Clinicopathological phenotype and outcomes of NCAM-1+ membranous lupus nephritis.

INTRODUCTION: No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. METHOD: We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. RESULTS: Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P = 0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P = 0.007], serum creatinine [60 µmol/L (IQR 50-70) versus 70 (54-114); P = 0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P = 0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P = 0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P = 0.668 and P = 0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8% vs. 8.1%, P = 0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P = 0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. CONCLUSION: The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.

Glomerular Exostosin-Positivity is Associated With Disease Activity and Outcomes in Patients With Membranous Lupus Nephritis.

Introduction: The relationship of exostosin 1 and exostosin 2 (EXT1/EXT2) expression and outcomes in membranous lupus nephritis (MLN) was controversial. Methods: EXT1/EXT2 was performed by immunohistochemistry (IHC) in 283 consecutive patients with MLN. Clinicopathological characteristics and outcomes of EXT1/EXT2-positive patients were compared with EXT1/EXT2-negative patients. The primary end points were adverse renal events, including death, dialysis, and renal transplantation. Results: Of the patients with MLN, 29.3% were positive for EXT1/EXT2. The prevalence of EXT1/2-positive MLN was significantly higher in pure class V MLN than those for mixed class V MLN (44.2% vs. 19.4%, P < 0.001). For EXT1/EXT2-positive patients, the median time between onset of lupus and renal biopsy, and lupus nephritis and renal biopsy is shorter (6 [interquartile range, IQR: 2-25] months vs. 12 [IQR: 3-49] months, P = 0.008 and 3 [IQR: 2-18] months vs. 6 [IQR: 2-23] months, P = 0.039) and they had significantly lower systemic lupus erythematosus Disease Activity Index (SLEDAI) scores (P = 0.015) and lower serum creatinine levels (P < 0.001), higher hemoglobin (P = 0.006) as well as lower blood pressure. The EXT1/EXT2-positive patients had significantly fewer chronicity features (glomerulosclerosis, P < 0.001; interstitial fibrosis, P = 0.006; and tubular atrophy, P = 0.002) and fewer activity indicators (endocapillary hypercellularity, P = 0.012; cellular crescents, P = 0.007; and fibrocellular crescents, P < 0.001) on renal biopsy. After a median follow-up of 65 (28-126) months, EXT1/EXT2-positive patients were less likely to experience adverse renal events (2.4% vs. 16.0%, P = 0.001). Conclusion: Compared with EXT1/EXT2-negative patients, the EXT1/EXT2-positive patients presented with lower disease activity and were less likely to experience adverse renal events in relationship with the chronicity index.

Direct oral anticoagulants compared with warfarin in patients with left ventricular thrombus: a cohort study from China.

Background: Current guidelines recommend vitamin K antagonist (VKA) for left ventricular (LV) thrombus. This study aimed to compare the effectiveness and safety of direct oral anticoagulant (DOAC) and warfarin in Chinese patients with LV thrombus. Methods: Patients with LV thrombus admitted to Beijing Anzhen Hospital of Capital Medical University between January 2018 and January 2022, were enrolled in this cohort study. The primary endpoint was defined as thrombus resolution within 90 days. The secondary endpoints included thrombus resolution within 180 days, major bleeding events, and minor bleeding events. All patients were followed up for at least 90 days after diagnosis of LV thrombus. Patients were divided into the VKA and DOAC groups according to the anticoagulants. Differences in clinical endpoint events between the two groups were compared. Results: This study included 129 and 111 patients in the VKA and DOAC groups, respectively. After adjusting for gender and smoking status, no significant difference was observed in thrombus resolution within 90 days between the VKA and DOAC groups. Additionally, there was no difference between the two groups in the secondary endpoints of thrombus resolution within 180 days, major bleeding, and minor bleeding. In subgroup analysis, rivaroxaban and dabigatran did not show significant differences in primary and secondary endpoints. Conclusions: This study showed no significant difference in thrombus resolution between DOAC and warfarin. DOAC might be an alternative to warfarin for the treatment of LV thrombus. However, further large prospective studies are required to explore the efficacy and safety of DOAC in patients with LV thrombus.

