated with IV fluids and pain medication. His condition improved and he was discharged home without a definitive diagnosis.
He felt well for four months and then developed recurrent mild, diffuse, sharp, steady abdominal pain. He denied weight loss, nausea, vomiting, or bowel complaints. Physical examination showed normal vital signs, afebrile. His abdomen was soft, nontender, and otherwise unremarkable. Basic laboratory studies, serum amylase, and lipase were normal. Repeat upper GI endoscopy showed a firm submucosal mass with intact overlying mucosa and a central umbilication. Biopsy of the lesion revealed normal gastric mucosa (). Abdominal CT with IV contrast () revealed minimal residual perigastric inflammatory changes (left arrow) and focal, heterogeneous gastric thickening, consistent with residual inflammatory changes (right arrow). Endoscopic ultrasound demonstrated an oval, intramural lesion 3.3 cm by 1.3 cm with irregular borders, which was aspirated by fine needle aspiration (FNA).
Findings were nondiagnostic, but inconsistent with leiomyoma or leiomyosarcoma.
Open gastric antrectomy with a Billroth I technique was performed for a preoperative diagnosis of gastric adenocarcinoma. Histology of the resected specimen revealed ectopic pancreatic tissue, including excretory ducts, acini, and islet cells within the gastric muscularis layer (). Evidence of chronic pancreatitis was present, including fibrosis and dilated ducts containing proteinaceous material. Also noted was an abscess believed to be related to focal acute pancreatitis in the ectopic tissue. At discharge, pain had resolved. He remained asymptomatic at 1-year follow-up. |
pmc-6431424-1 | In August 2017, a 58-year-old white man was referred to our center of Hepatobiliary Surgery and Liver Transplantation at the Policlinic Hospital of Padua for paracaval, subdiaphragmatic recurrent HCC in the absence of underlying liver disease. He had a history of multiple abdominal surgeries: in August 2015, a laparotomic right hepatectomy for HCC (with negative oncological margins, R0); in April 2016, excision of cutaneous HCC metastases; and in January 2017, a local intrahepatic recurrence of HCC occurred, treated with liver and diaphragm en bloc resection with right diaphragmatic patch located near the resection margin. Both resections were performed in another hospital via a J-shaped incision.
During the follow-up, a thoracoabdominal triple-phase computed tomography (CT) scan showed a HCC nodule of 18 × 14 mm located immediately upstream of the confluence of the middle hepatic vein with the inferior vena cava (Fig. a, b). Abdominal US evaluation did not clearly detect the hepatic lesion due to lung and bowel interposition. He was asymptomatic, had a normal level of alpha-fetoprotein (AFP), negative hepatitis viral markers, and normal liver function: Child–Pugh A5 and Model for End-Stage Liver Disease (MELD) 6. His body mass index (BMI) was 24. |
pmc-6431431-1 | A 16-year-old girl, with a free past medical history, presented with a palpable mass on the left side of the neck, complaining of dysphagia and cervical pain associated with dizziness. Neurologic examination was unremarkable and diagnostic tests for Epstein–Barr infection were negative. The patient underwent a thyroid ultrasound (US), which did not reveal any significant findings from the thyroid gland. However, a 27.5mm oval shaped, well-defined, hypoechoic, solid lesion was found at the left carotid triangle. The lesion showed high vascularity. Magnetic resonance imaging (MRI) of the neck followed showing an ovoid mass measuring 26x21x30mm between the left internal and external carotid arteries. A computed tomography angiography (CTA) was also performed with similar findings, suggesting the diagnosis of a CBP (Figures and ). The patient was electively admitted in our vascular unit in order to be treated surgically. A mass 2.5 cm was removed which was classified as Shamblin II (). The histopathology results showed “zellballen” growth pattern of paraganglioma with central round/oval chief cells containing abundant eosinophilic granular or vacuolated cytoplasm, uniform nuclei with dispersed chromatin-nests of cells. Prominent fibrovascular stroma separated characteristic nests of paraganglioma tissue and there was no evidence of malignancy ().
The patient had no postoperative neurologic symptoms except a transient episode of left parietal hypoesthesia. This was further investigated with an MRI of the brain and carotid ultrasound, which did not reveal sinister findings.
She had an uneventful postoperative recovery and was subsequently discharged on the 3rd postoperative day (POD). |
pmc-6431431-2 | A 15-year-old teenage boy initially presented in a district hospital, with a swelling at the right side of his neck, without any significant clinical symptoms. Although full details of the work-up performed at the time are not available, he was diagnosed with a branchial cleft cyst and was offered surveillance with follow-up imaging. Eight years later, he visited our unit. Physical examination revealed a painless palpable well-defined mass () within the right carotid triangle with positive Fontaine and Kocher I signs []. There was no palpable lymphadenopathy. An ultrasound scan was performed depicting a solid mass of mixed echogenicity in the right carotid triangle echogenicity in the left carotid triangle. This was suspected to be neurogenic in origin because of its location. A digital subtraction angiography (DSA) () followed, which revealed a 60x35mm protruding mass in the right carotid bifurcation, causing local compressive effects and posterior displacement of the vessels. The patient was admitted in our unit in order to be treated surgically. During the operation a large CBP was identified as seen in . The tumor was classified as Shamblin II and was completely excised. Histopathology study showed a 3 cm carotid body paraganglioma with characteristic “zellballen” growth pattern and cell nests surrounded by prominent fibrovascular stroma, with no evidence of malignancy (). The patient had an unremarkable recovery and was discharged home on the second POD.
The surgical technique adopted in both patients consisted of an oblique incision along the sternal head of the left sternocleidomastoid muscle under general anesthesia. Our strategy was to expose, dissect, and isolate the proximal common carotid artery using a vascular tape. The ansa cervicalis was also exposed early in the operation. The carotid bifurcation was exposed in a caudocranial approach. The proximal external and the proximal internal carotid arteries were isolated and controlled with vessel loops. Dissection was extended to the level of the digastor muscle in order to expose and control the distal internal carotid artery. During this process, the hypoglossal nerve was identified and preserved, by following the ansa cervicalis. The external carotid artery was cross-clamped temporarily. Finally, the tumor was removed with sharp dissection from the bifurcation with meticulous technique in order to avoid injury to the internal carotid artery and the cranial nerves. The reported plane of dissection reported as a white interface plane between the tumor and the vessels was not identified in the first patient as the tumor was severely adhering to the vessel wall and was typically found in the second patient. Following the removal of the CBP, the carotid sheath and platysma were approximated and the skin closed with a continuous subcuticular suture, after performing meticulous hemostasis (Figures and ).
Both patients had an annual postoperative follow-up with cervical ultrasound and carotid duplex ultrasonography with no evidence of local recurrence. Familial disease was excluded clinically, by screening the patient's first degree relatives with ultrasound imaging. |
pmc-6431445-1 | A 66-year-old Aboriginal male presented to his family physician with a 2-month history of early satiety, nausea, and abdominal distension. An abdominal CT scan revealed a 20 cm Bosniak IV left renal mass. This occupied much of the left hemiabdomen and displaced the great vessels laterally. No evidence of metastatic disease was found on further workup ().
The patient underwent a radical left nephrectomy. A thoracoabdominal approach was selected due to size and superior polar location of the renal mass. No intraoperative complications were encountered, and the procedure was well tolerated. A 28 Fr chest tube was placed prior to the closure of the thoracic cavity and was connected to low suction. A nasogastric tube (NGT) was placed in anticipation of a postoperative ileus. Intraoperative estimated blood loss (EBL) was 400cc.
The patient's NGT was clamped on postoperative day 2 and removed on postoperative day 3. The epidural was discontinued on postoperative day 2, and the patient was weaned off intravenous analgesia on postoperative day 4. The following day, on postoperative day 5, the chest tube was removed. The patient was subsequently discharged on postoperative day 6 without incident for a total length of stay (LOS) of 6 days.
Final pathological analysis confirmed a type 1 papillary renal cell carcinoma. Surgical margins were negative with no evidence of lymphovascular invasion (LVI), corresponding to pathological stage T2bNxMx. Tumour grade was recorded as Fuhrman nuclear grade 2/4. |
pmc-6431445-2 | A 50-year-old Caucasian male with a history of hypertension and benign prostatic hypertrophy was found to have microscopic hematuria on his annual urinalysis. An abdominal MRI found an incidental 12 cm left adrenal mass involving the superior pole of the left kidney, and possibly the splenic hilum and distal pancreas. Imaging findings were concerning for a locally invasive adrenocortical carcinoma ().
There was no evidence of lymphadenopathy or distant metastases on further workup. The patient had serum DHEAS, 17-ketosteroid, and cortisol functionality tests drawn, which were negative. Urine metanephrines were also negative, confirming a nonfunctional adrenal mass.
The patient subsequently underwent left nephroadrenalectomy. A thoracoabdominal approach was favoured due to the size, location, and locally invasive appearance of the mass. Intraoperatively, the spleen and pancreas were found to be uninvolved and did not require resection. No complications were encountered and EBL was 150cc. A 28 Fr chest tube was placed prior to the closure of the thoracic cavity and connected to low suction.
The chest tube was removed on postoperative day 3, and a follow-up radiograph confirmed the absence of a pneumothorax. The patient experienced modest difficulty weaning the epidural, which was discontinued on postoperative day 5. He was discharged on postoperative day 6 when pain was well managed with oral analgesia.
On pathological analysis, microscopic inspection revealed extensive fibrosis, hyalinization, focal dystrophic calcification, and ossification. Immunohistochemical studies (cytokeratin, S100, vimentin, and EMA) did not show evidence of neoplastic changes. Final pathological diagnosis confirmed an adrenal pseudocyst. No further follow-up was necessary. |
pmc-6431445-3 | A 67-year-old Aboriginal female with a history of hypertension and diabetes presented to her family physician with a 3-month history of 20 pound weight loss, early satiety, and fatigue. A CT scan of her abdomen revealed a 14 cm mass in the superior pole of the left kidney with suspected splenic hilar invasion. There was evidence of an enhancing soft tissue mass in the tail of the pancreas, suspicious for metastasis. Further metastatic workup revealed a small burden of pulmonary disease ().
After a thorough discussion with medical oncology and a full assessment of her functional status, the patient was enrolled in a tumour vaccine trial, which required cytoreductive nephrectomy. With the assistance of the general surgery team, she underwent a left radical nephrectomy, splenectomy, distal pancreatectomy, and retroperitoneal lymph node dissection (RPLND). A 28 Fr chest tube was placed prior to the closure of the thoracic cavity and connected to low suction. Due to the size and location of the tumour, and the suspected local invasion, a thoracoabdominal approach was pursued. No complications were encountered intraoperatively and EBL was 400cc.
The patient's postoperative course was uneventful. The epidural and chest tube were discontinued on postoperative day 4. She was weaned off intravenous analgesia by postoperative day 6 and was discharged on postoperative day 8 when fully mobile.
Final pathological analysis confirmed a clear cell renal cell carcinoma. Surgical margins were negative with no evidence of LVI. As suspected, a metastatic lesion in the distal pancreas was confirmed. Two lymph nodes were included in the analysis, both of which were negative for malignancy. Final pathological stage was defined as T3aN0M1. The tumour grade was recorded as Fuhrman nuclear grade 3/4. |
pmc-6431445-4 | A 61-year-old Caucasian male had previously seen a urologist for recurrent low-grade bladder cancer, which required multiple resections. Unfortunately, he was lost to follow-up and presented to his family physician several years later with abdominal discomfort and weight loss. An abdominal CT scan was ordered, which found a 10 cm cystic mass in the superior pole of the left kidney, concerning for malignancy with suspected splenic hilar invasion. A full metastatic workup was undertaken. No evidence of metastatic disease was identified ().
The patient underwent a radical left nephrectomy, splenectomy, distal pancreatectomy, completion nephroureterectomy, and RPLND. In anticipation of a difficult resection, the thoracoabdominal approach was selected to maximize surgical exposure. Intraoperatively, the tumour was found to involve the distal pancreas, which was resected with assistance from the general surgery team. During the kidney dissection, an incidental left upper ureteric mass was identified. Given the patient's history of recurrent bladder cancer, urothelial malignancy was suspected, and a completion nephroureterectomy was performed. A 28 Fr chest tube was placed prior to the closure of the thoracic cavity and connected to low suction. No complications were encountered during the procedure and EBL was 4000cc. Three units of packed red blood cells and 1 L of fresh frozen plasma were administered intraoperatively.
