A 48-year-old male patient with end-stage renal disease on hemodialysis underwent an expanded criteria donor KT. The donor’s age was in the early 60s and cause of death was a cerebrovascular event. The donor did not have a history of diabetes or hypertension and terminal creatinine was 1 mg/dL. Our patient received Alemtuzumab and one dose of steroids as induction therapy, and the cold and warm ischemia times were 26 h and 1 h and 15 min, respectively. His primary kidney disease was presumed to be hypertension and diabetes. Three years prior to KT, he presented with an episode of hypertensive urgency, paroxysmal atrial fibrillation and an ischemic cardiovascular accident involving the right posterior corona radiata. Following this, he was placed on anticoagulation therapy with warfarin and a few months later suffered an intraventricular haemorrhage. This left him with significant deficits, in particular, mild cognitive impairment and Broca’s aphasia. Two years after this episode, he also underwent a coronary artery bypass graft surgery. Post-operatively, he was on amiodarone for 11 months and this was stopped after KT.
Post-KT, our patient experienced delayed graft function and required dialysis once, within 24 h of transplantation due to hyperkalemia. Following that, he had renal function recovery and achieved a baseline creatinine of 1.2 mg/dL, with no proteinuria. He had a human leukocyte antigen mismatch of six on the A, B and DR loci and had a pre-transplantation panel reactive antibody of 0. Thus, he was maintained on dual immunosuppression: tacrolimus with a trough target of 4–8 ng/mL and mycophenolic acid 720 mg twice a day. On a routine urine test 19-months post-transplant, he was noted to have proteinuria of 0.088 g/mmol (normal ≤0.017 g/mmol); thus a graft biopsy was pursued.
The graft specimen consisted of five cores, with ¾ cortex and ¼ medulla, for a total of 76 glomeruli (three globally sclerosed) and 11 arteries. The technician noted a brown discoloration while processing the sample. Given the patient’s post-transplant status, the Banff criteria were applied []. The biopsy showed endocapillary inflammatory cells in the glomeruli and in the peritubular spaces, which was given a score of moderate glomerulitis (Fig. a) and peritubular capillaritis (Fig. b), but there was no significant staining for C4d in the peritubular capillaries. Also noted, were tubular changes of acute tubular necrosis or acute drug toxicity. The immunofluorescence was non-contributory. A diagnosis suspicious for acute antibody-mediated rejection was rendered. However, in addition to this, diffuse brown granular pigments in the tubular epithelial cells were seen on hematoxylin and eosin stain. The pigment was found in the cytoplasm of the tubular epithelial cells, ranging from 1 to 4 μm (Fig. c). Upon subsequent histologic examination with special stains, the granules were magenta on Masson Trichrome (Fig. d) and periodic acid Schiff (Fig. e), blue on Schmorl reaction (Fig. f), and dark black on Fontana stain (Fig. g). They were not reactive with iron staining by Prussian blue (Fig. h) and negative on Jone’s silver (Fig. i). The tubular cells showed autofluorescence (Fig. j). Electron microscopy examination revealed intracellular lamellar inclusions that had a granular matrix and were surrounded by mitochondria (Fig. k). All of these features were characteristic of LD (Fig. ) [, –].
Since the transplant and during the biopsy intervals, the patient had fairly good metabolic parameters: hemoglobin A1c < 7.2%, total cholesterol < 3 mmol/L, and BMI < 25 kg/m2. Overall, his BP was well controlled on 2 to 3 agents. No donor-specific antibody to the human leukocyte antigen was noted except that the patient had an indeterminate antibody level against the major-histocompatibility-complex class I-related chain A (MICA). He was treated with our antibody-mediated rejection protocol which entailed three doses of steroids intravenously, two doses of Rituximab 375 mg/m2, and six treatments with plasmapheresis. Following this, we increased his maintenance immunosuppression regimen by increasing the target tacrolimus trough to 8–10 ng/mL and adding prednisone 5 mg to his maintenance immunosuppression. We also started monthly intravenous immunoglobulin. Unfortunately, a protocol biopsy at 6-months did not show much improvement in his inflammatory scores; although the MICA antibody was no longer present (Table ). In conjunction with this, significant LD was still noted despite augmented immunosuppression.
After his second biopsy, we discussed initiating the same protocol again, or using Bortezomib and/or Tocilizumab. However, the patient was tolerating augmented immunosuppression poorly, with recurrent infectious episodes requiring hospitalizations. Hence, it was decided that we will be pragmatic with his care and treat him with anti-proteinuric therapy only. At the 12-month mark post the first biopsy, his creatinine was stable and at his baseline but he had nephrotic range proteinuria of 0.4–0.5 g/mmol.


We report a case of a 34-year-old Mediterranean woman living in a rural area in Thi-Qar Province in southern Iraq. She presented to our hospital with upper abdominal pain, anorexia, and nausea. She also had a 1-week history of low-grade fever and fatigue. She had no other symptoms upon general systematic inquiry; in particular, she had no history of gastrointestinal symptoms, no joint pain symptoms, and no photosensitivity or history of abortions. She had a regular menstrual cycle. Two weeks prior to her presentation, she underwent a thyroidectomy for a suspicious thyroid nodule. The histology of the nodule was confirmed as benign. She was not exposed to halothane during general anesthesia. She had been commenced on 50 μg of levothyroxine 10 days prior to this presentation.
She had no other past medical history of note and had received no previous prescribed medication. In particular, she had no history of blood transfusion, liver disease, or alcohol consumption. She did not report a family history of liver disease. She had never smoked, and she lived with her husband and young children at home. She was a stay-at-home mother and held no other occupation. On examination, she had normal vital signs: Her pulse rate was regular at 68 beats per minute with normal volume, respiratory rate was 10 breaths per minute, temperature was 36.8 °C, and blood pressure was 108/63 mmHg. Pulse oximetry revealed saturation of 96% on room air at rest. Her physical examination did not reveal any jaundice, and she had no stigmata of chronic liver disease. Examination of her cardiorespiratory systems revealed pure heart sounds with no murmur, and her respiratory auscultation revealed vesicular breath sounds and central trachea with no localizing signs or added sounds. A complete neurological examination confirmed a normal Mini Mental State Examination score, and she was oriented to time, place, and person. Her cranial nerves were intact, and the tone, power, reflexes, and sensory examination of the upper and lower limbs were symmetrically normal. Investigations confirmed acute hepatitis with raised urinary bilirubin, raised serum bilirubin 1.4 mg/dl, alanine aminotransferase (ALT) 549 U/L, aspartate aminotransferase (AST) 372 U/L, and alkaline phosphatase (AP) 338 U/L (see Table ). A gamma-glutamyl transferase measurement was not available at the time of presentation. The result of the patient’s abdominal ultrasonography was normal.
She had a negative virology screen (anti-hepatitis A virus antibody immunoglobulin M [IgM]-negative, hepatitis B surface antigen-negative, anti-hepatitis C virus-negative, anti-hepatitis E virus IgM-negative, anti-cytomegalovirus IgM-negative). Results of an autoantibody screen, including antinuclear antibody, anti-smooth muscle antibody, and anti-liver kidney microsome type 1 antibody, were negative. Serum ceruloplasmin was normal at 46 g/dl. We suspected levothyroxine-induced acute hepatitis and asked the patient to discontinue her medication. No baseline liver tests were available before the introduction of levothyroxine. Within 1 week, the patient had a dramatic response clinically. Biochemically, her liver enzymes (ALT, AST, and AP) and serum bilirubin normalized. The patient consulted another clinician privately, who attempted low-dose rechallenge with levothyroxine, and this led to recurrence of her liver enzyme derangement, which again subsequently subsided upon withdrawal of the drug. The patient’s hypothyroidism was treated with triiodothyronine 35 μg/day with subsequent clinical and biochemical improvement, and no evidence of recurrence of liver enzyme derangement was observed.
The patient was treated by cessation of the levothyroxine, which led to normalization of her liver enzymes. Her hypothyroidism was treated with triiodothyronine instead. The patient’s clinical progress and her thyroid and liver function tests were kept under surveillance over the next 6 months. Her thyroid function responded favorably to the introduction of triiodothyronine, and her liver enzymes completely normalized within 4 weeks after discontinuation of levothyroxine and remained normal until her 6-month follow-up appointment.


A 54-year-old female was referred to nephrology department due to abnormal urinalysis. The patient was detected to have proteinuria in a screening examination 1 month ago. She had no complaints such as skin lesions, corneal opacity, neuropathic limb pain, temperature sensitivity, abnormal sweating, or gastrointestinal symptoms. She had medical history of type 2 diabetes mellitus diagnosed about 5 years ago for which she was being treated with gliclazide. Other than which she was not taking any medication, and did not have past exposure to medications such as chloroquine or amiodarone. The patient denied family history of any genetic disease including Fabry disease. Physical examination, electrocardiogram, ophthalmic examination, and blood tests including immunoglobulin and complement tests were done. A renal biopsy was performed to determine the reason of proteinuria. Two needle biopsy cores including about 25 glomeruli were submitted. Renal biopsy, with subsequent immunofluorescent, and electron microscopic interpretation were done. After obtaining the patient's informed consent, mutation analysis (Sanger sequencing and RFLP method) was performed.
Physical examination was unremarkable. Repeat urinalysis showed proteinuria (protein/creatinine 1.26 g/g). Kidney function was normal (blood urea nitrogen 5.51 mmol/L, creatinine 65.4 μmol/L), liver function, electrolytes, and complete blood count were within normal limits. Total protein and albumin were 64.6 and 40.4 g/L, respectively. Hemoglobin A1c was 5.9%. Immunology tests showed IgA and C3 level to be slightly decreased, 0.71 g/L (normal range 0.82–4.53 g/L) and 0.77 g/L (normal range 0.79–1.52 g/L), respectively. Other immunoglobulin and complement levels were normal. Electrocardiogram showed signs of left ventricular hypertrophy and ophthalmic examination revealed no abnormalities.
Light microscopy showed hypercellularity and mesangial expansion in glomeruli and glomerular collapse with hyalinosis, other glomeruli contained strikingly enlarged and vacuolated podocytes (Fig. A, B). Vacuolated changes were also observed in some tubular epithelium cells (Fig. A, B). Immunofluorescence microscopy revealed 2+ granular IgM deposits in mesangial areas (Fig. C), while being negative for IgA, IgG, C3, C4, and C1q. Examination of toluidine blue-stained semi-thin sections and electron microscopy was performed, revealing blue bodies (Fig. D) and myelin-like bodies (Fig. E) in the cytoplasm of podocytes, respectively.
The mutation analysis identified a missense mutation c.902G > A (p.R301Q) in exon 6 (codon 301), which resulted due to the replacement of a glutamine for an arginine residue. Based on these findings, the patient was diagnosed with coexisting Fabry disease and IgM nephropathy. We decided to start therapy with angiotensin-converting enzyme inhibitors. Enzyme replacement therapy (ERT), however, was not administered due to financial constraints of the patient. After 2 months of treatment the patient demonstrated urine protein to creatinine ratio of 0.21 g/g.