Risk factors and prediction model for thrombocytopenia following coronary artery bypass graft surgery in elderly Chinese population.

Background: Thrombocytopenia, a common complication of coronary artery bypass graft (CABG) surgery, is particularly prevalent among elderly individuals. This study developed a risk prediction model utilizing preoperative and intraoperative variables to identify high-risk elderly patients prone to developing thrombocytopenia. Methods: The patients were retrospectively recruited from Beijing Anzhen Hospital between February 2019 and December 2020. Postoperative thrombocytopenia was defined as a postoperative platelet (PLT) count <100×109/L as measured within 7 days after surgery. The entire population was randomly split into derivation and validation sets in a 7:3 ratio. The derivation set underwent variable screen by the least absolute shrinkage and selection operator (LASSO) regression method. To evaluate the predictive ability of the model for thrombocytopenia, decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were generated in the derivation and validation sets. Results: A total of 1,773 patients were recruited in this study, with random assignment to either the derivation set (1,242 cases) or the validation set (531 cases). LASSO regression was utilized the risk factors associated with thrombocytopenia, resulting in selection of preoperative baseline variables: body mass index (BMI), estimated glomerular filtration rate (eGFR), B-type natriuretic peptide (BNP), preoperative PLT, and use of beta-blocker, and intraoperative variables: red blood cell (RBC) transfusion, plasma transfusion, use of intra-aortic balloon pump (IABP) and cardiopulmonary bypass (CPB), reoperation for bleeding, washed RBC transfusion volume, and use of epinephrine. The logistic regression was employed to establish the risk prediction. The area under the ROC curve (AUC) for the derivation set was 0.900 [95% confidence interval (CI): 0.880-0.920], while for the validation cohort, it was 0.897 (95% CI: 0.866-0.928). Conclusions: The model incorporating significant preoperative and intraoperative variables exhibited good predictive performance for thrombocytopenia in elderly patients undergoing CABG surgery.

A Natural Small Molecule Mitigates Kidney Fibrosis by Targeting Cdc42-mediated GSK-3ß/ß-catenin Signaling.

Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay-guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti-renal fibrotic lead. DA shows significant anti-kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down-regulates its downstream phospho-protein kinase Cζ(p-PKCζ)/phospho-glycogen synthase kinase-3ß (p-GSK-3ß), thereby promoting ß-catenin Ser33/37/Thr41 phosphorylation and ubiquitin-dependent proteolysis to block classical pro-fibrotic ß-catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs.

Nondual Antiplatelet Therapy Versus Dual Antiplatelet Therapy Before Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-analysis.

ABSTRACT: Transcatheter aortic valve replacement (TAVR) is an interventional procedure performed in patients with severe aortic stenosis and often required perioperative antiplatelet therapy. Most previous studies have focused on antiplatelet therapy following TAVR. However, few studies have investigated the prognostic effect of preoperative antiplatelet therapy in patients undergoing TAVR. This study aimed to compare the efficacy and safety of nondual antiplatelet therapy (non-DAPT) and DAPT before TAVR. We performed a systematic search of Embase, PubMed, and Web of Science until February 2023. Studies were eligible if they compared non-DAPT (single antiplatelet therapy or no antiplatelet therapy) with DAPT in patients before TAVR. A total of 5 studies, including 2329 patients, met the inclusion criteria and were included in the meta-analysis. Preoperative non-DAPT significantly decreased minor bleeding events compared with preoperative DAPT [odds ratio 0.58; 95% confidence interval: 0.44-0.76]. There were no significant differences in the incidence of other bleeding events, transfusions, stroke, myocardial infarction, or all-cause death. Preoperative single antiplatelet therapy significantly decreased the incidence of major bleeding compared with DAPT (odds ratio 0.14; 95% confidence interval: 0.04-0.48). Preoperative non-DAPT significantly reduced minor bleeding events in patients undergoing TAVR, without increasing the risk of stroke and myocardial infarction.

Prevalence, contemporary trends and associated factors of potentially inappropriate prescription of edoxaban in real-world clinical practice: A subanalysis of the SUNSHINE registry.