The patient's postoperative course was slow, but uneventful. The epidural and chest tube were discontinued on postoperative day 5, and he was discharged on postoperative day 9, once deemed physically fit for independent living by physiotherapy and occupational therapy.
Final pathological analysis confirmed high-grade transitional cell carcinoma (TCC) with extensive tumour necrosis. Tumour was found to be invading peripelvic fat, renal parenchyma, perinephric fat, and the tail of the pancreas. The resection margins, including the pancreatic margin and the bladder cuff resection margin, were involved by TCC. Two lymph nodes were included in the specimen, which were negative for malignancy. Final pathological stage was defined as T4N0M1. The patient was referred to medical oncology for consideration of systemic therapy. |
pmc-6431456-1 | A 67-year-old female presented with three months of hoarseness and dysphagia following an upper respiratory infection. Her past medical history included invasive ductal carcinoma of the breast (ER positive, PR negative, and HER2 negative) treated by mastectomy two years prior to presentation. On clinical examination, she was found to have paralysis of the right vocal cord, and a follow-up CT scan of the neck revealed an enlarged thyroid gland with multiple bilateral thyroid nodules. FNA of a right-sided 3.5 cm thyroid nodule was diagnosed as atypia of undetermined significance (Bethesda category III). A repeat FNA three months later yielded a diagnosis of benign follicular nodule (Bethesda category II). Persistent hoarseness and compressive symptoms, combined with atypical findings on the initial FNA, necessitated right thyroid lobectomy and right vocal cord injection. Intraoperatively, the right thyroid lobe was noted to be moderately enlarged with multiple nodules but no evidence of extrathyroidal extension.
The right lobectomy specimen measured 4.6 cm in greatest dimension and weighed 16 grams. The cut surfaces of the thyroid parenchyma showed multiple variably sized brown gelatinous nodules, with focal areas of hemorrhage and cystic change.
Histologic examination revealed evidence of nodular thyroid hyperplasia, along with multiple scattered subcentimeter foci of metastatic breast carcinoma, which were present in 7 out of the 16 submitted tissue sections. Most of the smaller metastatic foci, measuring around 1 millimeter each, consisted of a few irregularly shaped nests of epithelioid tumor cells interspersed between thyroid follicles (). The largest metastatic focus measured 0.6 cm and was comprised of tumor cell nests arranged along the periphery of a sclerotic stroma containing cords of tumor cells showing retraction artifact (Figures –). These areas resembled the dense amyloid-type stroma often seen in medullary thyroid carcinoma (MTC). Additionally, there were numerous areas of rimming of the thyroid follicles by the tumor cells, which mimicked the appearance of C cell hyperplasia (CCH) (). Where arranged as nests, cell borders were distinct between the tumor cells, which contained centrally placed monomorphic round nuclei, finely granular chromatin, prominent nucleoli, and a moderate amount of eosinophilic cytoplasm ().
Immunohistochemical stains showed that the tumor cells were positive for cytokeratin AE1/AE3, ER, GATA3, and e-cadherin (), while they were negative for CK7, CK20, GCDFP/mammaglobin, TTF-1, thyroglobulin, calcitonin, and synaptophysin. Biomarker testing was performed and was scored by image analysis; the metastasis was ER positive (91.2%; moderate staining), PR positive (1.4%; weak staining), and HER2 negative (score 0 by IHC).
At the one-week postoperative visit, the patient complained of right-sided hearing loss which had started the day of her surgery, as well as a two-day history of right-sided facial weakness. Audiologic testing showed a profound right-sided sensorineural hearing loss. Given these acute changes, she was directly admitted to the hospital for further workup where a brain MRI showed a right cerebellopontine angle mass concerning for further metastasis. A lumbar puncture was negative for malignancy; therefore, the patient underwent a retrosigmoid craniotomy for tissue diagnosis which confirmed metastatic breast cancer. Due to her extensive disease, no further surgical intervention was pursued. |
pmc-6431461-1 | A 50-year-old Caucasian male with no significant past medical history underwent biopsy of a left flank lesion. Pathology revealed malignant melanoma, nodular type with 3.37 mm Breslow depth, Clark's level IV, nonulcerated, and mitotic grade of 4/mm2. PET/CT did not reveal metastatic disease. He underwent wide local excision with no residual melanoma. Two sentinel lymph nodes from the left axilla and left inguinal region were biopsied of which left inguinal lymph node showed microscopic foci of metastatic melanoma. Thereafter, he underwent left inguinal lymphadenectomy. Overall, 14 lymph nodes were dissected, and no melanoma was identified. Adjuvant interferon was tried, but he could not tolerate it. He thereafter continued to follow-up with surveillance imaging. Three and a half years later PET/CT revealed uptake in the right inguinal region. An ultrasound-guided fine needle aspiration revealed metastatic melanoma of the right inguinal lymph node bed. There was no evidence of any other site of metastasis, and the patient was determined to be stage IV (T3a, N1a, and M1a) melanoma. He started treatment on a clinical trial of talimogene laherparepvec with ipilimumab (). His Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 0.
In this phase Ib/II study, talimogene laherparepvec was administered intratumorally in week 1 (10(6) plaque-forming units/mL), then in week 4 and every 2 weeks thereafter (10(8) plaque-forming units/mL) along with ipilimumab (3 mg/kg) administered intravenously every 3 weeks for four dosages, beginning week 6 [, ]. The patient experienced fatigue, fever, chills, rigors, pruritus, rash, headaches, blurry vision, and abdominal discomfort (all grade 1) during treatment. Four months into the trial and after 2 months of finishing ipilimumab, the patient continued to show persistent right inguinal lymph nodes with no evidence of disease progression (Figures and ). A fine needle aspiration revealed only reactive lymph nodes. A decision was made to perform a limited right femoral lymphadenectomy. Pathology review of all excised lymph nodes did not reveal any evidence of melanoma (0/5 ). He did not develop any significant complications after lymphadenectomy. The patient was on active surveillance after lymph node dissection and continues to be in remission for the last 5 years without any subsequent treatment. |
pmc-6431461-2 | A 57-year-old female with no significant comorbidities was diagnosed with melanoma of right upper back after a biopsy. Pathology revealed Clark's level IV, Breslow thickness 0.87 mm superficial spreading melanoma with no ulceration, and mitosis rate of 1/mm2. She underwent wide local excision with no residual melanoma. No sentinel lymph node biopsy was done. She was followed by active surveillance without evidence of disease, until approximately 5 years later when she had a palpable right axillary mass, biopsy of which confirmed metastatic melanoma. PET/CT and MRI brain did not reveal any other metastatic sites, and she was determined to be as stage IIIC (pT1b, pN2b, and cM0) melanoma. The patient started treatment on a clinical trial of talimogene laherparepvec with ipilimumab () [, ]. Her ECOG PS was 0. The patient experienced right axillary and shoulder pain and burning, fatigue, and nausea (all grade 1). Two and a half years into the trial, the patient experienced partial response with persistent evidence of lymph nodes on CT scans (Figures –). A decision was made to perform adjuvant right axillary lymph node dissection after the patient had undergone 66 talimogene laherparepvec injections. Pathology review of 11 dissected lymph nodes did not show any evidence of melanoma (). After surgery, she developed right breast lymphedema, but no lymphedema in the right upper arm. The patient continues to be in remission for the last 8 months. |
pmc-6431470-1 | A 48-year-old female patient was known to have left-sided ulcerative colitis (UC) since 2005 under treatment with oral (2 to 4 g/day) and rectal mesalamine with good clinical and biological response. She presented flare up in 2013 and 2015 with rapid clinical and biologic response to steroid therapy. She was in clinical and biologic remission since 2016. On January 2018, after 13 years of initial diagnosis and while she was clinically asymptomatic, a screening colonoscopy for colorectal cancer showed diffuse superficial ulcerations surrounded by an erythematous inflamed mucosa from the rectum to the splenic flexure (), a solitary sessile well circumscribed polyp in the cecum with normal adjacent mucosa, not amenable to endoscopic resection (Figures , , and ). Histologic examination revealed mucosal extension supported by submucosa consisting of a variable mixture of inflammatory tissue, which is histologically consistent with an inflammatory pseudopolyp ()
Two weeks later, she developed moderate flare up with bloody diarrhea and diffuse abdominal pain with no signs or symptoms of obstruction. Laboratory findings showed normal hemoglobin, albumin of 3.7 g/dl, normal liver function tests, and C-reactive protein of 25 (normal < 5). Infectious causes including cytomegalovirus and clostridium difficile were ruled out; a rectosigmoidoscopy revealed diffuse superficial ulceration with pseudomembranes in the rectum and the sigmoid; upper limit of lesions was not seen. Biopsies showed architectural mucosal distortion with polymorph nuclear infiltrates and abscesses, compatible with active UC with no cytomegalovirus (CMV) inclusion. She was started on intravenous (IV) steroids as an induction therapy with marked clinical and biological improvement. Adalimumab infusion, subcutaneously, was initiated as a maintenance therapy at a dose of 160 mg followed by 80 mg after 2 weeks and then 40 mg every other week. Eight months later, a surveillance colonoscopy showed complete regression of the giant pseudopolyp (Figures and ) with partial endoscopic remission of the previously noted inflammation of rectum and sigmoid. |
pmc-6431471-1 | A 63-year-old female with history of end stage renal disease secondary to IgA nephropathy, who underwent a living related kidney transplantation in 1995, presented to our hospital with generalized malaise, dyspnea on exertion, and cough which started 6 months prior. Her other past medical history included type 2 diabetes mellitus and chronic kidney allograft dysfunction due to recurrent IgA nephropathy. Immunosuppressive regimen included cyclosporine 100 mg every 12 hours, azathioprine 50 mg daily, and prednisone 5 mg daily. On arrival to the hospital, the patient was hypotensive with a blood pressure of 75/48 mmHg and febrile with a temperature of 100.6 F. Norepinephrine drip and broad-spectrum antibiotics were initiated, although a source of infection was not obvious at that time. Laboratory testing was notable for anemia, thrombocytopenia, and elevated lactate dehydrogenase (LDH) and C-reactive protein (CRP). CMV viral load was positive with a titer of 3.6 log10 IU/ml and valganciclovir therapy was initiated as a result. Morning cortisol level was substantially suppressed at 0.6mcg/dL, and, due to concern for adrenal insufficiency, stress dose hydrocortisone was administered, followed by conversion to prednisone taper. Patient's hypotension and fever resolved within 24 hours from the initial presentation, and she was subsequently discharged in stable condition with a diagnosis of CMV infection, on appropriate dose of valganciclovir with plan for follow-up as an outpatient. Unfortunately, the patient was rehospitalized 4 times in the subsequent 2 months with fever, shock, and fatigue. During each admission she received stress dose hydrocortisone and vasopressor with or without empiric antibiotics. Every time, her symptoms resolved rapidly (within 24 hours of initiation of therapy) without a clear diagnosis. Initially CMV was considered to be the cause of recurrent fever and hematologic abnormalities, but she had recurrent severe symptoms despite resolution of CMV viremia in the setting of valganciclovir treatment (summary in ).
