Hybrid feature selection in a machine learning predictive model for perioperative myocardial injury in noncoronary cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Perioperative myocardial injury (PMI) is associated with increased mobility and mortality after noncoronary cardiac surgery. However, limited studies have developed a predictive model for PMI. Therefore, we used hybrid feature selection (FS) methods to establish a predictive model for PMI in noncoronary cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This was a single-center retrospective study conducted at the Fuwai Hospital in China. Patients aged 18-70 years who underwent elective noncoronary surgery with CPB at our institution from December 2018 to April 2021 were enrolled. The primary outcome was PMI, defined as the postoperative cardiac troponin I (cTnI) levels exceeding 220 times of upper reference limit (URL). Statistical analyses were conducted by Python (Python Software Foundation, version 3.9.7 and integrated development environment Jupyter Notebook 1.1.0) and SPSS software version 26.0 (IBM Corp., Armonk, New York, USA). RESULTS: A total of 1130 patients were eventually eligible for this study. The incidence of PMI was 20.3% (229/1130) in the overall patients, 20.6% (163/791) in the training dataset, and 19.5% (66/339) in the testing dataset. The logistic regression model performed the best AUC of 0.6893 (95 CI%: 0.6371-0.7382) by the traditional selection method, and the random forest model performed the best AUC of 0.6937 (95 CI%: 0.6416-0.7423) by the union of Wrapper and Embedded method, and the CatBoost model performed the best AUC of 0.6828 (95 CI%: 0.6304-0.7320) by the union of Embedded and forward logistic regression technique, and the Naïve Bayes model achieved the best AUC with 0.7254 (95 CI%: 0.6746-0.7723) by forwarding logistic regression method. Moreover, the decision tree, KNeighborsClassifier, and support vector machine models performed the worse AUC in all selection forms. Furthermore, the SHapley Additive exPlanations plot showed that prolonged CPB, aortic clamp time, and preoperative low platelets count were strongly related to the PMI risk. CONCLUSIONS: In total, four category feature selection methods were utilized, comprising five individual selection techniques and 15 combined methods. Notably, the combination of logistic regression and embedded methods demonstrated outstanding performance in predicting PMI risk. We also concluded that the machine learning model, including random forest, catboost, and Naive Bayes, were suitable candidates for establishing PMI predictive model. Nevertheless, additional investigation and validation are imperative for substantiating these finding.

Effect of Perioperative Nicorandil on Myocardial Protection in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass, a Retrospective Study.

Background: The potential myocardial protective effect of nicorandil (NICD) in patients undergoing percutaneous coronary intervention has been established. However, its efficacy in the context of cardiac surgery remains controversial. The present study aimed to evaluate the myocardial protective effect of perioperative NICD use in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: We retrospectively gathered data from patients undergoing cardiac bypass surgery between 12/2018 and 04/2021 in Fuwai Hospital. Subsequently, the patients were divided into two groups, NICD group and non-nicorandil (non-NICD) group. A 1, 3 propensity score matching (PSM) was conducted. The primary outcome was the incidence of myocardial injury. The secondary outcomes included the mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of chest drainage, the drainage volume, the total cost, the incidence of acute kidney injury (AKI), and the incidence of acute liver injury (ALI). Subsequently, we divided the entire population into two distinct subgroups based on their administration of NICD, and performed a comprehensive subgroup analysis. Results: A total of 2406 patients were ultimately included in the study. After PSM, 250 patients in NICD group and 750 patients in non-NICD group were included in the analysis. Perioperative NICD reduced the incidence of myocardial injury (47.2% versus 38.8%, P=0.025). Our subgroup analysis revealed that preoperative NICD administration not only provided myocardial protection benefits (45.7% vs 35.8%, OR 0.66, 95% CI [0.45-0.97], P=0.041), but also demonstrated statistically significant reduction in ALI, the ICU and hospital LOS, and the duration of chest drainage (all P<0.05). Conclusion: The perioperative NICD administration may confer myocardial protection in patients undergoing cardiac surgery with CPB. Furthermore, the preoperative utilization of NICD has the potential to mitigate the incidence of postoperative ALI, a reduction in the ICU and hospital LOS, and the duration of chest drainage.

Novel sizing role of 3D transesophageal echocardiography in a novel left atrial appendage clip device for patients undergoing video-assisted atrial fibrillation ablation: a cohort study.

