Summary. Background: The interaction of collagen-von Willebrand factor (VWF)-GPIb is essential for platelet adhesion, especially under high shear conditions. VWF, which acts as a bridge between platelets and exposed subendothelium, interacts with collagen through its A3 domain, which is a new target for the antithrombotic agent. Objective: To develop functional blockers that specifically inhibit VWF-dependent adhesion of platelets to collagen under high shear stress. Methods: To develop murine antihuman VWF A3 monoclonal antibodies (mAbs) by standard hybridoma technology, and characterize their abilities to block interactions between VWF A3 and collagen as well as platelet function. Results: Thirty anti-VWF-A3 mAbs were obtained. Among them, two mAbs, designated as SZ-123 and SZ-125, were found to inhibit VWF-collagen type III interaction. SZ-123 and SZ-125 inhibited the binding of purified human VWF (1.5 or 3 lg mL ), SZ-123 and SZ-125 inhibited platelet adhesion on human placenta collagen-or calf skin collagen-coated surfaces. Both mAbs also inhibited platelet aggregation induced by ristocetin, botrocetin or bovine plasma. Conclusions: SZ-123 and SZ-125 inhibited VWF-collagen and VWF-platelet interactions.

Previous investigations showed inconsistent results for comparison in renal recovery, in‐hospital, and in‐intensive care unit (ICU) mortalities between acute kidney injury (AKI) patients treated with continuous renal replacement therapy (CRRT) and some kinds of intermittent renal replacement therapies (IRRTs). We systematically searched for articles published in the databases (PubMed, Web of Science, EMBASE, Medline, and Google Scholar) until June 2019. We made all statistical analysis using STATA 12.0 software. In the present meta‐analysis, relative risks with 95% confidence intervals were calculated for binary outcomes (renal recovery status or mortality). The present study indicated no significant differences in renal recovery, in‐hospital mortality, and in‐ICU mortality between AKI patients given CRRT and those given sustained low‐efficiency dialysis (SLED). Additionally, the study showed no significant difference in in‐hospital mortality between AKI patients given CRRT and those given intermittent hemodialysis (IHD), whereas elevated in‐ICU mortality was detected in AKI patients given CRRT, compared to those given IHD. The three modalities (CRRT, IHD, and SLED) have their own advantages and disadvantages. More rigorous trials design with large cohort should be made to explore the differences in renal recovery, in‐hospital, and in‐ICU mortalities between different kinds of RRTs.

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ObjectivesTo systematically review the effects of dezocine (DZC) on the occurrence rate and severity of opioid-induced cough (OIC).DesignSystematic review and meta-analysisData sourcesPubMed, Embase, Cochrane Library, Ovid, Web of Science as well as Chinese BioMedical Literature & Retrieval System, China National Knowledge Infrastructure, Wanfang and VIP Data were searched from 1978 to 31 December 2020.Inclusion criteriaAll randomised controlled trials (RCTs) comparing DZC with placebo on the occurrence rate and severity of OIC.Data analysisAll data were analysed by using RevMan V.5.3. Each outcome was tested for heterogeneity, and randomised-effects or fixed-effects model was used in the presence or absence of significant heterogeneity.ResultsOur search yielded 33 RCTs including 4442 patients, and 2521 patients were allocated into the DZC group and 1921 into the control group. Fentanyl was administrated in 1880 patients and sufentanil in 2562 patients during the induction of general anaesthesia. The meta-analysis demonstrated that DZC significantly reduced the occurrence rate of OIC induced by either fentanyl (8.8% vs 49.7%, OR=0.07, 95% CI 0.04 to 0.12, p<0.00001) or sufentanil (5.0% vs 41.5%, OR=0.07, 95% CI 0.04 to 0.12, p<0.00001). The meta-analysis also indicated that the occurrence rate of mild, moderate and severe OIC in the DZC group was remarkably lower than that of the control group (mild: 3.6% vs 13.6%, OR=0.19, 95% CI 0.14 to 0.25, p<0.00001; moderate: 2.0% vs 13.6%, OR=0.12, 95% CI 0.09 to 0.18, p<0.00001; severe: 1.0% vs 13.9%, OR=0.08, 95% CI 0.05 to 0.12, p<0.00001). Additionally, the current meta-analysis indicated that DZC pretreatment was not associated with increased occurrence rate of adverse effects (7.0% vs 4.2%, OR=2.34, 95% CI 0.60 to 9.14, p=0.22) except for dizziness (11.8% vs 0%, OR=8.06, 95% CI 1.40 to 46.35, p=0.02).ConclusionThis meta-analysis demonstrated that DZC significantly inhibited OIC and may be used to manage OIC. More high-quality RCTs are needed to complement the safety of DZC.PROSPERO registration numberCRD42019141255.

