Background: Infections are risk factors for venous thromboembolism (VTE), especially if severe and acute. The role of chronic infections such as active tuberculosis is ill defined, although several case reports and small series have suggested an association between tuberculosis and VTE.
Methods: Using data from the Premier Perspective database (27 659 947 admissions), we performed a multivariate analysis to assess the specific VTE risk associated with tuberculosis. The analysis was adjusted on classic risk factors for VTE.
Results: The prevalence of VTE among patients with active tuberculosis was 2.07% (95% confidence interval [CI], 1.62%-2.59%). In a multivariate analysis model, adults with active tuberculosis had a greater risk of VTE than those without (odds ratio, 1.55 [95% CI, 1.23-1.97], P < .001), close to the previously reported risk associated with neoplasia. No particular link was found between pulmonary tuberculosis and pulmonary embolism, or between extrapulmonary tuberculosis and deep vein thrombosis. This may suggest the preponderant role of a systemic hypercoagulable state over an intrathoracic venous compression mechanism. In-hospital mortality of patients with both active tuberculosis and VTE (11/72 [15%]) was higher than mortality of patients with only active tuberculosis (92/3413 [2.7%]) or only VTE (5062/199 480 [2.5%]) (P < .001). Pulmonary embolism was more frequent in black patients, suggesting that this population, which is also more likely to suffer from tuberculosis, should be followed carefully.
Conclusions: Tuberculosis must be considered as a pertinent risk factor for VTE and should be included in thromboembolism risk evaluation similar to any acute and severe infection.
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Int J Mol Sci
January 2025
Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Street, 22, Ekaterinburg 620137, Russia.
The synthetic approach based on a sequence of Buchwald-Hartwig cross-coupling and annulation through intramolecular oxidative cyclodehydrogenation has been used for the construction of novel 4-alkyl-4-thieno[2',3':4,5]pyrrolo[2,3-]quinoxaline derivatives. For the first time, these polycyclic compounds were evaluated for antimycobacterial activity, including extensively drug-resistant strains. A reasonable bacteriostatic effect against HRv was demonstrated.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Medical Chemistry, Institute of Chemistry, Saint Petersburg State University, Saint Petersburg 199034, Russia.
The use of the concept of privileged structures significantly accelerates the search for new leads and their optimization. 6-(methylsulfonyl)-8-(4-methyl-4-1,2,4-triazol-3-yl)-2-(5-nitro-2-furoyl)-2,6-diazaspiro[3.4]octane has been identified as a lead, with MICs of 0.
View Article and Find Full Text PDFBMC Public Health
January 2025
Zambia Field Epidemiology Training Program, Lusaka, Zambia.
Background: Geographical factors can affect infectious disease transmission, including SARS-CoV-2, a virus that is spread through respiratory secretions. Prioritization of surveillance and response activities during a pandemic can be informed by a pathogen's geographical transmission patterns. We assessed the relationship between geographical factors and SARS-CoV-2 prevalence in Zambia.
View Article and Find Full Text PDFLancet Microbe
December 2024
Institute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU Munich, Germany; German Center for Infection Research, Munich Partner Site, Munich, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology, Infection, and Pandemic Research, Munich, Germany; Unit Global Health, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. Electronic address:
Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.
Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.
Biochem Biophys Res Commun
January 2025
Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands. Electronic address:
The enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) catalyses the first step of the MEP pathway, a key process for isoprenoid biosynthesis in bacteria that is absent in humans, making it a promising drug target. We present the structure of Mycobacterium tuberculosis DXPS in its apo form, obtained through a soaking method that removes thiamine diphosphate (ThDP) and metals from pre-formed crystals. The apo structure had three regions with absence of electron density near the active site that are unique to the apo form of the enzyme.
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