Heritable Chronic Cholestatic Liver Diseases: A Review.

Chronic cholestasis due to heritable causes is usually diagnosed in childhood. However, many cases can present and survive into adulthood. The time course varies considerably depending on the underlying etiology.

Etiologies of Splenic Venous Hypertension: A Review.

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic vein. Usually, it presents with upper gastrointestinal bleeding in the absence of liver disease. Etiologies can be classified based on the mechanism of development of splenic vein hypertension: compression, stenosis, inflammation, thrombosis, and surgically decreased splenic venous flow.

Remdesivir for Treatment of COVID-19 Requiring Oxygen Support: A Cross-Study Comparison From 2 Large, Open-Label Studies.

Background: Remdesivir, an RNA-polymerase prodrug inhibitor approved for treatment of coronavirus disease 2019 (COVID-19), shortens recovery time and improves clinical outcomes. This prespecified analysis compared remdesivir plus standard of care (SOC) with SOC alone in adults hospitalized with COVID-19 requiring oxygen support in the early stage of the pandemic.

Methods: Data for 10-day remdesivir treatment plus SOC from the extension phase of an open-label study (NCT04292899) were compared with real-world, retrospective data on SOC alone (EUPAS34303).

Assessing the performance of methods for central statistical monitoring of a binary or continuous outcome in multi-center trials: A simulation study.

Background: Quality study monitoring is fundamental to patient safety and data integrity. Regulators and industry consortia have increasingly advocated for risk-based monitoring (RBM) and central statistical monitoring (CSM) for more effective and efficient monitoring. Assessing which statistical methods underpin these approaches can best identify unusual data patterns in multi-center clinical trials that may be driven by potential systematic errors is important.

Good Statistical Monitoring: A Flexible Open-Source Tool to Detect Risks in Clinical Trials.

Background: Risk-based quality management is a regulatory-recommended approach to manage risk in a clinical trial. A key element of this strategy is to conduct risk-based monitoring to detect potential risks to critical data and processes earlier. However, there are limited publicly available tools to perform the analytics required for this purpose.

Subnormal Serum Liver Enzyme Levels: A Review of Pathophysiology and Clinical Significance.

Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases can be observed in vitamin B deficiency and chronic kidney disease. Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia, Wilson's disease, deficiencies of divalent ions, or malnutrition.

Changes in Dickkopf-1, but Not Sclerostin, in Gingival Crevicular Fluid Are Associated with Peroral Statin Treatment in Patients with Periodontitis.

: Periodontitis is marked by the destruction of alveolar bone. Sclerostin (SOST) and dickkopf-1 (DKK-1) act as inhibitors of the Wingless-type (Wnt) signaling pathway, a key regulator of bone metabolism. Recent studies have suggested that statins play a role in bone resorption and formation by influencing Wnt signaling.

Genetics of Gallstone Disease and Their Clinical Significance: A Narrative Review.

Gallstone (GS) disease is common and arises from a combination of genetic and environmental factors. Although genetic abnormalities specifically leading to cholesterol GSs are rare, there are clinically significant gene variants associated with cholesterol GSs. In contrast, most bilirubin GSs can be attributed to genetic defects.

Focal Nodular Hyperplasia: A Comprehensive Review with a Particular Focus on Pathogenesis and Complications.

Focal nodular hyperplasia is a benign tumor of the liver that is often found incidentally with imaging. The purpose of this review is to discuss the pathophysiology, rare complications that can occur due to these lesions, and management options. A literature review was performed on clinical trials and case reports involving focal nodular hyperplasia complications and management of these, as well as the proposed pathogenesis underlying these tumors.

Unique Genetic Features of Lean NAFLD: A Review of Mechanisms and Clinical Implications.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. About 20% have a normal body mass index (BMI) and a variant known as lean NAFLD. Unlike typical NAFLD cases associated with obesity and diabetes, lean NAFLD causes liver disease by mechanisms not related to excess weight or insulin resistance.

Novel Approaches to Inhibition of HBsAg Expression from cccDNA and Chromosomal Integrants: A Review.

Hepatitis B virus (HBV) is a widely prevalent liver infection that can cause acute or chronic hepatitis. Although current treatment modalities are highly effective in the suppression of viral levels, they cannot eliminate the virus or achieve definitive cure. This is a consequence of the complex nature of HBV-host interactions.

Laryngopharyngeal Reflux Scoring in a Pediatric Population.

In recent years, the prevalence of laryngopharyngeal reflux has risen, especially among pediatric patients. The diagnosis of laryngopharyngeal reflux relies on patient history and clinical assessment using the Reflux Finding Score and Reflux Symptom Index as crucial diagnostic tools. Some studies have proposed a link between pepsin and laryngopharyngeal reflux, potentially triggering palatine tonsil hypertrophy.

