Cholangiocyte derived carcinomas and local microbiota.

Trillions of bacteria are present in the gastrointestinal tract as part of the local microbiota. Bacteria have been associated with a wide range of gastrointestinal diseases including malignant neoplasms. The association of bacteria in gastrointestinal and biliary tract carcinogenesis is supported in the paradigm of Helicobacter pylori and intestinal-type gastric cancer. However, the association of bacterial species to a specific carcinoma, different from intestinal-type gastric cancer is unresolved. The relationship of bacteria to a specific malignant neoplasm can drive clinical interventions. We review the classic bacteria risk factors identified using cultures and PCR (polymerase chain reaction) with new research regarding a microbiota approach through 16S rRNA (16S ribosomal ribonucleic acid gene) or metagenomic analysis for selected carcinomas in the biliary tract.

The K18-Human ACE2 Transgenic Mouse Model Recapitulates Non-severe and Severe COVID-19 in Response to an Infectious Dose of the SARS-CoV-2 Virus.

A comprehensive analysis and characterization of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection model that mimics non-severe and severe coronavirus disease 2019 (COVID-19) in humans is warranted for understating the virus and developing preventive and therapeutic agents. Here, we characterized the K18-hACE2 mouse model expressing human (h)ACE2 in mice, controlled by the human keratin 18 (K18) promoter, in the epithelia, including airway epithelial cells where SARS-CoV-2 infections typically start. We found that intranasal inoculation with higher viral doses (2 × 103 and 2 × 104 PFU) of SARS-CoV-2 caused lethality of all mice and severe damage of various organs, including lung, liver, and kidney, while lower doses (2 × 101 and 2 × 102 PFU) led to less severe tissue damage and some mice recovered from the infection. In this hACE2 mouse model, SARS-CoV-2 infection damaged multiple tissues, with a dose-dependent effect in most tissues. Similar damage was observed in postmortem samples from COVID-19 patients. Finally, the mice that recovered from infection with a low dose of virus survived rechallenge with a high dose of virus. Compared to other existing models, the K18-hACE2 model seems to be the most sensitive COVID-19 model reported to date. Our work expands the information available about this model to include analysis of multiple infectious doses and various tissues with comparison to human postmortem samples from COVID-19 patients. In conclusion, the K18-hACE2 mouse model recapitulates both severe and non-severe COVID-19 in humans being dose-dependent and can provide insight into disease progression and the efficacy of therapeutics for preventing or treating COVID-19. IMPORTANCE The pandemic of coronavirus disease 2019 (COVID-19) has reached nearly 240 million cases, caused nearly 5 million deaths worldwide as of October 2021, and has raised an urgent need for the development of novel drugs and therapeutics to prevent the spread and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To achieve this goal, an animal model that recapitulates the features of human COVID-19 disease progress and pathogenesis is greatly needed. In this study, we have comprehensively characterized a mouse model of SARS-CoV-2 infection using K18-hACE2 transgenic mice. We infected the mice with low and high doses of SARS-CoV-2 to study the pathogenesis and survival in response to different infection patterns. Moreover, we compared the pathogenesis of the K18-hACE2 transgenic mice with that of the COVID-19 patients to show that this model could be a useful tool for the development of antiviral drugs and therapeutics.

Successful Liver Transplantation for Adolescent Patient With Pyruvate Kinase Deficiency-induced Cirrhosis.

We present the case of a successful liver transplant in a young adult patient with cholestasis and cirrhosis secondary to severe pyruvate kinase (PK) deficiency. Liver transplant resulted in resolution of liver dysfunction, decreased need for blood transfusions and eligibility for bone marrow transplantation. This case represents the third reported patient in the literature with severe PK deficiency who successfully underwent liver transplant as a result of profound cholestasis and liver failure. Explant pathology demonstrated a lack of significant iron deposition indicating that PK deficiency predisposes the liver to injury independent of transfusion-related iron overload.

Tissue micro-array: a cost and time-effective method for correlative studies by regional and national cancer study groups.

Tissue micro-arrays have been used for molecular and immunohistochemical studies. We sought to evaluate whether such arrays could substitute for whole sections in correlative studies performed by the Radiation Therapy Oncology Group. Four multitumor 150-sample arrays were built using formalin-fixed, paraffin-embedded, archival prostate, brain, and head/neck tumor blocks from RTOG tissue bank. p53 immunostaining of arrays and whole sections was done. Blind evaluation of each slide was made, and agreement rates between the two techniques were determined in various scenarios. Cost was also evaluated. Results demonstrate excellent agreement for p53 between slides and arrays. Agreement improved when three or four replicate arrays were used. Findings based on one to four arrays agree well with those obtained from analysis of the whole tissue samples. Minimal tissue damage, improved tissue salvage, cost reduction, ease of interpretation, and significant time savings were realized by using the arrays. Tissue micro array technique is a valuable tool for evaluation of patient materials associated with clinical trials.