A new score for predicting intracranial hemorrhage in patients using antiplatelet drugs.

Antiplatelet drugs in patients increase the risk of intracranial hemorrhage (ICH), which can seriously affect patients' quality of life and even endanger their lives. Currently, there is no specific score for predicting the risk of ICH caused by antiplatelet drugs. We aimed to identify factors associated with ICH in patients on antiplatelet drugs and to construct and validate a predictive model that would provide a validated tool for the clinic. Data were obtained from the patient medical records inpatient system. Prediction models were built by logistic regression, the area under the curve (AUC), and column line plots. Internal validation, analytical identification and calibration of the model using AUC, calibration curves and Hosmer-Lemeshow test. The registration number of this study is ChiCTR2000031909, and the ethical review number is 2020KY087. This single-center retrospective study enrolled 753 patients treated with antiplatelet drugs, including 527 in the development cohort. Multifactorial analysis showed that male, headache or vomiting, hypertension, cerebrovascular disease, CT-defined white matter hypodensity, abnormal GCS, fibrinogen and D-dimer were independent risk factors for ICH, and lipid-lowering drugs was a protective factor. The model was constructed using these nine factors with an AUC value of 0.949. In the validation cohort, the model showed good discriminatory power with an AUC value of 0.943 and good calibration (Hosmer-Lemeshow test P value of 0.818). Based on 9 factors, we derived and validated a predictive model for ICH with antiplatelet drugs in patients. The model has good predictive value and may be an effective tool to reduce the occurrence of ICH.

A new mechanism in negative pressure wound therapy: interleukin-17 alters chromatin accessibility profiling.

Negative pressure wound therapy (NPWT) is extensively used in clinical settings to enhance the healing of wounds. Despite its widespread use, the molecular mechanisms driving the efficacy of NPWT have not been fully elucidated. In this study, skin wound-healing models were established, with administration of NPWT. Vimentin, collagen I, and MMP9 of skin tissues were detected by immunofluorescence (IF). Gene expression analysis of skin wound tissues was performed by RNA-sequencing (RNA-seq). Protein expression was assayed by a Western blotting or IF assay, and mRNA levels were quantified by quantitative PCR. Chromatin accessibility profiles of fibroblasts following NPWT or IL-17 exposure were analyzed by ATAC-seq. In rat wound-healing models, NPWT promoted wound repair by promoting reepithelialization, extracellular matrix (ECM) synthesis, and proliferation, which mainly occurred in the early stage of wound healing. These differentially expressed genes (DEGs) in NPWT wounds versus control wounds were enriched in the IL-17 signaling pathway. IL-17 was identified as an upregulated factor following NPWT in skin wounds. Moreover, the IL-17 inhibitor secukinumab (SEC) could abolish the promoting effect of NPWT on wound healing. Importantly, chromatin accessibility profiles were altered following NPWT and IL-17 stimulation in skin fibroblasts. Our findings suggest that NPWT upregulates IL-17 to promote wound healing by altering chromatin accessibility, which is a novel mechanism for NPWT's efficacy in wound healing.NEW & NOTEWORTHY To our knowledge, this is the first report of the efficacy of negative pressure wound therapy (NPWT) in promoting wound healing via IL-17. Moreover, NPWT and IL-17 can alter chromatin accessibility. Our study identifies a novel mechanism for NPWT's efficacy in wound healing.

Direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) for extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis.

