Purpose: The NCCN guidelines do not recommend surgery for T3–4N0M0/T1–4N1–2M0 small cell lung cancer (SCLC) due to a lack of evidence. Methods: Data of patients with T3–4N0M0/T1–4N1–2M0 SCLC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to determine the impact of surgery on this population. The Kaplan–Meier method, univariable and multivariable Cox proportional hazard regression, and propensity score matching (PSM) were used to compare the overall survival (OS) between the surgery and non-surgery groups. In addition, we explored whether sublobectomy, lobectomy, and pneumonectomy could provide survival benefits. Results: In total, 8572 patients with SCLC treated without surgery and 342 patients treated with surgery were included in this study. The PSM-adjusted hazard ratio (HR, 95% CI) for surgery vs. no surgery, sublobectomy vs. no surgery, lobectomy vs. no surgery, pneumonectomy vs. no surgery, and lobectomy plus adjuvant chemoradiotherapy vs. chemoradiotherapy were 0.71 (0.61–0.82) (P < 0.001), 0.91 (0.70–1.19) (P = 0.488), 0.60 (0.50–0.73) (P < 0.001), 0.57 (0.28–1.16) (P = 0.124), and 0.73 (0.56–0.96) (P = 0.023), respectively. The subgroup analysis demonstrated consistent results. Conclusions: Lobectomy improved OS in patients with T3–4N0M0/T1–4N1–2M0 SCLC, while pneumonectomy also demonstrated a tendency to improve OS without statistical significance; however, sublobectomy showed no survival benefit.

Background: The clinical efficiency of routine oxygen therapy is uncertain in patients with acute heart failure (AHF) who do not have hypoxemia. The aim of this study was to investigate the association between oxygen therapy and clinical outcomes in normoxemic patients hospitalized with AHF using real-world data. Methods: Normoxemic patients diagnosed with AHF on ICU admission from the electronic ICU (eICU) Collaborative Research Database were included in the current study, in which the study population was divided into the oxygen therapy group and the ambient-air group. Propensity score matching (PSM) was applied to create a balanced covariate distribution between patients receiving supplemental oxygen and those exposed to ambient air. Linear regression and logistic regression models were performed to assess the associations between oxygen therapy and length of stay (LOS), and all-cause in-hospital as well as ICU mortality rates, respectively. A series of sensitivity and subgroup analyses were conducted to further validate the robustness of our findings. Results: A total of 2922 normoxemic patients with AHF were finally included in the analysis. Overall, 42.1% (1230/2922) patients were exposed to oxygen therapy, and 57.9% (1692/2922) patients did not receive oxygen therapy (defined as the ambient-air group). After PSM analysis, 1122 pairs of patients were matched: each patient receiving oxygen therapy was matched with a patient without receiving supplemental oxygen. The multivariable logistic model showed that there was no significant interaction between the ambient air and oxygen group for all-cause in-hospital mortality [odds ratio ( OR ) 1.30; 95% confidence interval (CI) 0.92–1.82; P = 0.138] or ICU mortality ( OR 1.39; 95% CI 0.83–2.32; P = 0.206) in the post-PSM cohorts. In addition, linear regression analysis revealed that oxygen therapy was associated with prolonged ICU LOS ( OR 1.11; 95% CI 1.06–1.15; P < 0.001) and hospital LOS ( OR 1.06; 95% CI 1.01–1.10; P = 0.009) after PSM. Furthermore, the absence of an effect of supplemental oxygen on mortality was consistent in all subgroups. Conclusion: Routine use of supplemental oxygen in AHF patients without hypoxemia was not found to reduce all-cause in-hospital mortality or ICU mortality.

Background: Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell lung cancer with a high mortality rate. Identifying causal plasma proteins associated with LUSC could provide new insights into the pathophysiology of the disease and potential therapeutic targets. This study aimed to identify plasma proteins causally linked to LUSC risk using proteome-wide Mendelian randomization (MR) and colocalization analyses. Methods: Proteome-wide MR analysis was conducted using data from the UK Biobank Pharma Proteomics Project and deCODE genetics. Summary-level data for LUSC were obtained from the ILCCO Consortium, the FinnGen study, and a separate GWAS study. A total of 1,046 shared protein quantitative trait loci (pQTLs) were analyzed. Sensitivity analyses included the HEIDI test for horizontal pleiotropy and colocalization analysis to validate the causal associations. Results: MR analysis identified six plasma proteins associated with LUSC risk: HSPA1L, PCSK7, POLI, SPINK2, TCL1A, and VARS. HSPA1L (OR = 0.47; 95% CI: 0.34–0.65; P = 4.89 × 10 ^–6 ), SPINK2 (OR = 0.68; 95% CI: 0.58–0.80; P = 3.17 × 10 ^–6 ), and VARS (OR = 0.44; 95% CI: 0.31–0.63; P = 5.94 × 10 ^–6 ) were associated with a decreased risk of LUSC. Conversely, PCSK7 (OR = 1.37; 95% CI: 1.21–1.56; P = 1.40 × 10 ^–6 ), POLI (OR = 4.50; 95% CI: 2.25–9.00; P = 2.13 × 10 ^–5 ), and TCL1A (OR = 1.72; 95% CI: 1.34–2.21; P = 1.89 × 10 ^–5 ) were associated with an increased risk. The SMR analysis and HEIDI test confirmed the robustness of these associations. HSPA1L, SPINK2, and VARS showed significant inverse associations, with strong colocalization evidence for TCL1A (PPH4 = 0.817). Conclusions: This study identified six plasma proteins potentially causal for LUSC risk. HSPA1L, SPINK2, and VARS are associated with decreased risk, while PCSK7, POLI, and TCL1A are linked to increased risk. These findings provide new insights into LUSC pathogenesis and highlight potential targets for therapeutic intervention.

Background: The optimal first-line treatment for advanced BRAF V600-mutant non-small cell lung cancer (NSCLC) remains uncertain. We compared the real-world effectiveness of first-line Dabrafenib plus trametinib (Dab+Tram) with immunochemotherapy (ICT) and other systemic regimens. Methods: This single-centre retrospective cohort study included 142 patients with unresectable stage III/IV BRAF-mutant NSCLC treated between April 2017 and May 2024. Patients were grouped by first-line regimen Dab+Tram, ICT, chemotherapy alone, or others. Primary endpoint was real-world progression-free survival (rwPFS). Propensity score matching (PSM) and multivariable Cox regression were applied to reduce measured confounding. Results: Forty-seven patients received Dab+Tram and 30 received ICT. In unadjusted analysis, Dab+Tram yielded significantly longer median rwPFS than ICT (32.5 vs. 13.3 months; p = 0.004). After PSM (25 pairs), median rwPFS was 19.6 months for Dab+Tram versus 12.6 months for ICT (HR = 1.74, 95%CI 0.85–3.66, p = 0.12). Multivariable Cox regression showed ICT, chemotherapy alone, and other regimens were independently associated with worse rwPFS versus Dab+Tram (all p < 0.05). Overall survival showed no significant difference. Dab+Tram showed some antitumor activity in later-line settings. Findings regarding pyrexia and PD-L1 subgroups were exploratory. Conclusions: In this real-world cohort, first-line Dab+Tram suggested a potential rwPFS benefit over ICT and chemotherapy. The matched comparison did not reach statistical significance, but multivariable analysis consistently supported an association between Dab+Tram and improved rwPFS. These findings provide complementary real-world evidence and require prospective validation.