AIM: As the direct oral anticoagulant most recently approved in China, data pertaining to clinical edoxaban use are still scarce. This study investigated the prevalence of and contemporary trends in edoxaban prescription among Chinese patients as well as factors associated with its inappropriate use in a multicentre registry of patients treated in real-world clinical practice. METHODS: This real-world, prospective, multicentre and non-interventional study included 1005 inpatients treated with edoxaban. According to National Medical Products Administration and European Heart Rhythm Association guidelines, edoxaban therapy was determined to be appropriate or inappropriate in each case. RESULTS: The median patient age was 70.0 years (interquartile range 61.0-78.0 years) and 46.3% were women. Overall, 456 (45.4%) patients received inappropriate edoxaban therapy, and common issues included an inappropriately low dosage (183, 18.2%) or wrong drug selection (109, 10.8%), high dosage (73, 7.3%), unreasonable off-label use (49, 4.9%), contraindicated medication combinations (27, 2.7%) and incorrect administration timing (16, 1.6%). Several factors, such as age ≥75 years (odds ratio [OR] = 1.921, 95% confidence interval [CI] 1.355-2.723, P < 0.001), weight >60 kg (OR = 2.657, 95%CI 1.970-3.583, P < 0.001), severe renal insufficiency (OR = 1.988, 95% CI 1.043-3.790, P = 0.037), current anaemia (OR = 1.556, 95% CI 1.151-2.102, P = 0.004) and history of bleeding (OR = 2.931, 95% CI 1.605-5.351, P < 0.001) were associated with an increased risk of inappropriate edoxaban therapy, whereas factors associated with cardiovascular specialties, such as admission to a cardiovascular department (OR = 0.637, 95% CI 0.464-0.873, P = 0.005), dronedarone use (OR = 0.065, 95% CI 0.026-0.165, P < 0.001) and amiodarone use (OR = 0.365, 95% CI 0.209-0.637, P < 0.001) decreased this risk. CONCLUSION: In this real-world study, 45.4% of patients received an inappropriate treatment with edoxaban. Multiple clinical characteristics can help identify patients who should receive edoxaban. Further development and implantation of educational activities and management strategies are needed to ensure the correct use of edoxaban.

Pharmacokinetics and bioequivalence of two metoprolol succinate extended release tablets in healthy Chinese subjects under fasting and fed conditions.

AIMS: The aims of this study were to evaluate and compare the pharmacokinetic profiles and establish bioequivalence of test and reference metoprolol succinate extended-release (ER) tablets in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: Subjects were randomly assigned to either the fasting or the fed group and also to one of the two treatment sequences (test-reference or reference-test), according to which they received a single 47.5-mg dose of the test or reference metoprolol ER tablet in the study periods. During each period, blood samples were collected at pre-dose and at intervals up to 48 hours after dosing. Plasma concentrations of metoprolol were determined by liquid chromatography. The safety of both ER tablets was monitored throughout the study. RESULTS: 60 subjects were enrolled and all completed the study, with 30 participants each in the fasting and fed groups. In both groups, the 90% confidence intervals for AUC0-48h, AUC0-inf, and Cmax were within the acceptable bioequivalence range (80 - 125%). There were no significant differences in adverse event (AE) reporting between the subjects receiving test or reference ER tablet. No serious AEs occurred during the study period. CONCLUSION: The test metoprolol ER tablet was bioequivalent to the reference metoprolol ER tablet (Betaloc ZOK) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.