BACKGROUND: The use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for extended thromboprophylaxis of abdominal/pelvic cancer-related postoperative thromboembolism (VTE) is unclear. We aim to investigate the efficacy and safety of DOACs vs. LMWH in these patients. METHODS: A systematic review was conducted using EMBASE, MEDLINE, CENTRAL, and Web of science through May 19th, 2023 for all randomized controlled trials (RCTs) and observational studies that compared the outcomes with DOACs vs. LMWH for extended thromboprophylaxis among patients undergoing abdominal/pelvic cancer surgery. Primary efficacy outcome was clinical VTE, and safety outcome was clinically relevant bleeding complications reported within the 30-day postoperative period. This study was registered in PROSPERO (CRD42023413175). RESULTS: We identified 5078 articles and selected 29 full-text articles for eligibility. A total of 9 studies (2 RCTs and 7 observational studies) encompassing 2651 patients were included for systematic review and 7 for meta-analysis. When compared with LMWH extended thromboprophylaxis, DOACs had a similar incidence of VTE (RR: 0.65 [95% CI: 0.32-1.33], I2 = 0%), major bleeding (RR: 1.68 [95% CI: 0.36-7.9], I2 = 26%), and clinically relevant non-major bleeding (RR: 0.68 [95% CI: 0.39-1.19], I2 = 0%). Subgroup analysis suggested no difference according to the study type (RCTs versus observational studies) regarding clinical VTE or major bleeding (Pinteraction = 0.43 and Pinteraction = 0.71, respectively). CONCLUSION: Our results suggest that DOACs for extended thromboprophylaxis were an effective and safe alternative to LMWH after major abdominal/pelvic cancer-related surgery.

Risk factors for anticoagulant-associated gastrointestinal hemorrhage: a systematic review and meta-analysis.

BACKGROUND/AIMS: There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB. METHODS: A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review. RESULTS: We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc. CONCLUSION: The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.

New score for predicting thromboembolic events in patients with atrial fibrillation using direct oral anticoagulants.

Determinants of thrombotic events remain uncertain in patients with atrial fibrillation treated with direct oral anticoagulants (DOACs). Our aim was to identify risk factors associated with thromboembolism in patients with at atrial fibrillation on DOACs and to construct and externally validate a predictive model that would provide a validated tool for clinical assessment of thromboembolism. In the development cohort, prediction model was built by logistic regression, the area under the curve (AUC), and Nomogram. External validation and calibration of the model using AUC and Hosmer-Lemeshow test. This national multicenter retrospective study included 3263 patients with atrial fibrillation treated with DOACs. The development cohort consisted of 2390 patients from three centers and the external validation cohort consisted of 873 patients from 13 centers. Multifactorial analysis showed that heavy drinking, hypertension, prior stroke/transient ischemic attack (TIA), cerebral infarction during hospitalization were independent risk factors for thromboembolism. The Alfalfa-TE risk score was constructed using these four factors (AUC = 0.84), and in the external validation cohort, the model showed good discriminatory power (AUC = 0.74) and good calibration (Hosmer-Lemeshow test P value of 0.649). Based on four factors, we derived and externally validated a predictive model for thromboembolism with DOACs in patients with atrial fibrillation (Alfalfa-TE risk score). The model has good predictive value and may be an effective tool to help reduce the occurrence of thromboembolism in patients with DOACs.

Interpretable machine learning models for predicting venous thromboembolism in the intensive care unit: an analysis based on data from 207 centers.

BACKGROUND: Venous thromboembolism (VTE) is a severe complication in critically ill patients, often resulting in death and long-term disability and is one of the major contributors to the global burden of disease. This study aimed to construct an interpretable machine learning (ML) model for predicting VTE in critically ill patients based on clinical features and laboratory indicators. METHODS: Data for this study were extracted from the eICU Collaborative Research Database (version 2.0). A stepwise logistic regression model was used to select the predictors that were eventually included in the model. The random forest, extreme gradient boosting (XGBoost) and support vector machine algorithms were used to construct the model using fivefold cross-validation. The area under curve (AUC), accuracy, no information rate, balanced accuracy, kappa, sensitivity, specificity, precision, and F1 score were used to assess the model's performance. In addition, the DALEX package was used to improve the interpretability of the final model. RESULTS: This study ultimately included 109,044 patients, of which 1647 (1.5%) had VTE during ICU hospitalization. Among the three models, the Random Forest model (AUC: 0.9378; Accuracy: 0.9958; Kappa: 0.8371; Precision: 0.9095; F1 score: 0.8393; Sensitivity: 0.7791; Specificity: 0.9989) performed the best. CONCLUSION: ML models can be a reliable tool for predicting VTE in critically ill patients. Among all the models we had constructed, the random forest model was the most effective model that helps the user identify patients at high risk of VTE early so that early intervention can be implemented to reduce the burden of VTE on the patients.

A new model (Alfalfa-Warfarin-GIB) for predicting the risk of major gastrointestinal bleeding in warfarin patients.