A 43-year-old Iranian (Persian) woman was admitted to the Shahid Madani Hospital with palpitations and dyspnea. She had been experiencing palpitations for 2 years and recently (since about 10 days before admission) had developed dyspnea with New York Heart Association functional class II. Her past medical history was unremarkable, including usual childhood illnesses and no history of rheumatic fever. She never experienced atrial fibrillation and was receiving a low dosage of propranolol (10-mg tablet daily), fluoxetine (10-mg capsule daily), and alprazolam (0.5-mg tablet daily) for her palpitations. She was not receiving oral contraceptive medications. She was the mother of two healthy children, who were both delivered through normal vaginal delivery. She did not have any history of abortion. Her familial history was also unremarkable. She was a housewife who lived with her husband and her two children, never had a job, and was financially supported by her husband. She had never smoked or consumed alcohol or opiates, and she did not follow any special diet.
At the time of admission, her vital signs were within normal ranges (blood pressure 110/70 mmHg, pulse rate 95 beats/minute, respiratory rate 23/minute, oxygen saturation 95%), and her physical examinations revealed nothing considerable. Her extraocular motions full, her gross visual fields were full to confrontation, and her conjunctiva were clear. Her scleras were nonicteric, her pupils equal round and reactive to light and accommodation, and her fundi were also normal. Her hearing was normal. Her tympanic membrane landmark was well visualized. Pharyngeal injection with exudates was not noted. Her uvula moved up in midline. She had a normal gag reflex. Her jugular venous pressure was 8 cm, and her thyroid was not palpable. She had no masses and no adenopathy. Her lung auscultation was normal. She had no rales, rhonchi, wheezes, or rubs. No dullness to percussion was detected. Her diaphragm moved well with respiration. She had no heaves or thrills. She had a normal S1 heart sound, and her S2 sound was narrowly split. No murmur or abnormal heart sound was detected by auscultation. Her pulses were notable for sharp carotid upstrokes. Distal pulses of her extremities were 2+ and symmetric. Her neurologic examination revealed that she was awake, alert, and fully oriented. Her cranial nerves I–XII were intact. Her strength was normal. Her sensory examination revealed normal responses to touch and pinprick. No edema of her arms or head was noticeable. She had no tremor or dysmetria.
Her basic laboratory test results and cardiac enzyme findings were normal, except for mild leukocytosis (white blood cell count 14,400), which remained in the same range until discharge. The results of some other laboratory tests were as follows: hemoglobin, 12.5 g/dl; hematocrit, 41.0%; mean corpuscular volume, 89.0 fl; platelets, 256,000; reticulocyte index, 1.6%; Na+, 140 mEq/L; K+, 4.2 mEq/L; blood glucose, 102 mg/dl; blood urea nitrogen, 19 mg/dl; serum creatinine 1.0 mg/dl; total bilirubin, 0.5 mg/dl; direct bilirubin, 0.1 mg/dl; alkaline phosphatase, 135 mg/dl; aspartate aminotransferase, 45 IU/L; alanine aminotransferase, 27 IU/L; lactate dehydrogenase, 413 IU/L; erythrocyte sedimentation rate in first hour, 27 mm; creatine phosphokinase, 21 IU/L; creatine kinase-MB, 12%; cardiac troponin I, 0.1 ng/ml; hepatitis B surface antigen, negative; C-reactive protein, negative; and rheumatoid factor, negative. Urine analysis revealed specific gravity, 1.003; pH, 6.5; protein, negative; blood, negative; white blood cell count, 2–3; red blood cell count, negative; and bacteria, negative. Arterial blood gas tests revealed pH, 7.43; pCO2, 38 mmHg; PO2, 88 mmHg; HCO3−, 23 mEq/L; and oxygen saturation, 98% on room air.
Electrocardiography demonstrated tachycardia (rate about 100 beats/minute) without any cardiac arrhythmia. No sign of RV overload was noticeable. Primary transthoracic echocardiography revealed a mass in the RA; therefore, transesophageal echocardiography (TEE) was performed. TEE revealed RA enlargement and a huge, dense, multilobulated, hypermobile mass in the RA (1.4 cm × 7.4 cm) and extending into the right RV, which appeared to be emanating from the SVC (Fig. ). Furthermore, the mass was noted in the upper part of the SVC (20 mm from the mouth); however, the left ventricle (LV) and right ventricle (RV) had normal size, and their normal systolic functions were preserved (LV ejection fraction, 55%). Although the RA area was enlarged (23cm2), its systolic pressure was 43 mmHg, displaying moderate pulmonary hypertension. The main pulmonary artery and its branches were also dilated. The valvular evaluation demonstrated mild mitral regurgitation and mild tricuspid regurgitation, but no septal defect or patent foramen ovale was seen.
Systemic anticoagulation was immediately instituted with intravenous heparin, and the patient was transferred to the cardiac intensive care unit. Likewise, computed tomographic (CT) angiography demonstrated a partial filling defect in the SVC that was connected to another filling defect in the RA (46 mm × 26 mm) (Figs. and ). Moreover, partial filling defects were visible in the distal part of the right and left pulmonary arteries, extending to their branches, proposing massive pulmonary emboli (Fig. ). Atelectatic bundles were seen in the middle and lingual lobes, but the size of the heart was normal, and no pleural effusions were detectable.
The contrast-enhanced CT scans and ultrasonographic findings for the chest and abdomen did not show any evidence of tumor or malignancy. Also, there was no evidence of venous filling defects below the diaphragm or deep vein thrombosis (DVT) of the lower extremities. Because of the hypermobile huge mass in the RA and following a cardiac surgeon’s consultation, the patient was indicated for surgery and later was prepared for cardiac surgery. Anticoagulation therapy was continued until the patient was transferred to the operating room. Coagulation test results prior to the surgery were prothrombin time 12 seconds (international normalized ratio [INR] 1) and partial thromboplastin time 60 seconds.
At the time of surgery, following a median sternotomy, cardiopulmonary bypass (CPB) was instituted following cannulation of the ascending aorta and the inferior vena cava. The RA and SVC were opened, and the long-standing “white clots” were extracted. Afterward, the heart was arrested with St. Thomas’ Hospital cardioplegic solution, and circulatory arrest with antegrade cerebral perfusion was initiated. Clots were also removed from the branches of both the right and left pulmonary arteries (Fig. ). All the suture lines were closed, and the patient was weaned from CPB following 152 minutes with cross-clamping and circulatory arrest times of 112 and 20 minutes, respectively. Intraoperative TEE after clot removal revealed normal LV size and systolic function, and there were not any signs of clots in the SVC, RA, or other parts. The patient tolerated the procedure well and had an uncomplicated postoperative course. The final TTE did not show any signs of recurrence of the masses or pulmonary hypertension. The pathologic evaluations confirmed that all the surgically removed specimens were thromboses. A complete coagulation workup revealed heterozygosity in the following genes: factor V Leiden HR2 (4070 A/G), methylenetetrahydrofolate reductase (MTHFR) (1298 A/C), β-fibrinogen (− 455 G/A), glycoprotein Ia (807 C/A), plasminogen activator inhibitor 1 (PAI-1; 5G/4G), tissue plasminogen activator (intron 8 del/ins), and apolipoprotein E (E2/E3).
The patient’s symptoms, including palpitation and dyspnea, dissolved completely after the surgery, and she was discharged on warfarin to maintain an INR of 2–3. Finally, she was followed for 1 year after her discharge for any symptoms and signs of the clots, but the follow-up results were all negative. No pulmonary hypertension was detected by TTE in follow-up.


