Reappraisal of Morphological Differences between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-Deficient Renal Cell Carcinoma

Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded

Case Report and Literature Review Illustrating the Clinical, Endoscopic, Radiologic, and Histopathologic Findings with Prepouch Ileitis after IPAA and Restorative Proctocolectomy for Refractory Ulcerative Colitis

Prepouch ileitis (PI) is an uncommon complication of ileal pouch anal anastomosis (IPAA) and restorative proctocolectomy (RPC) for treatment of refractory ulcerative colitis (UC). A case is reported of PI in a 16-year-old girl who presented with severe UC that was initially stabilized with infliximab therapy but re-presented 1 year later with severe UC, refractory to infliximab and corticosteroid therapy, which required IPAA and RPC. Her symptoms resolved postoperatively, but she re-presented 1 year later with 10 loose, bloody, bowel movements/day and involuntary 6-Kg weight-loss. Computerized tomographic enterography showed focal narrowing and mucosal enhancement of the pouch and focal narrowing, abnormal mucosal enhancement, and mural thickening of the prepouch ileum. Pouchoscopy revealed exudates and ulcerations in both the pouch and prepouch ileum up to 50 cm proximal to pouch, as confirmed by histopathology of pouch and ileal biopsies. Capsule endoscopy revealed no small intestinal lesions beyond 50 cm from the pouch. She required antibiotics, hydrocortisone enemas, and eventually azathioprine to control her symptoms. She remains asymptomatic 4 years later while chronically administered azathioprine therapy. Comprehensive literature review demonstrates that this case illustrates the classical clinical, radiologic, endoscopic, and histopathologic findings in PI, a relatively rare syndrome

Infectious Aortitis: A Life-Threatening Endovascular Complication of Nontyphoidal Salmonella

A 65-year-old Japanese man living in the United States presented with pyrexia and chills associated with intermittent lower abdominal and back pain for 5 days. He denied recent travel, rash, diarrhea, or rectal bleeding. Physical examination revealed spiking pyrexia, and routine laboratory tests revealed mild leukocytosis and neutrophilia. Abdominal CT with contrast showed findings highly compatible with aortitis. Comprehensive autoimmune evaluation was negative. Salmonella enterica serotype Enteritidis was isolated from blood cultures. IV antibiotics were administered, but the patient continued to experience low-grade pyrexia and mild leukocytosis, and follow-up abdominal CT showed progressive aortic inflammation. The patient therefore underwent resection of the affected aortic segment with in-situ graft replacement and lifelong suppressive antibiotics. The patient is asymptomatic with no complications at 18 weeks of follow-up. This case report illustrates that patients with infectious aortitis from nontyphoidal Salmonella may (1) present with nonspecific and nonlocalizing symptoms and signs except for sepsis; (2) have diagnostic blood cultures and abdominal CT findings; and (3) typically require aggressive, prolonged IV antibiotic therapy and surgery for potential cure of this life-threatening infection

Upper Gastrointestinal Bleeding from Gastric Amyloidosis in a Patient with Smoldering Multiple Myeloma

Amyloidosis is a common complication of patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM). This proteinaceous material can be deposited intercellularly in any organ system, including the gastrointestinal (GI) tract. In the GI tract, amyloidosis affects the duodenum most commonly, followed by the stomach and colorectum. Gastric amyloidosis causes symptoms of nausea, vomiting, early satiety, abdominal pain, and GI bleeding. A case of upper GI bleeding from gastric amyloidosis is presented in a patient with SMM. Esophagogastroduodenoscopy (EGD) revealed a gastric mass. Endoscopic biopsies revealed amyloid deposition in the lamina propria, consistent with gastric amyloidosis. Liquid chromatography tandem mass spectrometry performed on peptides extracted from Congo red-positive microdissected areas of paraffin-embedded stomach specimens revealed a peptide profile consistent with AL- (lambda-) type amyloidosis. Based on this and multiple other case reports, we recommend that patients with GI bleeding and MGUS, SMM, or MM undergo EGD and pathologic examination of endoscopic biopsies of identified lesions using Congo red stains for amyloidosis for early diagnosis and treatment