Background: Three-dimensional (3D) transesophageal echocardiography (TEE) has been successfully used in the sizing of left atrial appendage (LAA) occlusion devices, but its use has not yet been studied in LAA clip devices. We sought to develop and validate the novel use of 3D-TEE sizing in a novel LAA clip device for atrial fibrillation (AF) patients undergoing video-assisted thoracic surgery (VATS) ablation. Methods: Consecutive patients with isolated AF undergoing LAA clipping or excision during VATS ablation were included in the study between June 2021 and September 2022 at Fuwai Hospital. The patients underwent 3D-TEE examinations preoperatively and postoperatively. The VATS length, LAA clip effective length, and LAA excision margin length were recorded. A correlation analysis, intraclass correlation coefficient (ICC) analysis, and Bland-Altman plot analysis were conducted to examine the TEE parameters, VATS length, LAA clip effective length, and LAA excision margin length. Results: In total, 26 AF patients undergoing LAA clipping and 15 undergoing LAA excision were included in the study. In the LAA clipping group, in which the Atriclip size served as the control, the 3D-TEE with volumetric measurement (the perimeter-derived maximum orifice diameter) (R=0.938; ICC =0.934; Bland-Altman plot variability, 3.85%) showed the best sizing efficacy for the LAA clip device among the 3D-TEE with multiplanar reformatting sizing (the perimeter-derived maximum orifice diameter) (R=0.808; ICC =0.772; Bland-Altman plot variability, 3.85%), VATS sizing (R=0.851; ICC =0.756; Bland-Altman plot variability, 11.54%), and VATS plus 0.5-cm sizing (R=0.851; ICC =0.775; Bland-Altman plot variability, 11.54%) measurements (all P<0.001). In addition, for the distribution of matched sizing in the LAA clip group, 3D-TEE with volumetric measurement sizing (20/26) had a higher proportion than 3D-TEE with multiplanar reformatting sizing (11/26, P=0.011), VATS sizing (9/26, P=0.002), and VATS plus 0.5-cm sizing (14/26, P=0.08). Using the LAA excision margin length as the control, the mean difference in the LAA diameter was 1.17 cm [95% confidence interval (CI): 0.71-1.62 cm , P<0.001] in the maximum orifice diameter of two-dimensional-TEE, 0.15 cm (95% CI: -0.32 to 0.61 cm , P=0.523) in the perimeter-derived 3D multiplanar reformatting (the maximum orifice diameter), and 0.03 cm (95% CI: -0.47 to 0.53, P=0.901) in the perimeter-derived 3D volumetric (3DV) measurement (the maximum orifice diameter), and the related Pearson correlation coefficients for these modalities were 0.760 (P=0.001), 0.843 (P<0.001), and 0.963 (P<0.001), respectively. Conclusions: Our study showed that 3D-TEE might be employed in the sizing of a novel LAA clip device using the VATS approach in patients with AF. The 3DV measurement (the perimeter-derived maximum orifice diameter) was superior to the VATS measurement. These findings might also apply to LAA VATS excision patients with AF.

Development and validation of a machine learning prediction model for perioperative red blood cell transfusions in cardiac surgery.

OBJECTIVE: Several machine learning (ML) models have been used in perioperative red blood cell (RBC) transfusion risk for cardiac surgery with limited generalizability and no external validation. Hence, we sought to develop and comprehensively externally validate a ML model in a large dataset to estimate RBC transfusion in cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: A retrospective analysis of a multicenter clinical trial (NCT03782350). PATIENTS: The study patients who underwent cardiac surgery with CPB came from four cardiac centers in China and Medical Information Mart for Intensive Cared (MIMIC-IV) dataset. MEASUREMENTS: Data from Fuwai Hospital were used to develop an individualized prediction model for RBC transfusion. The model was externally validated in the data from three other centers and MIMIC-IV dataset. Twelve models were constructed. MAIN RESULTS: A total of 11,201 eligible patients were included in the model development (2420 in Fuwai Hospital) and external validation (563 in the other three centers and 8218 in the MIMIC-IV dataset). A significant difference was observed between the Logistic Regression and CatboostClassifier (0.72 Vs. 0.74, P = 0.031) or RandomForestClassifier (0.72 Vs. 0.75 p = 0.012) in the external validation and MIMIV-IV datasets (age ≤ 70:0.63 Vs. 0.71, p < 0.001; age > 70:0.63 Vs. 0.70, 0.63 Vs. 0.71, p < 0.001). The CatboostClassifier and RandomForestClassifier model was comparable in development (0.83 Vs. 0.82, p = 0.419), external (0.74 Vs. 0.75, p = 0.268), and MIMIC-IV datasets (age ≤ 70: 0.71 Vs. 0.71, p = 0.574; age > 70: 0.70 Vs. 0.71, p = 0.981). Of note, they outperformed other ML models with excellent discrimination and calibration. The CatboostClassifier and RandomForestClassifier models achieved higher area under precision-recall curve and lower brier loss score in validation and MIMIC-IV datasets. Additionally, we confirmed that low preoperative hemoglobin, low body mass index, old age, and female sex increased the risk of RBC transfusion. CONCLUSIONS: In our study, enrolling a broad range of cardiovascular surgeries with CPB and utilizing a restrictive RBC transfusion strategy, robustly validates the generalizability of ML algorithms for predicting RBC transfusion risk. Notably, the CatboostClassifier and RandomForestClassifier exhibit strong external clinical applicability, underscoring their potential for widespread adoption. This study provides compelling evidence supporting the efficacy and practical value of ML-based approaches in enhancing transfusion risk prediction in clinical practice.