Prediction of acute kidney injury following coronary artery bypass graft surgery in elderly Chinese population.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication following coronary artery bypass graft (CABG) surgery. Advanced age is an independent risk factor for the development of AKI, and the incidence of AKI in the elderly increases more rapidly than that in younger patients. This study aimed to develop and validate the risk prediction model for AKI after CABG in elderly patients. METHODS: Patients were retrospectively recruited from January 2019 to December 2020. AKI after CABG was defined according to the criteria of Kidney Disease Improving Global Outcomes (KDIGO). The entire population was divided into the derivation set and the verification set using random split sampling (ratio: 7:3). Lasso regression method was applied to screen for the variables in the derivation set. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were plotted to analyze the predictive ability of the model for AKI risk in the derivation set and the verification set. RESULTS: A total of 2155 patients were enrolled in this study. They were randomly divided into the derivation set (1509 cases) and the validation set (646 cases). Risk factors associated with AKI were selected by Lasso regression including T2DM, diabetes mellitus type intraoperative use of intra-aortic ballon pump (IABP), cardiopulmonary bypass (CPB), epinephrine, isoprenaline, and so on. The model was established by Lasso logistic regression. The area under the ROC curve (AUC) of the model for the derivation set was 0.754 (95% CI: 0.720 - 0.789), and that for the validation cohort was 0.718 (95% CI: 0.665 - 0.771). CONCLUSION: In this study, the model with significant preoperative and intraoperative variables showed good prediction performance for AKI following CABG in elderly patients to optimize postoperative treatment strategies and improve early prognosis.

Simultaneous surgical treatment of aortic coarctation and aortic root disease: a report of case series.

Background: Aortic coarctation (CoA) is a common congenital aortic disease, which is often accompanied by aortic root disease. This study aimed to explore the simultaneous surgical treatment of aortic root replacement and ascending-abdominal aortic bypass grafting for patients with CoA and aortic root disease. Case Description: From June 2014 to December 2019, nine patients with CoA and aortic root disease underwent simultaneous surgical treatment involving ascending-abdominal aortic bypass grafting and aortic root replacement (Bentall operation in eight patients and Wheat's operation in one patient). The degree of constriction, cardiopulmonary bypass time, ascending aorta occlusion time, operation time, artificial vessel diameter, ventilator support time and blood loss were recorded and analyzed. The blood pressure data of the limbs were measured pre- and postoperatively. All patients were followed up for 24±7 months. The mean extracorporeal circulation time was 130±17 minutes. The mean duration of the aortic clamp occlusion was 85±14 minutes. The mean operation time was 6.2±1.9 hours. The mean blood loss during and after surgery was 1,958±849 mL. The mean ventilator support time after operation was 20.3±11.6 hours. There were no operative mortalities. The arterial pressure gradient in the upper and lower limbs significantly improved. Postoperative computer-enhanced transvenous angiograms showed that the grafts were open with fluent flow. None of the patients experienced gastrointestinal complications, and no adverse events were observed during the follow-up. Conclusions: Simultaneous surgical treatment with ascending-to-abdominal aorta bypass grafting and aortic root replacement is feasible for patients with CoA and aortic root disease.

Anticoagulation strategies in patients with extracorporeal membrane oxygenation: A network meta-analysis and systematic review.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) plays an important role in providing temporary life support for patients with severe cardiac or pulmonary failure, but requires strict anticoagulation and monitoring. This network meta-analysis systematically explored the most effective anticoagulation and monitoring strategies for patients receiving ECMO. METHODS: MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to January 31, 2023, for studies comparing unfractionated heparin (UFH), argatroban (Arg), bivalirudin (Biv), and/or nafamostat mesylate (NM) in patients receiving ECMO. The primary outcomes included device-related thrombosis, patient-related thrombosis, and major bleeding events. The secondary outcomes included ECMO survival, ECMO duration, and in-hospital mortality. RESULTS: A total of 2522 patients from 23 trials were included in the study. Biv was associated with a decreased risk of device-related thrombosis (odd ratio [OR] 0.51, 95% confidence interval [CI]: 0.33-0.84) compared with UFH, whereas NM (OR 2.2, 95% CI: 0.24-65.0) and Arg (OR 0.92, 95% CI: 0.43-2.0) did not reduce the risk of device-related thrombosis compared with UFH. Biv was superior to Arg in decreasing the risk of device-related thrombosis (OR 0.14, 95% CI: 0.03-0.51). Biv reduced the risk of patient-related thrombosis compared with UFH (OR 0.44, 95% CI: 0.18-0.85); NM (OR 0.65, 95% CI: 0.14-3.3) and Arg (OR 3.1, 95% CI: 0.94-12.0) did not decrease risk of patient-related thrombosis compared with UFH. No significant difference was observed in the risk of major bleeding between three alternatives and UFH: Biv (OR 0.54, 95% CI: 0.23-1.3), Arg (OR 1.3, 95% CI: 0.34-5.8), and NM (OR 0.60, 95% CI: 0.13-2.6). NM showed a reduced risk of in-hospital mortality compared with UFH (OR 0.27, 95% CI: 0.091-0.77), whereas Arg (OR 0.43, 95% CI: 0.15-1.2) and Biv (OR 0.75, 95% CI: 0.52-1.1) did not decrease risk of in-hospital mortality. CONCLUSIONS: Compared with UFH and Arg, Biv reduces the risk of thrombosis and appears to be a better choice for patients requiring ECMO. NM was associated with a reduced risk of in-hospital mortality.