BACKGROUND: This study aimed to analyze the factors influencing warfarin-related major gastrointestinal bleeding (GIB) and to develop a score that would provide a reference for assessing the risk of major GIB associated with warfarin treatment. METHODS: This was a retrospective analysis of clinical and follow-up data from warfarin-treated patients. Scores were analyzed using logistic regression. The area under the subject working characteristic curve (AUC), sensitivity, specificity, and Hosmer-Lemeshow test were used to evaluate the scoring performance. RESULTS: A total of 1591 patients who met the requirements for warfarin use were included in this study, and 46 developed major GIB. After univariate analysis as well as multivariate logistic regression analysis, nine factors were found to be associated with increased risk of major GIB, namely age ≥ 65 years, history of peptic ulcer, history of major bleeding, abnormal liver function, abnormal renal function, cancer, anemia, labile international normalized ratio, and combination of antiplatelet agents/non-steroidal anti-inflammatory drugs. The Alfalfa-Warfarin-GIB score was constructed using these nine factors. The AUC and Bootstrap method-corrected AUC of the Alfalfa-Warfarin-GIB score were 0.916 (95% CI: 0.862-0.970, P < 0.001) and 0.919 (95% CI: 0.860-0.967, P < 0.001), respectively, which were higher than those of the HAS-BLED score (AUC = 0.868, 95% CI: 0.812-0.924, P < 0.001). CONCLUSION: Based on nine risk factors, the Alfalfa-Warfarin-GIB score was constructed to predict the risk of warfarin-related major GIB. The newly developed Alfalfa-Warfarin-GIB score has a better predictive value than the HAS-BLED score and may be an effective tool to help reduce the occurrence of major GIB in patients on warfarin.

Non-major bleeding risk of direct oral anticoagulants versus vitamin K antagonists for stroke prevention with atrial fibrillation: a systematic review and network meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We aimed to determine the risk of non-major bleeding using different DOACs to prevent strokes in atrial fibrillation (AF). METHODS: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting non-major bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Nineteen randomized controlled trials (RCTs) (involving 85,826 patients) were included. For clinically relevant non-major bleeding, the risk for bleeding was lowest for apixaban (SUCRA, 93.9), followed by that for VKAs (SUCRA, 47.7), dabigatran (SUCRA, 40.3), rivaroxaban (SUCRA, 35.9), and edoxaban (SUCRA, 32.2). The minor bleeding safety of DOACs was ranked from highest to lowest as follows: apixaban (SUCRA, 78.1), edoxaban (SUCRA, 69.4), dabigatran (SUCRA, 48.8), and VKAs (SUCRA, 3.7). CONCLUSIONS: Based on current evidence, for stroke prevention in patients with AF, the safest DOAC is apixaban in terms of non-major bleeding. This suggests that apixaban may have a lower risk of non-major bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.

Risk factors for thrombolysis-related intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND: Thrombolysis-related intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been updated. AIM: We conducted a systematic review to identify risk factors for thrombolysis-related intracranial hemorrhage. METHOD: The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316160). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. RESULTS: Of 6083 citations, we included 105 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with age, National Institutes of Health stroke scale, leukoaraiosis, hypertension, atrial fibrillation, diabetes, total cholesterol, proteinuria, fibrinogen levels, creatinine, homocysteine, early infarct signs, antiplatelet therapy and anticoagulant therapy; In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and weight, sex, platelet count, uric acid, albumin and white matter hyperintensity. Leukoaraiosis, cardiovascular disease, total cholesterol, white blood cell count, proteinuria, fibrinogen levels, creatinine, homocysteine and early CT hypodensities are not included in most intracranial hemorrhage risk assessment models. CONCLUSION: This study informs risk prediction for thrombolysis-related intracranial hemorrhage, it also informs guidelines for intracranial hemorrhage prevention and future research.

Risk Factors for Anticoagulant-Associated Intracranial Hemorrhage: A Systematic Review and Meta-analysis.

