Development and Validation of a Noninvasive Model for the Detection of High-Risk Varices in Patients With Unresectable Hepatocellular Carcinoma.

Background & Aims: Noninvasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a noninvasive algorithm for the prediction of varices in patients with unresectable HCC.

Methods: We performed a retrospective cohort study in 21 centers in the United States including adult patients with unresectable HCC and Child-Pugh A5-B7 cirrhosis diagnosed between 2007 and 2019.

Tissue-specific and endogenous protein labeling with split fluorescent proteins.

The ability to label proteins by fusion with genetically encoded fluorescent proteins is a powerful tool for understanding dynamic biological processes. However, current approaches for expressing fluorescent protein fusions possess drawbacks, especially at the whole organism level. Expression by transgenesis risks potential overexpression artifacts while fluorescent protein insertion at endogenous loci is technically difficult and, more importantly, does not allow for tissue-specific study of broadly expressed proteins.

Atypical RhoUV GTPases in development and disease.

RhoU and RhoV are members of the Rho family of small GTPases that comprise their own subfamily. RhoUV GTPases are classified as atypical due to the kinetics of their GTP/GDP binding cycles. They also possess unique N- and C-termini that regulate their subcellular localization and activity.

Endodermal cells use contact inhibition of locomotion to achieve uniform cell dispersal during zebrafish gastrulation.

The endoderm is one of the three primary germ layers that ultimately gives rise to the gastrointestinal and respiratory epithelia and other tissues. In zebrafish and other vertebrates, endodermal cells are initially highly migratory with only transient interactions among one other, but later converge together to form an epithelial sheet. Here, we show that during their early, migratory phase, endodermal cells actively avoid each other through contact inhibition of locomotion (CIL), a characteristic response consisting of 1) actin depolymerization and membrane retraction at the site of contact, 2) preferential actin polymerization along a cell-free edge, and 3) reorientation of migration away from the other cell.

Clinical outcomes: endoscopic resection of duodenal ampullary lesions.

Background: Ampullary adenomas are lesions at the duodenum's major papilla commonly associated with familial adenomatous polyposis (FAP) but may also occur sporadically. Historically, ampullary adenomas were removed surgically, however endoscopic resection has become the preferred method of resection. Most of the literature on management of ampullary adenomas are small single-center retrospective reviews.

COVID-19-Associated Liver Injury.

This review analyzes data regarding liver injury associated with COVID-19 infection. We discuss reported effects on the liver from both COVID-19 and COVID-19 treatment as well as pathophysiology, review the potential role of drug-induced liver injury as an etiology of COVID-19-associated liver injury, and touch on other reports of significant outcomes including COVID-19 cholangiopathy and autoimmune hepatitis. Finally, we review the implications of COVID-19 infection in liver transplant recipients.

Immunotherapy Use Prior to Liver Transplant in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide, and its incidence has increased rapidly in the United States over the past two decades. Liver transplant is considered curative, but is not always possible, and pre-transplant immunotherapy is of great interest as a modality for downstaging the tumor burden. We present a review of the literature on pre-liver transplant immunotherapy use in patients with HCC.

Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

Background: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients.

Highlights of the drug-induced liver injury literature for 2021.

Introduction: In 2021, over 3,000 articles on Drug-Induced Liver Injury (DILI) were published, nearly doubling the annual number compared to 2011. This review selected DILI articles from 2021 we felt held the greatest interest and clinical relevance.

Areas Covered: A literature search was conducted using PubMed between 1 March 2021 and 28 February 2022.

Real-world incidence of venetoclax toxicities in British Columbia.

Introduction: Venetoclax is used to treat relapsed/refractory chronic lymphocytic leukemia (r/r CLL). Tumour lysis syndrome (TLS) is a serious toxicity associated with venetoclax, and real-world studies suggest that the incidence may be higher than in clinical trials. The purpose of this study is to describe the incidence of venetoclax toxicities in British Columbia (BC).

Herbal and dietary supplement induced liver injury: Highlights from the recent literature.

Herbal-induced liver injury (HILI) is an important and increasingly concerning cause of liver toxicity, and this study presents recent updates to the literature. An extensive literature review was conducted encompassing September 2019 through March 2021. Studies with clinically significant findings were analyzed and included in this review.

Drug-Induced Liver Injury: Highlights and Controversies in the Recent Literature.

Drug-induced liver injury (DILI) remains an important, yet challenging diagnosis for physicians. Each year, additional drugs are implicated in DILI and this year was no different, with more than 1400 articles published on the subject. This review examines some of the most significant highlights and controversies in DILI-related research over the past year and their implications for clinical practice.

