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Aim: This observational study investigated the association between remdesivir treatment during hospitalization for COVID-19 and 30-day COVID-19-related and all-cause readmission across different variants time periods. Patients & methods: Hospitalization records for adult patients discharged from a COVID-19 hospitalization between 1 May 2020 to 30 April 2022 were extracted from the US PINC AI Healthcare Database. Likelihood of 30-day readmission was compared among remdesivir-treated and nonremdesivir-treated patients using multivariable logistic regression models adjusted for age, corticosteroid treatment, Charlson comorbidity index and intensive care unit stay during the COVID-19 hospitalization. Analyses were stratified by maximum supplemental oxygen requirement and variant time period (pre-Delta, Delta and Omicron). Results: Of the 440,601 patients discharged alive after a COVID-19 hospitalization, 248,785 (56.5%) patients received remdesivir. Overall, remdesivir patients had a 30-day COVID-19-related readmission rate of 3.0% and all-cause readmission rate of 6.3% compared with 5.4% and 9.1%, respectively, for patients who did not receive remdesivir during their COVID-19 hospitalization. After adjusting for demographics and clinical characteristics, remdesivir treatment was associated with significantly lower odds of 30-day COVID-19-related readmission (odds ratio 0.60 [95% confidence interval: 0.58-0.62]), and all-cause readmission (0.73 [0.72-0.75]). Significantly lower odds of 30-day readmission in remdesivir-treated patients was observed across all variant time periods. Conclusion: Treating patients hospitalized for COVID-19 with remdesivir is associated with a statistically significant reduction in 30-day COVID-19-related and all-cause readmission across variant time periods. These findings indicate that the clinical benefit of remdesivir may extend beyond the COVID-19 hospitalization.

OBJECTIVE: This study evaluated the impact of local treatment modalities in the management of large non-small cell lung cancer (NSCLC) tumors using a nationwide population-based dataset. MATERIAL AND METHODS: Patients with NSCLC tumors >7 cm that were cN0-1M0 in the Surveillance, Epidemiology, and End Results (SEER) registry from 2010 to 2015 were stratified by local management strategy (surgery, radiation therapy, no local treatment) and evaluated using Kaplan–Meier survival analyses, Cox proportional-hazard methods, and propensity-matched analysis. RESULTS: A total of 3156 patients were identified, of which 1580 (50.1%) underwent surgical resection, 920 (29.2%) received radiation only, 655 (20.7%) received no local treatment. Overall, the 5-year survival of patients undergoing surgical resection was 40.7%, compared to 14.7% and 5.3% for the radiation only and no local treatment groups, respectively (P < .001). Surgery with or without radiation continued to have an independent association with improved survival in multivariable analysis (HR 0.23, P < .0001). Other factors associated with improved survival included younger age, negative nodal disease, and chemotherapy use. In propensity-matched sub-analyses, 5-year survival remained significantly better after surgery alone compared to radiation alone (38.5% vs. 13.6%, P < .001), while survival after radiation alone was better than no local treatment, though both were largely poor (12.4% vs. 7.5%, P < .001). CONCLUSIONS: Survival of patients with large NSCLC managed non-surgically is very poor. Despite the significant long-term survival benefit with surgical intervention, nearly half of the study cohort did not undergo surgery. Patients and clinicians can use these results to estimate specific potential benefits when considering possible treatment strategies for large NSCLC tumors. [ABSTRACT FROM AUTHOR]

Reduction in muscle contractile force associated with many clinical conditions incurs serious morbidity and increased mortality. Here, we report the first evidence that JAK inhibition impacts contractile force in normal human muscle. Muscle biopsies were taken from patients who were randomized to receive tofacitinib (n = 16) or placebo (n = 17) for 48 h. Single-fiber contractile force and molecular studies were carried out. The contractile force of individual diaphragm myofibers pooled from the tofacitinib group (n = 248 fibers) was significantly higher than those from the placebo group (n = 238 fibers), with a 15.7% greater mean maximum specific force ( P = 0.0016). Tofacitinib treatment similarly increased fiber force in the serratus anterior muscle. The increased force was associated with reduced muscle protein oxidation and FoxO-ubiquitination-proteasome signaling, and increased levels of smooth muscle MYLK. Inhibition of MYLK attenuated the tofacitinib-dependent increase in fiber force. These data demonstrate that tofacitinib increases the contractile force of skeletal muscle and offers several underlying mechanisms. Inhibition of the JAK-STAT pathway is thus a potential new therapy for the muscle dysfunction that occurs in many clinical conditions., (© 2024 Shrager et al.)

