Background Patients with initially unresectable intrahepatic cholangiocarcinoma (iCCA) have poor prognoses and the current first-line treatments remain unsatisfactory. Our study aimed to evaluate gemcitabine-based chemotherapy plus PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (TKIs) for iCCA. Methods In this multicenter retrospective cohort study, 392 patients were included in the full cohort analysis. For the primary analysis, 88 patients received gemcitabine-based chemotherapy (GEMCIS or GEMOX), and 177 patients received the same chemotherapy backbones combined with PD-1/PD-L1 inhibitors and TKIs. The primary outcome was to evaluate overall survival (OS). The propensity score matching (PSM) method was utilized to reduce potential confounders. Results Overall, 392 patients were included from 12 hospitals across China, with data from January 2016 to December 2024. In the full cohort analysis, the combination of GEMCIS/GEMOX with PD‑1/PD‑L1 inhibitors and TKIs significantly prolonged median OS compared to GEMCIS/GEMOX alone (26.7 vs. 15.3 months; hazard ratio [HR] 0.47, 95% CI: 0.35–0.63, P < 0.001). In the primary analysis, the combination strategy was associated with a median OS of 24.8 months and median progression-free survival (PFS) of 11.0 months, with HRs of 0.56 (95% CI: 0.38–0.83, P = 0.004) for OS and 0.46 (95% CI: 0.32–0.66, P < 0.001) for PFS after PSM. Importantly, our treatment strategy increased the rate of conversion surgery to 42% for locally advanced disease, ultimately resulting in significantly improved overall outcomes (HR for OS: 0.17 [95% CI: 0.05–0.61]). Conclusion Combining gemcitabine-based chemotherapy with PD-1/PD-L1 inhibitors and TKIs may provide a promising new first-line treatment option for patients with initially unresectable iCCA.

Abstract Background In cancer patients, dexamethasone has been linked to long-term survival outcomes, but there is uncertainty as to its effect on survival outcomes among patients with hepatocellular carcinoma (HCC) who undergo transcatheter arterial chemoembolization (TACE). Methods We retrospectively reviewed HCC patients who underwent TACE as the initial treatment between January 2014 and December 2016. Patients were categorized into the dexamethasone group and no dexamethasone group. We conducted propensity score matching (PSM), inverse probability weighting (IPTW) and adjusted for propensity score. Our endpoints were progression-free survival (PFS) and overall survival (OS). We also performed exploratory analyses in subgroups to assess the association between hepatic arterial dexamethasone and survival outcomes in pre-specified subgroups. Results Hepatic arterial dexamethasone was correlated with a favorable long-term survival in unadjusted and multivariate analysis. IPTW showed patients receiving hepatic arterial dexamethasone had prolonged PFS (HR = 0.69, 95%CI 0.49–0.95, P = 0.024) and OS (HR = 0.72, 95%CI 0.52-1.00, P = 0.047). Similar trends were observed in PSM and another propensity score analysis. Survival benefit of hepatic arterial dexamethasone remained in the subgroup undergoing platinum-based TACE. Conclusion Hepatic arterial dexamethasone might be associated with better long-term survival in HCC patients undergoing TACE. This study highlights the clinical significance of hepatic arterial dexamethasone in HCC patients undergoing TACE.

Myocardial infarction (MI) triggers complex cardiac remodeling, including endothelial dysfunction, fibrosis, and angiogenesis. Characterizing the spatial distribution and cellular localization of regulatory molecules is critical for understanding cardiac repair mechanisms. This study investigated the histochemical localization and functional role of T-cell death-associated gene 51 (TDAG51) in endothelial cells during post-MI angiogenesis and cardiac remodeling. We established a murine MI model and silenced TDAG51 with adeno-associated virus. Histochemical assays were used to determine TDAG51 localization and its relation to vascular density, and Masson staining was used to evaluate myocardial fibrosis. In vitro, we exposed human coronary artery endothelial cells (HCAECs) to oxygen-glucose deprivation (OGD) to examine TDAG51 expression and endothelial function. We performed Western blot and transcriptomic analyses to explore the involvement of the PI3K-AKT signaling pathway. Histochemical analyses revealed that TDAG51 was predominantly localized in CD31-positive endothelial cells and was significantly upregulated in the infarcted myocardium, particularly in the peri-infarct regions. TDAG51 silencing markedly increased capillary density and reduced fibrotic area, as demonstrated by immunohistochemistry and Masson staining. In vitro, TDAG51 knockdown enhanced endothelial proliferation, migration, and tube formation. Mechanistically, these effects were associated with activation of the PI3K-AKT signaling pathway, while pharmacological inhibition of PI3K attenuated the pro-angiogenic phenotype. This study provides histochemical evidence that TDAG51 is enriched in ischemic myocardial endothelial cells and negatively regulates angiogenesis. TDAG51 inhibition promotes vascular remodeling and enhances cardiac repair following myocardial infarction, highlighting TDAG51 as a promising therapeutic target for improving post-MI recovery.