On the 5th admission, she presented again with hypotension and fever. The remainder of a review of symptoms was negative. Physical examination was unremarkable. Laboratory testing revealed a white blood cell count of 7,200/mm3, persistent anemia with a hemoglobin of 8.2 g/dl, and thrombocytopenia with a platelet count of 83,000/mm3. LDH and CRP were yet again elevated (410 IU/L and 153.0 mg/L, respectively). Alanine aminotransferase and aspartate aminotransferase were mildly elevated at 50 IU/L and 41 IU/L, respectively. The patient's serum triglyceride level was 547 mg/dl (normal range 0–149 mg/dl) and ferritin level was remarkably elevated at 3311 ng/ml (normal range 13–150 ng/ml). As outlined above, CMV viral load was undetectable. Vasopressor and stress dose hydrocortisone were administered. As patient's hypotension resolved, vasopressor was discontinued within 24 hours from the time of admission. A computed tomography scan of the chest, abdomen, and pelvis showed patchy ground glass opacities at the lung apices bilaterally. Bronchoscopy with broncho-alveolar lavage was performed, though it did not reveal any evidence of infection, including Pneumocystis jirovecii. Further testing was performed to exclude rheumatologic disease, macrophage activation syndrome, malignancy, and autoinflammatory syndromes. Complement levels were within normal limits; antinuclear antibodies and rheumatoid factor resulted as negative. Serum protein electrophoresis test showed normal levels of all immunoglobulins and no monoclonal component. EBV viral load was negative. Patient inevitably underwent a bone marrow biopsy, which revealed histiocytes with engulfed red cells, platelets, and neutrophils (), suggesting HLH. High dose intravenous methylprednisolone was started at 1 gram intravenously daily and continued for 5 days, after which she was continued on oral prednisone at 1 mg/kg/day. Soluble Interleukin 2 receptor (sIL-2R) was elevated (15490 pg/ml, normal range <1033). Based on this, patient was diagnosed with HLH and discharged on high dose oral prednisone.
She remained afebrile, but suffered from severe persistent weakness. Subsequent outpatient laboratory testing revealed reduction of the platelet count and increased ferritin, indicating ongoing macrophage activation. Patient underwent thorough and extensive genetic testing, which was not consistent with familial HLH. Torso imaging was repeated to rule out an underlying malignancy, with positron emission tomography, and a magnetic resonance imaging did not reveal any suspicious neoplastic lesion. Given clinical and laboratory signs concerning for HLH exacerbation, chemotherapy with etoposide was started. She received four doses of etoposide in combination with daily dexamethasone. Unfortunately, patient developed acute hypoxic respiratory failure due to aspiration pneumonia in the setting of progressive encephalopathy, combined with Enterococcal and Neisseria bacteremia, and ultimately passed away within 3 months of her initial presentation. |
pmc-6431476-1 | A 26-year-old female patient presented herself to our emergency department due to malaise, headache, and right-sided cervical lymphadenopathy for approximately eight weeks. Previous laboratory diagnostics brought by the patient included a negative serology result for Epstein-Barr-Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV). Symptomatic therapy with mefenamic acid brought only mild release. The patient reported an uncomplicated bite without any signs of an infection by her parrot four months prior to the start of symptoms. Previous medical history revealed no significant medical illnesses and surgical history was positive for breast augmentation surgery only. Family history was negative and the patient reported no travels outside Switzerland recently. The patient had no regular medication and no illicit drug abuse was reported.
The patient presented in good general state of health with subfebrile temperatures and cardiopulmonary vital parameters were in range. Physical examination showed a right-sided cervical lymphadenopathy ranging from the mandibular angle to the clavicle. On the left side an enlarged lymph node was palpated ventral of the M. sternocleidomastoideus. The lymphadenopathy was tender to palpation. The remainder of the physical examination was unremarkable.
C-reactive protein (CRP) level was slightly elevated at 9 mg/L, just as the erythrocyte sedimentation rate (ESR) at 28 mm/h. Other laboratory results, including differential blood count, serum electrolytes, renal retention parameters, liver enzymes, and lactate dehydrogenase (LDH), were all in normal range. Serum protein electrophoresis was compatible with an inflammatory reaction. Further laboratory examinations, including serology results, are given in .
Further diagnostics were performed including pharyngeal swabs which were negative. Sonography of the abdomen revealed a slight enlargement of the spleen (12cm). MRI showed a significant enlargement of the cervical lymph nodes ().
We suspected a rheumatologic disease causing the lymphadenopathy—thus ANA, ANCA, was performed. ANA titer was elevated at 1:320. Anti-ds-DNA was negative. Considering the clinical presentation of the patient was oligosymptomatic for collagenosis, together with inconclusive laboratory results, we decided to perform a biopsy of the enlarged lymph nodes.
The core needle biopsy revealed signs of a necrotizing lymphadenitis rich in histiocytes. Additional immunophenotypical and molecular analysis underpinned the reactive nature of this lesion (Figures –). The differential diagnosis was raised between KFD and an autoimmune disease of SLE type.
As the patient did not meet diagnostic criteria by the American College of Rheumatology for SLE we suspected KFD.
Consequently, we started a therapy with NSAIDS, resulting in no improvement of the patients' malaise and no regression of the lymphadenopathy. Subsequently, we established steroid therapy at a dose of 1 mg/kg body weight for seven days, followed by a tapering regimen.
After establishment of the steroid therapy, a quick remission of the lymphadenopathy was achieved and the malaise of the patient was resolved.
Due to a three-time relapse of symptoms after steroid withdrawal, the tapering regimen was prolonged for a total of seven months.
After having been without symptoms for approximately 1 year, a relapse of symptoms for some weeks with another episode of contralateral cervical lymphadenopathy occurred, which was again successfully treated with a short steroid taper. The patient has been without symptoms since then. |
pmc-6431484-1 | Firemen found a 22-year-old male in his car presenting hyperthermia, bilateral mydriasis, and general contracture. The patient was brought to the emergency room of our teaching hospital in Dijon. According to his family, his medical history only included a polydrug use of cannabis, cocaine, and MDMA. He had no family medical history. A CT-scan was performed upon arrival and revealed no lesions. Toxic analysis returned positive for MDMA and cannabis.
Initial physical examination showed a patient with a Glasgow Coma Scale of 13/15, mydriasis, sweating, and a body temperature of 37.1°C. He had no tremors or any clinical signs of a pyramidal syndrome. His respiratory rate was 26/min, his heart rate 72 bpm, and his blood pressure 167/110 mmHg. The patient then quickly became comatose and presented hyperthermia (42.5°C), tachycardia (172 bpm), and high blood pressure (175/101 mmHg). The first arterial blood gas displayed acidosis with a pH at 7.238 and severe hypoxemia with a PaO2 at 99 mmHg on 100% O2. The bloodwork also showed HCO3− 20.4 mmol/L, sodium 134 mmol/L, potassium 4.6 mmol/L, creatinine 118 μmol/L, uraemia 5.4 mmol/L, and CPK 1197 mmol/L.
He was therefore transferred to our ICU where he was sedated, curarized, and intubated, and four litres of crystalloid were infused. A few minutes later, he suffered from ventricular tachycardia then ventricular fibrillation followed by electromechanical dissociation. He received an external electric shock as well as intravenous dantrolene. Because of sustained hemodynamic instability without rhythmic recovery, extra-corporal life support was implanted with introduction of norepinephrine and dobutamine.
The heart function rapidly improved after a few episodes of ventricular tachycardia that were treated with intravenous amiodarone. The patient was supported with norepinephrine for the first day and with dobutamine until the 4th day when a transthoracic echocardiography revealed a LVEF of 35% with normal cardiac output. The ECLS was withdrawn on the 4th day. On the 9th day, he developed an ARDS with ventilator associated pneumonia for which he was treated with antibiotics and steroids. After the first unsuccessful extubation, he was finally weaned from invasive ventilator support on the 20th day.
In addition to heart failure he presented multiple organ failure (renal, hepatic, and metabolic). He was treated with one session of extracorporeal haemodialysis because of anuric acute renal failure and metabolic acidosis. He developed hepatic failure with elevated liver enzymes and bilirubin as well as a major drop in the level of prothrombin and factor V. However, hepatic function improved on the 5th day. He also presented rhabdomyolysis with a peak of serum creatine phosphokinase at 15000 UI/L on the 3rd day.
Throughout his stay in ICU, he was sedated with propofol and sufentanil mainly to treat his ARDS. During the weaning of these drugs, he presented agitation, tachypnoea, sweating, and mydriasis, requiring treatment by cyamemazine, buprenorphine, and clorazepate. After a toxicologic analysis of his past drug abuses and the chronology of the therapies we introduced, we diagnosed an opioid-specific withdrawal syndrome. |
pmc-6431524-1 | A 37-year-old Japanese man presented to our hospital with a nonproductive cough of two weeks in duration. He did not have fever or dyspnea. He had a history of right hemiparesis, intellectual disability with pica, and symptomatic epilepsy caused by intracerebral hemorrhage, which occurred at two years of age. He had never smoked or consumed alcoholic beverages.
His initial vital signs were as follows: blood pressure, 105/55 mm Hg; pulse rate, 70 beats/minute; respiratory rate, 18 breaths/min; SpO2, 93% in room air; body temperature, 36.5°C. There was no lymphadenopathy. Auscultation revealed no chest rales. A cardiovascular examination was normal, and no murmurs, rubs, or gallops were detected. Abdominal and neurological examinations were unremarkable, and the patient had no rash or petechiae. A chest radiograph revealed bilateral diffuse infiltration (). Chest computed tomography (CT) revealed bilateral airspace consolidation and ground-glass opacity ().
The patient's laboratory test values were as follows: hemoglobin, 14.9 g/dl; white blood cell count, 8,850/mm3 with a left shift; platelets, 329,000/mm3; serum aspartate aminotransferase 29 U/L (normal, 0-35 U/l); serum alanine aminotransferase, 31 U/L (normal, 0-35 U/l); serum lactate dehydrogenase, 425 U/L (normal, 119-229 U/l); serum total protein, 5.3 g/dl (normal, 6.5-8 g/dl); serum albumin, 2.1 g/dl (normal, 4-5 g/dl); serum C-reactive protein, 9.18 mg/dl (normal, < 0.2 mg/dl); serum KL-6, 2940 U/ml (normal, < 500 U/ml); serum surfactant protein D, 173.0 ng/ml (normal, < 109.9 ng/mL); and serum surfactant protein A, 115.0 ng/ml (normal, < 43.8 ng/mL). The patient's serum was negative for rheumatoid factor and antinuclear antibodies. The serum levels of immunoglobulin M, G, and A were within the normal ranges. An electrocardiogram revealed normal findings. An examination of the patient's sputum showed no predominant pathogen and no acid-fast organisms were observed on staining. Two sets of blood cultures were prepared at the time of admission; however, they did not yield any organisms.
The patient underwent a fiberoptic bronchoscopic examination that revealed a normal endobronchial system, and combined bronchoalveolar lavage (BAL)/transbronchial biopsy (TBLB) was performed. BAL fluid (BALF) was obtained from the right middle lobe. The results of the BALF analysis were as follows: histiocytes, 87%; neutrophils, 6%; lymphocytes, 4%; and eosinophils, 3%. Routine cultures of bronchial the washings were negative. The TBLB sample from the right upper lobe revealed alveolar septal thickening due to chronic inflammation, as well as collagen-type fibrosis.
After these examinations, the patient was diagnosed with acute interstitial pneumonia, and intravenous levofloxacin (500 mg) was administered once daily with corticosteroid pulse therapy (methylprednisolone [1000 mg] for three days) followed by prednisolone (1 mg/kg/day). On the 5th day after the initiation of therapy, his respiratory condition worsened and noninvasive positive pressure ventilation was started. His interstitial pneumonia was thought to be getting worse, and cyclophosphamide (500 mg/body) was administered intravenously. On the same day, an additional examination revealed the elevation of the serum (1-3) β-D glucan (BG) level (104.3 pg/ml; normal, <6.0 pg/ml). He was therefore suspected to have fungal infection or PCP, and voriconazole (200 mg, every 12 hours) and sulfamethoxazole trimethoprim (1600 mg and 320 mg, respectively, every 8 hours) were started. An additional HIV antibody test was negative and the serum protein electrophoresis revealed normal findings. Despite the additional antifungal therapy, his respiratory status gradually worsened, and intravenous corticosteroid pulse therapy (methylprednisolone [1000 mg] for three days) and cyclophosphamide therapy (500 mg/body) were each administered a second time, on the 8th and 11th days, respectively, without improvement. The patient died due to respiratory failure on the 12th day.