Effect of percutaneous cerebral oximetry-guided anaesthetic management on postoperative delirium in older adults undergoing off-pump coronary artery bypass grafting: study protocol for a single-centre prospective randomised controlled trial in a tertiary academic hospital in China.

INTRODUCTION: Postoperative delirium is a prominent and clinically important complication in older adults after coronary artery bypass grafting (CABG) surgery, resulting in prolonged hospital stay, long-term cognitive impairment and increased morbidity and mortality. Many studies have shown that cerebral desaturation is associated with increased risk of postoperative delirium during on-pump cardiac surgery. However, few studies have focused on the effect of optimising regional cerebral oxygen saturation (rSO2) on postoperative delirium during off-pump CABG. The purpose of this study is to investigate whether intraoperative anaesthetic management based on percutaneous cerebral oximetry monitoring decreases the incidence of postoperative delirium in older adults undergoing off-pump CABG. METHODS: This single-centre randomised controlled trial will randomly assign 200 patients to the intervention group or the control group at a ratio of 1:1. The patients in the intervention group will be observed by percutaneous cerebral oximetry monitoring that the desaturation (a drop of more than 20% from baseline value or rSO2 less than 55% for >60 consecutive seconds at either probe) during the procedure triggered the intervention strategies, while the cerebral oximetry data of the control group will be hidden from the clinical team and patients will be anaesthetised by the usual anaesthetic management. The primary outcome will be the incidence of postoperative delirium during the first 7 days after off-pump CABG. Delirium will be comprehensively evaluated by the combination of the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the intensive care unit. The secondary outcomes will include the incidence of postoperative acute kidney injury and myocardial infarction during the hospital stay, as well as the intensive care unit and hospital length of stay. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of the Chinese Academy of Medical Sciences, Fuwai Hospital (No 2022-1824). Written informed consent will be obtained from each patient or their legal representatives before enrolment. The results of this trial will be published in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ChiCTR2300068537.

Postoperative elevated cardiac troponin levels predict all-cause mortality and major adverse cardiovascular events following noncardiac surgery: A dose-response meta-analysis of prospective studies.

STUDY OBJECTIVE: To perform a dose-response meta-analysis for the association between postoperative myocardial injury (PMI) in noncardiac surgery and the risk of all-cause mortality or major adverse cardiovascular event (MACE). DESIGN: Dose-response meta-analysis of prospective studies with weighted (WL) or generalized (GL) linear and restricted cubic spline (RCS) regression. SETTING: Teaching hospitals. PATIENTS: Adult patients undergoing noncardiac surgery. INTERVENTIONS: No. MEASUREMENTS: The primary outcome was all-cause mortality. The secondary outcome was MACE. MAIN RESULTS: 29 studies (53,518 patients) were included. The overall incidence of PMI was 26.0% (95% CI 21.0% to 32.0%). Compared to those without PMI, patients with PMI had an increased risk of all-cause mortality at short- (<12 months) (cardiac troponin[cTn]I: unadj OR 1.71,95%CI 1.22 to 2.41, P < 0.001; cTnT: unadj OR 2.33,95%CI 2.07 to 2.63, P < 0.001), and long-term (≥ 12 months) (cTnI: unadj OR 1.80, 95%CI 1.63 to 1.99; cTnT: unadj OR 1.47,95%CI 1.33 to 1.62) (All P < 0.001) follow-up. For MACE, the group with elevated values was associated with an increased risk (cTnI: unadj OR 1.98, 95% CI 1.13 to 3.47, P = 0.018; cTnT: unadj OR 2.29, 95% CI 1.88 to 2.79, P < 0.001). Dose-response analysis showed positive associations between PMI (per 1× upper reference limit[URL] increment) and all-cause mortality both at short- (unadj OR) (WL, OR 1.09, 95% CI 1.09 to 1.10; GL, OR 1.06, 95% CI 1.06 to 1.07; RCS in the range of 1-2× URL, OR = 2.43, 95%CI 2.25 to 2.62) and long-term follow-up (unadj HR) (WL, OR 1.16, 95% CI 1.14 to 1.17; GL, OR 1.15, 95% CI 1.13 to 1.16; RCS in the range of 1-2.75× URL, OR = 1.23, 95%CI 1.13 to 1.33), and MACE at longest follow-up (unadj OR) (WL: OR 1.53, 95% CI 1.49 to 1.57; GL: OR 1.46, 95% CI 1.42 to 1.50; RCS in the range of 1-2 x URL, OR = 3.10, 95%CI 2.51 to 3.81) (All P < 0.001). For mild cTn increase below URL, the risk of mortality increased with every increment of 0.25xURL (WL, OR 1.03, 95% CI 1.02 to 1.03; GL, OR 1.05, 95% CI 1.03 to 1.07; RCS in the range of 0-0.5 URL, OR = 9.41, 95% CI 7.41 to 11.95) (All P < 0.001). CONCLUSIONS: This study shows positive WL or GL and RCS dose-response relationships between PMI and all-cause mortality at short (< 12 mons)- and long-term (≥ 12 mons) follow-up, and MACE at longest follow-up. For mild cTn increase below URL, the risk of mortality also increases even with every increment of 0.25× URL.