Nirmatrelvir plus ritonavir remains effective in vaccinated patients at risk of progression with COVID-19: A systematic review and meta-analysis.

Background: The efficacy of nirmatrelvir plus ritonavir (NMV-r) for vaccinated COVID-19 patients at high risk of progression is not adequately recognised. To address this gap, we conducted a systematic review and meta-analysis of current literature. Methods: We searched PubMed, Web of Science, Embase, Cochrane Library, and medRxiv for articles published up to 8 January 2023 on NMV-r in outpatients. At least two researchers screened articles, extracted data, and assessed the quality of selected studies. We evaluated the results via risk ratios (RRs) with 95% confidence intervals (CIs) and tested for heterogeneity using I2 statistics. Results: We included seven observational cohort studies comprising 224 238 vaccinated patients. According to our meta-analysis, NMV-r reduced 47% incidence of all-cause death or hospitalisation within 30 days for vaccinated patients (RR = 0.53; 95% CI = 0.40-0.70; I2 = 81%). After excluding the most influential result by sensitivity analysis, NMV-r still reduced risk of all-cause death or hospitalisation by 38% (RR = 0.62; 95% CI = 0.56-0.69; I2 = 0%). In our secondary outcome, NMV-r also showed its benefits in reducing all-cause death in vaccinated patients (RR = 0.40; 95% CI = 0.19-0.85; I2 = 23%). Conclusions: We found positive evidence for the use of NMV-r for vaccinated patients at high-risk of progression with mild to moderate COVID-19. However, large-scale RCTs are needed to confirm these findings. Registration: PROSPERO CRD42023391349.

Serum levels of IL-6/IL-10/GLDH may be early recognition markers of anti-tuberculosis drugs (ATB) -induced liver injury.

To explore the potential value of serum glutamate dehydrogenase (GLDH) combined with inflammatory cytokines as diagnostic biomarkers for anti-tuberculosis drug -induced liver injury (ATB-DILI). We collected the residual serum from the patients who met the criteria after liver function tests. We have examined these parameters including GLDH which were determined by enzyme-linked immunosorbent assay and cytokines which were determined by cytokine combination detection kit. Multivariate logistics stepwise forward regression was applied to establish regression models. A total of 138 tuberculosis patients were included in the diagnostic markers study of ATB-DILI, including normal liver function group (n = 108) and ATB-DILI group(n = 30). Serum GLDH, IL-6 and IL-10 levels were significantly increased in the ATB-DILI group. Receiver operating characteristic curve (ROC) curve showed that the area under curve (AUC) of serum GLDH, IL-6 and IL-10 for the diagnosis of ATB-DILI were 0.870, 0.714 and 0.811, respectively. In logistic regression modeling, the AUC of GLDH combined with IL-10 as an ATB-DILI marker is 0.912. Serum IL-6、IL-10 and GLDH levels began to rise preceded the increase in ALT by 7 days, with significant differences in IL-6 compared with 7 days. Serum GLDH, IL-6 and IL-10 levels were correlated with the severity of liver injury. In conclusion, we found that GLDH, IL-6 and IL-10 alone as diagnostic markers of ATB-DILI had good diagnostic efficacy. Logistic regression model established by GLDH and IL-10 had better diagnostic efficacy and IL-6 may be an early predictor of liver injury in the setting of ATB poisoning.

