Two Acute Liver Injuries in a Patient With Malnutrition.

Chronic starvation and refeeding have been associated with liver injury (LI). We present a patient with anorexia nervosa who exhibited both phenomena of malnutrition-related LI. At presentation, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were elevated at 154 and 136 U/L, respectively, and rose rapidly to peaks of 750 and 638 U/L, respectively, as nutrition was introduced. Mechanisms of starvation-related LI include impaired degradation and secretion of lipids, as well as starvation-induced autophagy. LI during refeeding may be related to rapid increase in glucose availability. These phenomena are crucial to consider in patients with chronic starvation undergoing refeeding.

Continuing Undergraduate Pathology Medical Education in the Coronavirus Disease 2019 (COVID-19) Global Pandemic: The Johns Hopkins Virtual Surgical Pathology Clinical Elective.

CONTEXT.­: In the early months of the response to the coronavirus disease 2019 (COVID-19) pandemic, the Johns Hopkins University School of Medicine (JHUSOM) (Baltimore, Maryland) leadership reached out to faculty to develop and implement virtual clinical clerkships after all in-person medical student clinical experiences were suspended. OBJECTIVE.­: To develop and implement a digital slide-based virtual surgical pathology (VSP) clinical elective to meet the demand for meaningful and robust virtual clinical electives in response to the temporary suspension of in-person clinical rotations at JHUSOM. DESIGN.­: The VSP elective was modeled after the in-person surgical pathology elective to include virtual previewing and sign-out with standardized cases supplemented by synchronous and asynchronous pathology educational content. RESULTS.­: Validation of existing Web communications technology and slide-scanning systems was performed by feasibility testing. Curriculum development included drafting of course objectives and syllabus, Blackboard course site design, electronic-lecture creation, communications with JHUSOM leadership, scheduling, and slide curation. Subjectively, the weekly schedule averaged 35 to 40 hours of asynchronous, synchronous, and independent content, approximately 10 to 11 hours of which were synchronous. As of February 2021, VSP has hosted 35 JHUSOM and 8 non-JHUSOM students, who have provided positive subjective and objective course feedback. CONCLUSIONS.­: The Johns Hopkins VSP elective provided meaningful clinical experience to 43 students in a time of immense online education need. Added benefits of implementing VSP included increased medical student exposure to pathology as a medical specialty and demonstration of how digital slides have the potential to improve standardization of the pathology clerkship curriculum.

Extreme chromosome 17 copy number instability is a prognostic factor in patients with gastroesophageal adenocarcinoma: A retrospective cohort study.

Gastric and esophageal cancers frequently show genomic instability and aneuploidy. Chromosomal copy number instability (CIN) is a form of genomic instability that exerts pleiotropic effects on cellular biology and is a source of genetic heterogeneity in a population of cells. CIN results in cell-to-cell variation in chromosome copy number which can be detected and quantified by fluorescence in situ hybridization (FISH). CIN is a biomarker associated with differential response to a number of chemotherapy compounds. We quantified chromosome 17 copy number instability (CIN-17) in 348 gastroesophageal adenocarcinomas by centromeric FISH in cases that were tested for HER2 amplification. We evaluated the association between CIN-17 and clinical outcome after surgical and nonsurgical treatment. CIN-17 was detected in 45.4% (158/348) and extreme CIN-17 in 28.4% (99/348). Extreme CIN-17 had no association with outcome in surgically treated patients. However, in patients treated with conventional radiation and/or chemotherapy, extreme CIN-17 was associated with 55% reduction in overall mortality (hazard ratio, 0.448; 95% confidence interval, 0.263-0.763) after adjusting for age and clinical stage at diagnosis. Extreme CIN-17 is detected in over a quarter of gastroesophageal adenocarcinomas and is a favorable prognostic marker in patients treated nonoperatively.

Disparate Regulatory Mechanisms Control Fat3 and P75NTR Protein Transport through a Conserved Kif5-Interaction Domain.

Directed transport delivers proteins to specific cellular locations and is one mechanism by which cells establish and maintain polarized cellular architectures. The atypical cadherin Fat3 directs the polarized extension of dendrites in retinal amacrine cells by influencing the distribution of cytoskeletal regulators during retinal development, however the mechanisms regulating the distribution of Fat3 remain unclear. We report a novel Kinesin/Kif5 Interaction domain (Kif5-ID) in Fat3 that facilitates Kif5B binding, and determines the distribution of Fat3 cytosolic domain constructs in neurons and MDCK cells. The Kif5-ID sequence is conserved in the neurotrophin receptor P75NTR, which also binds Kif5B, and Kif5-ID mutations similarly result in P75NTR mislocalization. Despite these similarities, Kif5B-mediated protein transport is differentially regulated by these two cargos. For Fat3, the Kif5-ID is regulated by alternative splicing, and the timecourse of splicing suggests that the distribution of Fat3 may switch between early and later stages of retinal development. In contrast, P75NTR binding to Kif5B is enhanced by tyrosine phosphorylation and thus has the potential to be dynamically regulated on a more rapid time scale.