Early results of frozen elephant trunk in acute type-A dissection in 1445 patients.

BACKGROUND: We aimed to briefly describe the use of total arch replacement with frozen elephant trunk in our center's 12-year treatment of acute type A dissection and the early postoperative results. We summarized the practical experience of this procedure in our center and performed regression analyses to find the independent risk factors for major complications. METHODS: Consecutive patients with acute type A dissection having surgical total arch replacement with the implantation of a frozen elephant trunk were collected from January 2010 to December 2021 and were included in the analysis. For each major operation-related complication, independent risk factors were identified using both univariate and multivariate regression models. RESULTS: In our institution, the total arch replacement with frozen elephant trunk procedure is used more frequently each year and makes up 70% of the surgical procedures for acute type A dissection. The overall postoperative mortality rate was 6.2%, which declined as the techniques (including surgical procedures, organ perfusion protection etc.) improved. Other complications include: 11.7% for continuous renal replacement therapy, 5.7% for stroke, 17.8% for ICU stay longer than 7 days, 10.9% for prolonged mechanical ventilation, and so on. According to regression analysis, different major complications had different independent risk factors. Several factors, such as advanced age, impaired renal function, and extended cardiopulmonary bypass time, were found to be implicated in nearly all of the complications. CONCLUSION: Total arch replacement plus frozen elephant trunk strategy is a safe surgical method for extensive acute type A dissection. Some factors, such as advanced age, impaired renal function, and prolonged cardiopulmonary bypass time, might be associated with poor prognosis.

The effects of chemotherapy, primary tumor location and histological subtype on the survival of stage III colon cancer patients.

OBJECTIVE: Colon cancer (CC) is one of the most common cancers worldwide and has a poor prognosis. Surgery followed by adjuvant chemotherapy is the standard treatment strategy for stage III CC patients. Primary tumor location (PTL) is an important factor for the long-term survival of CC. However, the difference in the prognosis between the histological subtypes of mucinous adenocarcinoma (MAC) and nonspecific adenocarcinoma (AC) in stage III CC patients is unclear. The correlation of chemotherapy, PTL and histological subtype with the overall survival (OS) of stage III CC patients has not yet been explored. METHODS: Patients diagnosed with stage III CC from 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The clinicopathological features and OS were analyzed according to the chemotherapy, PTL and histological subtype. RESULTS: A total of 28,765 eligible stage III CC patients were enrolled in this study. The results showed that chemotherapy, left-sided CC (LCC) and AC were favorable prognostic factors for OS. Right-sided CC (RCC) had worse OS than LCC regardless of chemotherapy. MAC had worse OS than AC in the patients with chemotherapy, but the survival benefits disappeared in the patients without chemotherapy. Additionally, in LCC, MAC had worse OS than AC regardless of chemotherapy. However, in RCC, MAC had worse OS than AC in patients with chemotherapy but had similar OS to AC in patients without chemotherapy. In the AC group, RCC had worse OS than LCC regardless of chemotherapy. In the MAC group, RCC had comparable OS to LCC regardless of chemotherapy. Four subgroups, i.e., RCC/MAC, RCC/AC, LCC/MAC and LCC/AC, all showed benefits from chemotherapy. Among them, LCC/AC had the best OS, and RCC/MAC had the worst OS compared with the other three subgroups. CONCLUSION: The prognosis of MAC is worse than that of AC in stage III CC. LCC/AC has the best OS, while RCC/MAC has the worst OS but still benefits from chemotherapy. The impact of chemotherapy on survival is greater than that of histological subtype, but the impact of histological subtype on survival is similar to that of PTL.

Development and Validation of a Machine Learning Predictive Model for Cardiac Surgery-Associated Acute Kidney Injury.

