Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) often coexists with obstructive sleep apnea (OSA) due to overlapping metabolic risk factors. Whether continuous positive airway pressure (CPAP) influences hepatic outcomes in MASLD remains uncertain. This systematic review, using updated criteria for MASLD, evaluated the effects of OSA treatment on liver and metabolic outcomes. Methods: PubMed, Web of Science, and CINAHL were searched for randomized controlled trials (RCTs) and observational studies in adults with MASLD and OSA treated with CPAP, lifestyle interventions, pharmacotherapy, or surgery. Outcomes included liver stiffness, fat content, enzymes, fibrosis scores, HbA1c, lipids, and anthropometrics. Risk of bias was assessed with RoB 2 (RCTs) and ROBINS-I (non-randomized studies) and certainty of evidence with GRADE. Results: Eight studies (three RCTs, five observational; n = 1006; 73.5% male) met criteria. Studies evaluated CPAP for from 4 weeks to 3 years, with adherence ≥ 4 h/night in most. CPAP produced modest, inconsistent reductions in alanine aminotransferase and aspartate aminotransferase, small improvements in HbA1c and triglycerides, and minimal changes in liver stiffness, steatosis, weight, or anthropometrics. No RCT demonstrated significant improvement in fibrosis or steatosis. Risk of bias was low in one RCT, “some concerns” in two, and moderate in observational studies; one study had serious confounding risk. Conclusions: CPAP may modestly improve liver enzymes and select metabolic parameters in MASLD with OSA, but evidence for salutary effects on steatosis, fibrosis, and body composition is limited. Level of evidence was low due to methodological limitations, heterogeneity, and imprecision. High-quality, longitudinal trials are needed.

Objective: Gut microbiota dysbiosis has been implicated in the pathogenesis of autoimmune and immune-mediated arthritis. Biologics may influence gut microbiota composition; however, it is uncertain whether biologics act directly on microbial communities or indirectly through disease modulation and restoration of immune homeostasis. This systematic review explores how biologic therapies modulate gut microbiota in autoimmune arthritis and their potential as biomarkers for treatment response and disease activity. Methods: We searched PubMed, Scopus, Cochrane Library, and Web of Science for studies assessing gut microbiota changes induced by any biologic therapy in immune-mediated or autoimmune arthritis. The outcomes included changes in microbiota and the potential for microbiota as predictive biomarkers for treatment response and disease activity. Results: A total of 12 studies were included. Biologic agents, predominantly tumor necrosis factor inhibitors and interleukin 17 inhibitors, significantly altered gut microbiota composition and diversity, with most studies showing increased α-diversity and normalization of β-diversity post therapy; however, these effects were not uniformly consistent. Treatment restored beneficial short-chain fatty acid–producing taxa, including Faecalibacterium prausnitzii , Megamonas , Lachnoclostridium , and Blautia , while reducing inflammatory genera such as Escherichia - Shigella and Klebsiella . Certain taxa, notably Lachnospiraceae and Megamonas , correlated with clinical improvement and reduced disease activity. Conclusion: Biologic therapy modulates gut microbiota composition in autoimmune and immune-mediated arthritis, promoting a shift toward eubiosis. Specific microbial taxa, including Lachnospiraceae , Blautia , and F. prausnitzii , show potential as noninvasive biomarkers for treatment response and disease activity. These findings guide further longitudinal and interventional studies to validate microbial signatures and their clinical applicability.

Background/Objectives: Perforated peptic ulcer (PPU) represents a surgical emergency with substantial morbidity and mortality. Despite declining overall peptic ulcer disease (PUD) incidence, contemporary population-based data comparing outcomes between perforated and non-perforated PUD remain limited, particularly during the COVID-19 pandemic. This study aimed to characterize the clinical and economic burden of PPU and identify independent predictors of adverse outcomes. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (2016–2021), identifying 2,561,379 weighted hospitalizations for PUD. Hospitalizations were stratified by the presence (n = 207,970, 8.1%) or absence (n = 2,353,409, 91.9%) of perforation. The primary outcome was in-hospital mortality; secondary outcomes included sepsis, septic shock, acute kidney injury (AKI), prolonged length of stay (≥7 days), and high healthcare costs (≥$12,000). We performed 1:1 propensity score matching and multivariable logistic regression to assess independent predictors of adverse outcomes in the PPU cohort. Results: After propensity matching, PPU demonstrated significantly higher mortality than non-perforated PUD (7.2% vs. 3.0%, p < 0.001), along with increased rates of sepsis (21.8% vs. 8.2%, p < 0.001), septic shock (12.9% vs. 3.5%, p < 0.001), and AKI (29.5% vs. 22.8%, p < 0.001). Nearly half (45.6%) of PPU admissions exceeded 7 days, and 69.2% incurred costs ≥$12,000. Among PPU hospitalizations, multivariable analysis identified age ≥ 65 years (aOR 5.79, 95% CI 4.60–7.28), liver cirrhosis (aOR 1.93, 95% CI 1.62–2.30), chronic heart failure (aOR 1.73, 95% CI 1.56–1.92), and concurrent COVID-19 infection (aOR 4.35, 95% CI 3.46–5.47) as independent predictors of mortality. Chronic kidney disease strongly predicted AKI (aOR 2.81, 95% CI 2.64–2.98). Mortality increased from 6.9% (2016) to 8.0% (2021) in PPU hospitalizations (p < 0.001 for trend), with higher rates observed during the 2020 to 2021 period that coincided with the COVID-19 pandemic. Conclusions: Perforation complicates approximately 8% of hospitalized PUD cases but accounts for disproportionate mortality, sepsis, organ failure, and healthcare costs. Older age, cirrhosis, heart failure, and chronic kidney disease identify high-risk PPU patients requiring intensive monitoring and aggressive management. These findings support risk-stratified approaches focused on timely diagnosis, source control, and sepsis management to reduce the clinical and economic burden of PPU.