BACKGROUND: Anticoagulant-associated intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been published. METHODS: We conducted a systematic review to identify risk factors for anticoagulant-associated intracranial hemorrhage. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316750). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. I2 statistics were used to evaluate heterogeneity. RESULTS: Of 7322 citations, we included 20 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with race, Glasgow Coma Scale, stroke, leukoaraiosis, cerebrovascular disease, tumor, atrial fibrillation, previous bleeding, international normalized ratio, serum albumin, prothrombin time, diastolic blood pressure, and anticoagulant. Low-certainty evidence may be associated with age, cerebral microbleeds, smoking, alcohol intake, platelet count, and antiplatelet drug. In addition, we found very low-certainty evidence that there may be little to no association between the risk of intracranial hemorrhage and hypertension and creatinine clearance. Leukoaraiosis, cerebral microbleeds, cerebrovascular disease, and international normalized ratio are not included in most risk assessment models. CONCLUSIONS: This study informs risk prediction for anticoagulant-associated intracranial hemorrhage and informs guidelines for intracranial hemorrhage prevention and future research.

Risk factors for antiplatelet drug-associated intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND: Antiplatelet drug-associated intracranial hemorrhage has a high mortality rate, and many factors can cause antiplatelet drug-associated intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been published. AIM: We conducted a systematic review to identify risk factors of antiplatelet drug-associated intracranial hemorrhage. METHOD: The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022311647). All studies written in English that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for antiplatelet drug-associated intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. I2 statistics were used to evaluate heterogeneity. RESULTS: Of 2844 citations, we included 6 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with race, low BMI, GCS, severe bleeding, headache or vomiting, cerebrovascular disease, lacunar small vessel disease, cardiovascular disease, blood sugar, blood pressure, CT-defined white matter hypodensity, antihypertensive drugs, and antiplatelet therapy. In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and age, sex, and dual antithrombotic treatment or anticoagulant. CT-defined white matter hypodensity is not included in most intracranial hemorrhage risk assessment models. CONCLUSION: This study summarizes risk factors for antiplatelet drug-associated intracranial hemorrhage, which is significant in preventing intracranial hemorrhage.

Circulation autoantibodies against C-terminus of NuMA in patients with Behçet's disease.

Circulating autoantibodies have a close association with autoimmune diseases, which may be seen even in healthy individuals. These are also considered as promising source of new biomarkers in various autoimmune diseases. However, their profile is not completely understood till now. Here, we evaluated autoantibodies against nuclear mitotic apparatus protein located at the carboxy terminus (C-NuMA)in blood circulation of Han Chinese patients, using different technical approaches to discover pathological reaction leading to Behçet's disease (BD). In the first step, the recombinant human carboxy-terminal region of NuMA peptide (C-NuMA) was over-expressed and purified. In the second step, the indirect immunofluorescence method was used with patients' sera, and commercial anti-NuMA antibody was used to determine the NuMA as a potential autoantigen. Results were confirmed at cell level by western blots, indicating that two of ten patients with Behçet's disease could react with the recombinant C-NuMA,and the presence of antibodies were further verified by immunoprecipitation technique. Finally, the corresponding immunoassay (ELISA) was developed and optimized with specific recombinant C-NuMA as an in vitro method to test the confirmed patients with Behçet's disease. Our findings demonstrated that C-terminus of NuMA is an immune target of Behçet's disease in Han Chinese patients.

Electron Transfer Flavoprotein Subunit Beta Is a Candidate Endothelial Cell Autoantigen in Behçet's Disease.

Behçet's disease (BD) is a chronic inflammatory disease with multisystem involvement, and it is listed as a rare disease in the United States but is common in the Middle East, China, and Japan. The aim of this study was to identify novel autoantigens in Chinese patients with BD. First, the candidate autoantigens were screened by Western blotting, and the sequences of putative antigens were identified by LC-MALDI-TOF/TOF mass spectrometry. Next, the screened protein was cloned, expressed and purified. Then, an optimized ELISA was developed, and the serological criteria were evaluated using a large number of confirmed patients. One antigen with a molecular weight of approximately 28 kDa was identified as electron transfer flavoprotein subunit beta (ETFB). Positive reactivity was detected in recombinant human ETFB sera from 38 of 92 BD patients (41 %) and 1 of 90 healthy controls (1 %).