In July 2006, a 50-year-old female presented to the dermatology clinic with a complaint of painful skin changes in her bilateral lower extremities. She was employed as a dog groomer, and her past medical history was significant for type 2 diabetes mellitus with insulin requirements, gastritis, and severe valvular heart disease affecting the tricuspid, mitral, and aortic valves with surgical repair of the aortic valve. On physical examination, the patient was found to have linear, hyperpigmented macules on the bilateral lower legs with foci of scarring and ulceration. Two biopsies of the proximal and distal left lower leg suggested livedoid vasculopathy pending clinical correlation. She was additionally found to have an elevated antithrombin 3 activity of 124 (reference range 70.0–120.0), which is strongly suggestive of an underlying prothrombotic component to her condition []. At this time, therapeutic options for livedoid vasculopathy were considered and offered to the patient.
The patient's preferences and past medical history presented several obstacles to treatment of her LV. She repeatedly refused anticoagulant therapy because her husband had previously had issues with the diet restrictions and INR monitoring mandated by the use of warfarin. Antiplatelet agents were avoided due to her history of severe gastritis that was onset prior to our management of her LV. Intravenous immunoglobulin was considered; however, the patient could not afford the co-pay and her cardiologist recommended against IVIG due to the risk of these hyperosmolar preparations causing fluid overload in this patient with severe valvular heart disease. The patient was eventually started on an acceptable treatment regimen consisting of oral dapsone 100 mg once daily and prednisone 10 mg once daily, with the addition of doxepin or tramadol for intermittent pain control. With these medications, she achieved intermittent remission of her LV for several years.
In 2015, she began having intermittent, painful flares of her LV which were managed by increasing her dapsone to 150 mg once daily and increasing her prednisone to 20 mg. She sometimes required burst doses of 60 mg once daily. Attempts to wean her prednisone back down to 10 mg were rarely successful, and this dosing became an ongoing concern in 2018 when she began having severe hyperglycemic episodes which resulted in a brief hospitalization. Her insulin delivery was also switched to a pump system.
In the fall of 2018, she presented to dermatology during an acute LV pain flare and was coincidentally found to have an erythematous papule at the right dorsal forearm, which she attributed to a possible insect bite or a scratch from her dog. Three weeks later, she reported worsening of this right forearm lesion as well as new onset of two painful, ulcerative lesions on her right thigh and right forearm. On examination, the right dorsal forearm was now found to have two firm, tender erythematous papulonodules, one with central ulceration (). The right lateral thigh was found to have a single purpuric patch with central ulceration and necrosis (). The bilateral forearms additionally had a few scattered linear superficial abrasions consistent with animal scratches. No other new lesions were found on examination. She perceived these lesions as dissimilar from her typical LV, but at this time mycophenolate mofetil 500 mg twice daily was added for her ongoing LV flares. A 4 mm punch biopsy of a right dorsal forearm lesion revealed suppurative, granulomatous inflammation in the deep reticular dermis with demonstration of acid-fast organisms on AFB stain ().
The patient was subsequently evaluated for systemic mycobacterial disease. A chest X-ray showed no evidence of pulmonary mycobacterial disease. Laboratory testing was negative for HIV, AFB blood culture, and Tb QuantiFERON. Her CRP was elevated at 13.3, and the CBC revealed a mild leukocytosis of 13.00 with mild neutrophilia of 79.4%, elevated absolute neutrophils (10.3), and absolute immature granulocytes (0.4).
The state Department of Health identified rapidly growing Mycobacterium abscessus/chelonae on her right forearm tissue culture. Susceptibility testing and treatment guidance was subsequently provided by a national center specializing in mycobacterial consultation. Susceptibility results revealed resistance to cefoxitin, doxycycline, sulfamethoxazole-trimethoprim, and amoxicillin-clavulanic acid and sensitivity to clarithromycin, azithromycin, linezolid, imipenem, and amikacin. There was also intermediate sensitivity to ciprofloxacin and moxifloxacin.
The physicians of the Dermatology and Infectious Disease departments then coordinated management of her simultaneously flaring livedoid vasculopathy and disseminated cutaneous mycobacterial infection. The patient had a PICC line placed for her antimycobacterial regimen which consisted of oral azithromycin 250 mg once daily, intravenous imipenem 500 mg every 12 hours, and finally intravenous amikacin 12–15 mg/kg on Mondays, Wednesdays, and Fridays. Additional treatment with fluoroquinolones was not considered because she had a previously documented allergic reaction of a blistering skin eruption. This regimen was initially to be continued for a total of 8–12 weeks depending on her response, followed by oral azithromycin monotherapy for at least an additional 6 months. Lifelong suppression with oral monotherapy is also being considered pending her clinical response and tolerance to azithromycin.
At 10 weeks of treatment her physical exam revealed improvement of the ulcers of the right forearm, right thigh, and left foot. However, she also developed three new left knee ulcers consistent in appearance with her other mycobacterial lesions. For this reason, her current regimen is to be continued until her follow-up appointment for PICC line removal at 17 weeks of treatment. At that time, she will transition to daily maintenance therapy of oral azithromycin if she demonstrates adequate improvement in the existing lesions.
Meanwhile, the treatment of her livedoid vasculopathy was optimized by the dermatology team. Her prednisone was tapered down to 10 mg once daily, and both the dapsone and mycophenolate mofetil were discontinued. She has since been started on warfarin 1 mg once daily. This low dose was chosen due to reports of supratherapeutic INR from interaction of warfarin and azithromycin []. Her LV was found to be stable at her follow-up appointment 9 weeks after initiating and continuing the same dose of warfarin.


A 65-year-old female presented with anterior chest pain and chest computerized tomography (CT) revealed a tumor in the anterior mediastinum. The size on CT images was measured at 36 mm, and there was no evidence of infiltration into adjacent tissue; thus, a thymoma was suspected. A surgical resection procedure was scheduled for diagnostic and therapeutic purposes. Partial resection of the thymus was performed using video-assisted thoracoscopic surgery and the intraoperative diagnosis was suspected thymoma. The tumor size was 33 × 28 × 20 mm, the operation time was 64 min, and the amount of bleeding was small. The postoperative pathological diagnosis was LELC. Histologically, tumor cells with edematous large and round nuclei formed a solid corded net on the background of dense lymphocyte infiltration. Immunohistochemically tumor cells were positive for Bcl2 and Cytokeratin AE1 + AE3, while infiltrated lymphocytes were positive for CD3 and CD5 and negative for CD99 (Fig. ). Microscopic invasion into surrounding adipose fatty tissue beyond the capsular portion was noted. EB-encoded RNA in situ hybridization of the tumor was negative. We also performed 18F-fluorodexyglycose positron emission tomography/CT (FDG-PET/CT), with no abnormal accumulation seen to indicate distant metastasis.
Two months after the first operation, a total thymectomy and lymph node dissection were performed median sternotomy, with an operation time of 220 min and bleeding totaling 100 ml. Postoperative pathological findings revealed no tumor cells in the residual thymus and no lymph node metastasis. The TNM classification was p-T1aN0M0 stage I, while it was stage II in accordance with the Masaoka staging system. Ten months after the first operation, the patient had no recurrence and no adjuvant therapy was performed.


Chest X-ray findings in a medical checkup examination of an 81-year-old female showed an abnormal shadow. She came to our institution and chest CT results revealed a tumor in the anterior mediastinum. The size on CT images was 41 mm and there was no apparent infiltration of adjacent tissues; thus, a thymoma was suspected. An FDG-PET/CT examination revealed uptake (SUVmax 6.5) in the tumor. A total thymectomy and pretracheal lymph node dissection were performed by a median sternotomy combined with resection of the pericardium. The operation time was 114 min and bleeding was 50 ml, while the tumor size was 58 × 45 × 26 mm. Postoperative pathological findings revealed edematous large and round nuclei in the tumor cells, which formed a solid corded net on the background of dense lymphocyte infiltration. Microscopic invasion by the tumor into surrounding adipose tissue beyond the capsule was found, while there was no evidence of lymph node metastasis. Immunohistochemical analysis revealed tumor cells were positivity for Bcl2, CD5, and p40, while infiltrated lymphocytes were positive for CD3 and negative for CD99 (Fig. ). EB-encoded RNA in situ hybridization of the tumor was negative. The diagnosis was thymic LELC, classified as p-T1aN0M0 stage I in the TNM classification and stage II according to the Masaoka staging system.
Five months after the operation, follow-up CT findings showed enlargement of lymph nodes in the right supraclavicular fossa, right axillary region, and right mandibular, as well as mediastinal lymph nodes. FDG-PET/CT revealed uptake (SUVmax 6.6) between the chest muscles and axillary lymph node, and needle biopsy results led to a diagnosis of lymph node metastasis from thymic LELC. Chemotherapy was planned for treating metastasis. However, the patient died from another disease at 8 months after the operation.


A 27-year-old male patient visited the emergency department with left periorbital swelling due to a traffic accident. He complained of mild discomfort when he gazed bilaterally but no diplopia. In CT scan images, a 1.45 cm2-sized fracture and bone defect were observed in the medial wall of the left orbit (). At six days after injury, he underwent operation with resorbable meshed plate and allogenic cancellous bone. After 12 months of follow-up, exophthalmometric measurement discrepancy between the affected and unaffected eyes was reduced from 2 to 0.5 mm. The CT images showed weak signal intensity of bone formation. The highest width discrepancy was 1.1 mm, and volume discrepancy was calculated as 1.8 cm3. He presented no enophthalmos or other complications during the follow-up period.


A 29-year-old male presented with diplopia upon his arrival at the emergency department. The fracture had occurred by fist injury and he was operated on two days after the assault with combined implant. Initial fracture area size was measured as 1.81 cm2. The 15-month follow-up CT showed a well-reduced state with the highest width discrepancy being 1.06 mm and volume discrepancy being 0.8 cm3(). He complained of no problems during the follow-up period except temporary diplopia, which resolved spontaneously within two weeks after surgery.


The patient was a 72-year-old man with a history of coronary artery disease treated with four-vessel CABG in 1996. In September 2014, he presented to an outside emergency department with acute onset of substernal chest pain. New-onset atrial fibrillation was diagnosed. His troponin and chest X-ray were normal. Electro-cardioversion performed in the emergency department restored normal sinus rhythm. Coronary angiography revealed severe and moderate stenosis of four native arteries and an ectatic and unusual-appearing saphenous graft to the posterior descending artery. The differential diagnosis included aneurysm, pseudoaneurysm, and arteriovenous malformation. Computed tomography (CT) angiogram demonstrated the saphenous graft extending from the aorta to the right coronary artery with a 5 x 6 x 6 cm pseudoaneurysm near the coronary anastomosis with a large associated thrombus and extrinsic compression of the right atrium (Figure ).
Repeat sternotomy, two-vessel CABG, and clot evacuation were performed. Intraoperatively, the pseudoaneurysm measured 10 cm and was adjacent to the right atrium with substantial pericardial adhesions (Figure ). The clot was evacuated (Figures -). The pseudoaneurysm remained in situ and a new saphenous graft was laid in the splayed pseudoaneurysm bed. The patient tolerated the operation well and his postop course was unremarkable. Pathology found irregular clusters of malignant cells lining the surface of the thrombus, which were immunostain-positive for AE1/3, CD-31, and CD-34, consistent with an epithelioid angiosarcoma. An outside academic pathology department with expertise in sarcoma reviewed the case and confirmed the diagnosis. There was no evidence of regional or distant metastases on PET-CT. The resection bed demonstrated residual soft tissue and complex fluid density in the area of the repaired pseudoaneurysm with moderate fluorodeoxyglucose (FDG) avidity, which were attributed to post-surgical changes and wound healing. No gross residual disease was present. The patient was referred to our institution for specialized oncology care. The pathology was reviewed by a sarcoma-specialized pathologist at our hospital with concordant findings.
The multidisciplinary tumor board recommended adjuvant radiotherapy without chemotherapy. Four-dimensional CT was used for treatment planning to account for organ motion, and a plan was designed to deliver 60 Gy in 30 fractions using seven-field static beam intensity-modulated radiotherapy (Figures -). This radiation dose was selected given the extent of heart tissue (right atrium and ventricle) that was incorporated in the radiation target volumes. The clinical target volume (CTV) was derived from a discussion with the cardiac surgeon and a review of the operative report, photos of the surgical specimen, post-operative PET-CT, and post-operative CT-cardiac angiogram. The CT angiogram was fused to the treatment planning CT to identify the pathway of the involved bypass graft (starting at the insertion to the ascending aorta), and a 1.5 cm radial margin expansion was added, not extending into the lung, bowel, liver, or uninvolved chambers of the heart. The entire operative bed, including the involved retrosternal fat and pericardium, was included in the CTV. The final CTV abutted the lateral walls of the right ventricle and right atrium. The planning target volume (PTV) consisted of a 5 mm universal expansion of the CTV. The dose-volume objectives for targets and organs at risk were met (Figure and Table ). The patient tolerated therapy well and continued his cardiac rehabilitation program throughout radiotherapy. Post-treatment surveillance consisted of a CT chest every three months.
In April 2016, he presented with hemoptysis and a CT chest revealed a new 4.5 cm left hilar mass, several suspicious mediastinal lymph nodes, and multiple enlarged bilateral pulmonary nodules. The primary site was stable. Bronchoscopy demonstrated an obstructive mass in the lingular bronchus; biopsy was positive for angiosarcoma. He tolerated a palliative radiotherapy course directed at the new mass of 40 Gy in 10 fractions well. His hemoptysis resolved by treatment completion. However, cancer rapidly progressed, and he presented several weeks later with recurrent hemoptysis attributed to two, new, large, right peripheral lung masses, which were treated with a single fraction of 8 Gy. He desired to attempt systemic therapy, and paclitaxel was recommended. He received only one infusion in June 2016 before he was admitted 1.5 weeks later for hemoptysis and an ST-elevated myocardial infarction. His hospital course was complicated by sepsis. Ultimately, he selected comfort-focused care and died at home surrounded by family several weeks later, at 21 months from his initial resection.


