HER2 overexpression is a key resistance mechanism to osimertinib in EGFR-mutant non-small cell lung cancer (NSCLC). However, real-world evidence remains limited. This first real-world study included 3,589 EGFR-mutant NSCLC patients from six PLAGH medical centers, and 50 patients with HER2 overexpression (immunohistochemistry (IHC) 2+/3+) met the inclusion criteria. HER2 overexpression was either present at diagnosis (n = 33, Cohort P) or acquired under osimertinib therapy (n = 17, Cohort A). Clinicopathological data, objective response rate (ORR), progression-free survival (PFS), and adverse events were analyzed. The most common EGFR mutation was exon 21 L858R (n = 29), and TP53 (n = 24) was the most common co-mutation. In Cohort P, 3 patients received trastuzumab deruxtecan (T-DXd) plus osimertinib achieved PFS exceeding 14.0 months (individual PFS: 14.0, 15.8, and 29.0 months), with the ORR of 66.7
Phosphodiesterase (PDE) inhibitors have been investigated as potential therapies for chronic obstructive pulmonary disease (COPD), and combined PDE3 and PDE4 inhibition has been proposed to provide complementary anti-inflammatory and bronchodilatory effects. This network meta-analysis compared the efficacy and safety of oral roflumilast, inhaled tanimilast, and inhaled ensifentrine. A systematic search (PubMed, Embase, Web of Science, Cochrane Library) through January 2026 identified randomized controlled trials (RCTs) comparing PDE inhibitors with placebo or active controls. The endpoints comprised forced expiratory volume in one second (FEV₁), St. George’s Respiratory Questionnaire (SGRQ), annualized acute exacerbation rate (AAER), and adverse events (AEs). A frequentist random-effects network meta-analysis (NMA) was conducted. We included 17 reports describing 20 distinct RCTs (18,672 patients). Ensifentrine (mean difference [MD] = 75.82 mL) and roflumilast (MD = 55.60 mL) significantly improved FEV₁ compared with placebo, whereas tanimilast did not. The FEV₁ and SGRQ networks were anchored by the common placebo comparator, with no active-treatment head-to-head comparisons available. Ensifentrine had the highest surface under the cumulative ranking curve (SUCRA) value for FEV₁ improvement (0.9381). No intervention significantly improved SGRQ scores or reached the 4-point minimal clinically important difference. Ensifentrine and roflumilast significantly reduced the annualized acute exacerbation rate. Oral roflumilast was associated with higher risks of total adverse events and adverse-event-related treatment discontinuation versus placebo, whereas no statistically significant differences from placebo were observed for the evaluated safety outcomes of inhaled ensifentrine and tanimilast. Ensifentrine had the largest FEV₁ point estimate, the lowest exacerbation rate ratio, and the highest SUCRA value for FEV₁ in the primary analysis. These findings support further evaluation of inhaled dual PDE3/4 inhibition as an add-on maintenance strategy for COPD. Not applicable.
Serial oxygenation measurements may describe early risk in acute hypoxemic respiratory failure (AHRF), but incremental prediction beyond an initial PaO₂/FiO₂ (P/F) ratio is uncertain. We studied operationally defined AHRF in MIMIC-IV and replicated the trajectory framework in eICU-CRD. Mean P/F during 0–6 h (≥ 150 versus < 150 mmHg) and change during the second window ( ≥ + 30 versus < + 30 mmHg) defined four groups. Mortality prediction used a 12-hour landmark and a common MIMIC-IV sample, with repeated five-fold cross-validation, C-statistics, Brier scores, integrated Brier scores, and calibration. Among 14,322 eligible MIMIC-IV patients, 3,358 had paired early P/F measurements; 651 died within 28 days. Mortality was 11.6
The clinical benefit of Pseudomonas aeruginosa (P. aeruginosa) eradication or suppression is well established in patients with Cystic Fibrosis who are colonized with P aeruginosa. However, for patients with non-Cystic Fibrosis bronchiectasis, it remains unclear. The objective of this systematic review (PROSPERO registration number: CRD42023434134 ) is to investigate the clinical effects of antibiotic eradication or suppression treatment in patients with non-CF bronchiectasis who are colonized, or by some professionals referred to as chronically infected, with P. aeruginosa on sputum culture positivity, exacerbations, hospitalization, lung function, and quality of life, compared to non-treated patients. The Ovid MEDLINE and EMBASE databases were used to identify 7 relevant articles for this review. In these articles, different P. Aeruginosa eradication or suppression schemes, which consist of inhaled antibiotic treatments, were used. None of these studies demonstrated an effect on the sputum density of P. aeruginosa during the follow-up period. Two studies showed a significant effect of nebulized gentamicin and dual-release ciprofloxacin for inhalation on the number of exacerbations. Only one study demonstrated significantly fewer admissions and days of admission in the aerosolised tobramycin group compared with placebo. None of the studies demonstrated an effect on lung function and all studies showed a varying effect on quality of life. Evidence on the clinical effects of P. aeruginosa eradication/suppression treatment in non-CF patients with bronchiectasis who are colonized with P. aeruginosa is limited. Eradication or suppression does not affect the sputum bacterial density and lung function during follow-up. At most, only minimal effects are to be expected on the number of exacerbations, hospitalizations, and quality of life.
For idiopathic pulmonary fibrosis (IPF), pulmonary rehabilitation (PR) offers clinical benefits but faces accessibility challenges. Tele-rehabilitation (TR) utilizes digital solutions to expand PR access. This systematic review evaluates the therapeutic impact of TR on pulmonary function, exercise capacity, dyspnea severity, and health-related quality of life among patients with IPF. A systematic search of 5 international databases identified qualifying studies published up to April 2025. Analyses were carried out in R software, with effect estimates presented as mean differences (MDs) and 95