Glutamate dehydrogenase combined with ferrochelatase as a biomarker of liver injury induced by antituberculosis drugs.

AIMS: To explore the potential value of serum glutamate dehydrogenase (GLDH), ferrochelatase (FECH), heme oxygenase-1 (HO-1) and glutathione-S-transferase-α (GST-α) as diagnostic biomarkers for liver injury caused by antituberculosis drugs. METHODS: We established a rat model of isoniazide-induced liver injury and recruited 122 hospitalized tuberculosis patients taking antituberculosis drugs. We detected the concentration of GLDH, FECH, HO-1 and GST-α by enzyme-linked immunosorbent assay. GraphPad Prism8 and SPSS 26.0 were used for statistical analysis. RESULTS: In the rat model, serum GLDH concentration gradually increased during isoniazid (INH) administration, while serum FECH, HO-1 and GST-α concentrations significantly increased after INH administration was stopped. The receiver operating characteristic curve showed that the areas under the curve (AUCs) of serum GLDH and FECH for the diagnosis of anti-tuberculosis (TB) drug-induced liver injury (anti-TB-DILI) were 0.7692 (95% confidence interval [CI] 0.5442-0.9943) and 0.7284 (95% CI 0.4863-0.9705) and the diagnostic accuracies were 81.25% and 78.79%, respectively. In clinical research, the AUCs of GLDH and FECH were 0.9124 (95% CI 0.8380-0.9867) and 0.6634 (95% CI 0.5391-0.7877), and the optimal thresholds were 10.40 mIU/mL and 1.304 ng/mL, respectively. The diagnostic accuracy, specificity and positive predictive value (PPV) of GLDH were 82.61%, 79.38% and 47.22%. We performed a joint diagnostic test for GLDH and FECH. The diagnostic accuracy (90.43%), specificity (91.75%) and PPV (65.21%) of serial tests were better than for GLDH and FECH alone. CONCLUSIONS: GLDH in the diagnosis of liver injury induced by anti-TB drugs has high sensitivity, but low specificity and low PPV. The combination of GLDH and FECH could significantly improve the specificity, PPV and diagnostic accuracy, and reduce the false-positive rate of anti-TB-DILI.

Metformin use is associated with reduced acute kidney injury following coronary artery bypass grafting in patients with type 2 diabetes: An inverse probability of treatment weighting analysis.

STUDY OBJECTIVE: Acute kidney injury (AKI) is a common and serious complication after coronary artery bypass grafting (CABG) surgery. Patients with diabetes are commonly associated with renal microvascular complications and have a greater risk of AKI after CABG surgery. This study aimed to explore whether preoperative metformin administration could reduce the incidence of postoperative AKI following CABG in patients with type 2 diabetes. DESIGN: Patients with diabetes who underwent CABG were retrospectively included in this study. AKI after CABG was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The effects of metformin on postoperative AKI following CABG in patients were compared and analyzed. DATA SOURCE: Patients were enrolled in this study between January 2019 and December 2020 in Beijing Anzhen Hospital. PATIENTS: A total of 812 patients were enrolled. The patients were divided into the metformin group (203 cases) and the control group (609 cases) according to whether metformin was used preoperatively. INTERVENTION: Inverse probability of treatment weighting (IPTW) was applied to minimize baseline differences between the two groups. IPT-weighted p values were analyzed to evaluate the postoperative outcomes between the two groups. MEASUREMENTS AND MAIN RESULTS: The incidence of AKI in the metformin group and the control group was compared. After IPTW adjustment, the incidence of AKI in the metformin group was lower than the control group (IPTW-adjusted p < 0.001). In the subgroup analysis, metformin showed significant protective effects in the estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2 and eGFR 60-90 mL/min per 1.73 m2 subgroups, which was not observed in the eGFR ≥90 mL/min per 1.73 m2 subgroup. No significant differences in the incidence of renal replacement therapy, reoperation due to bleeding, in-hospital mortality, or red blood cell transfusion volume were observed between the two groups. CONCLUSIONS: In this study, we provided evidence that preoperative metformin was associated with a significant reduction of postoperative AKI following CABG in patients with diabetes. Metformin showed significant protective effects in patients with mild-to-moderate renal insufficiency.

