Five-Year Survival Outcomes With Atezolizumab After Chemotherapy in Resected Stage IB-IIIA Non-Small Cell Lung Cancer (IMpower010): An Open-Label, Randomized, Phase III Trial.

IMpower010 (ClinicalTrials.gov identifier: NCT02486718) previously showed that atezolizumab improved disease-free survival (DFS) versus best supportive care (BSC) after adjuvant chemotherapy in patients with resected non-small cell lung cancer (NSCLC). We report DFS final analysis, second overall survival (OS) interim analysis, and safety with a ≥5-year follow-up. Patients with completely resected stage IB-IIIA NSCLC were randomly assigned to atezolizumab (1,200 mg once every 3 weeks, 16 cycles) or BSC after platinum-based chemotherapy. At clinical cutoff (January 26, 2024), stratified hazard ratios (HRs; 95% CI) for DFS were 0.85 (95% CI, 0.71 to 1.01; P = .07) in the intention-to-treat (n = 1,005), 0.83 (95% CI, 0.69 to 1.00) in the all-randomized stage II-IIIA (n = 882), and 0.70 (95% CI, 0.55 to 0.91) in stage II-IIIA PD-L1 tumor cell (TC) ≥1% (n = 476) populations. Stratified HRs (95% CI) for OS were 0.97 (95% CI, 0.78 to 1.22), 0.94 (95% CI, 0.75 to 1.19), and 0.77 (95% CI, 0.56 to 1.06), respectively. The unstratified HRs (95% CI) in the stage II-IIIA PD-L1 TC ≥50% population (n = 229) were 0.48 (95% CI, 0.32 to 0.72) for DFS and 0.47 (95% CI, 0.28 to 0.77) for OS, and the unstratified HRs in the stage II-IIIA PD-L1 TC ≥50% without EGFR/ALK alterations (n = 209) population were 0.49 (95% CI, 0.32 to 0.75) and 0.44 (95% CI, 0.26 to 0.74). No new safety signals were reported. IMpower010 is the first study to report survival outcomes with a ≥5-year follow-up and continued to show benefit with atezolizumab versus BSC after adjuvant chemotherapy in patients with resected stage II-IIIA PD-L1-selected NSCLC

Identification and targeting of regulators of SARS-CoV-2-host interactions in the airway epithelium.

The impact of SARS-CoV-2 in the lung has been extensively studied, yet the molecular regulators of host-cell programs hijacked by the virus in distinct human airway epithelial cell populations remain poorly understood. Some of the reasons include overreliance on transcriptomic profiling and use of nonprimary cell systems. Here we report a network-based analysis of single-cell transcriptomic profiles able to identify master regulator (MR) proteins controlling SARS-CoV-2-mediated reprogramming in pathophysiologically relevant human ciliated, secretory, and basal cells. This underscored chromatin remodeling, endosomal sorting, ubiquitin pathways, as well as proviral factors identified by CRISPR assays as components of the viral-host response in these cells. Large-scale drug perturbation screens revealed 11 candidate drugs able to invert the entire MR signature activated by SARS-CoV-2. Leveraging MR analysis and perturbational profiles of human primary cells represents an innovative approach to investigate pathogen-host interactions in multiple airway conditions for drug prioritization

Differences in door-to-device times in a retrospective cohort of patients with ischemic stroke who received CTA only or CTA and CTP imaging.

Background: In the treatment of acute ischemic stroke, there are differing views about the utility of computerized tomography perfusion (CTP). Two approaches are employed depending on hospital preference. The first approach is to perform non-contrast computed tomography (CT) scans followed by vascular imaging with computed tomography angiography (CTA) for patients arriving within 6 h of last known well. In the first approach, CTP is reserved for patients who arrive 6-24 h after last known well. The second approach is to utilize both CTA and CTP regardless of the time window in which the patient presents. In this study, we sought to answer whether patients triaged with CTP and CTA had increased door-to-device times compared to those only triaged with CTA. Methods: We investigated a retrospective cohort of 1,357 patients with ischemic stroke who received endovascular therapy (EVT) and were triaged with CTA only or CTA and CTP. Patients were stratified by when they arrived at the hospital (\u3c 6 h and 6-24 h from last known well). Linear mixed-effects models (LMM) were used to investigate the association between door-to-device times and CTA/CTP usage. Results: Our results showed that using CTP and CTA was not associated with increased time to treat compared to CTA alone. There was no increase in time from door to device in patients presenting within 6 h. Furthermore, for patients who arrived 6-24 h of last known well, the use of CTP and CTA was associated with an accelerated time to treatment with EVT. Conclusions: CTA and CTP usage was not associated with added time costs with respect to door-to-device in this patient cohort. Our results are consistent with other data showing that radiologists have faster read times when given both CTP and CTA. It is noteworthy that the majority of EVT patients in our dataset (70.6 %) presented in the \u3c 6-hour time window