A 64-year-old man with a medical history significant for hypertension and tobacco abuse presented to the internal medicine clinic, complaining of fatigue and abdominal pain of six-month duration. He denied any hematemesis, melena, or hematochezia. The physical exam was unremarkable. Laboratory findings were significant for microcytic hypochromic anemia with hemoglobin level 8 g/dl, mean cell volume 70.6 fl, and mean cell hemoglobin 21.1 pg. Serum vitamin B12 and folate were normal. The iron profile panel showed a low iron level, low iron saturation, and low ferritin, with an increased total iron-binding capacity. The celiac panel was negative. He was referred for an esophagogastroduodenoscopy (EGD) and a colonoscopy. The colonoscopy revealed normal findings. EGD showed normal mucosa. The biopsies from the stomach were negative for Helicobacter pylori (H. pylori). Duodenal biopsy showed normal mucosa and trophozoite forms (tear-drop-shaped) morphologically consistent with Giardia duodenalis (Figures -). CD117 and Giemsa stains also showed positivity for Giardia duodenalis (Figure ). The patient was treated with a one-week course of 400 mg metronidazole three times a day. He was also given a prescription for 325 mg ferrous sulfate once daily. At the four-month follow-up, the patient reported a marked improvement in his symptoms. Repeat complete blood count showed hemoglobin of 14 g/dl.


A 47-year-old woman with a past medical history significant for alcohol use disorder, gastroesophageal reflux disease, and severe malnutrition presented to our institution with hematemesis following multiple episodes of induced vomiting. When asked, her rationale was to detoxify her body from recent heavy drinking. At presentation, the patient was hypotensive and required multiple normal saline boluses. She was also started on intravenous omeprazole and admitted to the intensive care unit. A complete blood count showed a drop in her hemoglobin level from a baseline of 9 mg/dl (normal range, 12 to 15.5 mg/dl) to 4.6 mg/dl; hence, she was transfused two units of packed red blood cells. After clinical stabilization, urgent esophagogastroduodenoscopy (EGD) was performed and showed diffuse esophageal ulcerations, erosions, and necrosis; these findings are consistent with acute esophageal necrosis (Figure ) and active diffuse gastric bleeding. The patient’s hemoglobin continued to drop and fell below 4 mg/dl, necessitating a massive blood transfusion. Shortly after, she was intubated for airway protection and started on vasopressors for her refractory hemorrhage. Four days later, the patient’s blood pressure normalized, with no further drop in her hemoglobin, and she was successfully extubated. She was discharged to her home on an oral proton pump inhibitor and sucralfate. Follow-up EGD performed two weeks after discharge (Figure ) revealed a significant interval improvement in the previously noted mucosal changes.


A 62-year-old man was treated with pembrolizumab for right lung adenocarcinoma, which showed high PD-L1 expression (80%), with multiple intestinal, lymph node, and bone metastases. The TNM classification for NSCLC was cT2N3M1c (OSS, LYM, PER, OTH), stage IVB (eighth edition). Tumor reduction was observed, but pembrolizumab was stopped after three courses owing to drug-induced pneumonitis. Dexamethasone was used for the treatment of pneumonitis. One month after drug withdrawal, the patient was transported to the emergency department of our hospital with the complaint of severe stomachache. On physical examination, he had a rigid abdomen and generalized tenderness. His blood pressure was in the normal range (110/82 mmHg), the heart rate was elevated but regular at 100 beats per minute, and the body temperature was elevated at 38.9 °C. The peripheral capillary oxygen saturation was 98% at room air. Laboratory evaluation showed a high inflammatory response with a white blood cell count of 18,200/mm3 and C-reactive protein level of 20.8 mg/dL. CT examination showed abdominal free air and ascites with perforation of the existing lung adenocarcinoma metastasis (Fig. ). We diagnosed bowel perforation with acute diffuse peritonitis. Emergency laparotomy was performed, and multiple small intestinal metastasis with mesenteric lymph node metastasis and ascites containing intestinal fluid were observed. The perforation site was located in the metastatic jejunum about 40 cm on the anal side from Treitz’s ligament. We resected this part about 20 cm and anastomosed with functional end-to-end anastomosis. There was no complication after surgery, and he was discharged on post-operative day 15. Pathological examination indicated lung adenocarcinoma metastasis in the perforated intestine, and the metastasis was partly scarred owing to the effect of pembrolizumab (Fig. ). Tumor cells in the perforation site had a high degree of degeneration and necrosis, and the pathological response for the efficacy of pembrolizumab was grade 1b (Japanese Classification of the Colorectal Carcinoma, seventh edition) (Fig. ). In the perforated part, the tumor cells were observed in all layers, but in the vicinity on the serosa side. Inflammatory change due to enteritis was not found in this site. Pembrolizumab was re-administrated about 1 month after discharge. To prevent drug-induced pneumonitis, dexamethasone was used daily.


A 70-year-old African-American woman presented to the clinic complaining of pruritic reddish discoloration of her neck, chest, and both forearms after being exposed to the sun. Her medical history was significant for hypertension, AF, prior hospitalization for cerebrovascular accident (CVA) with no residual weakness, and with no known history of allergies. One month prior to presentation, she was admitted for CVA with left-sided hemiplegia. During her hospitalization, she was diagnosed with new-onset AF with a rapid ventricular response and was started on dronedarone for rhythm control along with Eliquis. She was later discharged home on aspirin, dronedarone, Eliquis, Lipitor, and losartan/hydrochlorothiazide (HCTZ). She mentioned that she had been exercising, walking for about three miles daily while being exposed to the sun. She stated that she otherwise felt well and had no additional complaints. Review of systems, likewise, was unremarkable.
The physical examination revealed a cheerful elderly woman in no apparent distress. She was alert, awake, and orientated to time place and person. There appeared an in-confluent, well-demarcated, erythematous maculopapular rash over the neck, bilateral forearms, and anterior chest (Figure ). The cardiovascular and respiratory examination was also normal. Routine laboratory investigations included complete blood count (CBC) and a comprehensive metabolic panel (CMP). Given the relation of the symptoms with dronedarone, it was discontinued. For the treatment of AF, she was started on metoprolol, and Eliquis was continued. She was advised to follow up in two weeks. Upon her follow-up, her CBC and CMP tests from two weeks back were normal, and her rash had entirely resolved.


A 40-year-old female presented to the ED complaining of facial swelling, bleeding, and odynophagia after undergoing dental fillings earlier the same day. Earlier that day, the patient reported that she had dental fillings completed on the upper left and lower right molar teeth. On evaluation, she was afebrile and hemodynamically normal, and on physical examination, she was hemodynamically stable without evidence of respiratory compromise. The patient did have right-sided facial swelling and crepitus extending down the neck without skin discoloration. Her lung fields were clear to auscultation, and she did not have any adenopathy. Initial laboratory evaluation was significant for a leukocytosis of 12,500/mcL. Computed tomography (CT) of the facial soft tissues and chest demonstrated extensive subcutaneous emphysema and pneumomediastinum extending from the lower neck and surrounding the trachea and upper lobe bronchi (Figures -). The patient was transferred to the ICU for close observation, where she was started on broad-spectrum intravenous antibiotics and intravenous fluids. Thin barium esophagogram was performed, without evidence for perforation. After 24 hours, the patient’s facial swelling improved, and she was discharged home. Her follow-up was unremarkable.


We present the case of a 57-year-old male with past medical history significant for coronary artery disease, hypertension and granuloma annulare (GA) who was admitted with rapid decline in renal function and shortness of breath. GA was being treated with adalimumab for the last two years. Eight months prior to admission, he was noted to have an asymptomatic elevation in his blood urea nitrogen and creatinine (Table ) which worsened five months later. Renal ultrasound was performed which showed bilateral echogenic kidneys. He was lost to follow up and represented to his primary care provider three months later with a one-week history of epistaxis, hemoptysis, anorexia and weight loss. He was asked to report to the emergency room.
CT chest showed bilateral pulmonary consolidation and ground glass opacities (Figures , ). Renal biopsy performed revealed pauci-immune, rapidly progressive glomerulonephritis with some fibrosis (Figure ). ANCA with perinuclear staining and myeloperoxidase antibody were positive. He was started on hemodialysis immediately. He also received intravenous methylprednisolone 500 mg daily for three days followed by oral prednisone 60 mg daily, oral cyclophosphamide 125 mg daily (which was eventually transitioned to intravenous monthly pulses of cyclophosphamide) and trimethoprim-sulfamethoxazole for pneumocystis prophylaxis. Adalimumab was discontinued.
Two months after his hospitalization, pulmonary infiltrates have resolved, but there has been no recovery of renal function.


