Eshal Amir

Objectives: NSCLC is the leading cause of cancer-related mortality. While combined therapy including savolitinib and osimertinib appears promising, there exists a lack of comprehensive pooled evidence regarding its anti-oncological activity. : The objective of this study is to evaluate the efficacy and safety of combined therapy in patients with NSCLC. Methods: A comprehensive literature search was conducted in MEDLINE, the Cochrane Central Register of controlled trials, and ClinicalTrials.gov. Randomized controlled trials and prospective single-arm studies evaluating savolitinib combined with osimertinib were included. A random-effects single-arm meta-analysis of proportions was performed using logit transformation and inverse variance weighting, with restricted maximum likelihood (REML) estimation and Knapp-Hartung adjustment. Results were reported with a 95% CI, and heterogeneity was assessed using the I ² statistic. Sensitivity analysis was conducted using the Freeman-Tukey transformation. Results: The primary analysis included 4 post-TKI, MET-selected combination cohorts (SACHI, SAVANNAH, and TATTON Part B; n=338) from 7 reports of 5 trials after de-duplication of overlapping data sets. First-line (FLOWERS) and MET-unselected (Yoh) cohorts were analyzed separately. The pooled objective response rate (ORR) was 53.9% (95% CI: 45.1-62.4), disease control rate (DCR) was 85.2% (79.2-89.8), 6-month progression-free survival (PFS) rate was 59.8%, and grade ≥3 adverse events occurred in 48.8% of patients. ORR estimates were consistent across studies and remained robust across sensitivity and subgroup analyses. Conclusions: Combined therapy shows encouraging results in selected MET, post-TKI NSCLC. However, reliance on single-arm data warrants further randomized controlled trials.

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.