In people with foot ulcers due to diabetes, HBOT significantly improved the ulcers healed in the short term but not the long term and the trials had various flaws in design and/or reporting that means we are not confident in the results. More trials are needed to properly evaluate HBOT in people with chronic wounds; these trials must be adequately powered and designed to minimise all kinds of bias.
Several pathogenic bacteria exploit human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) for adhesion to and invasion into their host cells. CEACAM isoforms have characteristic expression patterns on epithelial, endothelial, or hematopoietic cells, providing bacteria with distinct sets of receptors on particular tissues. For example, while CEACAM1 and CEACAM6 have a wide tissue distribution, CEACAM3, CEACAM4, and CEACAM8 are uniquely expressed on primary human granulocytes, whereas CEA and CEACAM7 are limited to epithelia. By reconstitution of a CEACAM-deficient cell line with individual CEACAMs, we have analyzed the requirements for CEACAM-mediated internalization of Neisseria gonorrhoeae. Our results point to two mechanistically different uptake pathways triggered by either epithelial CEACAMs (CEACAM1, CEA, and CEACAM6) or the granulocyte-specific CEACAM3. In particular, CEACAM3-mediated uptake critically depends on Src family protein tyrosine kinase (PTK) activity, and CEACAM3 associates with the SH2 domains of several Src PTKs. In contrast, epithelial CEACAMs require the integrity of cholesterol-rich membrane microdomains and are affected by cholesterol depletion, whereas CEACAM3-mediated uptake by transfected cells or the opsonin-independent phagocytosis by human granulocytes is not altered in the presence of cholesterol chelators. These results allow the subdivision of all human CEACAMs known to be utilized as pathogen receptors into functional groups and point to important consequences for bacterial engagement of distinct CEACAM isoforms.
IMPORTANCE Tranexamic acid (TXA) is an efficient antifibrinolytic agent; however, concerns remain about the potential adverse effects, particularly vascular occlusive events, that may be associated with its use.OBJECTIVE To examine the association between intravenous TXA and total thromboembolic events (TEs) and mortality in patients of all ages and of any medical disciplines.DATA SOURCE Cochrane Central Register of Controlled Trials and MEDLINE were searched for eligible studies investigating intravenous TXA and postinterventional outcome published between 1976 and 2020.STUDY SELECTION Randomized clinical trials comparing intravenous TXA with placebo/no treatment. The electronic database search yielded a total of 782 studies, and 381 were considered for full-text review. Included studies were published in English, German, French, and Spanish. Studies with only oral or topical tranexamic administration were excluded.DATA EXTRACTION AND SYNTHESIS Meta-analysis, subgroup and sensitivity analysis, and meta-regression were performed. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES Vascular occlusive events and mortality.RESULTS A total of 216 eligible trials including 125 550 patients were analyzed. Total TEs were found in 1020 (2.1%) in the group receiving TXA and 900 (2.0%) in the control group. This study found no association between TXA and risk for total TEs (risk difference = 0.001; 95% CI, −0.001 to 0.002; P = .49) for venous thrombosis, pulmonary embolism, venous TEs, myocardial infarction or ischemia, and cerebral infarction or ischemia. Sensitivity analysis using the risk ratio as an effect measure with (risk ratio = 1.02; 95% CI, 0.94-1.11; P = .56) and without (risk ratio = 1.03; 95% CI, 0.95-1.12; P = .52) studies with double-zero events revealed robust effect size estimates. Sensitivity analysis with studies judged at low risk for selection bias showed similar results. Administration of TXA was associated with a significant reduction in overall mortality and bleeding mortality but not with nonbleeding mortality. In addition, an increased risk for vascular occlusive events was not found in studies including patients with a history of thromboembolism. Comparison of studies with sample sizes of less than or equal to 99 (risk difference = 0.004; 95% CI, −0.006 to 0.014; P = .40), 100 to 999 (risk difference = 0.004; 95% CI, −0.003 to 0.011; P = .26), and greater than or equal to 1000 (risk difference = −0.001; 95% CI, −0.003 to 0.001; P = .44) showed no association between TXA and incidence of total TEs. Meta-regression of 143 intervention groups showed no association between TXA dosing and risk for venous TEs (risk difference, −0.005; 95% CI, −0.021 to 0.011; P = .53).CONCLUSIONS AND RELEVANCE Findings from this systematic review and meta-analysis of 216 studies suggested that intravenous TXA, irrespective of dosing, is not associated with increased risk of any TE. These results help clarify the incidence of...
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