A Practical Statin Recommendation System Based on Real-World Data to Improve LDL-C Management in Secondary Prevention.

ABSTRACT: Statins are considered the cornerstone of secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD). However, many patients fail to achieve the guide-recommended goal of low-density lipoprotein cholesterol (LDL-C) after statin monotherapy, leading to a high residual risk of cardiovascular events. Owing to individual differences in statin therapy, it is possible first to consider changing the type of statin before adding nonstatin medications in certain patients to improve LDL-C management. We developed and evaluated a statin recommendation system using real-world data. Ensemble learning was performed to develop the recommendation system that integrated the output results of support vector machines (SVM) and the similarity of patients. Model performance was assessed to investigate whether treatment according to the recommended model would increase the proportion of patients with the primary end point. Finally, a total of 3510 patients were enrolled in the development and validation of the recommender system. Of them, 1240 patients received atorvastatin (35.3%), 1714 patients received rosuvastatin (48.8%), and 556 patients received pitavastatin (15.8%). The statin recommendation system could significantly improve LDL-C target rate achievement in the recommended treatment group compared with the nonrecommended treatment group in the validation set (50.8% vs. 31.5%, P < 0.001). This study demonstrated that the statin recommendation system could significantly improve the achievement of LDL-C goals in ASCVD patients, providing a new approach to improve LDL-C management.

Clinical Outcomes of Individualized Antiplatelet Therapy Based on Platelet Function Test in Patients After Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis.

ABSTRACT: Platelet function test (PFT) is universally used to assess platelet reactivity to antiplatelet drugs in patients after percutaneous coronary intervention (PCI). However, it remains controversial whether individualized antiplatelet therapy guided by PFT can improve the prognosis in patients after PCI. This meta-analysis was conducted to explore the efficacy and safety of individualized antiplatelet therapy guided by PFT in patients after PCI. Studies that compared PFT-guided antiplatelet therapy with standard antiplatelet therapy were researched. The risks of major adverse cardiovascular and cerebrovascular events (MACCE) and major bleeding events were assessed. Pooled odds ratios (ORs) with 95% CIs were obtained. Finally, a total of 16,835 patients from 22 studies met the criteria and were included in the meta-analysis. Compared with standard antiplatelet therapy, individualized antiplatelet therapy guided by PFT significantly decreased the risk of MACCE (OR: 0.58, 95% CI: 0.43-0.77) in patients after PCI. There was no significant difference in major bleeding events (OR: 0.85, 95% CI: 0.70-1.05, P = 0.13). This study identified that PFT-guided individualized antiplatelet therapy could reduce the incidence of MACCE without increasing the risk of hemorrhage in patients after PCI.

Efficacy and Safety of Clopidogrel Versus Ticagrelor for Stabilized Patients With Acute Coronary Syndromes After Percutaneous Coronary Intervention: Results From a Real-World Registry in China.

BACKGROUND: The first 3 months after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) is a high-risk period for adverse events, including ischemic and bleeding events, which decrease greatly with time. It is worth investigating whether the use of potent P2Y12 inhibitors is necessary after the early stage. The purpose of this study was to investigate the differences in clinical outcomes between clopidogrel and ticagrelor in stable patients without ischemic or major bleeding events during the first 3 months after PCI. METHODS: Data for this study were obtained from the PHARM-ACS registry (NCT04184583). Patients who were free from ischemic and major bleeding events in the first 3 months after PCI were enrolled. Inverse probability of treatment weighting (IPTW) and Cox proportional hazards model were applied to compare the differences in clinical outcomes between the 2 groups. Major adverse cardiovascular and cerebrovascular events (MACCE) were considered the primary end point, and major bleeding was considered the secondary end point. RESULTS: A total of 6662 patients were included in this study. Of these, 3465 were treated with clopidogrel plus aspirin (clopidogrel group) and 3197 with ticagrelor plus aspirin (ticagrelor group). There were no significant differences in MACCE after IPTW adjustment for baseline variables (IPTW-adjusted HR, 1.06; 95% CI, 0.90-1.25) or major bleeding events (IPTW-adjusted HR, 0.97; 95% CI, 0.67-1.41) between the 2 groups. However, the incidence of minor bleeding in the clopidogrel group was significantly lower than that in the ticagrelor group (IPTW-adjusted HR, 0.65; 95% CI, 0.59-0.71). CONCLUSION: In patients with ACS who were free from ischemic or major bleeding events during the first 3 months after PCI, the subsequent clopidogrel treatment might reduce minor bleeding events without increasing the risk of MACCE compared with ticagrelor. However, the results still need to be confirmed by large randomized controlled studies in the future.

