Yale New Haven Hospital

Traumatic injury, stenosis, and malignancy involving large segments of the airway are difficult to reconstruct and require novel solutions. Despite advances in surgical techniques, the reconstruction of long-segment tracheal defects remains a significant challenge. Several bioengineering approaches have been explored for tracheal regeneration in vitro and in vivo, using cells in combination with three dimentional (3D) biological or synthetic scaffolds. This paper reviews recent advances in developing bioengineered trachea and the technologies utilized toward generating transplantable tracheal grafts. Specifically, the review will focus on the recellularization of tissue-engineered grafts using natural or synthetic scaffolds, highlighting relevant cell types used to reconstitute tracheal epithelium and cartilage. The promise of newly explored paradigms, including the application of pluripotent stem cells, will be discussed with an overview of associated challenges and necessary steps for future translation. Overall, these advances provide a foundation for the development of clinically viable tracheal grafts, bringing engineered tracheal reconstruction closer to reality.

Semaglutide, a glucagon-like peptide-1 receptor agonist, and resmetirom, a thyroid hormone receptor-β agonist, are approved therapies for noncirrhotic metabolic dysfunction–associated steatohepatitis (MASH) with moderate to advanced fibrosis. Their comparative economic value has not been established. To evaluate the cost-effectiveness of semaglutide and resmetirom compared with standard of care (SOC) in patients with noncirrhotic MASH and F2–F3 fibrosis. A state-transition model simulated disease progression in a hypothetical cohort with F2–F3 fibrosis over 5- and 10-year horizons from a U.S. healthcare payer perspective. Clinical efficacy inputs were derived from phase 3 trials (ESSENCE and MAESTRO-NASH), with costs and utilities obtained from published sources. Scenario analyses incorporated semaglutide’s cardiovascular mortality benefit. Deterministic and probabilistic sensitivity analyses assessed uncertainty. Semaglutide was cost-effective versus SOC at 5 years (ICER, $42,200/QALY) and 10 years (ICER, $44,138/QALY). Resmetirom produced higher ICERs ($95,981/QALY at 5 years; $107,002/QALY at 10 years) but remained below a $150,000/QALY threshold. Inclusion of cardiovascular mortality benefits improved semaglutide’s ICER to $38,324/QALY. Probabilistic analyses showed semaglutide had the highest probability of cost-effectiveness across willingness-to-pay thresholds. Over a 10-year horizon, treatment of 100,000 patients with F2–F3 MASH was projected to prevent 270 cases of decompensated cirrhosis, 10 cases of hepatocellular carcinoma, and 1,040 liver-related deaths with semaglutide, compared with 310 cases of decompensated cirrhosis, 10 cases of hepatocellular carcinoma, and 1,180 liver-related deaths with Resmetirom. Semaglutide demonstrated superior cost-effectiveness compared with SOC and resmetirom, with cardiovascular benefits further strengthening its economic value. Not applicable.

Silicosis is one of the most common forms of pneumoconiosis worldwide. In Rwanda, there is a lack of data on the silicosis burden and occupational risk among underground miners. We conducted a cross-sectional study among all miners from eight cassiterite (tin ore) mining sites in Kayonza district, eastern Rwanda. Questionnaire data and chest radiography were collected at Rwinkwavu District Hospital. Two radiologists reviewed all the chest radiographs using International Labour Organization (ILO) criteria, with a third radiologist reviewing films with ILO rating discrepancies. Logistic regression was performed to investigate risk factors associated with radiographic silicosis. In total, 1021 mine workers were included in the primary outcome (risk) analysis. The median age was 32 years (IQR 26-40), and 948 participants (93%) were male. Of all participants, 94 (9%) were diagnosed with silicosis in the primary analysis. Increased odds of silicosis were associated with working in a blasting station (adjusted OR (aOR) 3.30; 95% CI 1.68 to 6.45), excavation station (aOR 2.77; 95% CI 1.09 to 7.04), drilling station (aOR 2.51; 95% CI 1.34 to 4.70), exposure to tobacco (aOR 1.92; 95% CI 1.14 to 3.24) and increased time of working in mining (aOR 1.05 per year spent in mining; 95% CI 1.01 to 1.09). High-risk mining tasks, tobacco use and duration of mining employment were significantly associated with increased risk of having a silicosis diagnosis. Our results indicate that screening and preliminary occupational risk analysis in a rural mining cohort is technically feasible.

We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, retrieving data from PubMed, Elsevier, Web of Science, and Cochrane Central Register of Controlled Trials . Primary outcomes included changes from baseline in acute headache medication days and monthly migraine days (MMD). Secondary outcomes comprised the incidence of adverse events (AEs), common AEs, and the proportion of patients achieving a ≥ 50% reduction in MMDs. Five randomized controlled trials including 875 patients (mean age of 42.7 years) were analyzed. Erenumab treatment was associated with significant reductions in acute headache medication days (mean difference = -1.72; 95% confidence interval [CI]: -2.81 to -0.62; p = 0.002) and MMDs (mean difference = -1.88; 95% CI: -2.68 to -1.07; p < 0.001). Whereas erenumab increased the risk of common AEs such as constipation (risk ratio [RR] = 1.43; 95% CI: 1.17 to 1.76; I2 = 14%), the overall incidence of AEs was not significantly different compared to placebo (RR = 1.02; 95% CI: 0.92 to 1.14; I2 = 57%). A higher proportion of patients achieved a ≥50% reduction in MMDs after 3 months in the erenumab group (RR = 1.49; 95% CI: 1.26 to 1.77; I2 = 22%). Erenumab appears effective in reducing migraine frequency and symptomatic medication use among patients with chronic migraine MOH, with an acceptable tolerability profile.