Background: Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) are the two most common oncogenic drivers in lung adenocarcinoma, and their roles still need further exploration. Here we aimed to compare the clinical impact of EGFR and KRAS mutations on disease progression in resected unifocal and multifocal lung adenocarcinoma., Methods: Clinicopathologic and genomic data were collected for patients who underwent resection of lung adenocarcinoma from 2008 to 2022 at Stanford University Hospital. Retrospective review was performed in 241 patients whose tumors harbored EGFR (n=150, 62.2%) or KRAS (n=91, 37.8%) mutations. Clinical outcome was analyzed with special attention to the natural history of secondary nodules in multifocal cases wherein the dominant tumor had been resected., Results: We confirm that compared with EGFR mutations, patients with KRAS mutations had more smokers, larger tumor size, higher TNM stage, higher positron emission tomography (PET)/computed tomography (CT) standard uptake value max, higher tumor mutation burden, and worse disease-free survival and overall survival on univariate analysis. For patients with multifocal pulmonary nodules, the median follow-up of unresected secondary nodules was 55 months. Secondary nodule progression-free survival (SNPFS) was significantly worse for patients with KRAS mutations than those with EGFR mutations (mean 40.3±6.6 vs. 67.7±6.5 months, P=0.004). Univariate analysis showed tumor size, tumor morphology, pathologic TNM stage, and KRAS mutations were significantly associated with SNPFS, while multivariate analysis showed only KRAS mutations were independently associated with worse SNPFS (hazard ratio 1.752, 95% confidence interval: 1.017-3.018, P=0.043)., Conclusions: Resected lung adenocarcinomas with KRAS mutations have more aggressive clinicopathological features and confer worse prognosis than those with EGFR mutations. Secondary pulmonary nodules in multifocal cases with dominant KRAS -mutant tumors have more rapid progression of the secondary nodules., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-165/coif). N.S.L. received research grants with payments from Intuitive Foundation Centese, consulting fees as data safety monitor for clinical trial with payments from Intuitive Surgical, and honoraria for lecture from MEC MMC; W.L.T. purchased stock in these companies (Eli Lilly and Company, Amgen Inc. Kiniksa Pharmaceuticals) several months ago for reasons unrelated to this manuscript; L.M.B. received Research Grant from Department of Veterans Affairs, Chan Zuckerberg Foundation and NIH, and received speaker bureaus/honoraria from MJH Health Sciences, and from Kazan LLP and Craddick LLP for legal expert consulting, and served on Advisory Board for Genentech, Bristol Meyers Squibb, Astra Zeneca and Ethicon/Johnson& Johnson, and served as Board of Directors from Society of Thoracic Surgeons; J.B.S. received payment of consulting on immunotherapy for lung cancer from Astra Zeneca, and was Chair of Society of Thoracic Surgeons Workforce on General Thoracic Surgery (unpaid). The other authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

This study evaluated the impact of local treatment modalities in the management of large non-small cell lung cancer (NSCLC) tumors using a nationwide population-based dataset. Patients with NSCLC tumors >7 cm that were cN0-1M0 in the Surveillance, Epidemiology, and End Results (SEER) registry from 2010 to 2015 were stratified by local management strategy (surgery, radiation therapy, no local treatment) and evaluated using Kaplan-Meier survival analyses, Cox proportional-hazard methods, and propensity-matched analysis. A total of 3156 patients were identified, of which 1580 (50.1%) underwent surgical resection, 920 (29.2%) received radiation only, 655 (20.7%) received no local treatment. Overall, the 5-year survival of patients undergoing surgical resection was 40.7%, compared to 14.7% and 5.3% for the radiation only and no local treatment groups, respectively (P < .001). Surgery with or without radiation continued to have an independent association with improved survival in multivariable analysis (HR 0.23, P < .0001). Other factors associated with improved survival included younger age, negative nodal disease, and chemotherapy use. In propensity-matched sub-analyses, 5-year survival remained significantly better after surgery alone compared to radiation alone (38.5% vs. 13.6%, P < .001), while survival after radiation alone was better than no local treatment, though both were largely poor (12.4% vs. 7.5%, P < .001). Survival of patients with large NSCLC managed non-surgically is very poor. Despite the significant long-term survival benefit with surgical intervention, nearly half of the study cohort did not undergo surgery. Patients and clinicians can use these results to estimate specific potential benefits when considering possible treatment strategies for large NSCLC tumors.