Abstract Background The functions of circRNAs in hepatocellular carcinoma (HCC) till needs to be further elucidated. Methods We assessed the biological functions of circGDI2 in vitro and in vivo by gain or loss of function experiments. Then, fuorescence in situ hybridization (FISH), immunofluorescence (IF), RNA pull-down, mass spectrometry, and RNA immunoprecipitation (RIP) were applied to explore the interaction between circGDI2 and heterogeneous nuclear ribonucleoprotein C (HNRNPC). Finally, in vitro and in vivo experiments were performed to explore the influence of circGDI2 on the anti-tumor activity of LGK-974, a porcupine O-acyltransferase (PORCN) inhibitor. Results CircGDI2 was significantly overexpressed in HBV-related HCC, and its high expression was significantly associated with the growth and invasion characteristics of HCC. Functional experiments indicated that circGDI2 promoted the proliferation and metastasis of HCC cells both in vitro and in vivo. Mechanistic investigations revealed that circGDI2 physically binds to HNRNPC, facilitating its interaction with mPORCN, which stabilizes mRNA and promotes PORCN expression, thereby activating the Wnt signaling pathway and driving tumor proliferation and metastasis. Additionally, we found that the PORCN inhibitor LGK-974 effectively suppressed the proliferation and metastasis of HCC cells both in vitro and in vivo, and a series of experiments demonstrated that knocking down circGDI2 could enhance the antitumor effect of LGK-974, thereby maximizing the inhibition of HCC. Conclusion CircGDI2 played a crucial role in the progression of HCC by interacting with HNRNPC to promote the Wnt signaling pathway. Meanwhile, LGK-974 can effectively inhibit HCC and targeting circGDI2 can enhance the antitumor effect of LGK-974.

Background:Whether the preoperative anemia affects the prognosis and the therapeutic choice between coronary artery bypass grafting (CABG) or medical therapy alone in patients with ischemic cardiomyopathy (ICM) remains unclear. We assess the influence of preoperative anemia on long-term outcomes in ICM patients treated with medical therapy alone with or without CABG. Methods:Patients with preoperative hemoglobin were included from the Surgical Treatment of Ischemic Heart Failure (STICH) trial. The primary outcome was long-term all-cause mortality. Results:A total of 1,209 patients were enrolled, with 320 (26.5%) patients with anemia, and 889 (73.5%) without anemia. The median follow-up time was 9.7 years. Compared with patients without anemia, patients with anemia had a higher risk of all-cause mortality [adjusted hazard ratio (aHR): 1.15; 95% confidence interval (CI): 0.98 to 1.36] and cardiovascular mortality (aHR: 1.26; 95% CI: 1.04 to 1.53). Among patients with anemia, CABG provided a significant survival benefit compared with medical therapy alone (all-cause mortality: aHR: 0.64; 95% CI: 0.48 to 0.85; cardiovascular mortality: aHR: 0.54; 95% CI: 0.39 to 0.76). Though with borderline statistical significance, CABG also provided additional survival benefit among patients without anemia (all-cause mortality: aHR: 0.87; 95% CI: 0.73 to 1.03; cardiovascular mortality: aHR: 0.83; 95% CI: 0.68 to 1.01). Sensitivity analyses based on as-treated principle showed the consistent results. Conclusions:Preoperative anemia is an independent risk factor for mortality in patients with ICM, whereas preoperative anemia does not affect the long-term survival benefits associated with CABG, which might help surgeons in making rational therapeutic decisions during clinical practice.