A postmortem pathological examination of the lung tissue demonstrated that the alveolar spaces were filled with foamy amorphous material composed of abundant numbers of cystic forms of Pneumocystis jirovecii and cellular debris, as well as an inflammatory reaction with hyaline membranes (). Retrospectively, Grocott's methenamine silver (GMS) staining of the BALF and TBLB samples obtained on the day of admission revealed a small amount of the cystic form of Pneumocystis jirovecii (). It was therefore thought that PCP had been present on the day of his admission. |
pmc-6431525-1 | A 78-year-old woman was referred from the internal medicine due to symptoms of progressive fatigue, tiredness at small efforts, and intermittent claudication. During physical exam, she presented paleness and atrophic glossitis. Hemogram with pancytopenia and macrocytosis and high lactate dehydrogenase (LDH) (). |
pmc-6431525-2 | An 87-year-old man was checked in the emergency room presenting symptoms of mental confusion, tiredness at small efforts, and intense lumbar pain. During physical exam, he was clumsy and dehydrated. Lab exams showed he had anemia, hypercalcemia, and renal insufficiency. X-rays showed multiple lytic lesions in the axial skeleton (). |
pmc-6431525-3 | This is the case of a 65-year-old man, undergoing clinical follow-up due to lymphocytosis and thrombocytopenia in routine exams, and is asymptomatic (). |
pmc-6431612-1 | We studied an 8-year-old girl of mixed American ancestry born to non-consanguineous parents. At 7 months old she was diagnosed with polyarticular juvenile idiopathic arthritis after developing hip swelling and knee contracture. She was treated with corticosteroids, methotrexate, and eventually improved on TNF blockade with etanercept. At age 3, she developed recurrent fevers and suffered from severe bacterial, viral and fungal infections even after discontinuation of immunosuppressants (). Although she did not demonstrate hypogammaglobulinemia (IgG 645, IgM 25, and IgA 965 mg/dl), she lacked response to pneumococcal antigens upon vaccination. Given her clinical history, she was diagnosed with common variable immune deficiency (CVID). She also had a history of borderline cognitive delay and absence seizures, which might be attributed to a duplication on the chromosome 15q13.3 inherited from her asymptomatic mother (). On examination at the age of 7 years old she was noted to have eczematous dermatitis (), splenomegaly, and clubbing of her toes and fingers. Skin biopsy demonstrated superficial perivascular chronic inflammation with dense infiltration of CD4+ and focal MPO+ cells ( and ). Upper gastrointestinal endoscopy did not reveal histological evidence of lymphangiectasia. Serum creatine kinase, aldolase and echocardiography were normal, and muscle biopsy was not performed due to lack of clinical symptoms. Immunophenotyping of leukocyte surface markers demonstrated low memory B cells (). Consistent with the previous report of HOIP deficiency, the patient's B cell proliferation and CD80 expression were impaired after CD40 ligand (CD40L) stimulation and preserved after B cell receptor stimulation (). T lymphocyte proliferation following various stimuli were normal (). Currently, the patient is stable with minimal inflammation on subcutaneous immunoglobulin supplementation. |
pmc-6431731-1 | An 18-year-old woman with CF was considered as a candidate for bilateral LT. Her respiratory failure had advanced, so that a supplemental oxygen therapy and night-time non-invasive ventilation were initiated. Bilateral pneumothoraxes with subcutaneous emphysema were detected on an elective control in March 2015. At that time, her FEV1 had decreased to 1.35 L (34% of predicted). She was referred to the respiratory department where her ventilatory failure acutely progressed. After a short resuscitation she was connected to ventilator and subsequently to extracorporeal membrane oxygenation (ECMO). She was listed for a Scandinavian emergency LT. S. apiospermum was detected in fungal culture of the tracheal aspirate with susceptibility testing showing minimal inhibitory concentrations of: voriconazole 0.125mg/L, itraconazole 6mg/L, posaconazole 6mg/L and amphotericin B 12mg/L. After five days on ECMO, she underwent a bilateral LT (defined as day 0). Pseudomonas aeruginosa and S. apiospermum colonizations were detected in the extracted native lungs. The peri-operative course was complicated by pseudomonas septicemia which was treated with intravenous (IV) tazobactam/piperacillin, tobramycin, and oral ciprofloxacin with a good clinical outcome. IV caspofungin was started postoperatively for antifungal prophylaxis with a single loading dose of 70mg, followed by 50mg daily for 17 days.
Her baseline immunosuppression regimen consisted of tacrolimus, mycophenolate mofetil, and prednisolone. Prophylactic valganciclovir, azithromycin, trimethoprim/sulfamethoxazole and nebulized colistin and amphotericin B were initiated.
The first postoperative bronchoscopy at day 30 postoperatively revealed normal anastomotic healing process and otherwise unremarkable endobronchial findings. Bacterial and fungal cultures of bronchoalveolar lavage (BAL) were negative. Histological acute minimal rejection (A1B1) was detected in transbronchial lung biopsy (TBB). The patient was not treated with additional corticosteroids considering her good clinical condition and previous infections and colonizations.
At the second control visit 60 days postoperatively, she presented with upper back pain that radiated to the left leg. Symmetric, painful, palpable, and slightly pigmented nodules with small ulcerations had appeared on both legs (). The surgical wound had started to secrete. She had no fever. Her C-reactive protein was 31 mg/l, erythrocyte sedimentation rate 58 mm/h and leukocyte level 9.8 E9/l. Systemic fungal infection was suspected, and IV voriconazole was initiated at 300mg twice a day for 24 hours and at 200mg twice a day thereafter. At that time, her immunosuppression consisted of prednisolone, tacrolimus and mycophenolate mofetil. The latter was discontinued due to suspicion of systemic infection. Control bronchoscopy with TBB revealed no histological signs of rejection. In the following days, she developed neurological symptoms: headache, nausea, vertigo and her right side of the mouth was slightly dropped. Also, her left leg was numb, and the muscular strength was decreased. Computerized tomography showed no infiltrates in the lung parenchyma but there were small subcutaneous collections under the sternotomy. Brain magnetic resonance imaging (MRI) revealed multiple ring-enhancing lesions with perifocal oedema compatible with abscesses (a and b). Spine MRI showed oedema and multiple abscesses as well in cervical and thoracic spinal cord (c). Subsequently, the histopathological findings from initial skin nodule revealed septal panniculitis with fungal culture and nucleic acid test positive for S. apiospermum. S. apiospermum was also cultured from BAL fluid and the surgical wound secretion. Multiple blood cultures were taken with no signs of fungemia. We refrained from CNS biopsy due to consisted cultural findings matching with radiological appearance.
Neurological symptoms vanished gradually, and the patient was discharged from the hospital after three weeks of treatment. Intravenous voriconazole was continued at home for ten months. Miltefosine was combined to the therapy one month after initiation of voriconazole but it was discontinued after two days due to nausea, interactions with tacrolimus and on the other hand good clinical response to voriconazole. MRIs and clinical status were controlled every one to four months. After ten months of intravenous administration voriconazole was switched to oral tablets with a dose of 300mg twice daily. Therapeutic serum levels were confirmed by repeated measurements (target therapeutic limits 2–5.5mg/l). At a control visit in June 2018 three years after LT and 35 months of treatment, the voriconazole treatment was terminated. After the discontinuation of antifungal treatment, the patient has visited our clinic for two controls with no signs of fungal re-infection. The last visit was in January 2019, nearly four years after the LT and eight months after the termination of voriconazole. She was symptomless with preserved lung allograft function: Her FEV1 was 2.7 L (77% predicted). Brain MRI revealed only few residual lesions (d), which had been stable and inactive for months. |
pmc-6432692-1 | CB is a 16-month-old, previously healthy, female that initially presented to her primary care physician two weeks prior to presenting to our orthopaedic clinic with limping and intermittent refusal to bear weight through the left leg. The mother of the patient denied any previous trauma or constitutional symptoms but did endorse foreign travel; they were living in Japan at the time of presentation to our department. The patient was current on all vaccinations.
The initial orthopaedic evaluation revealed a well-appearing, healthy child in no acute distress. The gait exam revealed that she refused to weight bear on the left lower extremity. The patient had very mild generalized tenderness in the left midfoot region; otherwise, no other area of tenderness was appreciated upon further examination of the lower extremities. She had full, painless range of motion of her hip, knee, and ankle joints. There was no erythema or swelling of the left foot; however, there was a mild effusion of the ankle. She was neurovascularly intact with normal reflexes.
She was afebrile, and vital signs were within normal parameters. Radiographs of the left lower extremity revealed no osseous abnormality (). Laboratory findings revealed a slightly elevated erythrocyte sedimentation rate of 34 mm/hr; otherwise, the white blood cell count (10,200 cells/μL), differential (45% segmented neutrophils, no bands), and C-reactive protein (<0.05 mg/dL) were normal []. An MRI of her left ankle showed an ankle joint effusion, a 16 mm fluid collection with a high T2 signal with surrounding bone marrow edema, and a low signal on T1 (Figures and ). The findings were consistent with a Brodie abscess with surrounding osteomyelitis and a possible septic ankle. Furthermore, there was rim enhancement with gadolinium contrast, making an abscess more likely than a tumor () [].
The diagnosis and treatment were discussed with the parents, and she was consented for surgery. An anteromedial incision was used to approach the talus. Normal-appearing synovial fluid was encountered and cultured. The talus was then drilled through a nonarticular region with a 2.0 mm drill under fluoroscopic guidance, aiming in a posterolateral trajectory, resulting in an egress of purulent fluid which was sent for Gram stain and culture (). The cavity was then thoroughly irrigated with saline, a Penrose drain was placed into the wound, and the incision was loosely closed around the drain. A long leg splint was applied to protect the soft tissues and prevent weight bearing. Infectious diseases was consulted, and the patient was admitted to the hospital for empiric intravenous antibiotics (Clindamycin) while awaiting aerobic/anaerobic, fungal, and acid fast bacilli cultures.
Gram stain of the purulent fluid revealed Gram-negative rods. Synovial fluid Gram stain and final cultures were negative, as were the fungal and acid fast bacilli cultures. On postoperative day (POD) #1, ceftriaxone was added to Clindamycin for Gram-negative coverage. On POD #2, aerobic and anaerobic cultures grew Morganella morganii; Clindamycin was discontinued, and the patient remained on ceftriaxone. Antibiotic sensitivities revealed resistance to ampicillin/sulbactam but sensitivity to cefepime, ciprofloxacin, gentamycin, and trimethoprim/sulfamethoxazole. On POD #4, she was transitioned to a three-week course of oral cefixime and discharged with close follow-up. She recovered well without any recurrence of symptoms at her scheduled postoperative visits (). |
pmc-6432694-1 | A 45-year-old male with a previous history of tympanoplasty and functional endoscopic sinus surgery with septoplasty 10 years earlier presented to the ear, nose, and throat (ENT) clinic with several months of left moderate-to-severe otalgia and a sensation of ear blockage in his left ear accompanied by ipsilateral hearing loss. He gave a history of multiple failed ear wax removal in his left ear that had been performed at several ENT clinics, despite the use of alkaline ear drops.
On examination, the patient was comfortable and afebrile, and his vital signs were stable. Otoscopic examination of the left ear revealed impacted left ear wax covering the tympanic membrane, which could not be assessed. Otoscopic examination of the right ear also demonstrated mild ear wax, and the tympanic membrane was unremarkable. Oropharynx examination was unremarkable, the lymph nodes of the neck were not palpable, and all cranial nerves were intact upon examination. Nasal endoscopy revealed no pathologies. Ear wax removal under suction was attempted and failed. Another trial of removal after using alkaline ear drops for several days was also attempted but was unsuccessful. However, the surgeon became suspicious that the patient had KO rather than impacted ear wax because the wax was thick, had the appearance of keratin plugs, and was hard to remove after several attempts, despite the use of ear alkaline drops.
Blood test results of the patient were within normal limits. The patient was planned for microscope-guided examination of the ears under general anesthesia. The examination revealed that the left ear was full of wax that was accumulating in the skin and contained a thick keratinous plug that had dilated the external auditory canal (EAC) with pockets and bone remodeling. Furthermore, the patient ear canal was circumferentially distended with a normal annulus. The tympanic membrane became visible and was intact. The keratinous plug was removed, and a diagnosis of KO was established (). An ear pack was draped with antibiotics and placed in the left ear. The patient was extubated, shifted to the ward without any complications, and discharged the same evening with the ear pack, which was removed after 3 weeks in the outpatient clinic. The patient was started on ciprofloxacin ear drops and analgesia for 1 week.
