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Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. Design and Methods: This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Results: Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype (p = 0.045). ILK intensity (p = 0.032) and positive PD-L1 (p = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1–25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13–0.90, p = 0.029; advanced stage: HR 4.989; 95% CI 1.64–15.13, p = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1–25.4) vs. 31.3 (17.4–95.4) p = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival (p = 0.045, p = 0.019). Conclusions: In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer. [ABSTRACT FROM AUTHOR]

Background: Impairment in autonomic activity is a prognostic marker in patients with heart failure (HF), and its involvement has been suggested in cardiovascular complications of obstructive sleep apnea syndrome (OSAS) and Cheyne–Stokes respiration (CSR). This prospective observational study aims to investigate the implications of sleep-disordered breathing (SDB) on hemodynamic regulation and autonomic activity in chronic HF patients. Methods: Chronic HF patients, providing confirmation of reduced ejection fraction (≤35%), underwent polysomnography, real-time hemodynamic, heart rate variability (HRV), and baroreceptor reflex sensitivity (BRS) assessments using the Task Force Monitor. BRS was assessed using the sequencing method during resting conditions and stress testing. Results: Our study population (n = 58) was predominantly male (41 vs. 17), with a median age of 61 (±11) yrs and a median BMI of 30 (±5) kg/m2. Patients diagnosed with CSR were 13.8% (8/58) and 50.0% (29/58) with OSAS. No differences in the real-time assessment of hemodynamic regulation, heart rate variability, or baroreceptor reflex function were found between patients with OSAS, CSR, and patients without SDB. A subgroup analysis of BRS and HRV in patients with severe SDB (AHI > 30/h) and without SDB (AHI < 5) revealed numerically reduced BRS and increased LF/HF-RRI values under resting conditions, as well as during mental testing in patients with severe SDB. Patients with moderate-to-severe SDB had a shorter overall survival, which was, however, dependent upon age. Conclusions: Chronic HF patients with severe SDB may exhibit lower baroreceptor function and impaired cardiovascular autonomic function in comparison with HF patients without SDB. [ABSTRACT FROM AUTHOR]

Background: Adenosquamous carcinoma of the lung (ASC) is a rare non-small-cell lung cancer (NSCLC) subtype combining components of squamous cell carcinoma (SCC) and adenocarcinoma (AC). Data on ASC, particularly in Caucasian populations, are limited. Methods: We reviewed clinicopathological and radiological characteristics of ASC patients diagnosed between 1996 and 2023. Patients were classified into AC-predominant ASC (AC-ASC) and SCC-predominant ASC (SCC-ASC) groups for analysis. Results: Among the 66 patients included, the median overall survival was 41.7 (95% CI, 25.0–54.4), while it was 48.1 (95% CI, 27.3–88.0) in patients treated with curative surgery (n = 44) and 15.3 (95% CI, 6.5–42.6) months for palliative patients (n = 22). The five-year survival rates were 39% and 26%, respectively. Recurrence occurred in 43% of stage I patients and was associated with worse survival (HR 3.303 (95% CI, 1.10–9.89) p = 0.033). AC-ASCs (n = 17) more frequently showed air-bronchogram (p = 0.002) and pleural effusions (p = 0.054) compared to SCC-ASCs (n = 26). SCC-ASCs exhibited more vascular invasion (p = 0.006) and PD-L1 values between 1 and 49% (TPS) (p = 0.032). The subtype did not influence survival. EGFR and ALK alterations were found in 17% and 2% of patients, respectively. Conclusions: Despite early-stage disease, ASC patients had a high recurrence rate, associated with worse survival. Clinicopathologic differences between AC-ASCs and SCC-ASCs did not influence survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer screening (LCS) aims to detect lung cancer in an early stage. Currently, the majority of lung cancer cases are detected in a late stage of the disease, while early detection of lung cancer is associated with better survival rates compared to late-stage disease detection. This study aimed to assess the cost-effectiveness of LCS compared to no screening program in Austria. LCS exhibited an incremental cost-effectiveness ratio (ICER) of EUR 24,627 per quality-adjusted life year (QALY), indicating that LCS is cost-effective. Moreover, the study demonstrated that LCS could avert 11,906 premature lung cancer deaths. These findings provide valuable insights crucial for evidence-based decision making regarding the prospective implementation of LCS initiatives in Austria. This study assessed the cost-effectiveness of a lung cancer screening (LCS) program using low-dose computed tomography (LDCT) in Austria. An existing decision tree with an integrated Markov model was used to analyze the cost-effectiveness of LCS versus no screening from a healthcare payer perspective over a lifetime horizon. A simulation was conducted to model annual LCS for an asymptomatic high-risk population cohort aged 50–74 with a smoking history using the Dutch–Belgian Lung Cancer Screening Study (NEderlands-Leuvens Longkanker ScreeningsONderzoek, NELSON) screening outcomes. The principal measure utilized to assess cost-effectiveness was the incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analyses were employed to determine uncertainties surrounding the key model inputs. At an uptake rate of 50%, 300,277 eligible individuals would participate in the LCS program, yielding 56,122 incremental quality-adjusted life years (QALYs) and 84,049 life years gained compared to no screening, with an ICER of EUR 24,627 per QALY gained or EUR 16,444 per life-year saved. Additionally, LCS led to the detection of 25,893 additional early-stage lung cancers and averted 11,906 premature lung cancer deaths. It was estimated that LCS would incur EUR 945 million additional screening costs and EUR 386 million additional treatment costs. These estimates were robust in sensitivity analyses. Implementation of annual LCS with LDCT for a high-risk population, using the NELSON screening outcomes, is cost-effective in Austria, at a threshold of EUR 50,000 per QALY. [ABSTRACT FROM AUTHOR]

Abstract Background Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. Methods TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. Results Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. Conclusion TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

Background: Achalasia is an esophageal motor disorder characterized by aperistalsis and the failure of the relaxation of the lower esophageal sphincter. We want to find out whether external compression or recurrent micro-aspiration of undigested food has a functional effect on the airway. Methods: The aim of this research was to analyze the influence of achalasia on the peak expiratory flow and flow–volume curve. All of the 110 patients performed spirometry. Results: The mean diameter of the esophagus was 5.4 ± 2.1 cm, and nine of the patients had mega-esophagus. Seven patients had a plateau in the inspiratory part of the flow–volume curve, which coincides with the patients who had mega-esophagus. The rest of the patients had a plateau in the expiration part of the curve. The existence of a plateau in the diameter of the esophagus of more than 5 cm was significant (p 0.003). Statistical significance between the existence of a plateau and a lowered PEF (PEF < 80) has been proven (p 0.001). Also, a statistical significance between the subtype and diameter of more than 4 cm has been proved. There was no significant improvement in the PEF values after operation. In total, 20.9% of patients had a spirometry abnormality finding. The frequency of the improvement in the spirometry values after surgery did not differ significantly by achalasia subtype. The improvement in FEV1 was statistically significant compared to the FVC values. Conclusions: Awareness of the influence of achalasia on the pulmonary parameters is important because low values of PEF with a plateau on the spirometry loop can lead to misdiagnosis. The recognition of various patterns of the spirometry loop may help in identifying airway obstruction caused by another non-pulmonary disease such as achalasia. [ABSTRACT FROM AUTHOR]