Citations

ABSTRACT The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae represents a serious global health challenge. Rapid and accurate detection methods are essential to inform early and correct use of antimicrobial therapy to idealize patient outcomes and limit the spread of resistant isolates. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been evaluated for resistance detection, but its clinical application remains limited. In this study, MALDI-TOF MS was integrated with machine learning (ML) to improve detection of Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae isolates harboring KPC carbapenemase. Ensemble learning strategies were applied to 435 clinical isolates from different geographic locations (Spain, United States, South America, and Asia), with validation performed using external data sets. By constructing two peak matrices and applying four ML algorithms, as well as combinations of two and three in ensemble models, 92 different classifiers were tested. Ensemble combinations increased the specificity of classifiers to over 95%, while sensitivity reached 72%, being significantly higher than that of the MALDI Biotyper KPC module. Low sensitivity may be affected by technical variability during spectral acquisition. The first annotated MALDI-TOF MS spectrum for K. pneumoniae by in silico prediction of protein masses was developed to enable peak identification, including peaks potentially related to antimicrobial resistance. Overall, the results of this study show that combining MALDI-TOF MS with ensemble learning can enhance KPC detection performance. IMPORTANCE Rapid and accurate detection of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae informs early and correct use of antimicrobial therapy to idealize patient outcomes and limit the spread of antimicrobial resistance. In this study, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and ensemble machine learning were employed to detect KPC-producing isolates, using diverse isolate collections, obtaining excellent specificity. An annotated K. pneumoniae MALDI-TOF MS profile is provided with peak annotation, providing a resource for peak analysis.

Abstract Background Individuals with cancer are at increased risk of acute myocardial infarction (AMI), yet selecting optimal dual antiplatelet therapy (DAPT) remains challenging due to competing risks of thrombosis and bleeding. Aims This study examined patterns of DAPT use and associated outcomes following AMI in patients with active cancer. Methods Using the TriNetX global registry, we identified adults hospitalised with AMI and active cancer between January 2015 and January 2020. Outcomes assessed included all-cause mortality, major bleeding, and AMI readmission up to five years. Results Among 20,000 patients, 78.6% received clopidogrel, 17.6% ticagrelor, and 3.9% prasugrel as their second antiplatelet agent. Those prescribed clopidogrel were older (72.6 ± 10.5 years) than those on ticagrelor (69.8 ± 10.9) or prasugrel (67.2 ± 10.4; p < 0.001) and had a higher prevalence of cardiovascular comorbidities, including hypercholesterolemia (clopidogrel: 62% vs ticagrelor: 53% and prasugrel: 58%) and hypertension (clopidogrel: 77% vs ticagrelor: 69% and prasugrel: 72%). After adjustment for baseline characteristics, five-year mortality was lower with prasugrel and ticagrelor compared with clopidogrel (clopidogrel 29.1%, prasugrel 23.6%, p = 0.03; ticagrelor 30.1%, prasugrel 23.6%, p = 0.01). No significant differences were observed in major bleeding rates between treatment groups. Conclusion Clopidogrel remains the most frequently used second antiplatelet in patients with active cancer presenting with AMI. However, ticagrelor and prasugrel were associated with improved long-term survival without increasing bleeding risk. These findings suggest the need for further evaluation of more potent P2Y12 inhibitors in this high-risk population.

The studies demonstrate the differential effects of the nicotinic acetylcholine receptors (nAChRs) regulating airway hyperreactivity (AHR) and remodeling in a mixed allergen model of asthma. We compared wild-type (WT) versus global α7nAChR knockout (Glα7KO) versus smooth muscle-specific α7nAChR KO (smα7KO) mice. We found that smα7KO improved lung function and AHR in mice challenged with MA and in the presence of nicotine, whereas MA-challenged Glα7KO in the presence of nicotine showed worsened AHR.