Role of rifaximin in the management of alcohol-associated hepatitis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Alcohol-associated hepatitis (AAH) is an acute, inflammatory liver disease with severe short-term and long-term morbidity and mortality. AAH can lead to severe complications including hepatic failure, gastrointestinal bleeding, sepsis, and the development or decompensation of cirrhosis. Rifaximin is an antibiotic that reduces bacterial overgrowth and gut translocation, and it may have a role in decreasing systemic inflammation and infection in patients with AAH. Therefore, we conducted a systematic review and meta-analysis to evaluate the role of rifaximin in the management of AAH. METHODS: A comprehensive search strategy was used to identify studies that met our inclusion criteria in Embase, MEDLINE (PubMed), Cochrane Library, Web of Science Core Collection, and Google Scholar. Outcomes of interest included rates of infection, 90-day mortality, and overall mortality between the rifaximin versus non-rifaximin group. Open Meta Analyst software was used to compute the results. RESULTS: Three studies with a total of 162 patients were included in the final meta-analysis. Of the three studies, two were randomized control trials (RCTs), and one was a case-control study. There was a significantly lower rate of infection in the rifaximin group versus the non-rifaximin group (RR: 0.331, 95% CI: 0.159-0.689, I2  = 0%, P = 0.003). There was no significant difference in 90-day mortality in the rifaximin versus non-rifaximin group (RR: 0.743, 95% CI: 0.298-1.850, I2  = 24%, P = 0.523), nor was there a significant difference in overall mortality (RR: 0.624, 95% 95% CI: 0.299-1.3, I2  = 7.1%, P = 0.208). CONCLUSIONS: The use of rifaximin in AAH is associated with a lower rate of infection rate than the non-rifaximin group. Additional research is needed to determine whether this effect is more pronounced in patients concurrently being treated with prednisolone. Differences in 90-day or overall mortality did not reach statistical significance. Further studies, particularly large randomized controlled trials, are needed to establish the role of rifaximin in AAH, especially as an adjunct therapy with prednisolone.

Cardioprotective Role for Paraoxonase-1 in Chronic Kidney Disease.

Paraoxonase-1 (PON-1) is a hydrolytic enzyme associated with HDL, contributing to its anti-inflammatory, antioxidant, and anti-atherogenic properties. Deficiencies in PON-1 activity result in oxidative stress and detrimental clinical outcomes in the context of chronic kidney disease (CKD). However, it is unclear if a decrease in PON-1 activity is mechanistically linked to adverse cardiovascular events in CKD. We investigated the hypothesis that PON-1 is cardioprotective in a Dahl salt-sensitive model of hypertensive renal disease. Experiments were performed on control Dahl salt-sensitive rats (SSMcwi, hereafter designated SS-WT rats) and mutant PON-1 rats (SS-Pon1em1Mcwi, hereafter designated SS-PON-1 KO rats) generated using CRISPR gene editing technology. Age-matched 10-week-old SS and SS-PON-1 KO male rats were maintained on high-salt diets (8% NaCl) for five weeks to induce hypertensive renal disease. Echocardiography showed that SS-PON-1 KO rats but not SS-WT rats developed compensated left ventricular hypertrophy after only 4 weeks on the high-salt diet. RT-PCR analysis demonstrated a significant increase in the expression of genes linked to cardiac hypertrophy, inflammation, and fibrosis, as well as a significant decrease in genes essential to left ventricular function in SS-PON-1 KO rats compared to SS-WT rats. A histological examination also revealed a significant increase in cardiac fibrosis and immune cell infiltration in SS-PON-1 KO rats, consistent with their cardiac hypertrophy phenotype. Our data suggest that a loss of PON-1 in the salt-sensitive hypertensive model of CKD leads to increased cardiac inflammation and fibrosis as well as a molecular and functional cardiac phenotype consistent with compensated left ventricular hypertrophy.

Vascular Calcification in Chronic Kidney Disease: Diversity in the Vessel Wall.

Vascular calcification (VC) is one of the major causes of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). VC is a complex process expressing similarity to bone metabolism in onset and progression. VC in CKD is promoted by various factors not limited to hyperphosphatemia, Ca/Pi imbalance, uremic toxins, chronic inflammation, oxidative stress, and activation of multiple signaling pathways in different cell types, including vascular smooth muscle cells (VSMCs), macrophages, and endothelial cells. In the current review, we provide an in-depth analysis of the various kinds of VC, the clinical significance and available therapies, significant contributions from multiple cell types, and the associated cellular and molecular mechanisms for the VC process in the setting of CKD. Thus, we seek to highlight the key factors and cell types driving the pathology of VC in CKD in order to assist in the identification of preventative, diagnostic, and therapeutic strategies for patients burdened with this disease.

Learning on Lockdown: A Study on Medical Student Wellness, Coping Mechanisms and Motivation during the COVID-19 Pandemic.

This article was migrated. The article was marked as recommended. Background: The COVID-19 pandemic forced drastic changes to the educational settings and living conditions of medical students nationwide. Due to the sudden onset of remote learning, drastic educational changes likely induced fear and anxiety among students. Therefore, the purpose of this study was to assess medical students' academic and personal wellbeing, coping mechanisms, and motivation during the Stay at Home order through a survey-based study. Methods: The researchers obtained Institutional Review Board approval, and the study was classified as exempt category 2. In total, 705 medical students representing all four years were recruited from the researchers' institution. The survey was administered through an anonymous link in Qualtrics to the medical student listserv, and responses were collected over a two-week period. The instrument was comprised of four demographic questions, twenty-two closed-ended questions, and four open-ended questions. Results: A total of 188 medical students completed the survey for a response rate of 26.7%. Due to a very low response rate (n=3, 1.6%) from fourth-year students, quantitative data from this group were excluded. Quantitative analysis of the survey results showed that most respondents experienced nervousness and stress at some point during the pandemic. While most claimed to have successfully overcome challenges and achieved their goals, only about half of the participants admitted to being able to handle their personal problems, and nearly 70% of the respondents expressed difficulty focusing while studying. The qualitative data suggest that changes in study environment, long-term home confinement, and isolation were the most challenging aspects for participants. Conclusions:Overall, this study showed that the COVID-19 pandemic induced stress and anxiety among students; nevertheless, most were able to employ effective coping strategies, pursue mental wellness assistance, achieve goals, and maintain motivation during the pandemic.