Background and aimsMalnutrition is a well-recognized predictor of poor prognosis in malignancies. Recent studies suggest that the geriatric nutritional risk index (GNRI) is a more accurate determinant of prognosis in elderly patients than conventional body mass index (BMI). This study aimed to evaluate the GNRI and body composition parameters in elderly patients with intrahepatic cholangiocarcinoma (ICC) and assess their prognostic impact on long-term outcomes.MethodsA total of 157 elderly ICC patients (aged ≥65 years) who underwent radical resection between 2009 and 2018 were retrospectively analyzed. Skeletal muscle index (SMI), muscle attenuation (MA), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral-to-subcutaneous fat ratio (VSR) were quantified using computed tomography. Prognostic analyses were conducted using the Kaplan–Meier method, with adjustments using inverse probability weighting. A nomogram based on multivariate Cox regression was constructed and internally validated, comparing its prognostic accuracy with the TNM staging system.ResultsAmong the body composition parameters, low SMI (sarcopenia, 56.1%), high VSR (visceral adiposity, 54.8%), and low MA (intramuscular fat deposition, 50.3%) were significantly associated with overall survival (OS) and recurrence-free survival (RFS) (all p < 0.05). Low GNRI was also a strong predictor of poor prognosis (p < 0.001). Multivariate analysis identified low GNRI (p = 0.009), sarcopenia (p = 0.020), visceral adiposity (p = 0.033), and intramuscular fat deposition (p = 0.036) as independent prognostic factors for OS and RFS. The nomogram, incorporating GNRI, SMI, VSR, MA, microvascular invasion (MVI), CA19-9 levels, and lymph node invasion, demonstrated superior prognostic performance compared to the TNM stage, with a C-index of 0.734 (OS) and 0.704 (RFS) and an AUC of 0.809 (OS) and 0.815 (RFS).ConclusionGNRI, sarcopenia, IMF deposition, and visceral adiposity independently predict mortality and tumor recurrence in elderly ICC patients. Body composition is a major determinant of prognosis in patients with ICC. Our nomogram based on body composition reveals superior prognostic efficacy over TNM stages.

This study aims to improve hepatocellular carcinoma (HCC) diagnostic accuracy in non-high-risk populations by utilizing GPTs that incorporate integrated risk coefficients, and to explore its feasibility. Between August 2016 and June 2019, patients with focal liver lesions (FLLs) in non-high-risk populations, confirmed by histopathology or clinical/imaging evidence, were retrospectively included. A logistic regression model was developed using baseline characteristics and contrast-enhanced ultrasound (CEUS) features to identify independent HCC risk factors. Three ChatGPT-based models were evaluated: ChatGPT 4o (a general-purpose model developed by OpenAI), BaseGPT (a customized model with HCC diagnostic knowledge), and RiskGPT (a further customized model integrating HCC knowledge and identified risk factors). Their intra-agreement and diagnostic performance were compared. Logistic regression identified male, obesity, HBcAb or HBeAb positivity, elevated alpha-fetoprotein, and mild washout on CEUS as associated with HCC. RiskGPT achieved the highest area under a receiver operating characteristic curve (AUC) (0.89) and demonstrated superior accuracy (90.3

This study aims to develop a prediction model based on non-contrast computed tomography (NCCT) images to differentiate uric acid stones from non-uric acid stones before treatment. This study retrospectively enrolled 195 patients from Quzhou People’s Hospital between 2022 and 2024 who underwent dual-energy CT scans with confirmed renal stone composition. The patients were randomly divided into a training set (156 cases) and a test set (39 cases) in an 8:2 ratio. Regions of interest (ROIs) were manually delineated slice-by-slice on NCCT images to extract radiomic features. Feature dimensionality reduction and selection were performed using intraclass correlation coefficient (ICC), Spearman rank correlation coefficients, and least absolute shrinkage and selection operator (LASSO) regression. Radiomics and clinical models were developed using logistic regression (LR), support vector machine (SVM), multilayer perceptron (MLP), ExtraTrees, and LightGBM algorithms. Finally, a combined model was constructed by integrating the selected radiomic features with clinically significant risk factors. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), while clinical utility was assessed through decision curve analysis (DCA). Model interpretability was examined using Shapley additive explanations (SHAP). A total of 1834 radiomic features were extracted from each ROI. After feature dimensionality reduction and selection, 6 radiomic features remained for characterizing stone composition. The clinical, radiomics, and combined models all demonstrated favorable discriminatory power for uric acid stones. The AUC values of the three models in the training set were 0.744 (95

