Identifying potential drug targets for idiopathic pulmonary fibrosis: a mendelian randomization study based on the druggable genes.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic interstitial lung disease characterized by progressive dyspnea and decreased lung function, yet its exact etiology remains unclear. It is of great significance to discover new drug targets for IPF. METHODS: We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome wide association study (GWAS) of IPF from the International IPF Genetics Consortium as outcomes to simulate the effects of drugs on IPF by employing mendelian randomization analysis. Then colocalization analysis was performed to calculate the probability of both cis-eQTL of druggable genes and IPF sharing a causal variant. For further validation, we conducted protein quantitative trait locus (pQTL) analysis to reaffirm our findings. RESULTS: The expression of 45 druggable genes was significantly associated with IPF susceptibility at FDR < 0.05. The expression of 23 and 15 druggable genes was significantly associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLco) in IPF patients, respectively. IPF susceptibility and two significant genes (IL-7 and ABCB2) were likely to share a causal variant. The results of the pQTL analysis demonstrated that high levels of IL-7 in plasma are associated with a reduced risk of IPF (OR = 0.67, 95%CI: 0.47-0.97). CONCLUSION: IL-7 stands out as the most promising potential drug target to mitigate the risk of IPF. Our study not only sheds light on potential drug targets but also provides a direction for future drug development in IPF.

Differential efficacy of segmentectomy and wedge resection in sublobar resection compared to lobectomy for solid-dominant stage IA lung cancer: a systematic review and meta-analysis.

BACKGROUND: Currently, the impact of sublobar resection versus lobectomy on the prognosis of solid-dominant stage IA lung cancer is contradictory in different studies, which requires further exploration. METHODS: The authors analyzed 26 studies, including one randomized controlled trial and retrospective cohort studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models based on heterogeneity levels. RESULTS: The analysis included 12 667 patients, with 3488 undergoing sublobar resections and 9179 receiving lobectomies. The overall analysis revealed no statistically significant difference in overall survival (OS) (HR=1.28, 95% CI: 0.98-1.69) between sublobar resection and lobectomy, but lobectomy was associated with better recurrence-free survival (RFS) (HR=1.39, 95% CI: 1.10-1.75). Subgroup analyses revealed that, for tumors with a diameter ≤2 cm, sublobar resection versus lobectomy showed no significant difference in OS but sublobar resection had lower RFS. For 2-3 cm tumors, both OS and RFS were significantly lower in the sublobar resection group. When consolidation-to-tumor ratio (CTR) ranged from 0.5 to <1, OS did not differ significantly, but RFS was significantly lower in sublobar resection. Lung cancers with CTR=1 showed significantly lower OS and RFS in the sublobar resection group. Segmentectomy provided similar OS and RFS compared to lobectomy, while wedge resection had a detrimental effect on patient prognosis. However, wedge resection may have provided comparable outcomes for patients aged 75 years or older. CONCLUSION: Our findings suggest that segmentectomy and lobectomy yield similar oncological outcomes. However, compared to lobectomy, wedge resection is associated with a poorer prognosis. Nevertheless, for elderly patients, wedge resection is also a reasonable surgical option.

Video-assisted thoracic surgery drainage is feasible and safe for acute necrotizing mediastinitis: a retrospective cohort study.

Background: Acute necrotizing mediastinitis (ANM) is a severe infection of the mediastinal loose connective tissue. Traditionally, it has been treated with thoracotomy, but video-assisted thoracic surgery (VATS) is been increasingly used in patients with this condition. This study aimed to compare the outcomes of VATS and open thoracotomy in treating ANM. Methods: The medical records of patients with ANM who underwent surgery between March 2012 and April 2021 were retrieved. A retrospective screening was conducted based on clinical characteristics, bacterial pathogens, surgical approach, and outcomes. The patients were divided into a VATS group and an open thoracotomy (Open) group. The patient characteristics and surgical outcomes of the two groups were summarized and compared. Results: A total of 64 cases were enrolled in this study, including 48 in the VATS group (75%) and 16 in the Open group (25%). The most common site of infection was the neck (n=26, 40.6%). Streptococcus constellatus and Acinetobacter baumannii (A. baumannii) were the most frequently found pathogens in secretion culture. In sputum culture, the most common pathogens were Klebsiella pneumonia and A. baumannii. Postoperative outcomes, including blood transfusion (33.3% vs. 43.8%; P=0.45), duration of postoperative drainage {14 [1-47] vs. 17 [4-54] days; P=0.15}, length of antibiotic medication {14.5 [1-54] vs. 18 [4-54] days; P=0.29}, admission to intensive care unit (ICU) (87.5% vs. 75.0%; P=0.43), length of ICU stay {5 [1-58] vs. 8.5 [1-37] days; P=0.20}, postoperative hospital stay {17 [2-61] vs. 21 [5-56] days; P=0.22}, reoperation rate (12.5% vs. 6.25%; P=0.82), and mortality rate (14.6% vs. 12.5%; P>0.99) were comparable between the two groups. Conclusions: ANM treated by both the VATS and open approach had comparable outcomes. Therefore, VATS is a viable option for patients with ANM.