OBJECTIVE: We aimed to develop and validate a predictive machine learning (ML) model for cardiac surgery associated with acute kidney injury (CSA-AKI) based on a multicenter randomized control trial (RCT) and a Medical Information Mart for Intensive Care-IV (MIMIC-IV) dataset. METHODS: This was a subanalysis from a completed RCT approved by the Ethics Committee of Fuwai Hospital in Beijing, China (NCT03782350). Data from Fuwai Hospital were randomly assigned, with 80% for the training dataset and 20% for the testing dataset. The data from three other centers were used for the external validation dataset. Furthermore, the MIMIC-IV dataset was also utilized to validate the performance of the predictive model. The area under the receiver operating characteristic curve (ROC-AUC), the precision-recall curve (PR-AUC), and the calibration brier score were applied to evaluate the performance of the traditional logistic regression (LR) and eleven ML algorithms. Additionally, the Shapley Additive Explanations (SHAP) interpreter was used to explain the potential risk factors for CSA-AKI. RESULT: A total of 6495 eligible patients undergoing cardiopulmonary bypass (CPB) were eventually included in this study, 2416 of whom were from Fuwai Hospital (Beijing), for model development, 562 from three other cardiac centers in China, and 3517 from the MIMICIV dataset, were used, respectively, for external validation. The CatBoostClassifier algorithms outperformed other models, with excellent discrimination and calibration performance for the development, as well as the MIMIC-IV, datasets. In addition, the CatBoostClassifier achieved ROC-AUCs of 0.85, 0.67, and 0.77 and brier scores of 0.14, 0.19, and 0.16 in the testing, external, and MIMIC-IV datasets, respectively. Moreover, the utmost important risk factor, the N-terminal brain sodium peptide (NT-proBNP), was confirmed by the LASSO method in the feature section process. Notably, the SHAP explainer identified that the preoperative blood urea nitrogen level, prothrombin time, serum creatinine level, total bilirubin level, and age were positively correlated with CSA-AKI; preoperative platelets level, systolic and diastolic blood pressure, albumin level, and body weight were negatively associated with CSA-AKI. CONCLUSIONS: The CatBoostClassifier algorithms outperformed other ML models in the discrimination and calibration of CSA-AKI prediction cardiac surgery with CPB, based on a multicenter RCT and MIMIC-IV dataset. Moreover, the preoperative NT-proBNP level was confirmed to be strongly related to CSA-AKI.

Dietary cholesterol consumption and incidence of type 2 diabetes mellitus: A dose-response meta-analysis of prospective cohort studies.

BACKGROUND AND AIM: The purpose of this meta-analysis was to evaluate the dose-response relationship between dietary cholesterol (DC) consumption and the incidence of type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Prospective studies with the endpoint of T2DM were included. The Random-effect model weighted by inverse variance was used. Meta-regression and subgroup analyses were conducted to explore the potential sources of heterogeneity by specified study characteristics. Restricted cubic splines regression models were used to estimate the dose-response relationship. 11 prospective studies comprising of 355 230 subjects were included. Compared to lowest DC consumption, highest DC consumption was associated with an increased risk of T2DM (RR 1.15, 95% CI 1.03 to 1.28, P = 0.012; chi-squared = 31.41, I-squared 58.6%, P heterogeneity = 0.003). Subgroup analyses have shown that this positive association was more evident in western countries than in eastern countries (RR 1.19, 95% CI 1.06 to 1.36 VS 1.34, 95% CI 0.84 to 1.29; P subgroup difference = 0.02). For 100 mg/d increment in DC intake, the pooled RR was 1.05, (95% CI 1.04 to 1.07, Plinearity = 0.000, Pnonlinearity = 0.02), 1.06 (95% CI 1.04 to 1.07, Plinearity=0.000), and 1.01 (95% CI 0.98 to 1.05, Plinearity = 0.525) for the incidence of T2DM, in western and eastern countries, respectively. CONCLUSIONS: Our study suggests that there is a positive dose-response association between DC consumption and the incidence of T2DM, especially in western countries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020216318.

Incidence, risk factors, and outcomes in electroencephalographic seizures after mechanical circulatory support: A systematic review and meta-analysis.

