靳雨
中国医学科学院阜外医院 麻醉科
INTRODUCTION:Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis.METHODS:In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 -8 ). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR-Egger, and weighted median regression) were used to ensure that our results more reliable.RESULTS:All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30-1.58, P = 2.51 × 10 -13 ). The results of MR-Egger and weighted median regression exhibited similar trends (MR-Egger OR = 1.40 [95% CI, 1.08-1.81], P = 1.61 × 10 -2 ; weighted median OR = 1.39 [95% CI, 1.21-1.61], P = 1.62 × 10 -6 ). MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF.CONCLUSIONS:Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.
Chinese medical journal 2024
BACKGROUND:The ischemia-reperfusion (IR) environment during deep hypothermic circulatory arrest (DHCA) cardiovascular surgery is a major cause of acute kidney injury (AKI), which lacks preventive measure and treatment. It was reported that cold inducible RNA-binding protein (CIRP) can be induced under hypoxic and hypothermic stress and may have a protective effect on multiple organs. The purpose of this study was to investigate whether CIRP could exert renoprotective effect during hypothermic IR and the potential mechanisms.METHODS:Utilizing RNA-sequencing, we compared the differences in gene expression between Cirp knockout rats and wild-type rats after DHCA and screened the possible mechanisms. Then, we established the hypothermic oxygen-glucose deprivation (OGD) model using HK-2 cells transfected with siRNA to verify the downstream pathways and explore potential pharmacological approach. The effects of CIRP and enarodustat (JTZ-951) on renal IR injury (IRI) were investigated in vivo and in vitro using multiple levels of pathological and molecular biological experiments.RESULTS:We discovered that Cirp knockout significantly upregulated rat Phd3 expression, which is the key regulator of HIF-1α, thereby inhibiting HIF-1α after DHCA. In addition, deletion of Cirp in rat model promoted apoptosis and aggravated renal injury by reactive oxygen species (ROS) accumulation and significant activation of the TGF-β1/p38 MAPK inflammatory pathway. Then, based on the HK-2 cell model of hypothermic OGD, we found that CIRP silencing significantly stimulated the expression of the TGF-β1/p38 MAPK inflammatory pathway by activating the PHD3/HIF-1α axis, and induced more severe apoptosis through the mitochondrial cytochrome c-Apaf-1-caspase 9 and FADD-caspase 8 death receptor pathways compared with untransfected cells. However, silencing PHD3 remarkably activated the expression of HIF-1α and alleviated the apoptosis of HK-2 cells in hypothermic OGD. On this basis, by pretreating HK-2 and rats with enarodustat, a novel HIF-1α stabilizer, we found that enarodustat significantly mitigated renal cellular apoptosis under hypothermic IR and reversed the aggravated IRI induced by CIRP defect, both in vitro and in vivo.CONCLUSION:Our findings indicated that CIRP may confer renoprotection against hypothermic IRI by suppressing PHD3/HIF-1α-mediated apoptosis. PHD3 inhibitors and HIF-1α stabilizers may have clinical value in renal IRI.
Molecular medicine (Cambridge, Mass.) 2023
BACKGROUND:KDIGO and pRIFLE classifications are commonly used in pediatric acute kidney injury (AKI). As a novel AKI definition, pROCK considered the high variability of serum creatinine in children. This study aimed to compare the above three definitions for AKI in infants undergoing cardiac surgery.METHODS:We analyzed a clinical cohort of 413 infants undergoing cardiac surgery. AKI was defined and staged according to pRIFLE, KDIGO, and pROCK, respectively. Incidence differences and diagnostic agreement across definitions were assessed. The association between postoperative outcomes and AKI by each definition was investigated.RESULTS:Postoperative AKI was identified in 185 (44.8%), 160 (38.7%), and 77 (18.6%) patients according to pRIFLE, KDIGO, and pROCK, respectively. The agreement between pRIFLE and KDIGO was almost perfect (κ = 0.88), while there was only a slight agreement between pROCK and them. AKI by pROCK was independently associated with adverse outcomes (p = 0.003) and prolonged mechanical ventilation (p = 0.002).CONCLUSIONS:There were considerable differences in AKI incidence and staging among definitions. Compared with pRIFLE and KDIGO, AKI defined by pROCK was significantly reduced and better associated with postoperative adverse outcomes.