Light-Induced GFP Expression in Zebrafish Embryos using the Optogenetic TAEL/C120 System.

Inducible gene expression systems are an invaluable tool for studying biological processes. Optogenetic expression systems can provide precise control over gene expression timing, location, and amplitude using light as the inducing agent. In this protocol, an optogenetic expression system is used to achieve light-inducible gene expression in zebrafish embryos.

TAEL 2.0: An Improved Optogenetic Expression System for Zebrafish.

Inducible gene expression systems are valuable tools for studying biological processes. We previously developed an optogenetic gene expression system called TAEL that is optimized for use in zebrafish. When illuminated with blue light, TAEL transcription factors dimerize and activate gene expression downstream of the TAEL-responsive C120 promoter.

Patient-Physician Racial Concordance Associated with Improved Healthcare Use and Lower Healthcare Expenditures in Minority Populations.

Background: Racial concordance between patients and clinician has been linked to improved satisfaction and patient outcomes.

Objectives: (1) To examine the likelihood of clinician-patient racial concordance in non-Hispanic White, non-Hispanic Black, Asian, and Hispanic patients and (2) to evaluate the impact of patient-clinician race concordance on healthcare use and expenditures within each racial ethnic group.

Methods: We analyzed data from the 2010-2016 Medical Expenditure Panel Survey (MEPS).

Frequency of Advanced Cardiac Life Support Medication Use and Association With Survival During In-hospital Cardiac Arrest.

Purpose: Cardiopulmonary resuscitation is common in the United States, with >200,000 people experiencing an in-hospital cardiac arrest (IHCA) annually. Recent medication shortages have raised the question of the frequency and type of medication used during cardiac arrest resuscitation. We sought to determine the frequency and quantity of medications used during IHCA.

Preventable adverse drug events: Descriptive epidemiology.

Aim: Our objective was to identify preventable adverse drug events and factors contributing to their development.

Methods: We performed a retrospective chart review combining data from three prospective multicentre observational studies that assessed emergency department patients for adverse drug events. A clinical pharmacist and physician independently reviewed the charts, extracted data and rated the preventability of each adverse drug event.

Repeat adverse drug events associated with outpatient medications: a descriptive analysis of 3 observational studies in British Columbia, Canada.

Background: Adverse drug events are an important cause of preventable emergency department visits and hospital admissions. We examined repeat adverse drug events associated with outpatient medications resulting in acute care utilization.

Methods: This descriptive analysis combined data from 3 prospective multicentre observational studies, in which clinical pharmacists and physicians independently evaluated patients who visited the emergency department for adverse drug events in 3 hospitals in British Columbia.

Risk Factors for Misuse of Prescribed Opioids: A Systematic Review and Meta-Analysis.

Study Objective: Increasing opioid prescribing has been linked to an epidemic of opioid misuse. Our objective is to synthesize the available evidence about patient-, prescriber-, medication-, and system-level risk factors for developing misuse among patients prescribed opioids for noncancer pain.

Methods: We performed a systematic search of the scientific and gray literature for studies reporting on risk factors for prescription opioid misuse.

Methods for evaluating adverse drug event preventability in emergency department patients.

Background: There is a high degree of variability in assessing the preventability of adverse drug events, limiting the ability to compare rates of preventable adverse drug events across different studies. We compared three methods for determining preventability of adverse drug events in emergency department patients and explored their strengths and weaknesses.

Methods: This mixed-methods study enrolled emergency department patients diagnosed with at least one adverse drug event from three prior prospective studies.

Nodal signaling has dual roles in fate specification and directed migration during germ layer segregation in zebrafish.

During gastrulation, endodermal cells actively migrate to the interior of the embryo, but the signals that initiate and coordinate this migration are poorly understood. By transplanting ectopically induced endodermal cells far from the normal location of endoderm specification, we identified the inputs that drive internalization without the confounding influences of fate specification and global morphogenic movements. We find that Nodal signaling triggers an autocrine circuit for initiating endodermal internalization.

Glypican 4 and Mmp14 interact in regulating the migration of anterior endodermal cells by limiting extracellular matrix deposition.

During embryogenesis, the germ layers, including the endoderm, undergo convergence and extension movements to narrow and elongate the body plan. In zebrafish, the dorsal migration of endodermal cells during gastrulation is controlled by chemokine signaling, but little is known about how they migrate during segmentation. Here, we show that glypican 4 (Gpc4), a member of the heparin sulfate proteoglycan family, is required for efficient migration of anterior endodermal cells during early segmentation, regulating Rac activation to maintain polarized actin-rich lamellipodia.