A 42-year-old male with type two diabetes mellitus presented to our hospital with severe back pain, hemoptysis, mild pain in multiple joints, and low-grade fever for three months. He was seen by a rheumatologist and noted to have restricted left shoulder movement, right wrist swelling, and bilateral metacarpal squeeze test positive suggestive of inflammation. He also had microcytic hypochromic anemia (hemoglobin: 9.3 g/dL) with anisocytosis and rouleaux formation, erythrocyte sedimentation rate of 109 mm, and C-reactive protein of 44.4 mg/dL. He was found to have very high rheumatoid factor (RF) titer (505.3 IU/mL) which had increased from an RF of 339.2 IU/mL two weeks back and was clinically diagnosed with rheumatoid arthritis. However, anti-cyclic citrullinated peptide (anti-ccp) and antinuclear antibody were negative. He was being treated with prednisone, methotrexate, and hydroxychloroquine. On admission, he was screened for vasculitis including proteinase 3 anti-neutrophilic cytoplasmic antibody and myeloperoxidase anti-neutrophil cytoplasmic antibody (PR3-ANCA and MPO-ANCA), serum protein electrophoresis, and complement (C3 and C4) levels. Lumbar spinal X-ray with sacroiliac joints was done to rule out ankylosing spondylitis. Workup was insignificant except for mild hypergammaglobulinemia (2.38 g/dL) without monoclonal bands. Anti-streptolysin O, malarial parasite, and widal test were negative. MRI of the spine showed disc herniation at L4-L5 and L5-S1 levels with degenerative changes. A transthoracic echocardiography (TTE) was performed to investigate for IE and it showed vegetations on the ventricular side of the noncusp leaflets of the aortic valve associated with moderate aortic regurgitation. Prednisone, methotrexate, and hydroxychloroquine were subsequently discontinued. Later blood cultures were positive for Streptococcus gordonii (part of the group S. viridans), classified as a typical microbe in IE. Transesophageal echocardiography (TEE) confirmed vegetations on the aortic valve and also detected anterior mitral valve leaflet perforation with regurgitation (as shown in Figure ). Positron emission tomography (PET) scan showed areas of metabolic activity in L4 and L5 end plates. Antibiotic sensitivity showed sensitivity to ceftriaxone and gentamycin, which were continued after discharge for six and two weeks, respectively, with weekly blood cultures.


A 21-year-old woman presented to the ED after a septic abortion. She was managed by the gynecological team in the ED and was later shifted to the medical floor. After stabilization, she was discharged home but presented three weeks later with fever, nonproductive cough, swollen feet, orthopnea, and exertional shortness of breath. On further inquiry, she claimed that she had felt feverish for a few days following her discharge. She denied any facial swelling or shortness of breath on exposure to pollen/seasonal change/dust or smoke. She further denied any abnormality in her echocardiogram or electrocardiogram (EKG) done per routine prepregnancy or any other systemic symptoms like nausea, vomiting, diarrhea, joint pain, bowel or bladder symptoms.
Her physical examination revealed a blood pressure of 110/70 mmHg, pulse rate of 102 beats per minute, respiratory rate of 21 breaths per minute, and oxygen saturation of 97%. She appeared agitated. She had bilateral, grade two pitting edema of her ankles. On cardiovascular examination, there was a new systolic murmur over the apex. We noted no gallops or rubs. On auscultation, her chest had bilateral crackles, especially on the right side. The results of her abdominal and neurological examinations were unremarkable. Her past medical, social, sexual, or family history was not significant.
Her pertinent laboratory findings at this time revealed a WBC count of 28.2/µL; her creatinine was 1.8 mg/dL, and her hemoglobin was 10.6 g/dL. Transthoracic echocardiography (TTE) revealed vegetation at the mitral valve leaflets (see Figure ).
The TTE also revealed a flail mitral valve with regurgitation. Her electrocardiogram appeared normal. Her chest X-ray (CXR) revealed signs of pulmonary edema (see Figure ).
Both aerobic and anerobic blood cultures were sent to the hospital laboratory for evaluation. The patient was given paracetamol to take as needed, and IV furosemide 40 mg (twice daily). She was shifted to the cardiology floor for further management and observation. The blood cultures revealed E. coli as a possible cause, and sensitivity showed them to be susceptible to ciprofloxacin and amikacin. The patient was started on oral ciprofloxacin 500 mg twice daily and amikacin in an adjusted renal dose. In addition, she was given iron supplements to help with her anemia. During her stay, she had an episode of right-sided weakness lasting 39 minutes and was started on anticoagulation therapy.
Owing to persistently elevated WBCs, fever, and lack of improvement in her condition, she was chosen for, consulted on, and consented to valve replacement; the replacement procedure was performed on day 12 of her second stay. A 27-mm St. Jude Medical Biocor™ prosthesis (St. Jude Medical, Inc., St Paul, MN, USA) was used. Postprocedural TTE revealed that mitral regurgitation had resolved. Her symptoms began improving, and ultimately, diuresis and antipyretics were stopped.
Our patient was diagnosed using the modified Duke criteria for endocarditis. Our diagnosis was further strengthened by the positive intra-operative findings. The patient had no valvular defect or co-morbidity that may have led to this outcome, and the only causative factor was the septic abortion.
The causes of persistent fever despite appropriate management of the suggested culprit are extensive. Our patient had persistent fever and septicemia despite appropriate management of the apparent gynecological and medical cause. The patient had no indwelling catheters or indication of an infection with a super-bug. Furthermore, the patient had a healthy mitral valve and even more interestingly, no comorbidity.
She was subsequently discharged in a stable condition and advised to report for an outpatient follow-up evaluation. Ciprofloxacin was continued for six weeks and amikacin for four weeks. Two consecutive subsequent blood cultures were sterile. She denied any new active concerns and reported good compliance with medical advice and resolution of the previous symptoms.


A 42-year-old female presented with easy bruising and petechiae to her primary care physician and was thus transferred to hematology (Figure ). Her medical history included chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease (GERD), human papillomavirus (HPV), mitral valve prolapse (MVP), acute pyelonephritis, anxiety, asthma, essential hypertension, hyperlipidemia, hyperthyroidism, migraines, nephrolithiasis, and obstructive sleep apnea (OSA). The patient has been smoking a half pack of cigarettes daily for the past 10 years. During her office visit, her humoral survey revealed that she had specific antibodies reflecting non-protective titers against the pathogenic bacterium, Haemophilus, and diphtheria-tetanus. The reasons for the said visit included medication follow-up, vitamin level check, urinary urgency, and urinary frequency. These visit overviews reflect the attention given to the patient's symptoms and survey results.
The patient had multiple vitamin deficiencies, vitamin C being the most notable of them; her vitamin C count as of December 2018 was 22 umol/L, below what is deemed a healthy amount. However, the patient’s physical examination revealed perifollicular hemorrhage, petechiae, and bruising on various parts of the body (Figure ).


A 17-year-old male presented with a 2-month history of headaches. The patient had no known systemic disease or history of trauma, drug use, or smoking. His family history was unremarkable, with no consanguinity. On ophthalmologic examination, his uncorrected visual acuity was 10/10 (0.0 LogMAR) in both eyes. His pupils were isochoric and light reflexes were normal in both eyes; no afferent pupillary defect was observed. Color vision test using Ishihara cards was normal in both eyes. Slit-lamp anterior segment examination was also normal. Intraocular pressure was 14 mmHg in the right eye and 16 mmHg in the left eye. Fundus examination revealed bilateral optic disc swelling and blurred disc margins ().
Visual field was evaluated using the Swedish Interactive Thresholding Algorithm (SITA) standard 24-2 threshold test on a Humphrey Field Analyzer III 750 (Zeiss Humphrey Systems) automated perimetry device. Scotoma was not detected in the right eye, while a significant visual field defect was evident in the inferonasal quadrant in the left eye (). B-mode USG (AVISO, Quantel Medical, Clermont-Ferrand, France) revealed a hyperechogenic appearance consistent with bilateral ODD on the papilla (). FAF (Heidelberg Retinal Angiography 2, Heidelberg, Germany) imaging revealed oval hyperautofluorescent areas on the optic disc that were more prominent in the left eye (). On spectral domain OCT (Cirrus, Carl Zeiss Meditec Inc., Dublin, CA, USA), the mean retinal nerve fiber layer (RNFL) thickness was 69 µm in the right eye and 57 µm in the left eye despite the bilateral optic disc head swelling (). OCTA (RTVue XR ‘Avanti’, Optovue, Fremont, California, USA) of the optic disc revealed areas of capillary dropout in the retinal peripapillary layer that were more prominent in the nasal quadrant and reduced vascular density in both eyes (). Macular OCTA revealed a decrease in vascular density suggesting ischemia in the superficial and deep capillary plexus layers bilaterally (, ).


A 60-year-old man presented to our emergency department with acute chest pain that had persisted for the preceding 2 hours. On admission, his body temperature was 36.5 °C; pulse 70 beats/min (bpm); respiratory rate 20 breaths/min; and blood pressure 112/65 mmHg. There was history of hypertension and diabetes in the past 3 years. No obvious positive signs were found on physical examination. ECG showed sinus rhythm with a 2-mm ST-segment elevation in the inferior limb leads. He was diagnosed with AMI and transferred to the cardiac catheterization laboratory for primary percutaneous coronary intervention (PCI).
The initial attempt to selectively engage the left coronary artery and right coronary artery (RCA) was unsuccessful. Contrast injection through the pigtail catheter showed that the aortic cavity was divided into two chambers by a false pipe. This suggested that the coronary ostium originated from the false lumen of a Type-A AD. Subsequent CTA confirmed final diagnosis of Type-A AD from the aortic root to the abdominal aorta.
The patient underwent emergency aortic root replacement and elective RCA–ascending aorta coronary artery bypass graft surgery. During cardiac surgery, AD from the aortic root to the ascending aorta and dissection violations of the RCA ostium were confirmed.
The patient was discharged after 2 weeks. At a 1-year follow-up examination, computed tomography angiography (CTA) indicated that the patient had made a full recovery (Fig. ).


A 55-year-old woman was admitted to our emergency department with abdominal and back pain that had persisted for the preceding 7 hours. On admission, her body temperature was 36.0 °C; pulse 98 bpm; respiratory rate 23 breaths/min; and blood pressure 117/65 mmHg. No obvious positive signs were found on physical examination. Regarding her medical history, she had suffered from chronic hypertension for more than 10 years. ECG showed sinus rhythm with ST-segment elevation in the inferior limb leads. She was diagnosed with AMI and transferred to the cardiac catheterization laboratory for primary PCI.
The initial attempt to selectively engage the coronary ostium was unsuccessful. Contrast injection through the pigtail catheter showed that the aortic cavity was divided into two chambers by a false pipe. Subsequent CTA confirmed Type-A AD from the aortic root to the abdominal aorta and dissection violations of the coronary ostium (Fig. ).
The patient underwent emergency replacement of the ascending aorta, but died 6 days later.