BMC nephrology 2023
BACKGROUND:Acute kidney injury (AKI) is a common complication following cardiopulmonary bypass (CPB) which can affect morbidity and mortality. Goal-directed perfusion (GDP) intended to avoid the nadir oxygen delivery index below the critical value is associated with reduced postoperative AKI. However, current studies suggested that GDP can only decrease the incidence of AKI stage 1 but showed no effects on AKI stages 2-3 and mortality. The objective of the present meta-analysis is to deter the effects of GDP on postoperative AKI in any stage and mortality following cardiac surgery.METHODS:MEDLINE, Embase, and the Cochrane Library were searched to identify all clinical trials comparing GDP with control (standard care) during cardiopulmonary bypass conducting in adults undergoing cardiac surgery. The primary outcome was postoperative acute kidney injury. Secondary outcomes included postoperative mortality and length of ICU stay. Data synthesis was obtained by using risk ratio with 95% confidence interval by a random-effects model.RESULT:From 1094 potential studies, 3 trials enrolling 777 patients were included. Meta-analysis suggested the GDP strategy based on DO2i reduced postoperative AKI compared with standard CPB management (RR = 0.52; 95% CI: 0.38-0.70; p < .0001), especially in AKI stage I (RR = 0.47; 95% CI: 0.33-0.66; p < .0001). But the GDP strategy did not reduce the incidence of severe AKI (stages 2-3) and postoperative mortality.CONCLUSION:The GDP strategy based on DO2i during CPB obviously reduces AKI stage 1 and thus reduces overall AKI incidence. But it shows no effects on severe AKI (stages 2-3) and mortality.
Perfusion 2023
Background:Extracorporeal membrane oxygenation (ECMO) and COVID-19 significantly impact the coagulation system. A systematic review and meta-analysis were performed to explore the prevalence of thrombotic and bleeding events in patients with COVID-19 supported with ECMO, summarize anticoagulation regimens, and guide future research.Methods:Cochrane, EMBASE, Scopus, and PubMed were searched for studies examining thrombosis and bleeding in patients with COVID-19 requiring ECMO. The primary outcomes were the prevalences of different types of hemorrhage and thrombosis. The pooled estimated rates and relative risk (RR) were calculated to summarize the outcomes.Results:Twenty-three peer-reviewed studies involving 6878 subjects were included. For thrombotic events, the prevalence of circuit thrombosis was 21.5% (95% CI: 15.5%-27.6%; 1532 patients), that of ischemic stroke was 2.6% (95% CI: 1.5%-3.7%; 5926 patients), and that of pulmonary embolism (PE) was 11.8% (95% CI: 6.8%-16.8%; 5853 patients). For bleeding events, 37.4% of the patients experienced major hemorrhage (95% CI: 28.1%-46.8%; 1558 patients) and 9.9% experienced intracranial hemorrhage (ICH; 95% CI: 7.8%-12.1%; 6348 patients). COVID-19 cases on ECMO were complicated with more ICH than patients without COVID-19 on respiratory ECMO [RR = 2.23 (95% CI: 1.32-3.75)]. Anticoagulation strategies varied among centers.Conclusions:Circuit thrombosis and major bleeding were the most common thrombotic and bleeding events. The incidence of ICH was significantly higher when ECMO was indicated for COVID-19 than for other respiratory diseases. There is no evidence for stronger anticoagulation practice, and remains no consistent anticoagulation strategy to reduce the occurrence of thrombosis and bleeding under the double "hit" of COVID-19 and ECMO.