The Al2O3: Cr3+ light-converting materials were successfully synthesized via co-precipitation, resulting in a grain size ranging from 100 to 400 nm. Under excitation wavelengths spanning from 360 to 650 nm, a distinct near-infrared (NIR) emission at 695 nm was observed. Through optimization, it has been established that a Cr3+ doping concentration of 1.0 mol% results from the optimal emission intensity. The material shows relatively stable in water and it was employed to cultivate the H9C2 cells, and the NIR emission from the cells was observed, indicating the successful absorption of the material by the cells. Additionally, the toxicity of the material was examined, by reducing the concentration to 2 nM/mL, the toxicity of the material was significantly reduced to a promising level. Therefore, the suitable grain size, NIR emission and the biocompatibility renders this material a candidate in cell imaging.

BackgroundThe optimal treatment strategy for recurrent hepatocellular carcinoma (rHCC) remains unclear. This study is based on cases of rHCC after liver resection, aiming to evaluate the influence of preoperative risk factors on the long-term prognosis of patients with rHCC by comparing patients who underwent salvage liver transplantation (SLT) with those who underwent repeat hepatectomy (RH).MethodsWe retrospectively analyzed 401 consecutive patients with rHCC who underwent SLT or RH between March 2015 and December 2022. Next, we performed propensity score matching, subgroup analyses, and both univariate and multivariate analyses. In addition, Kaplan–Meier analysis was used to estimate the overall survival (OS) and recurrence-free survival (RFS) after recurrence.ResultsThe 1-, 3-, and 5-year OS and RFS rates in the SLT group were significantly higher than those in the RH group (p=0.0131 and p=0.0010, respectively), and similar results were observed after propensity score matching. In the presence of zero or one risk factors, the OS and RFS in the SLT group were significantly better than those in the RH group (p=0.0386 and p=0.0117, respectively). However, in the presence of two to four risk factors, no significant differences in OS or RFS were detected between the two groups (p=0.1119 and p=0.1035, respectively).ConclusionOur analysis identified a number of risk factors that were strongly correlated with a long term prognosis for patients with rHCC who underwent SLT and RH: multiple tumors, a maximum tumor diameter ≥5 cm, microvascular invasion, and a recurrence time ≤2 years. Our findings provide important reference guidelines for organ allocation and clinical decision-making.

Background: Lidocaine, the most widely used local anaesthetic, has anticancer effects in both laboratory findings and retrospective clinical studies. We explored the potential benefits of intra-arterial lidocaine on long-term survival in patients with hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolisation (TACE). Methods: This retrospective cohort study included patients with HCC who received TACE as initial treatment from August 2011 to October 2016. Eligible patients were categorised into no lidocaine and lidocaine groups. Propensity score matching was undertaken. Progression-free survival (PFS) and overall survival were compared between the two groups. Subgroup analysis was performed to explore the survival benefit of combining intra-arterial lidocaine with platinum-based chemotherapy during TACE. Results: Of 374 eligible patients, 96 were in the lidocaine group and 278 were in the no lidocaine group. Survival analysis showed that intra-arterial lidocaine was associated with longer PFS (P=0.004) and overall survival (P<0.001). After propensity score matching, PFS (P<0.001) and overall survival (P=0.001) benefits of lidocaine remained. Multivariate analysis showed that intra-arterial lidocaine was an independent prognostic factor for PFS (P=0.011) and overall survival (P=0.044). The impact of intra-arterial lidocaine was similar in patients receiving the TACE regimen with platinum (PFS: P=0.014; overall survival: P=0.023). Conclusions: Intra-arterial lidocaine might improve long-term survival in patients with HCC undergoing TACE and in the subgroup of patients receiving platinum. The study highlights the potential antitumour benefits of combining lidocaine and chemotherapeutics in patients with cancer.