Background: Individuals with inflammatory bowel disease (IBD) are at substantially increased risk for Clostridioides difficile infection (CDI), which leads to significantly higher morbidity and mortality compared to the general population. However, comprehensive national-level analyses of long-term mortality trends in this population remain limited. This study examines mortality trends associated with IBD and CDI in the United States from 1999 to 2023. Methods: This descriptive study utilized the CDC WONDER Multiple Cause-of-Death database. Deaths involving IBD (ICD-10: K50, K51) and CDI (A04.7) were identified among adults aged 25 years and older. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated with 95% confidence intervals and stratified by sex, race/ethnicity, urbanization, and census region. Joinpoint regression was applied to estimate the annual percent change (APC) in mortality. Results: Between 1999 and 2023, 76,084 deaths were recorded. Medical facilities accounted for 46% of deaths, followed by decedents’ homes (28.3%) and nursing home/long-term care facilities (16.5%). Overall mortality declined gradually from 1999 to 2018 (APC: −0.23, p < 0.05), increased sharply through 2021 (APC: +12.75, p < 0.05), and was then followed by a non-significant change through 2023 (APC: −2.69; 95% CI: −8.24 to 3.19), consistent with a plateau. Men consistently exhibited higher AAMRs than women. Non-Hispanic White individuals had the highest AAMRs (1.844 in 2023), while Non-Hispanic Black individuals experienced a sustained increase from 2016 onward (APC: +7.11, p < 0.05). Hispanic mortality increased steadily throughout the study period (APC: +1.31, p < 0.05). Rural populations had higher overall AAMRs than urban populations. The Midwest recorded the highest regional AAMRs by 2023 (1.867). Conclusions: Mortality increased significantly between 2018 and 2021, coinciding with the COVID-19 pandemic, though our study design cannot prove causation. Disparities by race/ethnicity, urbanization, and region persisted. These findings underscore the need for ongoing antibiotic stewardship, equitable healthcare access, and targeted public health interventions for this vulnerable population.

Background: Respiratory failure (RF) is a frequently fatal complication of chronic liver disease (CLD), yet population-level data on RF-related mortality trends among adults with CLD are lacking. This study characterized temporal trends and demographic disparities in RF-related mortality among U.S. adults with CLD from 1999 to 2024. Methods: Death certificate data were obtained from the CDC WONDER database for adults aged ≥25 years with both RF (ICD-10: J96) and CLD (ICD-10: K70–K76) listed as an underlying or contributing cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated using the 2000 U.S. standard population. Joinpoint regression identified temporal inflection points and annual percentage change (APC). Results: Among 241,075 deaths, the overall AAMR increased 3.2-fold from 2.237 (1999) to 7.162 (2021) per 100,000, then declined to 6.132 by 2024. Joinpoint analysis identified four segments: moderate increase (1999–2006; APC +2.40%), accelerated increase (2006–2018; APC +5.37%), late acceleration period (2018–2021; APC +13.10%), and post-pandemic decline (2021–2024; APC −4.32%; all p < 0.001). The 2024 AAMR remained 174.2% above baseline. The male-to-female rate ratio narrowed from 2.02 to 1.50, with females showing steeper acceleration (+14.38% vs. +12.36%). American Indian or Alaska Native individuals had the highest AAMRs and the most dramatic surge (APC +26.90%). Rural areas surpassed urban AAMRs by 2020, with steeper post-2007 acceleration (+8.74% vs. +5.51%). The Western U.S. consistently had the highest regional rates. Younger adults aged 25–34 and 35–44 showed 2.96-fold and 2.37-fold increases in crude mortality rates, respectively. Approximately 80% of deaths occurred in inpatient settings. Conclusions: RF-related mortality among U.S. adults with CLD increased more than threefold from 1999 to 2021, with a dramatic surge followed by incomplete decline. Persistent disparities by sex, race/ethnicity, urbanization, and region highlight the need for targeted interventions, including expanded screening for alcohol-associated and metabolic liver disease and improved access to hepatology services in underserved communities.