Clarithromycin-Associated Acute Liver Failure Leading to Fatal, Massive Upper Gastrointestinal Hemorrhage from Profound Coagulopathy: Case Report and Systematic Literature Review

While erythromycin has caused numerous cases of acute liver failure (ALF), clarithromycin, a similar macrolide antibiotic, has caused only six reported cases of ALF. A new case of clarithromycin-associated ALF is reported with hepatic histopathology and exclusion of other etiologies by extensive workup, and the syndrome of clarithromycin-associated ALF is better characterized by systematic review. A 60-year-old nonalcoholic man, with normal baseline liver function tests, was admitted with diffuse abdominal pain and AST = 499 U/L and ALT = 539 U/L, six days after completing a 7-day course of clarithromycin 500 mg twice daily for suspected upper respiratory infection. AST and ALT each rose to about 1,000 U/L on day-2 of admission, and rose to ≥6,000 U/L on day-3, with development of severe hepatic encephalopathy and severe coagulopathy. Planned liver biopsy was cancelled due to coagulopathies. Extensive evaluation for infectious, immunologic, and metabolic causes of liver disease was negative. Abdominal computerized tomography and abdominal ultrasound with Doppler were unremarkable. The patient developed massive, acute upper gastrointestinal bleeding associated with coagulopathies. Esophagogastroduodenoscopy was planned after massive blood product transfusions, but the patient rapidly expired from hemorrhagic shock. Autopsy revealed a golden-brown heavy liver with massive hepatic necrosis and sinusoidal congestion. Rise of AST/ALT to about 1,000 U/L each was temporally incompatible with shock liver because this rise preceded the hemorrhagic shock, but the subsequent AST/ALT rise to ≥6,000 U/L each may have had a component of shock liver. The six previously reported cases were limited by failure to exclude hepatitis E (4), lack of liver biopsy (2), and uninterpretable liver biopsy (1) and by confounding potential etiologies including disulfiram, israpidine, or recent acetaminophen use (3), clarithromycin overdose (1), active alcohol use (1), and severe heart failure (1). Review of 6 previously reported and current case of clarithromycin-associated ALF revealed that patients had AST and ALT values in the thousands. Five patients died and 2 survived

Machine learning methods to predict mechanical ventilation and mortality in patients with COVID-19.

BackgroundThe Coronavirus disease 2019 (COVID-19) pandemic has affected millions of people across the globe. It is associated with a high mortality rate and has created a global crisis by straining medical resources worldwide.ObjectivesTo develop and validate machine-learning models for prediction of mechanical ventilation (MV) for patients presenting to emergency room and for prediction of in-hospital mortality once a patient is admitted.MethodsTwo cohorts were used for the two different aims. 1980 COVID-19 patients were enrolled for the aim of prediction ofMV. 1036 patients' data, including demographics, past smoking and drinking history, past medical history and vital signs at emergency room (ER), laboratory values, and treatments were collected for training and 674 patients were enrolled for validation using XGBoost algorithm. For the second aim to predict in-hospital mortality, 3491 hospitalized patients via ER were enrolled. CatBoost, a new gradient-boosting algorithm was applied for training and validation of the cohort.ResultsOlder age, higher temperature, increased respiratory rate (RR) and a lower oxygen saturation (SpO2) from the first set of vital signs were associated with an increased risk of MV amongst the 1980 patients in the ER. The model had a high accuracy of 86.2% and a negative predictive value (NPV) of 87.8%. While, patients who required MV, had a higher RR, Body mass index (BMI) and longer length of stay in the hospital were the major features associated with in-hospital mortality. The second model had a high accuracy of 80% with NPV of 81.6%.ConclusionMachine learning models using XGBoost and catBoost algorithms can predict need for mechanical ventilation and mortality with a very high accuracy in COVID-19 patients