Purpose: To estimate the overall incidence, risk factors, and clinical outcomes of electroencephalographic (EEG) seizures for adults and children after mechanical circulatory support (MCS). Method and measurements: This systematic review and meta-analysis were carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidance document. MEDLINE EMBASE and CENTRAL were investigated for relevant studies. The related information was retrieved by two independent reviewers and all analyses were conducted by STATA (version 16.0; Stata Corporation, College Station, TX, United States). Result: Sixty studies including 36,191 adult and 55,475 pediatric patients with MCS were enrolled for evaluation. The study showed that the overall incidence of EEG seizures in adults was 2% (95%CI: 1-3%), in which 1% (95%CI: 1-2%) after cardiopulmonary bypass (CPB), and 3% (95%CI: 1-6%) after extracorporeal membrane oxygenation (ECMO). For pediatrics patients, the incidence of EEG seizures was 12% (95%CI: 11-14%), among which 12% (9-15%) after CPB and 13% (11-15%) after ECMO. The major risk factors of EEG seizures after MCS in adults were redo surgery (coefficient = 0.0436, p = 0.044), and COPD (coefficient = 0.0749, p = 0.069). In addition, the gestational week of CPB (coefficient = 0.0544, p = 0.080) and respiratory failure of ECMO (coefficient = -0.262, p = 0.019) were also indicated to be associated with EEG seizures in pediatrics. Conclusion: EEG seizures after MCS were more common in pediatrics than in adults. In addition, the incidence of EEG seizure after ECMO was higher than CPB both in adults and children. It is expected that appropriate measures should be taken to control modifiable risk factors, thus improving the prognosis and increasing the long-term survival rate of MCS patients. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], identifier [CRD42021287288].

Effect of High- vs Low-Dose Tranexamic Acid Infusion on Need for Red Blood Cell Transfusion and Adverse Events in Patients Undergoing Cardiac Surgery: The OPTIMAL Randomized Clinical Trial.

Importance: Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery. Objective: To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants: Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to April 21, 2021; final follow-up was on May 21, 2021. Interventions: Participants received either a high-dose tranexamic acid regimen comprising a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose, and a 2-mg/kg prime (n = 1525) or a low-dose regimen comprising a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, and a 1-mg/kg prime (n = 1506). Main Outcomes and Measures: The primary efficacy end point was the rate of allogeneic red blood cell transfusion after start of operation (superiority hypothesis), and the primary safety end point was a composite of the 30-day postoperative rate of mortality, seizure, kidney dysfunction (stage 2 or 3 Kidney Disease: Improving Global Outcomes [KDIGO] criteria), and thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis, and pulmonary embolism) (noninferiority hypothesis with a margin of 5%). There were 15 secondary end points, including the individual components of the primary safety end point. Results: Among 3079 patients who were randomized to treatment groups (mean age, 52.8 years; 38.1% women), 3031 (98.4%) completed the trial. Allogeneic red blood cell transfusion occurred in 333 of 1525 patients (21.8%) in the high-dose group and 391 of 1506 patients (26.0%) in the low-dose group (risk difference [RD], -4.1% [1-sided 97.55% CI, -∞ to -1.1%]; relative risk, 0.84 [1-sided 97.55% CI, -∞ to 0.96; P = .004]). The composite of postoperative seizure, thrombotic events, kidney dysfunction, and death occurred in 265 patients in the high-dose group (17.6%) and 249 patients in the low-dose group (16.8%) (RD, 0.8%; 1-sided 97.55% CI, -∞ to 3.9%; P = .003 for noninferiority). Fourteen of the 15 prespecified secondary end points were not significantly different between groups, including seizure, which occurred in 15 patients (1.0%) in the high-dose group and 6 patients (0.4%) in the low-dose group (RD, 0.6%; 95% CI, -0.0% to 1.2%; P = .05). Conclusions and Relevance: Among patients who underwent cardiac surgery with cardiopulmonary bypass, high-dose compared with low-dose tranexamic acid infusion resulted in a modest statistically significant reduction in the proportion of patients who received allogeneic red blood cell transfusion and met criteria for noninferiority with respect to a composite primary safety end point consisting of 30-day mortality, seizure, kidney dysfunction, and thrombotic events. Trial Registration: ClinicalTrials.gov Identifier: NCT03782350.

Myocardial Injury Predicts Risk of Short-Term All-Cause Mortality in Patients With COVID-19: A Dose-Response Meta-Analysis.

Objective: Predictive value of myocardial injury as defined by elevated cardiac tropnins (cTns) in patients with COVID-19 has not been fully investigated. We performed a meta-analysis to evaluate the dose-response relationship between myocardial injury and short-term all-cause mortality. Methods: Pubmed, Embase, and the Cochrane Library database were searched for all the studies which evaluated the relationship between cTns and the risk of short-term all-cause mortality in patients with COVID-19. Results: Compared with patients without myocardial injury, the group with elevated cTns was associated with increased short-term mortality (11 studies, 29,128 subjects, OR 3.17, 95% CI 2.19-4.59, P = 0.000, I 2 = 92.4%, P for heterogeneity 0.00). For the dose-response analysis, the elevation of cTns 1 × 99th percentile upper reference limit (URL) was associated with increased short-term mortality (OR 1.99, 95% CI 1.53-2.58, P = 0.000). The pooled OR of short-term mortality for each 1 × URL increment of cTns was 1.25 (95% CI 1.22-1.28, P = 0.000). Conclusion: We found a positive dose-response relationship between myocardial injury and the risk of short-term all-cause mortality, and propose elevation of cTns > 1 × 99th percentile URL was associated with the increased short-term risk of mortality.