Background: Levosimendan (LEVO), is an inotropic agent which has been shown to be associated with better myocardial performance, and higher survival rate in cardiac surgical patients. However, preliminary clinical evidence suggested that LEVO increased the risk of post-operative bleeding in patients undergoing valve surgery. Currently, there has been no randomized controlled trials (RCTs) designed specifically on this issue. Therefore, we performed present systemic review and meta-analysis. Methods: Electronic databases were searched to identify all RCTs comparing LEVO with Control (placebo, blank, dobutamine, milrinone, etc). Primary outcomes include post-operative blood loss and re-operation for bleeding. Secondary outcomes included post-operative transfusion of red blood cells (RBC), fresh frozen plasma (FFP) and platelet concentrates (PC). For continuous variables, treatment effects were calculated as weighted mean difference (WMD) and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio (OR) and 95% CI. Results: Search yielded 15 studies including 1,528 patients. Meta-analysis suggested that, LEVO administration was not associated with increased risk of reoperation for bleeding post-operatively (OR = 1.01; 95%CI: 0.57 to 1.79; p = 0.97) and more blood loss volume (WMD = 28.25; 95%CI: –19.21 to 75.72; p = 0.24). Meta-analysis also demonstrated that, LEVO administration did not increase post-operative transfusion requirement for RBC (rate: OR = 0.97; 95%CI: 0.72 to 1.30; p = 0.83 and volume: WMD = 0.34; 95%CI: –0.55 to 1.22; p = 0.46), FFP (volume: WMD = 0.00; 95%CI: –0.10 to 0.10; p = 1.00) and PC (rate: OR = 1.01; 95%CI: 0.41 to 2.50; p = 0.98 and volume: WMD = 0.00; 95%CI: –0.05 to 0.04; p = 0.95). Conclusion: This meta-analysis suggested that, peri-operative administration of LEVO was not associated with increased risks of post-operative bleeding and blood transfusion requirement in cardiac surgical patients.

Background and Objective: This study aims to develop and validate a nomogram for the occurrence of in-hospital major adverse cardiovascular and cerebrovascular events (MACCE) in acute coronary syndrome (ACS) patients.Methods: A total of 1,360 ACS patients admitted between November 2014 and October 2019 from Zhongda Hospital and Yancheng Third People's Hospital were included. Patients admitted in Zhongda Hospital before 2018 were split into the training cohort (n = 793). Those admitted after 2018 in Zhongda Hospital and patients from Yancheng Third People's Hospital were split into the validation cohort (n = 567). Twenty eight clinical features routinely assessed including baseline characteristics, past medical history and auxiliary examinations were used to inform the models to predict in-hospital MACCE (all-cause mortality, reinfarction, stroke, and heart failure) in ACS patients. The best-performing model was tested in the validation cohort. The accuracy and clinical applicability were tested by the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses (DCA).Results: The in-hospital MACCE occurred in 93 (6.83%) patients. The final prediction model consists of four variables: age, Killip grading, fasting blood-glucose (FBG) and whether percutaneous coronary intervention (PCI) was performed at early stage. A nomogram was used to present the final result. Individualized nomogram exhibited comparable discrimination to the Global Registry of Acute Coronary Events (GRACE) score [AUC: 0.807 (95% CI 0.736–0.878) vs. 0.761 (95% CI 0.69–0.878)], P = 0.10) and a better discrimination than the Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) score [AUC: 0.807 (95% CI 0.736–0.878) vs. 0.723(95% CI 0.648–0.798), P = 0.01] in predicting the risk of in-hospital MACCE in ACS patients. A good prediction performance was maintained in the validation cohort (AUC =0.813, 95% CI 0.738–0.889). The prediction model also exhibited decent calibration (P = 0.972) and clinical usefulness.Conclusion: The nomogram may be a simple and effective tool in predicting the occurrence of in-hospital MACCE in ACS patients. Further longitudinal studies are warranted to validate its value in guiding clinical decision-making and optimizing the treatment of high-risk patients.

IntroductionCough is often observed when administrating a bolus of opioids. Opioid-induced cough (OIC) is mostly transient, benign and self-limiting, but could be associated with adverse effects. Numerous pharmacological and non-pharmacological interventions have been used to manage OIC with controversial efficacy and safety. Recent studies suggested that, pretreatment of intravenous dezocine (DZC) could completely suppress OIC during anaesthesia induction. To address this knowledge lack, we will perform a systemic review and meta-analysis to evaluate the efficacy of DZC on OIC and possible complications. We provide here a protocol that will outline the methods and analyses planned for the systematic review.MethodsPubMed, Embase, Cochrane Library, Web of Science as well as Chinese BioMedical Literature & Retrieval System (SinoMed), China National Knowledge Infrastructure, Wanfang Data and VIP Data will be searched from 1978 to 31 December 2019 to identify all randomised controlled trials comparing DZC with placebo on the incidence and severity of OIC. Primary outcomes of interest include the incidence and severity of OIC. Secondary outcomes of interest include possible complications or adverse effects of DZC. Two authors will independently extract relevant variables and outcome data. For continuous variables, treatment effects will be calculated as weighted mean difference and 95% CI. For dichotomous data, treatment effects will be calculated as OR and 95% CI. Each outcome will be tested for heterogeneity, and randomised-effects or fixed-effects model will be used in the presence or absence of significant heterogeneity. Sensitivity analyses will be done by examining the influence of statistical model and individual trial(s) on estimated treatment effects. Publication bias will be explored through visual inspection of funnel plots of the outcomes. Statistical significance will be defined as p<0.05.Ethics and disseminationThis study is a protocol of meta-analysis of previously published literatures, ethical approval was not necessary according to the Ethical Committee of Fuwai Hospital. The study will be submitted to a peer-reviewed journal and disseminated via research presentations.PROSPERO registration numberCRD42019141255.

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