Concomitant administration of warfarin and toremifene: A case report.

WHAT IS KNOWN AND OBJECTIVE: Antiestrogen agents have been reported to enhance the anticoagulant activity of warfarin. The use of tamoxifen with warfarin has been contraindicated. However, warfarin in combination with toremifene has not been reported. We report a case in which warfarin was combined with toremifene and applied warfarin dose prediction models to predict the dose of warfarin. CASE SUMMARY: We report the case of a 50-year-old woman with a history of breast cancer, who underwent long-term toremifene therapy after mastectomy. The patient was treated with warfarin after prosthetic valve replacement and had a fluctuating international normalized ratio (INR) following the concomitant administration of toremifene. We applied the warfarin dose prediction model to adjust the warfarin dose during treatment. Finally, her INR stabilized with a lower dose of warfarin, and there was no serious bleeding during the 1-year follow-up. WHAT IS NEW AND CONCLUSION: Warfarin does not have a serious interaction with toremifene in this case, but it needed about 37.5% dose reduction which was comparable to the interaction of some common antibiotics with warfarin.

Low-dose and standard-dose ticagrelor compared with clopidogrel in patients with acute coronary syndromes: A cohort study from china.

Purpose: Previous trials have demonstrated that ticagrelor was superior to clopidogrel in acute coronary syndrome (ACS) patients. However, several recent studies showed that ticagrelor was associated with a significantly higher risk of bleeding compared with clopidogrel, especially in East Asian patients. Low-dose ticagrelor might improve the safety of ACS patients in the Chinese population. Therefore, this study mainly explored the low-dose ticagrelor in Chinese ACS patients. Methods: A total of 199 ACS patients were enrolled in this study. The maximum platelet aggregation rate induced by adenosine-5-diphosphate (ADP) was detected by light transmittance aggregometry (LTA). Platelet aggregation rate induced by ADP of more than or equal to 42.9% was defined as high on-treatment platelet reactivity (HPR) to P2Y12 inhibitors. All patients were followed up for at least 12 months. Clinical outcomes, changes of antiplatelet regimen, medication compliance and adverse reactions were collected. Results: Patients were divided into three groups according to the P2Y12 inhibitors, including 87 cases in clopidogrel (75 mg once a day) group, 41 cases in ticagrelor 60 mg (twice a day) group, and 71 cases in ticagrelor 90 mg (twice a day) group. ADP-induced platelet aggregation rates in ticagrelor 60 mg group and 90 mg group were 28.4 (19.6, 42.9) and 22.33 (15.1, 34.7) respectively, which were significantly lower than those in clopidogrel group 49.3 (36.5, 61.0) with adjusted P < 0.001. At the same time, there was no significant difference in ADP-induced platelet aggregation rate between ticagrelor 60 mg and 90 mg group (adjusted P = 0.105). Compared with clopidogrel, the proportion of normal on-treatment platelet reactivity (NPR) of ticagrelor 60 mg and ticagrelor 90 mg were significantly higher than that of clopidogrel, and the proportion of NPR of ticagrelor 90 mg group was significantly higher than that of ticagrelor 60 mg group. Conclusions: Patients of ticagrelor 60 mg and ticagrelor 90 mg had comparable platelet aggregation rates induced by ADP, and both of them had significantly more potent antiplatelet aggregation activity detected by LTA than clopidogrel.