In the follow-up, the ear pack was removed, his hearing returned to normal level, and the pain disappeared. Pathological analysis of the removed plug revealed acellular lamellated keratin flakes and keratinous material (Figures and ), which confirmed our diagnosis. |
pmc-6432725-1 | We report the case of a previously healthy 17-year-old Caucasian male with exercise-induced pain of the right foot that had deteriorated over the course of three months. During the last week prior to presentation at our emergency department, the symptoms had progressed from intermittent to constant calf pain. At clinical examination, the right foot was pale and cool with delayed capillary refill and absent pedal pulses consistent with the clinical picture of acute limb ischemia. The left foot was warm and well perfused with palpable pedal pulses.
Doppler ultrasound study of the right lower limb showed an occlusion at the proximal part of the right popliteal artery (PA). With magnetic resonance angiography the presence of a four-centimeter thrombus occluding this section of the PA was confirmed.
Furthermore, Doppler ultrasound study of the asymptomatic, contralateral (left) popliteal region revealed an occlusion of the PA with sufficient collateralization and unimpaired three-vessel runoff to the foot.
By conventional transfemoral angiography, the previously identified occlusion of the right PA and its aberrant course were demonstrated again (). An attempt of continuous intraarterial thrombolysis of the occluded right PA was undertaken by the use of actilyse and continuous heparin applied via a lysis catheter over 24 hours. The required therapeutic dose was controlled with aPTT between 60 and 80 seconds. This resulted in a significant reduction of thrombotic material within the PA, but the vessel was still considerably occluded (70-80%). After 24 hours of catheter-directed thrombolysis, low-molecular-weight heparin (LMWH) in therapeutic dosage and continuous infusion of iloprost (over 4h) were given daily. Further investigations were started to identify the already suspected extravascular cause of occlusion.
Indeed, in magnetic resonance imaging the anomalous origin of the MHGM lateral to the medial condyle of the femur was detected. The muscle's tendon and belly crossed over a medialized PA and caused its compression (). This aberrant anatomy was present bilaterally, yet asymptomatic on the left side.
Hence, indication for surgical decompression was given. A posterior surgical approach was used to enter the popliteal fossa. The intraoperative anatomy presented as a PAES classification Type II with a popliteal artery course medial to the extremely lateralized MHGM. The artery did not show signs of stenosis or vascular wall hypertrophy; therefore only myotomy at the origin of the MHGM was performed. The artery was moved laterally into the popliteal fossa and the muscle was inserted at the correct position at the posterior surface of the medial femoral condyle.
Postoperatively, the patient recovered well and had a warm, pain-free foot with palpable pedal pulses. A three-month regimen of 60mg edoxaban was recommended after surgery. |
pmc-6432726-1 | A 27-year-old woman was referred to our department upon suspicion of polymyositis-dermatomyositis from the division of Endocrinology and Metabolism. One year ago, she had a stillbirth at 21 weeks of gestation. Blood tests performed at the time revealed a marked increase in creatine phosphokinase (CK) levels, and she had experienced symptoms of muscle weakness and exertional dyspnea since the discharge, but no detailed examination was performed. She became pregnant again, and her exertional dyspnea worsened at 8 weeks of gestation. She was administered insulin therapy for glucose metabolism disorder diagnosed in the first trimester by an obstetrician in the division of Endocrinology and Metabolism. As her muscle enzyme levels were relatively higher than those recorded in the previous year, she was suspected to have an autoimmune myositis (myopathy) and was referred to the division of Rheumatology and admitted to our hospital at 15 weeks of gestation.
She had elevated serum muscle enzymes (CK 3875 U/L, aldolase 29.5 U/L, and myoglobin 440 ng/mL), myalgia, muscle weakness, and arthritis; further, she showed myogenic change on electromyogram, inflammatory reaction, tested positive for anti-Jo1 antibodies (32-fold higher than normal), but no skin lesion; therefore, she was diagnosed with polymyositis based on Bohan's criteria []. Furthermore, she had exertional dyspnea, and the ambulatory SpO2 decreased to 84% (at room atmosphere), and blood tests revealed elevated interstitial lung disease marker levels (KL-6: 1572.0 U/mL; SPD: 195.5 ng/mL). We explained the risks associated with fetal exposure to radiation to the patient, and with her consent, we acquired a chest radiograph () and performed chest-computed tomography () and also conducted a respiratory function test. We observed ground-glass opacity with a partial honeycomb lung throughout the entire lung field and restrictive respiratory impairment of 46.0% in 1 s; thus, she was diagnosed with interstitial lung disease.
We explained to the patient the necessity for immediate initiation of steroid therapy and concomitant use of immunosuppressant as needed. We also explained that she might be difficult to tolerate labor if her respiratory condition worsened and have pregnancy complications including intrauterine growth restriction that was due to mother's hypoxia or immunosuppressive therapy and preterm birth; however, she and her family hoped to continue the pregnancy.
Administration of prednisolone (PSL) 42 mg/day (0.8 mg/kg) was started on the day of admission. 1 L/min oxygen therapy was required against exertional dyspnea. In management of glucose metabolism disorder, intensive insulin therapy was needed at the same time when high-dose steroid therapy was provided. After starting the therapy, muscle weakness improved rapidly and serum muscle enzyme levels were decreasing (). However, her symptom of exertional dyspnea did not significantly improve, and interstitial lung disease marker levels were increasing. Considering the risk of complications such as hypertensive disorders of pregnancy, infections aggravated by high-dose steroid therapy, and the risk of exacerbation of disease due to steroid tapering, administration of concomitant cyclosporine (CYA) 200 mg/day was started at 18 weeks of gestation.
After completion of high-dose steroid therapy, the PSL dose was decreased at a rate of 15%/week, and the CYA blood level was monitored by setting peak levels of 1500–2000 ng/ml and trough levels of 100–150 ng/ml before increasing the dose to 275 mg/day at 21 weeks of gestation. At that time, her dyspnea got improved, and interstitial lung disease marker levels decreased; further, oxygen therapy was discontinued at the time of discharge. After high-dose steroid therapy, a chest radiograph (Figures and ) showed improvement of radiological signs. An obstetrician regularly performed a fetal monitoring with ultrasound during hospitalization. Though fetal growth restriction (−1.6SD) was diagnosed with ultrasound at 22 weeks of gestation, the obstetrician decided to manage the fetus in the outpatient clinic, so that there was no any other signs suspecting uteroplacental dysfunction. The patient was discharged at 22 weeks of gestation.
Her steroid dose had been tapered in the outpatient clinic; however, her blood pressure increased and absence of end-diastolic flow velocity in the umbilical artery was observed at 34 weeks of gestation; therefore, she resulted in termination of pregnancy at 34 weeks and 1 day of gestation. She delivered a male baby by cesarean section, and the birth weight was 1,594 g, which was light for date, and the Apgar score was 8/9. The baby was hospitalized in the neonatal intensive care unit. The baby showed no obvious adverse effects of preterm birth, except hypoglycemia prolonged until Day 1. He was discharged at Day 38. The patient has undergone steroid tapering therapy as an outpatient even after the delivery, and her disease remains under stable condition. |
pmc-6432745-1 | A 73-year-old Caucasian woman with a past medical history (PMHx) of esophageal dysmotility, gastroesophageal reflux disease (GERD), lymphocytic colitis, chronic obstructive pulmonary disease (COPD), essential hypertension (HTN), hyperlipidemia (HLD), neuropathy, and depression presented with substernal pleuritic chest pain and lightheadedness that began 2 hours after an uncomplicated outpatient upper and lower endoscopy. She did not have any known allergies. Her family history was significant for myocardial infarction (MI) in her father and cerebrovascular accident in her mother. She was married with two children, retired, previously worked for an advertising agency, and resided in New York City. She smoked one pack of cigarettes per day for 30 years and quit in 2001. She drank two alcoholic drinks per night. Medications taken prior to admission, during hospitalization, and after discharge included a 10 mg oxybutynin extended-release oral tablet once daily for urinary symptoms, a 40 mg omeprazole oral tablet once daily for GERD, a 10 mg amlodipine oral tablet once daily for HTN, a 300 mg bupropion extended-release oral tablet once daily for depression, a 20 mg escitalopram oral tablet once daily for depression, a 100 mg topiramate oral tablet once daily for neuropathy, a 50 mg tramadol oral tablet as needed every 4 hours for pain, and a 135 mg fenofibric acid delayed-release oral tablet once daily for HLD. Prior to presentation, the patient had undergone three endoscopies, after which her postprocedure course was uncomplicated. Upper and/or lower endoscopies were done on March 11, 2013, May 29, 2014, and December 3, 2015, for epigastric abdominal pain, periumbilical abdominal pain, and chronic diarrhea, respectively.
Biopsies were taken throughout the esophagus, stomach, duodenum, jejunum, ileum, and colon. The upper endoscopy and lower endoscopy took 5 and 25 minutes to complete, respectively.
In the emergency room, her vital signs were as follows: afebrile (36.8 °C), heart rate of 101 beats/min, blood pressure of 116/59 mmHg, respiratory rate of 16 breaths/min, and oxygen saturation of 93% on room air. She was a well-appearing woman, alert, and in no acute distress. She was well hydrated and well nourished. Her skin color, texture, and turgor were all normal without any suspicious rashes or lesions. Her head was normocephalic and atraumatic without any masses, lesions, or tenderness. Her eye examination included anicteric sclera with pupils that were equally round and reactive to light and with intact extraocular movements. Her ear, nose, and throat examination were all normal. Her neck was supple without any adenopathy. Her thyroid was of normal size and symmetric without any bruits. Her lungs were clear to auscultation without any wheezing, rhonchi, or rales. Her heart sounds included a regular rhythm and rate without murmurs, rubs, or gallops. Her abdominal examination revealed a soft, nontender abdomen, normoactive bowel sounds, and was nonsignificant for masses or organomegaly. Her extremities did not show any deformities, edema, skin discoloration, clubbing, or cyanosis and had good capillary refill. No joint swelling, deformity, or tenderness was observed. Her peripheral pulses were normal. The patient was alert and oriented to person, place, and time. Her speech was fluent with appropriate repetition and comprehension. Cranial nerves II–XII were intact without any deficits. Her gait was normal and steady. Her sensation (light touch, pinprick, position sense, and vibration sense) was grossly intact. Her reflexes were 2+ and symmetric at the biceps, triceps, knees, and ankles. She had no pronator drift of outstretched arms; her muscle bulk and tone were normal; and she had full strength bilaterally.
Initial laboratory studies revealed a hemoglobin level of 11.5 g/dl (normal range for females, 12.0 to 15.0 g/dl), which was the patient’s baseline hemoglobin; a troponin I level of 8 ng/ml (normal range, 0 to 0.4 ng/ml); and a B-type natriuretic peptide level of 2900 pg/ml (normal range, up to 100 mg/L). Other laboratory findings, including electrolytes, liver function tests, renal function tests, complete blood count, serology, and urinalysis, were all within normal limits.
An initial ECG was notable for T-wave inversions in the anterolateral leads and submillimeter ST elevations in the V4–V6 precordial leads, concerning for ACS (Fig. ). A bedside transthoracic echocardiogram (TTE) revealed apical hypokinesis (Fig. ), and computed tomography of the chest, abdomen, and pelvis did not reveal pulmonary emboli or acute abdominal processes. Left heart catheterization demonstrated nonobstructive CAD with a left ventriculogram of 45% and diffuse wall hypokinesis, consistent with a diagnosis of takotsubo cardiomyopathy, thought to be precipitated by the patient’s recent upper and lower endoscopic procedures (Fig. a and b). The patient’s angina resolved after the procedure, and repeat ECG revealed less marked ST depressions and resolved ST elevations (Fig. ). She was discharged home on hospital day 7. She did not require any further intervention or medical management.
