COVID-19 Related Mortality During Management of a Hepatic Abscess.

The coronavirus disease (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in the capital city of the Hubei Province, Wuhan, China, in late 2019. Declared a pandemic by the World Health Organization on March 11th, 2020, COVID-19 has challenged healthcare systems to limit the spread of community and hospital-acquired disease. This article uses a patient case to highlight the importance of infection control during the height of the SARS-CoV-2 surge at a Level I affiliated community hospital in Western New York.

COVID-19-related arterio-ureteral fistula formation in a post-transplant patient.

Arterio-ureteral fistulas (AUF) are extremely rare and are not commonly suspected in the setting of patients with post-renal allograft transplantation. The diagnosis, while uncommon, can be potentially lethal which is only exacerbated by the clinical conundrum associated with their under-recognition and various treatment algorithms. This case identifies a unique patient with a history of 2 failed renal transplants who presents with new onset intermittent hematuria after contracting coronavirus disease 2019 (COVID-19). Despite the patient having his second renal transplant graft embolized, the patient continued to present with refractory hematuria, leading to the realization and identification of an AUF to his right renal graft. This sequence of events brings forth a case of unique significance, underscoring the potential ramifications that COVID-19 poses to the renal transplant population.

Genetic mechanisms in Apc-mediated mammary tumorigenesis.

Many components of Wnt/beta-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli) in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cre and WAP-cre transgenic mice that express Cre-recombinase in mammary progenitor cells and lactating luminal cells, respectively. Only the K14-cre-mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological heterogeneity, suggesting the multilineage progenitor cell origin of these tumors. These tumors harbored truncation mutation in a defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of beta-catenin signaling. Activating mutations at codons 12 and 61 of either H-Ras or K-Ras were also found in a subset of these tumors. Expression profiles of acinar-type mammary tumors from K14-cre; Apc(CKO/+) mice showed luminal epithelial gene expression pattern, and clustering analysis demonstrated more correlation to MMTV-neu model than to MMTV-Wnt1. In contrast, neither WAP-cre-induced Apc heterozygous nor homozygous mutations resulted in predisposition to mammary tumorigenesis, although WAP-cre-mediated Apc deficiency resulted in severe squamous metaplasia of mammary glands. Collectively, our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of beta-catenin signaling optimal for mammary tumor development and explain partially the colon- but not mammary-specific tumor development in patients that carry germline mutations in APC.

Severe Gastrointestinal Bleeding Due to Hemosuccus Pancreaticus in Chronic Pancreatitis Treated With Percutaneous Trans-splenic Embolization.

Hemosuccus pancreaticus is a life-threatening but rare cause of intermittent upper gastrointestinal bleeding caused by acute/subacute hemorrhage into a pancreatic duct or pancreatic pseudocyst because of a ruptured pseudoaneurysm. This entity is described in patients with pseudoaneurysms that develop in the context of severe pancreatic/peripancreatic inflammatory changes. Hemosuccus pancreaticus presents a difficult diagnostic and therapeutic conundrum because it tends to involve inflamed, friable, and tortuous vascular pathways. We present a rare case of hemosuccus pancreaticus because of splenic pseudoaneurysm presenting as duodenal hemorrhage and discuss trans-splenic embolization with a combined angiographic and ultrasound-guided approach.

Adenomatous polyposis coli (APC) is required for normal development of skin and thymus.

The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt signaling pathway that is involved in development and tumorigenesis. Heterozygous knockout mice for Apc have a tumor predisposition phenotype and homozygosity leads to embryonic lethality. To understand the role of Apc in development we generated a floxed allele. These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. Mice homozygous for the floxed allele that also carry the K14-cre transgene were viable but had stunted growth and died before weaning. Histological and immunochemical examinations revealed that K14-cre-mediated Apc loss resulted in aberrant growth in many ectodermally derived squamous epithelia, including hair follicles, teeth, and oral and corneal epithelia. In addition, squamous metaplasia was observed in various epithelial-derived tissues, including the thymus. The aberrant growth of hair follicles and other appendages as well as the thymic abnormalities in K14-cre; Apc(CKO/CKO) mice suggest the Apc gene is crucial in embryonic cells to specify epithelial cell fates in organs that require epithelial-mesenchymal interactions for their development.

Dose reponse behavior in a physiologically accurate defibrillation model.

Termination of an episode of ventricular fibrillation by electric countershock is a probabilistic phenomenon. In a clinical or experimental setting, defibrillation exhibits dose-response behavior. We demonstrate for the first time that a physiologically and anatomically accurate model of defibrillation is able to simulate this dose-response behavior. We also demonstrate the ability of this computational model to reproduce the full range of observed shock responses. Finally, we show that the brief cessation of electrical activity on the epicardial surface after a shock near the defibrillation threshold, the isoelectric window, can be explained by the slowed propagation velocity of transmural activation wavefronts around a filament of singularity in the myocardium.