Research and practice in thrombosis and haemostasis 2023
OBJECTIVES:This study sought to estimate the effect of dexmedetomidine (DEX) administration on mortality in critically ill patients with acute kidney injury (AKI).DESIGN:A retrospective cohort study.SETTING:The study sourced its data from the Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV), a comprehensive database of intensive care unit patients.PARTICIPANTS:A total of 15 754 critically ill patients with AKI were enrolled from the MIMIC-IV database.PRIMARY AND SECONDARY OUTCOME:Primary outcome was in-hospital mortality and secondary outcome was 180-day mortality.RESULTS:15 754 critically ill AKI patients were included in our analysis. We found that DEX use decreased in-hospital mortality risk by 38% (HR 0.62, 95% CI 0.55 to 0.70) and 180-day mortality risk by 23% (HR 0.77, 95% CI 0.69 to 0.85). After adjusting for confounding factors, DEX can reduce all three stages of AKI in in-hospital mortality.CONCLUSIONS:Our retrospective cohort study suggests that DEX significantly correlates with decreased risk-adjusted in-hospital and 180-day mortality in critically ill AKI patients. Nonetheless, future randomised controlled trials are warranted to validate our findings.
BMJ open 2023
BACKGROUND:Heparin resistance (HR) is a common finding in pediatric cardiac surgery and generally refers to decreased sensitivity to heparin. Antithrombin (AT) deficiency is considered the primary mechanism of HR; however, the etiology of HR may be multifactorial. Early identification of HR might help optimize heparin anticoagulation management. This study aimed to develop a predictive nomogram for HR in neonates and young infants undergoing cardiac surgery.METHODS:From January 2020 to August 2022, a total of 296 pediatric patients 1 to 180 days of age were included in this retrospective study. The patients were randomly divided into development and validation cohorts in a 7:3 ratio. Univariable logistic regression and the Least Absolute Shrinkage and Selection Operator (LASSO) regularization were used for variable selection. A multivariable logistic regression was performed to identify predictors and establish a nomogram to predict HR risk. Discrimination, calibration, and clinical usefulness were assessed in the development and validation cohorts.RESULTS:After the multistep variable selection, AT activity, platelet count, and fibrinogen were predictors for HR in neonates and young infants. The prediction model constructed using these 3 factors achieved an area under the receiver operating characteristic curve (ROC-AUC) of 0.874 and 0.873 in the development and validation cohorts. The Hosmer-Lemeshow test did not find evidence of a lack of fit (P = .768). The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, the model performed well in neonate and infant subgroups.CONCLUSIONS:A nomogram based on preoperative variables was developed to predict the HR risk in neonates and young infants undergoing cardiac surgery. This provides clinicians with a simple tool for the early prediction of HR, which may help optimize heparin anticoagulation strategies in this vulnerable patient population.
Anesthesia and analgesia 2023
PURPOSE:Extracorporeal membrane oxygenation (ECMO) is employed to support critically ill COVD-19 patients. The occurrence of ischemic stroke and intracranial hemorrhage (ICH), as well as the implementation of anticoagulation strategies under the dual influence of ECMO and COVID-19 remain unclear. We conducted a systematic review and meta-analysis to describe the ischemic stroke, ICH and overall in-hospital mortality in COVID-19 patients receiving ECMO and summarize the anticoagulation regimens.METHODS:EMBASE, PubMed, Cochrane, and Scopus were searched for studies examining ischemic stroke, ICH, and mortality in COVID-19 patients supported with ECMO. The outcomes were incidences of ischemic stroke, ICH, overall in-hospital mortality and anticoagulation regimens. We calculated the pooled proportions and 95% confidence intervals (CIs) to summarize the results.RESULTS:We analyzed 12 peer-reviewed studies involving 6039 COVID-19 patients. The incidence of ischemic stroke had a pooled estimate of 2.2% (95% CI: 1.2%-3.2%). The pooled prevalence of ICH was 8.0% (95% CI: 6.3%-9.6%). The pooled estimate of overall in-hospital mortality was 40.3% (95% CI: 33.1%-47.5%). The occurrence of ICH was significantly higher in COVID-19 patients supported with ECMO than in other respiratory ECMO [relative risk=1.75 (95% CI: 1.00-3.07)]. Unfractionated heparin was the most commonly used anticoagulant, and anticoagulation monitoring practice varied among centers.CONCLUSIONS:Ischemic stroke and ICH were common under the double "hit" of COVID-19 and ECMO. The prevalence of ICH was significantly higher in COVID-19 patients supported with ECMO than non-COVID-19 patients requiring ECMO. Individualized anticoagulation regimens may be a good choice to balance thrombosis and bleeding. More detailed research and further exploration are needed to clarify the underlying mechanism and clinical management decisions.