QTc Interval Prolongation Is Independently Associated with FGF23 and Predicts Mortality in Predialysis Chronic Kidney Disease.

Introduction: QTc interval prolongation is increasingly frequent as chronic kidney disease (CKD) advances and predicts death in dialysis. However, predictors and mortality risk in predialysis CKD are understudied. FGF23 induces left ventricular hypertrophy (LVH) which is associated with QTc interval prolongation and death, suggesting a possible pathway from FGF23 to death that entails LVH and QTc prolongation.

Biomarkers for Assessing Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus on Sodium-Glucose Cotransporter 2 Inhibitor Therapy.

In the current modern era of unhealthy lifestyles, non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and has become a serious global health problem. To date, there is no approved pharmacotherapy for the treatment of NAFLD, and necessary lifestyle changes such as weight loss, diet, and exercise are usually not sufficient to manage this disease. Patients with type 2 diabetes mellitus (T2DM) have a significantly higher risk of developing NAFLD and vice versa.

Current Reimbursement Landscape of Artificial Intelligence.

One of the biggest hurdles to widespread adoption of new procedures and technology such as artificial intelligence (AI) algorithms is payment and coverage policy. Noninvasive assessment of coronary fractional flow reserve is one AI imaging algorithm that will successfully achieve reimbursement through multiple pathways of CMS payment mechanisms in 2024. CMS is the largest provider of health care in the United States.

Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update.

Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients. However, with the introduction and validation of noninvasive tests (NITs) to evaluate advanced fibrosis, and the direct-acting antiviral agents for treatment of chronic hepatitis C virus (HCV), the role of NITs have become even more complex. There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response.

Primary Hepatic Extra-gastrointestinal Stromal Tumors: Molecular Pathogenesis, Immunohistopathology, and Treatment.

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. They originate from the interstitial cells of Cajal and are usually found in extrahepatic gastrointestinal sites. However, a small subset are derived from the liver and are known as primary hepatic gastrointestinal stromal tumors (PHGIST).

Primary Non-HFE Hemochromatosis: A Review.

Iron homeostasis is a complex process in which iron uptake and use are tightly balanced. Primary Type 1 or HFE hemochromatosis results from homozygous mutations in the gene that encodes human homeostatic iron regulator (known as human factors engineering, HFE) protein, a regulator of hepcidin, and makes up approximately 90% of all hemochromatosis cases. However, four types of hemochromatosis do not involve the HFE gene.

The Role of GLP1-RAs in Direct Modulation of Lipid Metabolism in Hepatic Tissue as Determined Using In Vitro Models of NAFLD.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to improve glucose and lipid homeostasis, promote weight loss, and reduce cardiovascular risk factors. They are a promising therapeutic option for non-alcoholic fatty liver disease (NAFLD), the most common liver disease, associated with T2DM, obesity, and metabolic syndrome. GLP-1RAs have been approved for the treatment of T2DM and obesity, but not for NAFLD.

A high throughput bispecific antibody discovery pipeline.

Bispecific antibodies (BsAbs) represent an emerging class of immunotherapy, but inefficiency in the current discovery has limited their broad clinical availability. Here we report a high throughput, agnostic, single-cell-based functional screening pipeline, comprising molecular and cell engineering for efficient generation of BsAb library cells, followed by functional interrogation at the single-cell level to identify and sort positive clones and downstream sequence identification and functionality characterization. Using a CD19xCD3 bispecific T cell engager (BiTE) as a model, we demonstrate that our single-cell platform possesses a high throughput screening efficiency of up to one and a half million variant library cells per run and can isolate rare functional clones at a low abundance of 0.

Impact of Infection on the Pathogenesis and Management of Nonalcoholic Fatty Liver Disease.

() infection is widely prevalent worldwide. infection has been reported to be a risk factor for the development of insulin resistance, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Because treatment for NAFLD, other than weight loss is limited, the treatment for infection is well established.

Seronegative Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) is a relatively rare liver disease with varying worldwide incidence of from 0.7 to 2 per 100,000 people. It is characterized by the presence of auto-antibodies.

Seen and not seen: How people judge ambiguous behavior during the COVID-19 pandemic.

Unlabelled: How do we judge others' behavior when they are both -when we observe their behavior but not the underlying traits or history that moderate the perceived riskiness of their behavior? We investigate this question in the context of the COVID-19 pandemic: How people make sense of, and judge, -behaviors, such as going to the gym or a bar, which are considered to be more or less risky and appropriate, depending on the target's vaccination status. While decision theoretic models suggest that these judgments should depend on the probability that the target is vaccinated (e.g.