Incidence, risk factors and prognostic effect of imaging left ventricular diastolic dysfunction in patients with COVID-19: protocol for a systematic review.

INTRODUCTION: Recent reports linked acute COVID-19 infection in critical patients to cardiac structure and function abnormalities. The left ventricular (LV) diastolic dysfunction could result in obvious adverse prognostic impacts. The aim of this meta-analysis is to summarise the incidence, risk factors and the prognostic effect of imaging LV diastolic dysfunction in adult patients with COVID-19. METHODS: Databases to be used for the pertinent literature are PubMed, EMBase, ISI Knowledge via Web of Science, and preprint databases (MedRxiv and BioRxiv) (until May 2023) to identify all cohort studies in adult patients with COVID-19. The primary outcome will be the incidence of LV diastolic dysfunction assessed by echocardiography or cardiac MRI. Secondary outcomes will include the risk factors for LV diastolic dysfunction and the association with all-cause mortality during hospitalisation. Additional outcomes will be septal or lateral é, average E/é, E/A, peak tricuspid regurgitation velocity, left atrial volume index and LV wall thickness. Univariable or multivariable meta-regression and subgroup analyses will be conducted for related risk factors and the association of LV diastolic dysfunction with all-cause mortality. Sensitivity analyses will be used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of LV diastolic dysfunction incidence and related risk factors, association with all-cause mortality and other LV diastolic dysfunction parameters. ETHICS AND DISSEMINATION: There was no need for ethics approval for the systematic review protocol according to the Institutional Review Board/Independent Ethics Committee of Fuwai Hospital. This meta-analysis will be disseminated through a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42021256666; URL: https://www.crd.york.ac.uk/prospero/.

Hypertensive status is associated with renoprotection by remote ischemic conditioning for acute myocardial infarction-a meta-regression and trial sequential analysis of randomized clinical trials.

The potential modifiable factors for remote ischemic conditioning (RIC) in reducing contrast-associated acute kidney injury (CA-AKI) in patients with acute myocardial infarction (AMI) have not been investigated. The aim of this meta-regression was to address these issues.We searched Pubmed, Embase and the Cochrane Library database for published randomized controlled trials (RCTs) with registration number CRD42020155532. Nine RCTs comprising of 1540 subjects were included in our meta-analysis. Compared with control group, RIC was associated with reduced incidence of CA-AKI [(9 studies, 1540 subjects, relative risk (RR) 0.51, 95% confidence intervals (CI) 0.35 to 0.76, p = 0.000, I2 = 52%, p for heterogeneity 0.04)] and major adverse cardiovascular events (MACE) (5 studies, 1078 subjects, RR 0.52, 95% CI 0.38 to 0.73, p = 0.000, I2 = 9%, p for heterogeneity 0.36) for AMI. In addition, both meta-regression and subgroup analyses have shown that RIC was more effective in the hypertensive patients in reducing CA-AKI for AMI (regression coefficient = -0.05, p = 0.021; for subgroup with more hypertensive patients: RR 0.36, 95% CI 0.25 to 0.52 vs the one with less hypertensive patients: RR 0.72, 95% CI (0.40 to 1.30, p for subgroup difference 0.008). Subsequent trial sequential analysis confirmed the effect of RIC in both CA-AKI and MACE. RIC is an effective strategy in reducing CA-AKI and MACE in patients with AMI, especially for patients with hypertension.

Prevalence, classification, risk factors and outcome impact of delirium in patients with COVID-19: a meta-analysis protocol for systematic review.

INTRODUCTION: Previous studies have shown mixed results that delirium may result in a high risk of adverse clinical outcomes in patients with COVID-19. The aim of this meta-analysis is to summarise the evidence of prevalence, classification, risk factors and outcomes impact of delirium in adult patients with COVID-19. METHODS: A systematic search will be performed in PubMed, EMBase, ISI Knowledge via Web of Science and preprint databases (MedRxiv and BioRxiv) (from inception until June 2021) to identify all cohort studies concerning delirium in adult patients with COVID-19. The primary outcome will be the prevalence of delirium with different classifications (hyperactive, hypoactive or mixed type). The secondary outcomes will include the association of risk factors and the association with all-cause mortality during hospitalisation. Univariable or multivariable meta-regression and subgroup analyses will be conducted for the study design and patient characteristics. Sensitivity analyses were used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of primary and secondary outcomes. ETHICS AND DISSEMINATION: Ethical approval is not an essential element for the systematic review protocol in accordance with the Institutional Review Board /Independent Ethics Committee of Beijing Hospital. This meta-analysis will be disseminated through a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42020224871.