The patient did well after discharge. After nine months post-discharge, she was admitted for worsening lower extremity edema. The TTE at the time was significant for a high left ventricular outflow tract (LVOT) gradient (peak LVOT gradients of 42 mmHg at rest and 122 mm Hg with Valsalva maneuver). Her ejection fraction (normal range, 55–70%) at the time was 81%, and pertinent results of TTE included fibrocalcific changes of the aortic valve with mildly reduced opening; moderate mitral annular calcification; systolic anterior motion of the anterior mitral valve leaflet; and normal functioning of the left atrium, right ventricle, tricuspid valve, and pulmonic valve. She was discharged with instructions on avoiding diuresis and beginning initiation of metoprolol (6.25 mg every 6 hours) for negative inotropy and to decrease systolic anterior motion. |
pmc-6432979-1 | A 65-year-old gentleman initially presented to the Dermatology clinic with a longstanding pedunculated skin lesion, which was diagnosed as nodular melanoma on excision biopsy. His past medical history included non-Hodgkin’s lymphoma, successfully treated with chemotherapy and radiotherapy 30 years ago (discharged from follow-up) and difficult-to-treat hypertension. He reported an extensive family history of malignancies, including two affected siblings (non-Hodgkin’s lymphoma) and his mother (lung cancer). ACT scan revealed an enlarged inguinal node and a 7 cm heterogeneous left adrenal mass, raising the suspicion of an adrenal melanoma metastasis. Fine-needle aspiration of the inguinal node was consistent with lymphatic melanoma metastasis. To complete the staging of his malignant disease, a CT-guided adrenal biopsy was arranged after biochemical exclusion of phaeochromocytoma with three negative 24-h urine catecholamine collections (adrenaline: 50, 44, 42 nmol (reference range (RR): <190 nmol); noradrenaline: 559, 516, 496 nmol (RR: 60–650 nmol); dopamine: 1433, 1490, 1830 nmol (RR: 60–3660 nmol), respectively). Histology revealed clusters of well-outlined, clear and granular/compact cells with no mitotic features, suggestive of benign adrenocortical adenoma. This was considered sufficient evidence to exclude adrenal metastasis; he was accordingly classified as stage 3B melanoma (T4aN1bM0). He underwent a left ilioinguinal block dissection followed by a ‘watchful wait’ management without follow-up imaging.
Thirty months later, an ultrasound scan prompted by abdominal discomfort revealed a significant increase in the size of the adrenal lesion. This was confirmed by cross-sectional imaging showing a 10 cm adrenal lesion indenting the inferior liver surface, with likely infiltration of the right adrenal vein (). Clinically, he was still hypertensive despite triple therapy with valsartan, bendroflumethiazide and amlodipine. |
pmc-6432979-2 | A 63-year-old woman presented with unprovoked deep vein thrombosis. CT imaging, arranged to exclude underlying malignancy, revealed a left adrenal tumour (6 cm). Her past medical history included type I neurofibromatosis, adrenalectomy for a right-sided phaeochromocytoma 20 years earlier and mastectomy for breast cancer 13 years earlier. |
pmc-6433083-1 | An 83-year-old man presented for a total body skin check. He had a prior history of 16 nonmelanoma skin cancers, actinic keratoses, seborrheic dermatitis, stasis dermatitis, and tinea pedis. In addition to sleep apnea (which was treated with two liters of oxygen via continuous positive airway pressure each night), his medical history was significant for thyroid (hypothyroidism), cardiac (congestive heart failure, coronary atherosclerosis, hyperlipidemia, hypertension, paroxysmal atrial fibrillation, and sick sinus syndrome) and renal (chronic kidney disease) conditions. His daily medications included amlodipine, carvedilol, febuxostat, ferrous sulfate, finasteride, folic acid, furosemide, levoxyl, pravastatin, tamsulosin, and warfarin.
Cutaneous examination demonstrated keratotic plaques on the scalp, face, and arms; the actinic keratoses were treated with liquid nitrogen cryotherapy. Both great toes had an elongation of the lateral aspect of the cuticle as seen in Figure ; the remainder of the cuticle was normal in appearance (Figure ). Lateral and medial views of the right and left great toes revealed that there was curling of the cuticles (Figures -).
A descriptive diagnosis, based on the clinical presentation, of curling cuticles was established. The patient had not been aware of his elongated and curly cuticles; indeed, additional history also revealed that he was not able to provide adequate hygiene to his toes since he could not reach them. Treatment was subsequently performed during a pedicure; the toes were soaked in water for five minutes and the curled cuticles were carefully cut at their base so that the cuticle was smooth and intact. |
pmc-6433085-1 | A 37-year-old male with a past medical history of attention-deficit hyperactivity disorder, anxiety disorder, untreated Hepatitis C, and history of polysubstance abuse including intravenous (IV) drug use (cocaine, marijuana, and benzodiazepines) presented to the ED requesting a dose of Clonazepam as he had “run out”. Of note, he is frequently seen in the ED for substance-related complaints, most recently two weeks prior. At the time of presentation, he reported that his refill for Clonazepam was not ready and had resorted to using cocaine as a replacement. Upon questioning, he became agitated, walking around the unit with his fists in the air, looking repeatedly at the ceiling and stating “Don’t let them attack”, ultimately requiring four-point restraints and intramuscular Diphenhydramine/Haloperidol/Lorazepam (50 mg/5 mg/2 mg, B52 protocol).
During observation, he was noted to have T wave inversions on telemetry, which were not recorded on subsequent EKG. Physical exam was unremarkable, with normal S1S2 heart sounds and regular rate and rhythm, lungs clear to auscultation bilaterally, and benign abdominal exam. He stated he had been using cocaine for the past three days, with associated audio and visual hallucinations of “seeing and hearing death”, but was not experiencing them during the examination, with benign neurological and psychiatric assessments. Osteopathic structural examination revealed blanching viscerosomatic reflexes from T7-L2 on the right and hypertonic, asymmetric paraspinal musculature from level T6-T12, along with other somatic dysfunctions (Figure ). Chapman’s points were appreciated on the right sixth intercostal area.
Laboratory findings revealed elevated ALT levels, with CBC, electrolytes, BUN, and creatinine within normal ranges. HCV antibody test done on previous admission was positive, however the patient declined follow-up with gastroenterology or infectious disease referrals. Subsequent EKG and cardiac enzyme levels were normal; however, he was admitted to medicine for psychiatric evaluation and referral to inpatient detox unit. |
pmc-6433086-1 | A 10-year-old girl of Indian origin presented to the pediatric outpatient department with a history of insidious onset and gradually progressive pain and weakness, predominantly affecting the proximal muscles of both upper and lower limbs, for the past four years. She also complained of dusky red rash with swelling, itching, and photosensitivity over the face and extremities, and pain and swelling over bilateral knee joints since the past three years. She also developed multiple hard ulcerated lesions with chalky white discharge over face, chest, trunk, and extremities over the last six months. Her past medical and family history were unremarkable. On general physical examination, the child appeared to be emaciated with a weight of 18 kg (less than the fifth percentile for age), a height of 120 cm (less than the fifth percentile for age), and a body mass index (BMI) of 12.5 kg/m2. Examination of skin revealed the presence of confluent violaceous, edematous macules around eyelids, forehead, cheek, and chin (heliotrope rash), and erythematous firm papules of size 0.5 X 0.5 cm over metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints (Gottron papules;Figure ).
She also had erythematous scaly plaques over the elbow and the knee joints and hypertrichosis and hyperpigmentation over the forehead, neck, and hands with a dystrophic and ragged cuticle (Samitz sign; Figure ).
Multiple tender ulcerated subcutaneous nodules measuring 0.5 x 0.5 cm to 1 x 1 cm over bilateral elbows, knees, and trunk were also noted (calcinosis cutis; Figure ).
On nail capillaroscopy, dilated and tortuous capillaries and capillary dropouts were noted. Musculoskeletal examination revealed minimal tenderness of the proximal muscles of upper and lower limbs with positive Gower’s sign (use of hands and arms to "walk" up the body from squatting position due to proximal myopathy affecting lower limbs). Muscle power in proximal muscles of both upper and lower limbs was 3/5.
On evaluation, her liver function tests, renal function tests, fasting plasma glucose, and serum electrolytes were within normal limits. She was found to have microcytic hypochromic anemia with hemoglobin of 9.6 g/dL. Test for antinuclear antibody (ANA) was negative, while lactate dehydrogenase (LDH) level was elevated at 825 U/L (N: 130-240 U/L). Chest radiograph and two-dimensional echocardiogram were also normal. Magnetic resonance imaging (MRI) of the hip, shoulder, and ankle region revealed multiple areas of subcutaneous and intramuscular calcifications. Electromyography (EMG) was suggestive of a myopathic pattern. A punch biopsy from the ulcerated lesion on the forehead was performed, which on histopathology revealed hyperkeratosis, acanthosis and follicular plugging in the epidermis. Mild vacuolar alteration at the dermo-epidermal junction was noted. Upper dermis showed mild edema along with moderate perivascular lymphocytic infiltration (Figure ).
Entire dermis showed a marked dense calcium deposition along with foreign body giant cell reaction (Figure ).
Taking into account the clinical, biochemical, and histopathological features, the girl was diagnosed with JDM. She was initiated on treatment with two immunomodulator drugs- prednisolone and methotrexate, along with supportive treatment for muscle weakness, rash, and calcinosis cutis. |
pmc-6433088-1 | A 55-year-old woman presented three days after a sudden onset of right-sided chest pain, pleuritic and positional in nature, associated with an acute onset of shortness of breath. She had gone to her primary care physician, who performed a chest X-ray and urged her to come to the hospital. Upon presentation at the emergency department, her oxygen saturation was above 95% on room air, and she was not in any respiratory distress, but her exam was significant for decreased breath sound on the right. A chest X-ray confirmed a large right-sided pneumothorax with small pleural effusion. A chest tube was inserted on the right side for the resolution of the pneumothorax, and subsequent computed tomography (CT) scan of the chest revealed bilateral diffuse bullous disease of the lung with multiple cysts (Figure -). The patient underwent video-assisted thoracoscopic surgery for right thoracoscopic wedge resection of a lung bleb and talc pleurodesis. Gross examination of the specimen revealed several dilated air-like spaces ranging from 0.2 cm to 0.4 cm in size. The hospital course was complicated by postsurgical pneumonia, but she recovered fully and was discharged to home with only minimal symptoms of dyspnea on exertion. Upon further investigations, she was found to have multiple small lesions of angiomyolipoma on the right kidney with diffuse retroperitoneal lymphadenopathy. One of the lymph nodes was biopsied, and pathology revealed predominantly spindle cells positive for HHF35 and smooth muscle actin, consistent with the diagnosis of leiomyoma. At the eight-month follow-up at the pulmonology clinic, her pulmonary function test (PFT) showed normal vital capacity and forced expiratory volume in one second (FEV1), but moderately reduced diffusion capacity, which may also be related to LAM. At her 12-month and 24-month follow-up visits, her PFT results showed improvements in peak flow and diffusion capacity, and the patient continues to report no symptoms other than minimal dyspnea on exertion. |
pmc-6433089-1 | A 90-year-old man presented for evaluation of asymptomatic pigmented lesions on his soles. His past medical history is significant for prostate cancer. He receives leuprolide acetate (Lupron) depot suspension 22.5 mg injection every three months.
Cutaneous examination showed black macules on his feet. An 8 x 8-mm black macule was present on his left plantar foot near the heel. A 10 x 10-mm black macule was present on the right plantar midfoot.
A 3-mm punch biopsy was performed at each site. Antibiotic prophylaxis, cephalexin 500 mg twice daily, was prescribed for 15 days. Topical mupirocin ointment (2%) was applied to the biopsy sites three times daily.
He returned for suture removal after two weeks. The left foot showed a combined (blue and junctional) nevus that was present in the lateral margins of the specimen; since this is a benign lesion, no further treatment was necessary. However, the right foot showed a junctional nevus with dysplastic features that also extended to the specimen’s lateral margins; the dermatopathologist recommended an additional biopsy.
A broader biopsy, using the shave technique, was done and included most of the residual pigmented lesions on his right foot. Cephalexin 500 mg twice daily was continued for an additional two weeks. He also continued to apply the mupirocin ointment (2%) to the area three times daily.
After an additional week of cephalexin—his third consecutive week receiving the antibiotic—he began to experience tenderness of his left Achilles tendon when walking. He was scheduled to return to the office one week later. He continued to take the antibiotic and his tendon pain progressively increased.