A 64-year-old woman presented to the emergency department with chest pain after a car accident. She was the restrained driver, wearing a seatbelt, with impact on the driver's side and there was airbag deployment. She met trauma alert criteria and was brought in on a backboard and cervical collar.
The patient did not have any loss of consciousness. She only complained of left lower back pain and chest pain. Her vital signs were: pulse 113 beats per minute, blood pressure 173/76 mm Hg, respiratory rate 16 breaths per minute, oxygen saturation 98% on room air, and temperature 97.90F. On physical examination, the patient was alert and oriented with a Glasgow Coma Scale (GCS) of 15. Examination of the thorax revealed ecchymosis in a seatbelt distribution. Her medical history included coronary artery disease with a myocardial infarction seven years prior (unknown which artery), diabetes mellitus, hypertension, and hyperlipidemia.
Due to her complaint of chest pain, an electrocardiogram (ECG) and computed tomography angiography (CTA) of the chest and abdomen were done. The ECG (Figure ) showed normal sinus rhythm, a right axis deviation, Q waves in the inferior leads without ST segment abnormalities. The chest CTA showed an incidental finding of a left ventricular aneurysm with a large amount of mural thrombus located within the aneurysm. Coronal CTA of the abdomen showed a large opacity seen connected with the left ventricle extending down near the left hemidiaphragm (Figure ). On the axial view, a large mass is seen adhering to the anterior left ventricular wall suggestive of a large mural thrombus within the left ventricular aneurysm (Figure ). Echocardiography confirmed aneurysmal dilatation of the left ventricle (Figure ) with a reduced ejection fraction (15-20%) with regional wall abnormalities and chest radiograph (CXR) revealing an abnormal heart contour suggestive of aneurysmal dilatation (Figure ).
Cardiothoracic surgery was consulted during hospitalization. No surgical interventions were considered necessary at the time as it appeared chronic, so she was instructed to follow up as an outpatient and to continue her current medications which include a Beta blocker, angiotensin-converting enzyme (ACE) inhibitor, and aspirin.


A-45-year old lady presented with melena for 20 days, she had two attacks of massive hematemesis before admission. The patient had no history of any medication intake before this presentation. The patient had history of renal cell carcinoma which was operated by right nephrectomy before 10 years.
At admission the pulse rate was 120 beats/minutes and the blood pressure was 95/60 mm Hg. Resuscitation was done in the form of 2 peripheral intravenous lines and 2 liter of Ringer’s lactate solution, the patient received 9 units of fresh whole blood and 15 units of fresh frozen plasma.
Upper GIT endoscopy was done, biopsy was not taken because of the risk of bleeding, .
Decision for surgery was done, during laparotomy and duodenotomy, there was a soft irregular 3*5 cm mass with areas of hemorrhage arising from the wall of the duodenum, complete excision was done and sent for frozen section examination which showed a benign lesion, .
The duodenum was closed transversely and the patient was discharged in the 5th postoperative day with no complications.
The histopathology report after the first surgery revealed a benign inflammatory lesion or a possibility of polyp.
Two months later she presented with melena and anemia. She received 6 units of blood.
Upper gastro-intestinal tract (GIT) endoscopy was done which showed recurrence of the mass, the patient was sent for CT-scan of the abdomen which showed a 7*4 cm mass with extension to the head of the pancreas, .
Decision for pancreaticoduodenectomy was done. During surgery a firm mass was found in the region of the head of pancreas found, pancreaticoduodenectomy was done and the sample was sent for histopathological examination which revealed a vascular mass lined by endothelial cells with intervening epithelioid spindle cells, there was no evidence of nuclear atypia, the tissue stained positively for CD 34, FL1, and pancreatin and stained negatively for CD117, S100, desmin and chromogranin A. These features were consistent of epithelioid hemangioendothelioma of the head of the pancreas, all the resection margins were free from the tumor, .
The patient was discharged 7 days after surgery with no complications. Follow up was done for 2 years after the surgery with no recurrence of the tumor.


In May 2017, a 34-year-old female presented with a nodule in the right thyroid lobe. The nodule was diagnosed as malignant upon cytological examination performed in another centre and classified Tir-5, according to the Italian Thyroid Classification (Category 6-Malignant according to the Bethesda system for reporting thyroid cytopathology) [, ].
The patient was affected by longstanding autoimmune thyroiditis treated with oral levothyroxine 100 μg/day.
The ultrasound (US) examination of the thyroid, performed in our institution, showed parenchymal disarray with a hypo-echoic nodule in the upper third of the right lobe, with a long-axis diameter of 1.3 cm, without peripheral halo nor increased vascular pattern in its inner area ().
Since the clinical staging was cT1b cN0 (TNM 7th ed) [], the patient underwent complete thyroidectomy (justified by her chronic autoimmune thyroiditis already in hormone-replacement therapy) and central neck lymph node dissection; all the four areas were resected (ABCD) following the institutional guidelines [].
Surgical specimens were fixed in buffered formalin for 24 hours, and at gross examination, we identified an ill-defined hard fibrous area, with a haemorrhagic focus, in the upper third of the right lobe.
Consequently, selected specimens of thyroid parenchyma were paraffin-embedded, cut in 5-μm slides and stained with standard Haematoxylin and Eosin stain (see ).
The fibrous ill-defined area corresponded to the carcinoma, with two different histological patterns: one constituted by a dense fibrous area with slender neoplastic cells, with PTC cytological features and foci of squamous metaplasia, intermingled with lymphoid cells; the second composed by broad papillary fronds encircled by columnar-cuboidal cells with a dense lymphoid infiltrate, with scattered germinal centres. Also, neoplastic cells in this area showed the cytological features of PTC. While the last area resembled a WTL-PTC (Warthin Like-Papillary Thyroid Carcinoma) (), the first component was similar to the diffuse sclerosing variant of PTC (). All identified lymph nodes were negative for metastatic tumour.
Given the different prognostic meaning of the Warthin-like and the diffuse sclerosing variants, we performed an immunohistochemical evaluation of cytokeratin 19, Galectin-3 and p40 expression according to manufacturer’s instructions (all markers were purchased from Dako, Dakopatts, Denmark).
We detected an intense immunoreactivity for cytokeratin 19 and Galectin-3 () in every neoplastic cell and a focal positivity for p40 in few neoplastic cells in sclerosing areas (). Moreover, we investigated BRAF and RET mutational status of the neoplastic population by next-generation sequencing (NGS) technology, applying the Oncomine Focus Assay (Thermo Fisher, Waltham, MA) according to the manufacturer’s instructions.
The most representative areas of both neoplastic components (about 1:1 ratio) were selected and were manually macrodissected before nucleic acid isolation (tumoural cell content after enrichment equal to 20%). Genomic DNA and RNA were extracted using the Qiagen AllPrep FFPE (Formalin Fixed and Paraffin Embedded) DNA/RNA Kit (Qiagen, Valencia, CA) and then quantified with the Qubit high-sensitivity DNA/RNA assay (Life Technologies, Carlsbad, CA). Libraries were constructed starting from 10 ng of DNA/RNA and templates were prepared using the Ion Chef Machine (Thermo Fisher, Waltham, MA). Sequencing of templates was performed on an Ion Torrent S5 Sequencer (Thermo Fisher, Waltham, MA) and the data were analysed using the Ion Reporter variant caller software v.5.6. The NGS analysis revealed a point mutation in exon 15 of BRAF (p.Val600Glu, p.V600E) with an allele frequency of 5% (coverage 1,995 reads) and a point mutation in exon 11 of RET (p.Ile638Val, p.I638V) (coverage 2,000 reads) with an allele frequency of 47%, never described before to the best of our knowledge. We additionally tested the corresponding normal thyroid tissue and found the same RET variant, (Variant allele frequency = 48%), confirming the germinal origin of the variant. Both variants were confirmed by real-time PCR and Sanger sequencing, respectively, according to Mu et al []. No RET-fusion genes were identified by NGS (). The patient was discharged after 4 days without any complications, in treatment with hormone replacement suppressive therapy (0.1 < TSH (Thyroid-Stimulating Hormone) > 0.5); she was free of disease at last follow-up.


A 48-year-old asymptomatic man was diagnosed with a type B aortic dissection, moderate aortic regurgitation, and a good biventricular function in March 2012. A contrast-enhanced computed tomography examination confirmed that the dissection originated distally to the left subclavian artery and traversed into the right common iliac artery. The left kidney was supplied by 2 renal arteries, one of which originated from the false lumen. The patient was managed conservatively with yearly serial echocardiography and computed tomography scan. In April 2016, another contrast-enhanced computed tomography examination revealed an aneurysmal dilatation in the descending thoracic aorta with a thrombosis in the proximal part of the false lumen, warranting surgical repair ().
Through a posterolateral thoracotomy in the left fourth intercostal space, cardiopulmonary bypass was instituted following the cannulation of the ascending aorta and the pulmonary artery. A left ventricular apical vent was placed, and the patient was core cooled to 18 °C. The ascending aorta was cross-clamped, and the aortic root cardioplegia was administered. The transverse aortic arch was clamped between the left common carotid artery (LCCA) and the left subclavian artery. The lower thoracic aorta was clamped distally to the aneurysm, and the lower body perfusion was begun with an additional left femoral artery cannulation. The aneurysm sac was opened. The clots and thrombus were evacuated from the false lumen. The true lumen was entered, and the intercostal arteries above the level of T6 were suture closed. The dissection flap was excised, and the aneurysm was replaced with a 30-mm interposition Dacron inlay graft (gelatin-sealed Uni-Graft® graft [B. Braun, Melsungen, Germany]) using a proximal first technique with a “reversed elephant trunk” left within ().
Distal anastomosis was performed after fenestrating the septum widely, with it including the intercostals below T6 level. The patient’s postoperative period was uneventful, and transthoracic echocardiography at the time of discharge was satisfactory.
Three months later, the patient presented with acute onset breathlessness of 2 weeks’ duration. Transthoracic echocardiography revealed an acute Stanford type A aortic dissection (TADA) with severe aortic regurgitation and left ventricular dysfunction. He underwent a Bentall procedure with arch replacement using a 28-mm Dacron conduit incorporated with a 25-mm St. Jude aortic bileaflet mechanical prosthesis. Through a median sternotomy, cardiopulmonary bypass was instituted using the right axillary artery and the right atrial cannulation. The arch of the aorta, the innominate artery, and the LCCA were looped. The ascending aorta was cross-clamped, and the left ventricle was vented through the right superior pulmonary vein. The patient was core cooled to 18 °C. An aortotomy was done, and Custodiol® HTK cardioplegia (Sandor, India) was given through the coronary ostia intermittently. The innominate artery and the LCCA were snugged, and selective unilateral antegrade cerebral perfusion was initiated. Bilateral cerebral perfusion was initiated by inserting a 16-F cannula into the LCCA. The intraoperative findings included a TADA involving the right coronary artery and extending into the undersurface of the arch with a severely non-coapting trileaflet aortic valve. The patient underwent a Bentall procedure with arch replacement using the composite conduit. The innominate artery and the LCCA were harvested as an island, and the arch was replaced using a 28-mm Dacron conduit. Distal anastomosis was done onto the previous graft in the descending thoracic aorta after the folded reversed elephant trunk was pulled out, incorporating the left subclavian artery onto the anastomosis. The innominate artery and the LCCA were reimplanted. Next deairing was done, the graft was clamped proximally, and the whole body circulation was re-established. The aortic root was replaced as in the standard Bentall procedure during rewarming. The root/arch replacement was completed by anastomosing the proximal and distal Dacron conduits (). The patient was weaned off bypass uneventfully. A computed tomography scan at the time of discharge was satisfactory ().
At 2 years’ follow-up, the patient was asymptomatic with a normal left ventricular function.


