Is Next-Generation Sequencing Appropriate for the Clinic?

Next-generation sequencing (NGS) has ignited a revolution in genomic medicine by eliminating the inherent limitations of conventional sequencing methods. Due to its high throughput and low-cost, clinics can use NGS to perform targeted and genome sequencing to make diagnoses or pre-screen for risk to future disease. Despite its clinical uses, many challenges exist before NGS becomes a mainstay in the clinic. There is a lack of understanding of the impact of genetic variants on health and disease and how to best apply genetic information to patient care. Nevertheless, the translation of base pair reads to clinical applications has truly begun

Gut Microbiota Modulation and Fecal Transplantation: An Overview on Innovative Strategies for Hepatic Encephalopathy Treatment

Hepatic encephalopathy (HE) is a major complication of cirrhosis, which is associated with gut microbial composition and functional alterations. Current treatments largely focus on gut microbiota using lactulose, rifaximin and other agents. However, despite these treatments, patients with HE have a high rate of readmission, morbidity and cognitive impairment. Fecal microbiota transplant (FMT) involves introduction of a donor microbiota into a recipient and is currently mainly used for recurrent C. difficile infection (rCDI). The role of FMT in cirrhosis and HE is evolving. There have been two randomized clinical trials (RCT) and several case reports/series in cirrhosis. Both RCTs were safety-focused phase 1 trials. One involved pre-FMT antibiotics and FMT enema versus standard of care, while the other involved 15 FMT capsules versus placebo without pre-FMT antibiotics. There was evidence of safety in both trials and the FMT group demonstrated reduction in hospitalizations compared to the non-FMT group. Changes in microbial function centered around short-chain fatty acids, bile acids and brain function showed improvement in the FMT groups. Long-term follow-up demonstrated continued safety and reduction in the antibiotic-resistance gene carriage. However, larger trials of FMT in HE are needed that can refine the dose, duration and route of FMT administration

Risk of cardio-nephro-metabolic disease from NAFLD to MAFLD: fact or fiction?

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common etiology for chronic liver disease. Despite this, our understanding of this illness is lacking. The previous paradigm is that central adiposity, hyperlipidemia, hypertension, and insulin resistance, also known as metabolic syndrome, lead to NAFLD, and this relationship is unidirectional. However, recent evidence clearly shows that the clinical burden of this illness extends well beyond liver-related morbidity and mortality and is associated with multiple extrahepatic complications, particularly metabolic consequences. Due to this, the professional consensus has proposed using the term metabolic associated fatty liver disease (MAFLD) to more accurately reflect pathogenesis and help in patient stratification for management. This review discusses the shared pathophysiological mechanisms that link these diseases and how this can be leveraged to prevent these complications in individuals with NAFLD/MAFLD

CELLULITIS: A mnemonic to increase accuracy of cellulitis diagnosis

Cellulitis, a bacterial infection of the skin and subcutaneous tissue, is often misdiagnosed. Cellulitis accounts for a large number of all infectious disease-related hospitalizations in the U.S. Cellulitis can be challenging to diagnose since it lacks pathognomonic findings. We reviewed all articles on cellulitis within the last 20 years that included a statistical analysis, with odds ratios (OR), of specific clinical features of cellulitis. We then constructed a mnemonic encompassing the features with the highest odds ratios. Our mnemonic is CELLULITIS for cellulitis history, edema, local warmth, lymphangitis, unilateral, leukocytosis, injury, tender, instant onset, and systemic signs. The first characteristic has the highest OR and may be the easiest to recall: past episode(s) of cellulitis

Glomerular filtration rate early after liver transplantation independently predicts atherosclerotic events.

Cardiovascular disease (CVD) is an important cause of mortality among liver transplantation (LT) recipients; however, the data on CVD risk stratification following LT are limited. Thus, the primary aim of this study was to evaluate the association between decline in renal function early after LT and atherosclerotic events. This retrospective study included all patients receiving LT between 2007 and 2019. Early renal function was quantified as estimated glomerular filtration rate (GFR) 6 months after LT. The primary endpoint for the study was a composite atherosclerotic cardiovascular event of three-point major adverse cardiovascular events (MACEs), which includes nonfatal myocardial infarction (MI), nonfatal stroke, or death from CVD. A total of 553 LT recipients met entry criteria. After a median follow-up of 74 months (interquartile range 46-111), 94 (17%) LT recipients died and CVD-associated death occurred in 20 patients. MACE-3 occurred in 66 (12%) patients, with nonfatal MI being the most common event (n = 30). A strong inverse relationship between early GFR and MACE-3 was noted in unadjusted analysis with hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.95-0.98; p = 0.0001) and remained significant even after accounting for age, sex, coronary artery disease, diabetes mellitus, hypertension, calcineurin inhibitor use, and Framingham Risk Score (FRS; HR 0.96, 95% CI 0.95-0.97; p = 0.0001 per unit increase in GFR). Furthermore, an independent interaction between GFR, FRS, and likelihood of developing an MACE-3 was noted. GFR 6 months following LT is a strong predictor of developing atherosclerotic events. This relationship is independent of traditional CVD risk stratification models (e.g. FRS) and thus has the potential to be incorporated into CVD risk assessment after LT but requires further validation