Follow-up examination, two weeks after the second biopsy (and four weeks after starting cephalexin), showed partial healing of the biopsy site on his left foot; there was neither inflammation nor tenderness. Pathology evaluation of the larger biopsy specimen demonstrated a benign compound nevus, having features consistent with congenital onset, and without any atypia. Based on the revised diagnosis, no further intervention was necessary for the residual lesion that extended to the deep and lateral margins of the specimen.
Examination of his Achilles tendons was also performed. His right tendon was asymptomatic. Similarly, at rest, his left tendon had no pain. However, on ambulation, the left Achilles tendon was very tender.
Cephalexin was discontinued; he had received four weeks of treatment. Ibuprofen was prescribed for symptomatic relief; however, the patient decided not to initiate oral therapy with the nonsteroidal anti-inflammatory drug. Within one week after stopping cephalexin, the left Achilles tendon pain spontaneously resolved and has not recurred. Subsequently, during the evaluation of his Achilles tendons two weeks after cephalexin had been withdrawn, there was no pain when walking. |
pmc-6433092-1 | An 18-year-old male patient presented to our emergency polyclinic with pain, swelling, deformity, and limited joint mobility in the right elbow. He had sustained an injury to his right elbow during a wrestling match. He had fallen backwards on an outstretched hand with his wrist in dorsiflexion and hyperpronation. The patient had a restricted active range of motion, especially the supination-pronation movements of the forearm. However, flexion-extension movements of the elbow joint were intact. Ecchymosis was present on the anteromedial aspect of the right elbow. Neurovascular status of the limb was normal.
X-ray images indicated isolated anteromedial radial head dislocation (Figure ).
A computed tomography (CT) scan of the elbow was performed (Figure ).
Closed reduction was attempted in the emergency room using various maneuvers; however, successful reduction could not be achieved.
Thus, an open reduction was considered. Boyd’s approach was used to expose the radial head. A plane was made between the extensor carpi ulnaris and anconeus, and the radiocapitellar joint was exposed. We found that the brachialis tendon was wrapped around the radial neck and noted that the tendon pulled the dislocated radial head anteromedially. The brachialis tendon restricted radial head reduction. We also detected that the annular ligament was ruptured. The brachialis tendon was released from the radial head and the joint was reduced (Figure ).
However, the reduction was unstable. Therefore, the annular ligament was repaired and a radioulnar Kirschner wire (K-wire) was used to maintain reduction of the proximal radioulnar joint (Figure ).
Postoperatively, a hinged long arm cast brace was applied and the patient was allowed to perform flexion-extension movements. Ectopic ossification was observed anterior to the joint at the time of first follow-up. Then, a single dose of 7-Gy radiotherapy was administered to the patient. No progression was detected in ectopic ossification at the subsequent follow-up. The wire and cast brace were removed after four weeks and elbow mobilization was initiated (Figure ).
During the course of subsequent follow-ups, it was observed that the patient had gradually resumed his normal activities. The functional outcome of the patient improved without pain or disability (Figure ). |
pmc-6433442-1 | A 64-year-old, African American female, with a history of metastatic poorly differentiated pleomorphic sarcoma of the right thigh and hypertension, presented to the emergency department with concerns over increased fatigue and generalized weakness which began 10 days ago, after a scheduled chemotherapy session with adriamycin, ifosfamide, and mensa. The patient also reported difficulty with ambulation and inability to accomplish full range of motion in the upper extremities against gravity. Associated symptoms included polyuria and polydipsia. On review of systems, the patient denied chest pain, shortness of breath, nausea, vomiting, diarrhea, abdominal pain, fevers, chills, night sweats, reduction in appetite, and weight loss. On further review of oncologic history, it appeared that the patient received neoadjuvant radiation therapy to the right thigh, followed by surgical resection. Unfortunately, the patient was later diagnosed with metastatic lesions in the lungs and was subsequently treated with six cycles of palliative chemotherapy (adriamycin, ifosfamide, and mesna). The total cumulative dose of ifosfamide was 45 g/m2. The patient also experienced severe neutropenia requiring a 25% dose reduction of adriamycin and ifosfamide during the second cycle of therapy. After the third cycle, imaging studies revealed disease stabilization. Prior to presentation, weekly laboratory studies revealed normal sodium, potassium, bicarbonate, creatinine, and phosphorus levels. On initial evaluation, the patient was hemodynamically stable; electrocardiogram (EKG) showed normal sinus rhythm and chest X-ray showed no pathologic cardiopulmonary process. Laboratory studies revealed a non-anion gap metabolic acidosis and acute kidney injury; markedly abnormal laboratory values include 152 mmol/L of sodium, 1.3 mmol/L of potassium, 16 mmol/L of bicarbonate, 1.1 mg/dL of phosphorus, 1.8 mg/dL of magnesium, and 3.3 mg/dL of creatinine. The blood glucose level was 123 mg/dL. The complete serologic data are listed in Table .
Urinalysis demonstrated a specific gravity of 1.012, protein level of 100 mg/dL, pH 6.0, and 20-50 epithelial cells per hpf. The complete urinalysis data are presented in Table .
After aggressive electrolyte repletion and intravenous fluid rehydration with normal saline, the patient experienced gradual improvement in weakness. The patient was soon after discharged with daily oral potassium supplementation. Chemotherapy has since been discontinued and electrolyte levels have remained stable. |
pmc-6433443-1 | A 33-year-old female patient presented with complaints of swelling and pain in the dorsum of the right hand. She had a 2x2 cm mass and a soft cystic lesion, which was diagnosed as a ganglion cyst at the dorsum of the hand (Figure ). Past medical history was unremarkable with American Society Anesthesiology (ASA) classification I. Surgical history examination revealed two cesarian-section operations. Ten milliliters of local anesthetic (bupivacaine 0.5%) was administered to encircle the radial nerve without entering the humeral side. Surgical anesthesia was achieved at the 25th minute after local anesthetic administration. A mild motor block was observed, as the patient could move her hand parallel to gravity. The patient was cooperative and reported minor discomfort during the excision of the cyst from its base where it originated, but there was no need for additional analgesic drugs during the surgery. There were no symptoms of cardiovascular, respiratory, or central nervous system side-effects. The surgery proceeded uneventfully and lasted about 20 minutes. The block was considered successful without the necessitation of conversion to general anesthesia. |
pmc-6433443-2 | A 28-year-old female patient with complaints of swelling in the wrist dorsum of the right hand. The patient's medical and surgical history was unremarkable and evaluated as ASA I class. Fifteen milliliters of local anesthesia (10 ml bupivacaine 0.5 % and 5 ml lidocaine 2%) was administered around the radial nerve under ultrasound guidance. The block procedure was uneventful. The patient was cooperative during the operation and did not report pain at the beginning of the surgery. During the excision of the cyst from its base, the patient complained of discomfort. Fentanyl 50 µg intravenous was administered and 3 milliliters of 2% prilocaine was infiltrated to the surgical area. The surgery lasted 30 minutes, uneventfully. The block was considered successful without the need for conversion to general anesthesia. |
pmc-6433443-3 | A 24-year-old male patient with a complaint of swelling at the wrist dorsum of the right hand was diagnosed with a ganglion cyst. The patient was evaluated as ASA I class with no remarkable medical and surgical history. After identifying the radial nerve under ultrasound guidance, 10 milliliters of 0.5% bupivacaine was administered. There were no symptoms of side effects during the block procedure. The patient reported minor discomfort, which was resolved with the administration of 50 µg intravenous fentanyl and infiltration of 3 milliliters 2% prilocaine into the surgical area. The surgical procedure was completed in 30 minutes without any complications. The block was considered successful, with no need of conversion to general anesthesia. |
pmc-6433444-1 | A 57-year-old Caucasian male was brought in by emergency medical services (EMS) with reports of severe substernal chest pain. The cardiac catheterization lab was activated for anterolateral ST-segment elevation noted on the electrocardiogram (ECG). He reported severe substernal chest pressure and belching followed by an unwitnessed syncopal episode. He had several seconds of cardiopulmonary resuscitation performed by bystanders prior to electromyostimulation (EMS) arrival. His past medical history includes gastroesophageal reflux disease and esophageal stricture with dilation.
The ECG on admission showed anterolateral ST-segment elevation (Figure ). His vital signs at presentation included a heart rate of 112 beats per minute (bpm), blood pressure of 138/104 mmHg, respiratory rate of 14 breaths per minute, and oxygen saturation of 95% on room air. On physical examination, the patient appeared in no distress. First and second heart sounds were normal without murmur, rub, or gallop. Lungs were clear to auscultation. Serum chemistries were normal including potassium 3.8 mmol/L (3.5-5.1 mmol/L), bicarbonate 25 mmol/L (22-29 mmol/L), creatinine 0.9mg/dL (0.7-1.2 mg/dL), ionized calcium 1.12 mmol/L (1.12-1.3 mmol/L), ionized magnesium 0.45 mmol/L (0.43-0.61 mmol/L), and troponin T was undetectable at <0.01 ng/mL. Thyroid studies were unremarkable. Emergent coronary angiography was performed and showed no significant coronary artery disease. Repeat ECG in the cardiac catheterization lab showed resolution of ST-segment elevation with new T wave inversion in the anterolateral leads (Figure ). The patient had a short run of ventricular tachycardia in the cardiac catheterization lab that resolved spontaneously. Transthoracic echocardiogram (TTE) was obtained and ruled out structural or valvular abnormalities and showed a normal ejection fraction. On hospital day two, the patient had an episode of chest pain, palpitation, and increased belching with associated telemetry findings of a wide complex rhythm (Figures -) which was diagnosed initially as ventricular tachycardia with a rate of 101 bpm. Symptoms resolved with sublingual nitroglycerin. Further review of telemetry revealed ST-segment elevation in Lead V4 prior to the onset of the wide complex arrhythmia. This led to the final diagnosis of AIVR following an episode of Prinzmetal’s angina. Cardiac magnetic resonance imaging (MRI) was unremarkable for structural abnormalities. He was treated with diltiazem, isosorbide mononitrate, and nitroglycerin as needed. On further questioning, he mentioned that these episodes of chest pain had been going on for a few years and were initially attributed to his esophageal disease. Retrospectively, these episodes of chest pain were likely Prinzmetal’s angina. |
pmc-6433445-1 | A 56-year-old female with a past medical history of Crohn's disease presented to the emergency room (ER) with complaints of diffuse abdominal pain, nausea, and vomiting. Her physical exam was remarkable only for diffuse tenderness to palpation of the abdomen and mild to moderate distention. Computed tomography (CT) abdomen/pelvis showed high-grade partial vs complete distal small bowel obstruction with terminal ileum thickening (Figure ).
CEA and CA19-9 were within normal limits. Colonoscopy resulted in ileocecal valve thickening suspicious for carcinoma. Surgery was performed and the specimen pathology showed a high-grade mixed adenocarcinoma/neuroendocrine tumor with metastasis in 3/10 lymph nodes. Immunohistochemistry was focally positive for chromogranin and synaptophysin (Figure ).
Post-surgery, positron emission tomography-computed tomography (PET-CT) was performed and showed changes from the recent ileocolonic resection with reanastomosis. There was no definitive evidence of metastatic disease. |
pmc-6433449-1 | A 72-year-old Caucasian female with a significant past medical history that includes stage IV chronic kidney disease, insulin-dependent diabetes mellitus, hypertension, peripheral artery disease with bilateral below-knee amputations, and atrial fibrillation presented to the emergency department with a chief complaint of a four-month history of progressive lower back pain that radiated into both buttocks and her anterior and posterior thighs. Additionally, over the prior two weeks, she began to have episodes of urinary incontinence and noticed paresthesia in her bilateral medial thighs, stating the left side was worse than the right. She denied any recent trauma, although she did elicit a history of falling out of her bed eight months prior to admission. She is wheelchair bound, and requires assistance for all her activities of daily living. Her physical examination was remarkable for morbid obesity, with a body mass index (BMI) of 43.5 kg/m2, and bilateral below-knee amputations. Neurologically, her examination was unremarkable other than diminished light touch sensation to bilateral medial thighs.