A 35-year-old man was injured, when a rotten bamboo branch penetrated his left orbit while working in a mountainous area, and was immediately treated at a local hospital. The local hospital medical records showed a 2-cm irregular wound in the left upper margin of his eyelid, proptosis, ophthalmoplegia, impaired visual acuity, a dilated pupil, and absence of pupillary light reflex in his left eye. Computed tomography (CT) showed both orbit and brain lesions (Fig. a). The patient was immediately treated with antibiotics and steroids. Furthermore, due to the development of disease in his left eye, the patient underwent three operations, namely the removal of an intraorbital foreign body, debridement, and transnasal endoscopic orbital decompression, over the course of 2 weeks at the local hospital.
The patient was transferred to our hospital without obvious improvement with the abovementioned treatments. CT showed proptosis, increased density in the orbit, and a discontinuous medial wall of the orbital bone in the left eye (Fig. b). Magnetic resonance imaging (MRI) showed hyperintensity in the superonasal region of the left eye (Fig. c). An ocular examination revealed the absence of light perception, orbital swelling, ptosis, proptosis, ophthalmoplegia, absence of pupillary light reflex, and purulent discharge from the inferonasal conjunctival sinus (Fig. a). Fundoscopic examination revealed retinal edema and macular cherry-red spot (Fig. b). No obvious abnormalities were found on a general examination, there was no increase in the C-reactive protein (0.8 mg/L, normal range 0–10 mg/L), other than abnormal laboratory exams including leukocytosis (22.62 × 109/L, normal range 3.5–9.5 × 109/L) and increased neutrophils (18.81 × 109/L, normal range 1.8–6.3 × 109/L).
Pus from the conjunctival sinus was taken for culturing. Antibiotics such as ceftazidime (2 g every 12 h) and metronidazole (0.5 g every 12 h) were administered immediately. Five days after admission, the patient underwent endoscope-assisted orbitotomy. We made an incision on the sinus and exposed the deep orbital tissue through the sinus tract. To avoid the limitation of a small operating visual field, orbital abscesses and a few orbital foreign bodies were removed using an endoscope. Purulent fluid was obtained for repeated culture. Multiple incisional biopsies were performed and sent for histopathological examination. On the first postoperative day, N. farcinica was cultured from the pus of conjunctival sinus (Fig. a-b). Histological examination of orbital tissues showed chronic pyogenic inflammation on the second postoperative day (Fig. c). The patient developed high fever and complained of headache. Laboratory examinations revealed moderate leukocytosis (16.93 × 109/L, normal range 3.5–9.5 × 109/L), increased neutrophils (14.3 × 109/L, normal range 1.8–6.3 × 109/L), and elevated C-reactive protein (30.77 mg/L, normal range 0–10 mg/L).
After 1 week of ceftazidime and metronidazole therapy and orbital surgical treatment, the patient was transferred to the infection department and immediately treated with oral trimethoprim-sulfamethoxazole (4 g every 12 h) and intravenous mannitol (25 g every 12 h). MRI of the head, chest, and abdomen showed no abnormalities. A lumbar puncture yielded clear cerebrospinal fluid with leukocytes 480/μL (normal range 0–10/μL, 45% neutrophils and 55% lymphocytes), glucose 1.98 mol/L (normal range 2.8–4.4 mol/L), chloride 118.2 mol/L (normal range 120–132 mol/L), protein 1046 mg/L (normal range 150–450 mol/L mg/L), and a positive Pandy’s test. Five days later, antibiotic therapy with 2 g ceftriaxone sodium every 12 h was initiated.
The patient responded well to the drug treatment with trimethoprime-sulfamethoxazole (4 g every 12 h) for 28 days, 20% mannitol (25 g every 12 h) for 19 days, and ceftriaxone sodium (2 g every 24 h) for 23 days, and a repeat MRI was performed 1 month postoperatively (Fig. a). However, blindness, ptosis, and ophthalmoplegia persisted (Fig. b). To prevent the recurrence of infection, the patient was advised to continue trimethoprim-sulfamethoxazole intake for 3 months. The dose in the first 2 months was 4 g every 12 h and subsequently, 3.2 g every 12 h for a month. The patient remained stable over a 14-month follow-up period.


A 69-year-old man (height 165 cm, weight 72 kg, body mass index 26 kg/m2) came to our hospital with a complaint of right medial knee pain and no apparent cause. Medical history was unremarkable, and there was no history of previous trauma, alcohol use, or intra-articular steroid use. The initial physical examination showed no effusion of the right knee, full range of motion, and normal tibiofemoral alignment (femorotibial mechanical axis angle of 177°). After about 5 months of conservative treatment, including intra-articular injection (hyaluronic acid), the knee pain had worsened. We found no ligamentous instability. McMurray’s test was positive medially, with tenderness to palpation at the medial joint line. Initial radiography was normal. Magnetic resonance imaging (MRI) showed a horizontal tear in the middle and posterior segments of the medial meniscus. Articular and osseous anatomy was unremarkable (A,B).
We conducted arthroscopic surgery of the right knee 7 months after the onset of pain. Ordinary infusion of normal saline solution was used to distend the joint. A tourniquet, inflated to 300 mmHg was used for 90 min total during the procedure. MRI findings of a horizontal tear in the middle and posterior segments of the medial meniscus were substantiated, and basket forceps and a radiofrequency assisted shaver (DYONICS ELECTROBLADE, Smith & Nephew, London, United Kingdom) were used to perform a partial medial meniscectomy (C). Radiographs from 10 months after the index surgery showed a small radiolucent area in the medial femoral condyle of the right knee (medial side of weight-bearing area) (A). Computed tomography was used to create a multiplanar reconstruction image showing a sclerotic band at the same part of the radiograph (B). T1-weighted MRI, performed immediately after the radiographic check-up, showed a low-intensity rounded band within the weight-bearing area of the medial femoral condyle and surrounded by a diffuse low-intensity area (C). T2-weighted MRI showed the same band, surrounded by an edematous lesion in the bone marrow (D). The weight-bearing area of the medial femoral condyle appeared to be slightly flattened. We judged that the posterior root of the medial meniscus had been preserved as described in the classification by Robertson et al. [] (E), and we diagnosed stage 2 SONK based on to the classification by Koshino []. Thirteen months after index surgery, the patient had unicompartmental knee arthroplasty.
During surgery, we noted slight irregularities in the cartilage surface of the medial femoral condyle but no detachment of the osteochondral lesion (A). A hook test showed no obvious instability of the drawing the medial meniscus, and no posterior root tears were noted. Pinching showed the stiffened area in the middle part of the meniscus to be much harder than other parts of the resected meniscus (B). The subchondral fracture of the medial femoral condyle was located at just over the stiffened area of the medial meniscus (C). Histopathologically, prominent callus formation was seen comprising reactive woven bone and granulation tissue on both sides of the fracture. Fracture-related bone debris was focally observed on the osteochondral side of the fracture (A,B). There was no histopathological evidence of any antecedent bone infarction, such as creeping substitution or bone marrow necrosis. The resected meniscus showed a proliferation of fibroblasts and collagen fibers corresponding to the stiffened area (C,D).


A 55-year-old female with lower back pain and bilateral lower leg numbness for months had an osteolytic bone lesion over the third lumbar vertebra (L3). In February 2017, an L3 vertebra biopsy showed metastatic adenocarcinoma, compatible with lung origin (TTF-1 positive, L858R mutation positive). Complete imaging of the right lower lobe (RLL) showed a spiculated mass about 3.4 × 2.2 cm with pleural traction. A trans-bronchoscopic lung biopsy revealed non-small cell carcinoma of lung origin (positive for TTF-1 and negative for p40). Tentative diagnosis was RLL adenocarcinoma, cT2aN0M1b, with bone metastasis at L3. Routine use of serum tumor markers for monitoring of the tumor burden revealed a higher carcinoembryonic antigen (CEA) level that was still within the normal range (4.9 < 5.0 ng/ml), and an abnormal level of CA-125 (37.1; normal range 35.0 U/ml). The EGFR-TKI afatinib was prescribed beginning April 2017. However, side effects (severe diarrhea, poor appetite, and body weight loss) required dosage reduction to 40 mg every other day. A November 2018 CT scan showed regression in the RLL lung mass, and the density of lumbar bone lesion became unapparent in the whole-body bone scan compared with scans from 2017 (Fig. ). A whole-body PET-CT showed RLL lung nodule with faint uptake and mildly increased uptake in the L3 vertebra. A series of declining serum CEA levels down to 1.1 ng/ml were noted after starting afatinib treatment with no signs of elevation prior to surgical intervention. Serum CA-125 level down to 16.8 U/ml (< 35) was also noted after starting afatinib treatment 3 months later, and there was no further follow-up due to stable of disease. For alternative treatment evaluation, the patient went to the surgical outpatient department and asked for possible surgical intervention of the primary tumor. After providing signed informed consent, the patient received uniportal video-assisted thoracoscopic RLL lobectomy and radical mediastinal lymph node dissection on December 25, 2018. The final pathology report was a fibrotic scar with no residual tumor cells, compatible with post-treatment status, ypT0N0 (Fig. ). Curative intent radiotherapy with 30 Gy/12 fraction was also applied to the L3 vertebra after the operation. The patient is still alive for more than 32 months after initially diagnosed with metastatic lung adenocarcinoma.


