Aims Unfractionated heparin (UFH) has been the primary anticoagulant of choice on extracorporeal membrane oxygenation (ECMO). However, it is debatable whether bivalirudin (BIV), a direct thrombin inhibitor, may be considered a better alternative anticoagulant option. Methods We searched Embase, Pubmed, Cochrane library, http://Clinicaltrials.gov, CNKI and Wanfang databases up to 15 June 2021. Randomized controlled trials and observational studies were considered eligible for inclusion. Random‐effects meta‐analyses, including subgroup analyses, were conducted. Results A total of 9 studies containing 994 patients were enrolled. All articles were retrospective cohort studies. Compared with UFH, BIV was associated with lower risks of major bleeding (risk ratio [RR]: 0.32, 95% confidence interval [CI] 0.22–0.49), ECMO in‐circuit thrombosis (RR: 0.57, 95% CI 0.43–0.74), stroke (RR: 0.52, 95% CI 0.29–0.95) and in‐hospital mortality (RR: 0.82, 95% CI 0.69–0.99), and higher rates of survival to ECMO decannulation (RR: 1.18, 95% CI 1.03–1.34). Pooled risk estimates did not show a significant association with clinical thrombotic events (RR: 0.69, 95% CI 0.45–1.07). Moreover, BIV was associated with a lower risk of ECMO in‐circuit thrombosis and in‐hospital mortality in the adult subgroup but not in the paediatric subgroup. However, leave‐one‐out sensitivity analyses indicated that the results of stroke, survival to ECMO decannulation and in‐hospital mortality should be interpreted with caution. Conclusion BIV appears to be a potential alternative to UFH in paediatric and adult patients requiring ECMO.

Background: DNA methylation is expected to become a kind of new diagnosis and treatment method of Alzheimer’s disease (AD). Neuroinflammation- and immune-related pathways represent one of the major genetic risk factors for AD. Objective: We aimed to investigate DNA methylation levels of 7 key immunologic-related genes in peripheral blood and appraise their applicability in the diagnosis of AD. Methods: Methylation levels were obtained from 222 participants (101 AD, 72 MC, 49 non-cognitively impaired controls). Logistic regression models for diagnosing AD were established after least absolute shrinkage and selection operator (LASSO) and best subset selection (BSS), evaluated by respondent working curve and decision curve analysis for sensitivity. Results: Six differentially methylated positions (DMPs) in the MCI group and 64 in the AD group were found, respectively. Among them, there were 2 DMPs in the MCI group and 30 DMPs in the AD group independent of age, gender, and APOE4 carriers (p <  0.05). AD diagnostic prediction models differentiated AD from normal controls both in a training dataset (LASSO: 8 markers, including methylation levels at ABCA7_1040077, CNR1_88166293, CX3CR1_39322324, LRRK2_40618505, LRRK2_40618493, NGFR_49496745, TARDBP_11070956, TARDBP_11070840, area under the curve [AUC] = 0.81; BSS: 2 markers, including methylation levels at ABCA7_1040077 and CX3CR1_39322324, AUC = 0.80) and a testing dataset (AUC = 0.84, AUC = 0.82, respectively). Conclusion: Our work indicated that methylation levels of 7 key immunologic-related genes (ABCA7, CNR1, CX3CR1, CSF1 R, LRRK2, NGFR, and TARDBP) in peripheral blood was altered in AD and the models including methylation of immunologic-related genes biomarkers improved prediction of AD.

This meta-analysis aimed to investigate the effect of the genotype on the pharmacokinetics and bleeding events of direct oral anticoagulants (DOACs) and comprehensively searched electronic databases. Weighted mean difference (WMD) was used to assess the kinetic indicators, odds ratio, and 95% confidence interval (CI) were used to calculate the clinical outcomes.Thirteen articles with 1543 participants were finally included in this study.The peak concentration (C max ) and area under the plasma concentration-time curve from time 0 to infinity of individuals with the ABCB1 rs 1045642 CT + TT were higher than that of the CC (WMD = −31.9, 95% CI [−49.94, −12.24], P = .02; WMD = −79.97, 95%CI [−152.38 to −7.56], P = .03, I 2 = 0). The C max of individuals with mutated genes in ABCB1 2677-3435 is higher than that the wild type (WMD = −19.20, 95%CI [36.62 to −1.79], P = .03, I 2 = 0). Carriers of the CYP3A5 rs776746 GG genotype had a higher C max than the GA gene (WMD = −51.22, 95%CI [−92.26 to −10.19], P = .01, I 2 = 0). Bleeding events were more common in the CES1 rs 2244613 AA + AC than in the CC (odds ratio, 2.62, 95%CI [1.06, 6.47], P = .04; I 2 = 0). The C max of DOACs was affected by individuals with ABCB1 rs 1045642, ABCB1 2677-343, and cytochrome P450 3A5 rs 776746. Carriers of the ABCB1 rs 1045642 affected the change of area under the plasma concentration-time curve from time 0 to infinity of DOACs. Bleeding events were affected by CES1 rs 2244613.