Magnetic resonance imaging (MRI) of the thoracic and lumbar spine was ordered that identified a subacute T11 burst fracture with bony retropulsion resulting in central canal stenosis, and severe cord compression at the T11/T12 interspace with associated myelomalacia (Figures -). Additionally, there was a segmental kyphotic deformity associated with this fracture. To better delineate the bony anatomy, a computed tomography (CT) of the thoracic spine was obtained. In addition to the T11 burst fracture and vacuum disc phenomenon from advanced degeneration at the T11/T12 intervertebral disc, an anatomical anomaly was identified. Duplication of the T11 vertebral pedicles in vertical alignment was demonstrated on axial and sagittal views (Figures -). To confirm this to be an actual anomaly and not an auto-fusion of adjacent vertebral bodies from a severe compression deformity, the ribs were counted and followed to their respective vertebral body (Figure ). The total rib count was 12 on each side, and was associated with the correct vertebral body.
To help alleviate the patient’s severe back pain, bilateral leg pain, and paresthesia, and to diminish the risk of permanent urinary and fecal incontinence, the patient underwent a T10 to T12 laminectomy with posterior instrumented fusion via pedicle screws inserted into T9, T10, T12, and L1 using stealth neuronavigation. Intraoperatively, the anomaly was visualized as an elongated T11 lamina with two pedicle screw entry points on each side into the T11 vertebral body identified with the stealth navigation probe. The laminectomy and instrumented fusion were performed in standard fashion. The patient tolerated the procedure well, and there were no intraoperative complications.
Postoperatively, the patient had improvement in her bilateral leg pain and paresthesia. Her Jackson-Pratt drains were removed on postoperative day two, at which time she was deemed stable for discharge to a rehabilitation facility. She was discharged to a skilled nursing facility on postoperative day six. She was readmitted to the hospital two months after surgery for hospital-acquired pneumonia. At that time, a CT of the chest was performed that showed the hardware to be in the proper position as well as help re-identify the T11 duplicated pedicle (Figure ). |
pmc-6433451-1 | A 67-year-old woman with a past medical history of asthma, tobacco smoking, hyperlipidemia, and hypertension presented to the hospital with persistent dry cough. Two weeks prior to presentation, she suddenly developed a violent dry cough that progressively worsened. The cough was constant throughout the day and was present on most days. She also described prodromal symptoms of malaise, myalgias, nasal congestion, and runny nose that preceded the cough. No traumas were reported. Five days after symptoms onset, she developed severe right-sided chest pain with extensive bruising on the right side of her chest extending down to her abdomen and right upper thigh. She was evaluated by her primary care physician who obtained a chest X-ray that revealed a right-sided ninth rib fracture (Figure ) for which she was treated conservatively with acetaminophen and as needed with ibuprofen. She was prescribed a codeine-based cough syrup for her presenting symptom.
Four days later, the patient presented to the emergency department for worsening right-sided chest wall pain and persistent dry cough. Her physical exam revealed normal vital signs, normal lung sounds with good air movement bilaterally, absence of wheezing and significant purple-colored ecchymosis starting at the right-side of the chest at the level of the ninth rib extending down to the right-side of the abdomen and the right upper thigh. Laboratory work-up was non-revealing with a normal complete blood count and chemistry. Computed tomography (CT) scan of the chest, abdomen and pelvis showed an acute fracture of the right ninth rib associated with a muscular abdominal wall hematoma in addition to right lower lung and right liver lobe extrusion between the right eighth and tenth ribs (Figure ).
Given these findings, a respiratory viral panel swab was obtained for testing, and it was positive for Bordetella pertussis using the polymerase chain reaction (PCR) method. Further exploration of the patient's prior vaccination history revealed that she did not receive the tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccine in her adulthood. She was diagnosed with pertussis causing persistent cough, leading to right-sided ninth rib fracture with extrusion of the right lower lung and liver. She was treated with azithromycin for a course of five days in addition to cough suppressants. Her pain was managed with acetaminophen and as needed oxycodone. Her abdominal wall hematoma was managed conservatively with serial monitoring of her hemoglobin levels which remained stable without requiring any blood transfusions. Chemoprophylaxis with azithromycin was provided to the close contacts of the patient. Surgical consultation was obtained, and the decision was to defer the elective surgical repair of extruded viscera until cough resolution.
On follow-up few weeks after discharge, the patient's symptoms dramatically improved. She underwent a successful surgical repair of the visceral extrusions. |
pmc-6433452-1 | This is a case of a 56-year-old Caucasian male who presented to our emergency department at a university hospital with an acutely altered mental status that had declined over 24 hours. He had a decreased appetite the week prior and had been experiencing syncope with falls. Most of the history was, therefore, obtained from the wife. Medical history was significant for poorly differentiated metastatic neuroendocrine carcinoma likely from a lower gastrointestinal (GI) source, renal cell carcinoma (RCC), and gastroesophageal reflux disease (GERD). Pertinent surgical history included recent kidney and liver biopsies consistent with a papillary renal neoplasm, as well as neuroendocrine carcinoma favoring a metastatic process from a lower GI source. Given that these malignancies were recently diagnosed within the past two months, the patient had been on etoposide/carboplatin-based chemotherapy three times a week and had also received filgrastim post-chemotherapy for neutropenia.
On admission, his vitals were stable with a heart rate of 95, SpO2 of 95%, respiratory rate of 18, and blood pressure of 113/67 mmHg. An initial arterial blood gas revealed a lactate level of 5.54 mmol/L, bicarbonate of 23.3, and a base excess of 24.4. On physical examination, the patient's mental status was altered and he was markedly confused but alert; however, he was not oriented to time and place. The review of a recent computerized tomography (CT) scan of the abdomen and pelvis showed metastatic liver disease, biopsy-positive for caudal type homeobox Type 2 (CDX 2), synaptophysin, cytokeratin (CK) 20, CK AE1/AE3 (anti-cytokeratin monoclonal antibodies), a right renal mass biopsy positive for CK 7, and racemase, as well as colonic lesions, representing the patient's recently diagnosed malignancies. A non-contrast CT scan of the head was unremarkable on admission. Admission labs revealed a white blood cell (WBC) count of 0.3 k/cmm suggesting neutropenia, a urinalysis positive for trace leukocyte esterase, ionized calcium of 1.67 mg/dL with corrected calcium of 15.6 mg/dL, initial troponin of 0.203, and total absolute neutrophil count of 0.030 k/cmm. Hematology/Oncology Service was consulted, and the patient was subsequently admitted to the intensive care unit (ICU) for further evaluation and treatment.
The patient’s assessment included hypercalcemia secondary to malignancy, sepsis - multifactorial, severe neutropenia, and metabolic encephalopathy. Complete workup was done with the initial treatment consisting of pressors (norepinephrine), intravenous fluids (IVF), and zoledronic acid. Blood cultures were positive for gram-negative Escherichia coli (E. coli) bacteremia and sputum cultures were positive for Klebsiella and Streptococcus pneumoniae. The patient was started on vancomycin, as well as meropenem; meanwhile, his condition continued to deteriorate, leading to acute hypoxic respiratory failure requiring mechanical ventilation. Shortly thereafter, his condition started to improve with his lactic acid levels trending down to as low as 2.54 mmol/L and a total absolute neutrophil count trending up to 10.173 k/cmm by ICU Day 5. At the same time, however, his WBC levels were trending up to as high as 11.6 k/cmm. His condition started to hemodynamically decline on ICU Day 6 with the development of fever (100.6°F), elevated total bilirubin (7.5 mg/dL), and increasing lactic acid levels. Infectious Disease Service was brought on board since lactic acid levels were as high as 4.07 mmol/L on ICU Day 6 regardless of appropriate antibiotic coverage (Figure ). The patient subsequently underwent percutaneous cholecystostomy drainage for possible infectious biliary sludge as well as diagnostic/therapeutic paracentesis removing 3.5 L of fluid, which was ultimately non-pathologic. Despite treating for probable causes of sepsis, by ICU Day 12 the WBC count and lactic acid continued to rise to 37.8 k/cmm (Figure ) and 9.85 mmol/L, respectively. This prompted the patient’s antibiotic regimen to be changed to linezolid, meropenem, and micafungin.
By ICU Day 13, the patient was hemodynamically stable and afebrile with the lactic acid still elevated at a value around 8.41 mmol/L. In spite of continued elevations in the lactic acid, a spontaneous breathing trial was performed with encouraging weaning numbers. The patient was subsequently extubated and maintained on very low dose norepinephrine, not for hemodynamic stability, but rather to improve end-organ perfusion in hopes that the lactic acid would trend down with optimized antibiotic therapy. The patient's condition was guarded, and the prognosis was poor. On ICU Day 14, the presumed cause of the patient's condition shifted to his underlying malignancies. Despite exhaustive measures, a decision was made after extensive thought and an ICU stay of 16 days to pursue comfort care measures. The patient passed away shortly thereafter with the cause of death presumed to be overwhelming sepsis vs. end-organ failure from underlying malignancies. |
pmc-6433453-1 | A 70-year-old male with history of amyotrophic lateral sclerosis (ALS), dysphagia status post gastrostomy tube placement, chronic respiratory failure status post tracheostomy, and gastroesophageal reflux disease presents with six-day duration of melanotic stools. The patient was mechanically ventilated with gastrostomy tube and tracheostomy in place. His physical exam otherwise was benign. He was found to have acute onset anemia with hemoglobin of 7.1 g/dl. He was suspected of having peptic ulcer disease secondary to NSAIDs given the history of chronic musculoskeletal pain with NSAID use. Due to continual decrease in hemoglobin requiring daily blood transfusions despite conservative management, upper endoscopy was performed. It demonstrated a bleeding ulcer distal to pylorus in the duodenal bulb. Endoscopic technique was used to remove the clot, but the procedure resulted in bleeding that could not be stopped leading to poor visualization despite epinephrine injections. Due to his multiple comorbidities, he was deemed to be a poor surgical candidate. The patient was referred to interventional radiology for embolization of gastroduodenal artery (GDA).
During the embolization of GDA, the celiac angiogram demonstrated no evidence of active extravasation, but contour irregularity at the level of the mid-GDA was noted. Prophylactic coil embolization of GDA was performed achieving GDA stasis. Post-embolization angiography of the SMA demonstrated no evidence of bleeding from IPDA branches. Incidentally noted was a replaced right hepatic artery arising from the SMA.
Despite embolization of GDA, patient’s hemoglobin continued to decrease to 6.8 g/dl and the patient continued to have melena and hematemesis resulting in hypotension. The patient required an additional nine units of packed red blood cells (pRBCs), six units of platelets, and five units of fresh frozen plasma. Computed tomographic angiography (CTA) showed a large bleed from IPDA off the SMA immediately posterior to the origin of the replaced RHA (Figure ).
The patient was referred for urgent embolization by interventional radiology.
During angiography, no active extravasation was identified and given that the GDA was already embolized, the most reasonable source vessel in the suspected territory would be the IPDA. The replaced RHA was selected and IPDA was identified as its first branch (Figures , ).
While the branch arising directly from the replaced RHA represented the posterior IPDA, the anterior IPDA was seen as collateral vessel going back to the middle colic artery (Figure ).
However, no focus of active bleeding could be identified from digital subtraction angiography from the posterior IPDA or the anterior IPDA. Cone beam computed tomography (CBCT) catheter angiography of the posterior IPDA was performed to identify the region of the duodenal bleed analogous to the region of active extravasation seen on abdominal CTA. The same location on the posterior wall of the duodenum seen on abdominal CTA was matched on CBCT angiography (Figure ).
Subsequently, the posterior IPDA was embolized using n-butyl cyanoacrylate (NBCA) (Trufill n-BCA Liquid Embolic, Codman Neurovascular, Raynham, Massachusetts, USA) mixed with ethiodol 1:4 dilution ratio administered via the microcatheter (Figure ).
Post-embolization angiography of the SMA demonstrated successful embolization of the posterior IPDA with sparing of the anterior IPDA. The patient became hemodynamically stable post procedure and no longer required blood products transfusion. His hemoglobin stabilized at 8.6 g/dl. The patient was successfully discharged to a skilled nursing facility to continue his recovery. At eight weeks follow-up the patient remained asymptomatic and he agreed to participate in this case report. |
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.