Perfusion 2023
Background:Pediatric postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients have high mortality and morbidity. There are currently three scoring systems available to predict mortality: the Pediatric Extracorporeal Membrane Oxygenation Prediction (PEP) model, Precannulation Pediatric Survival After VA-ECMO (Pedi-SAVE) score, and Postcannulation Pedi-SAVE score. These methods provide risk stratification scores for pediatric patients requiring ECMO for cardiac support. However, comparative validation of these scoring systems remains scarce. We aim to assess the ability of these models to predict outcomes in a cohort of pediatric patients undergoing VA-ECMO after cardiac surgery, and identify predictors of in-hospital mortality.Methods:A retrospective analysis of 101 children admitted to Fuwai Hospital who received VA-ECMO from January 1, 2010 to December 31, 2020 was performed. Patients were divided into two groups, survivors (n = 49) and non-survivors (n = 52) according to in-hospital mortality. PEP model and Pedi-SAVE scores were calculated. The primary outcomes were the risk factors of in-hospital mortality, and the ability of the PEP model, Precannulation Pedi-SAVE and Postcannulation Pedi-SAVE scores to predict in-hospital mortality.Results:Postcannulation Pedi-SAVE score accessing the entire ECMO process had the greatest area under receiver operator curve (AUROC), 0.816 [95% confidence interval (CI): 0.733-0.899]. Pre-ECMO PEP model could predict in-hospital mortality [AUROC = 0.691 (95% CI: 0.565-0.817)], and Precannulation Pedi-SAVE score had the poorest prediction [AUROC = 0.582(95% CI: 0.471-0.694)]. Lactate value at ECMO implantation [OR = 1.199 (1.064-1.351), P = 0.003] and infectious complications [OR = 5.169 (1.652-16.172), P = 0.005] were independent risk factors for in-hospital mortality.Conclusion:Pediatric cardiac ECMO scoring systems, including multiple risk factors before and during ECMO, were found to be useful in this cohort. Both the pre-ECMO PEP model and the Postcannulation Pedi-SAVE score were found to have high predictive value for in-hospital mortality in pediatric postcardiotomy VA-ECMO.
Frontiers in medicine 2022
Many measures have been proposed for myocardial protection in pediatric congenital heart surgeries, but little data is available for China. This study investigates myocardial protection strategies in pediatric cardiopulmonary bypass (CPB) throughout China. Online questionnaires were delivered to 100 hospitals in 27 provinces. The number of yearly on-pump pediatric cardiovascular surgeries in these hospitals varied greatly. About 91.0% of respondents believe that each surgery should have at least two perfusionists, while only 64.0% of hospitals actually met this requirement. For pediatric patients, crystalloid cardioplegia was more prevalent than blood-based cardioplegia. Histidine-tryptophan-ketoglutarate solution and St. Thomas crystalloid solution were dominant among crystalloid cardioplegia. Del Nido cardioplegia and St. Thomas blood-based cardioplegia ranked the top two in the popularity of blood-based cardioplegia. Dosages varied among different kinds of cardioplegia. In the choice of different cardioplegia, perfusionists mainly focused on myocardial protective effect and cost. Hypothermia of cardioplegia solution was maintained by ice buckets in 3/4 of the hospitals in this survey. In conclusion, the essence of myocardial protection management during pediatric CPB was cardiac arrest induced by cardioplegia under systemic hypothermia. However, there is no uniform standard for the type of cardioplegia, or dosages. Therefore, well-designed multicenter randomized controlled trials are warranted to provide tangible evidence for myocardial protection of cardioplegia in pediatric CPB.
Perfusion 2022