Comparison of outcomes between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in patients with locally advanced esophageal cancer: A network meta-analysis.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by surgery are two standard strategies in treating locally advanced esophageal cancer (EC). We aim to compare NCRT and NCT in the management of locally advanced EC patients. METHODS: MEDLINE, Embase, CENTRAL, and conferences were systematically searched for clinical trials published up to September 2021. Pairwise comparisons and Bayesian network meta-analyses were conducted to compare overall survival (OS) and disease-free survival (DFS) by reporting the hazard ratio (HR) and 95% credible intervals (CrIs). The study was registered at PROSPERO (CRD42020170619). FINDINGS: 25 trials with 4563 EC patients met inclusion criteria. NCRT improved OS (HR: 0·72, 95%CrI: 0·63-0·82) and DFS (HR: 0·72, 95%CrI: 0·63-0·81) compared to surgery alone. NCRT improved OS (HR: 0·83, 95%CrI: 0·69-0·99) and DFS (HR: 0·83, 95%CI: 0·69-0·99) compared to NCT. Subgroup analysis demonstrated that both NCRT (HR: 0·77, 95%CrI: 0·65-0·90) and NCT (HR: 0·81, 95%CrI: 0·67-0·99) improved OS than surgery in esophageal squamous cell carcinoma (ESCC) patients. No significant differences were observed between NCRT and NCT regarding OS (HR: 0·95, 95%CrI: 0·75-1·19) and DFS (HR: 0·90, 95%CrI: 0·50-1·62) in ESCC. The short-term outcomes were similar between NCRT and NCT. The three treatment strategies were comparable in esophageal adenocarcinoma (EAC) subpopulations. INTERPRETATION: The study corroborated current guidelines in addressing the importance of analysing EC according to histopathological types. The analysis suggested that in locally advanced ESCC patients, both NCRT and NCT improved OS as compared to surgery alone, whereas no clear evidence supported the optimal strategies between NCRT and NCT. More RCTs comparing different therapeutic strategies in EAC patients are warranted. FUNDING: Köln Fortune Program, University of Cologne.

IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth.

In pancreatic ductal adenocarcinoma (PDAC), the tumor stroma constitutes most of the cell mass and contributes to therapy resistance and progression. Here we show a hitherto unknown metabolic cooperation between pancreatic stellate cells (PSCs) and tumor cells through Interleukin 17B/Interleukin 17B receptor (IL-17B/IL-17RB) signaling. Tumor-derived IL-17B carrying extracellular vesicles (EVs) activated stromal PSCs and induced the expression of IL-17RB. PSCs increased oxidative phosphorylation while reducing mitochondrial turnover. PSCs activated tumor cells in a feedback loop. Tumor cells subsequently increased oxidative phosphorylation and decreased glycolysis partially via IL-6. In vivo, IL-17RB overexpression in PSCs accelerated tumor growth in a co-injection xenograft mouse model. Our results demonstrate a tumor-to-stroma feedback loop increasing tumor metabolism to accelerate tumor growth under optimal nutritional conditions.

Identification and Validation of Hypoxia-Related lncRNA Signature as a Prognostic Model for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most general malignant tumors. Hypoxia is a critical clinical characteristic and acts as a significant part in the development and cancers' prognosis. The prognostic value and biological functions of hypoxia-related lncRNAs in hepatocellular carcinoma is little known. Thus, we aim to establish a hypoxia-related lncRNA signature to predict the HCC patients' survival. First, we extracted the hypoxia-related genes and expression of lncRNAs from the MSigDB and TCGA database, respectively. The co-expression analysis among hypoxia-related mRNAs and lncRNAs was employed to identify hypoxia-related lncRNAs. Then, comprehensive analyses of lncRNAs expression level and survival data were applied to establish the signature. We built a prognostic signature on the foundation of the three differently expressed hypoxia-related lncRNAs. Kaplan-Meier curves indicated the low-risk group is associated with better survival. The 1-, 3-, and 5 years AUC values of the signature were 0.805, 0.672 and 0.63 respectively. The test set performed consistent outcomes. A nomogram was built grounded on the risk score and clinicopathological features. GSEA showed the immune-related pathways in high-risk group, while metabolism-related pathways in low-risk group. Besides, we found this model was correlated with the clinical features, tumor immune cell infiltration, immune checkpoints, and m6A-related genes. Finally, a novel signature based on hypoxia-related lncRNAs was established and validated for predicting HCC patients' survival and may offer some useful information for immunotherapies.