A man aged 61 years was diagnosed with bladder cancer, with the primary lesion invading the prostate; he underwent total cystectomy, urethral resection, and ileal conduit two months later. After five months, computed tomography and magnetic resonance imaging showed retroperitoneal dissemination and para-aortic lymph node metastasis. Although he was treated with gemcitabine and carboplatin, he relapsed three months later. He was referred to our hospital to begin treatment with the anti-human PD-1 monoclonal antibody pembrolizumab.
Pembrolizumab (200 mg) was administered every three weeks, and it was effective. Five days after the fifth pembrolizumab administration (102 days after the first administration), he had two or three bouts of diarrhea per day. His symptoms gradually worsened; he was admitted to our hospital presenting with diarrhea 10×/day, fatigue, palpitation, and body weight loss. His blood pressure was 117/72 mmHg, body temperature was 37.0°C. Electrocardiogram showed normal sinus rhythm, and heart rate was 98/min. Laboratory data showed hyperthyroidism, that is, undetectable serum thyroid-stimulating hormone (TSH) (<0.021 µIU/mL; standard range [SR] = 0.541–4.261) associated with elevated levels of both free triiodothyronine (FT3) (8.98 pg/mL; SR = 2.39–4.06) and free thyroxine (FT4) (3.45 ng/dL; SR = 0.71–1.52), with no goiter, no cervical pain, and no thyroidal ophthalmopathy on examination (). He was a smoker and had neither a personal nor a family history of thyroid disease. It was necessary to differentiate whether the diarrhea was caused by hyperthyroidism or by another factor. To suppress the excessive secretion of thyroid hormone, we prescribed potassium iodide (100 mg/day). Thyroid-stimulating hormone receptor antibody (TRAb) was positive (4.0 IU/L; SR = <2.0). Thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) were both negative (26 IU/mL; SR = ≤28, <9 IU/mL; SR = ≤15.9, respectively). The thyroglobulin (Tg) level was elevated (276 ng/mL; SR = 0–33.7). Thyroid-stimulating antibody (TSAb) was positive later (211%; SR = ≤120). Thyroid ultrasonography performed the day after iodine treatment showed an increase in the superior thyroid artery flow velocity (Right 50.1 cm/s, Left 44.0 cm/s; ≥50 cm/s as a criterion for increase) and a mild increase in the intrathyroidal blood flow signal (). Before the first pembrolizumab administration, his thyroid function was subclinical hyperthyroidism with negative TRAb (<0.5 IU/L). From these results, he was diagnosed as GD which had developed during pembrolizumab administration.
We also suggested that diarrhea had been caused by colitis, and thus we performed colonoscopy. Colonoscopy showed active colitis with granular mucosa, orange peel appearance, and loss of visible vascular pattern. Biopsy samples from terminal ileum, cecum, ascending colon, transverse colon, sigmoid colon, and rectum were active ileitis, typhlitis, and colitis with mild crypt atrophy, cryptitis, and crypt abscess. Stool culture, Clostridium difficile toxin, and glutamate dehydrogenase toxin were all negative. Therefore, he was diagnosed as having active colitis with diarrhea as Common Terminology Criteria for Adverse Events Grade 3. His diarrhea had not improved despite the reduction of thyroid hormone with potassium iodide treatment for 10 days. We decided that the diarrhea had been caused by immune-mediated colitis due to pembrolizumab treatment, and not by hyperthyroidism. Subsequently, his diarrhea was rapidly improved by prednisolone 60 mg (1 mg/kg/day).
On the other hand, his thyroid hormone was normalized with undetectable serum TSH for 2 weeks by iodine treatment, and thiamazole 10 mg/day was given in place of potassium iodide. TRAb was not detected after 15 weeks of thiamazole treatment. We were able to precisely document the development of GD induced by pembrolizumab, because his thyroid function was checked regularly. Although pembrolizumab administration was discontinued because of severe diarrhea, there has been no further progression of cancer to date.


The patient was a 19-year-old, male, third-ranked sumo wrestler (height, 185 cm; weight, 150 kg). He twisted his left foot during sumo training and felt pain. Two weeks later, he first visited our hospital. He complained of pain in the outside of his left foot. Radiography showed fractures of the proximal epiphysis of the fifth metatarsal bone (). At the fracture site, thickening of the periosteum was observed. His diagnosis was Jones fracture; we performed conservative treatment with cast fixation. One month after his first visit, he discontinued visiting the hospital and returned to sumo wrestling at his own discretion. Nine months later, he injured his anterior cruciate ligament and returned to the hospital. Radiography showed nonunion of the Jones fracture (), but he did not go down in rank after the fracture. Four years after the injury, bone union was observed ().


The patient was a 22-year-old, male, third-ranked sumo wrestler (height, 173 cm; weight, 136 kg). He was injured during sumo training. Two days after the injury, he visited our hospital. Radiography revealed fractures of the proximal epiphysis of the fifth metatarsal bone and thickening of the periosteum (). We diagnosed Jones fracture and performed conservative treatment with cast fixation for three weeks. Subsequently, we removed the cast and put on a brace. Radiography showed gradual bone union; thus, his amount of training gradually increased (Figures –). Six months after the injury, his foot was refractured (). We started treatment with Low-Intensity Pulsed Ultrasound (LIPUS) in combination with the brace [], but he discontinued treatment at his own discretion. However, he continued to sumo wrestle.


The patient was a 28-year-old, male, third-ranked sumo wrestler (height, 175 cm; weight, 133 kg). He felt pain in his right foot during a tournament. After the tournament, the pain in his right foot became worse and he visited another clinic. Radiography did not show a fracture, but the periosteum was thickened; thus, there was a possibility of fatigue fractures (). One week later, a reexamination revealed a fracture of the proximal epiphysis of the fifth metatarsal bone (). He was referred to our hospital with a diagnosis of Jones fracture. After consulting with him and his director about treatment options, he strongly desired operative treatment. We performed the operation 2 weeks after his first visit to the other clinic (). He underwent Acutrak headless compression screw fixation without bone transplantation. After the operation, he underwent rehabilitation with full weight bearing within pain. We started treatment with LIPUS on the fourth postoperative day. He gradually increased his training level, but returned to a tournament without permission one month postoperatively (). Although he had pain in his right foot, he continued to sumo wrestle. However, a screw broke four months postoperatively (). Although he had nonunion, he continued to sumo wrestle.


A 55-year-old man was referred from a regional hospital to a university hospital (level-one trauma center) for symptomatic nonunion of a right medial clavicle fracture that resulted from a fall injury. The patient was a smoker and was known for left reverse total shoulder arthroplasty, first right rib resection at a young age, bipolar disorder, and antisocial personality disorder. His baseline level of activity was low, as he was unemployed and did not practice a specific sport or physical activity. His range of motion of the left shoulder was limited due to his previous reverse total shoulder arthroplasty. When the patient was first evaluated at the outpatient clinic 5 months after the injury, the active range of motion of his right shoulder was reduced in all three planes to about 70 degrees in abduction, 90 degrees in flexion, and 30 degrees in external rotation due to pain and medial instability. The abduction strength was 4+ at the Jobe test. The primary complaint of the patient was not pain, but the sensation of instability at the fracture site during movement. Radiographic and CT imaging demonstrated a highly comminuted medial-end nonunion of the right clavicle (Figures and ).
Surgical management of the nonunion with an open reduction and internal fixation was performed. In a semisitting position, the nonunion site was opened using a 10-centimeter longitudinal incision at the SC joint. ORIF was completed using a locking clavicle distal-end plate (Stryker, Mahwah, NJ) and a 3.5 mm lag screw. A left-side plate was positioned so that the larger portion (usually lateral portion) could fit on the clavicular medial end. One lag screw was used to maintain fracture reduction. Four locking screws were used on the medial side of the fracture, and three locking screws were used on the lateral side (). The SC joint was not bridged by the plate, and a stable fixation was obtained. Two weeks of immobilization in a sling were recommended to the patient, but it was suspected that his compliance to the proposed treatment was inadequate.
During a follow-up appointment at his regional hospital five months postoperatively, the patient complained of increasing pain and instability at the SC joint. This injury limited the patient in some of his activities of daily living, such as dressing and personal hygiene. The wound healing seemed complete, and there was no sign of operative site infection. A new series of radiographs showed extensive plate loosening and migration of the five medial screws (4 locking+1 lag screw). Two medial locking screws were now over 3 centimeters away from the plate. The three distal screws remained properly positioned. The patient was referred to the university hospital for further evaluation. A CT scan of the shoulder and the affected SC joint confirmed hardware migration, displacement of the comminuted bone segments, and posterior displacement of the medial fragment of the clavicle with the SC joint still intact (Figures and ). A medial claviculectomy with stabilization of the remaining clavicle was proposed.
Under general anesthesia and in a semisitting position, the same longitudinal skin incision was opened to access the nonunion site. The plate and the three intact distal screws were removed. Three loose medial screws were removed, but two medial screws () remained unreachable. The comminuted bone fragments were removed, and the medial end of the right clavicle was resected for a total of 5 centimeters in length. Two 6-millimeter tunnels were drilled on both the sternum and medial clavicle in preparation for the figure-of-eight reconstruction technique. The tunnels were drilled directly through the medial end of the clavicle, while they were drilled with an oblique trajectory on the sternum from the anterior cortex towards its right articular surface. The patient's left palmaris longus tendon was harvested as the autograft of choice for this surgery, as the right palmaris longus was absent. A good quality, 15-centimeter-long palmaris longus tendon was obtained. The graft was passed through both tunnels in a figure-of-eight configuration and sutured near the SC joint (no pretightening). Both free ends were sutured to one another using Ethibond 1-0 (as described by Bae et al. []). Vicryl 0 sutures were used for subcutaneous closure, and staples were used for skin closure. Two weeks of immobilization were recommended to the patient with a shoulder sling.
Surgery was well tolerated by the patient. Cultures taken during revision surgery remained negative. Wound healing was uneventful. Two weeks after surgery, the patient presented to the clinic for evaluation. He reported minimal pain and had a range of motion of approximately 150° in flexion and abduction. Eight months postoperatively, the patient did not present any residual pain or limitation on range of motion. Outcomes at 3 years of follow-up were excellent, with no range of motion limitation, no pain, and no clinical instability. Control radiographs showed no sign of reconstruction failure (). The patient was able to return to his previous level of activity and was able to perform his activities of daily living without any limitation.


Patient 2: The second proband was a 1-year-old Japanese girl with no significant family medical history. In her prenatal period, she exhibited failure to thrive, hydrops, and anemia, for which blood transfusion via the placenta was performed. She was born at 33 weeks of gestation via emergent cesarean section due to fetal distress. Her birth weight was 1,334 g (−2.1 SD) and her head circumference was 23.5 cm (−3.4 SD). After birth, she had no spontaneous respiration, which needed mechanical ventilation, and had frequent myoclonic seizures. Her electroencephalography showed continuous burst-suppression patterns highly similar to that in patient 1 (Fig. ). At the age of 3 years, she had profound intellectual disability, severe motor developmental delay, and no spontaneous respiration. Her electroencephalogram persistently showed burst-suppression patterns. She continued to have frequent myoclonic seizures and epileptic spasms.