Background: Cholangiocarcinoma (CCA) is an epithelial malignancy with a dismal prognosis. Here, we presented the largest single-center experience in treating CCA using a novel surgical procedure, ex vivo liver resection and auto-transplantation (ELRA). Methods: We retrospectively enrolled 175 patients with CCA after tumor resection in our single center between September 2021 and June 2024, with the last follow-up conducted on November, 2024. The primary outcome was overall survival (OS). A 1:1 propensity score matching (PSM) approach was employed to adjust potential confounders between the ELRA cohort and the conventional liver resection (CLR) cohort. Results: After matching, a total of 27 pairs were included in our study. The median OS was significantly improved in the ELRA cohort compared to the CLR cohort, with a hazard ratio (HR) for death of 0.301 [95% confidence interval (CI): 0.107-0.847; P=0.02]. The survival rate was 95.7% in the ELRA cohort vs. 60.0% in the CLR cohort at 1 year, and 75.2% vs. 42.0% at 2 years. The median recurrence-free survival (RFS) was 17.0 months in the ELRA cohort as compared with 9.7 months in the CLR cohort (HR for disease recurrence or death =0.351; 95% CI: 0.161-0.766; P=0.006). Univariate and multivariate Cox regression analyses revealed that ELRA was an independently factor associated with improved outcomes in both OS (P=0.006) and RFS (P=0.009). Complications related to surgical procedures were observed in 66.7% of patients in the ELRA cohort compared to 59.3% in the CLR cohort (P=0.78). For the grade 3-5 complications, the rates were 14.8% in the ELRA cohort and 11.1% in the CLR cohort (P>0.99). Conclusions: ELRA was a promising method to improve outcomes for patients with CCA.

Recent studies have suggested that sVEGFR-3 is involved with cardiac disease by regulating lymphangiogenesis; however, results are inconsistent. The purpose of this study was to investigate the role and mechanism of sVEGFR-3 in myocardial ischemia/reperfusion injury (MI/RI). Plasma sVEGFR-3 levels were measured in patients with heart valve disease (HVD). sVEGFR-3 effects were evaluated in vivo in mice subjected to MI/RI, and in vitro using HL-1 cells exposed to hypoxia/reoxygenation. Echocardiography, TTC-Evans blue staining, ELISA, electron microscopy, immunofluorescence, Western blotting, and flow cytometry were used to investigate if sVEGFR3 attenuated I/R injury. TMT-based proteomics analysis was used to investigate the downstream mechanism of sVEGFR3. Results showed that plasma sVEGFR-3 levels were decreased in HVD patients compared to heathy control subjects. In patients undergoing cardiopulmonary bypass (CPB), sVEGFR-3 was significantly increased at 2 hours after release of the aortic cross-clamp and decreased slightly at 24 hours. In vivo, sVEGFR-3 pretreatment reduced cardiac dysfunction, infarct area, and myocardial injury indicators by reducing ROS production, apoptosis, and AIF expression. In vitro, sVEGFR-3 restored mitochondrial homeostasis by stabilizing the mitochondrial membrane potential (MMP) and preventing the opening of mitochondrial permeability transition pores (mPTP). And sVEGFR-3 inhibits mitochondrial apoptosis through the Ras/MEK/ERK pathway. Furthermore, I/R injury increased the proportion of M1 macrophages and CD4 + T cells in myocardial tissue, as well as serum IFN-γ and TNF-α levels, whereas sVEGFR-3 treatment attenuated these effects. sVEGFR-3 attenuates myocardial I/R injury by regulating mitochondrial homeostasis and immune cell infiltration, and reduces intrinsic ROS-mediated mitochondrial apoptosis via the Ras/MEK/ERK pathway.

BACKGROUND:Among various blood flow control techniques, the intermittent Pringle's maneuver (IPM) remains the most convenient and widely used method for reducing bleeding during hepatic resection (HR). However, the impact of IPM on human hepatocellular carcinoma (HCC) recurrence is still unclear. To date, no randomized controlled trial (RCT) has directly evaluated the impact of IPM on the tumor recurrence in HCC patients undergoing HR. Since 2019, our team has been investigating the effects of 25-min IPM on liver function and post-hepatectomy safety in HCC patients. To date, we have published two RCTs that confirm the safety and feasibility of 25-min IPM for HCC patients with Child-Pugh grade A liver function. However, these studies focused exclusively on short-term outcomes and did not assess tumor recurrence. Therefore, we are designing this RCT to compare the effects of 15-min IPM with 25-min IPM on early tumor recurrence in HCC patients undergoing HR. METHODS:This will be a single-center, parallel, double-blind, randomized controlled trial. A total of 334 consecutive patients who meet the inclusion and exclusion criteria will be enrolled and randomized into either the 15-min IPM group or the 25-min IPM group in a 1:1 ratio using a randomization protocol. Patients will be followed for 2 years after surgery. DISCUSSION:We designed this protocol to compare the effects of two different IPM methods on tumor recurrence in HCC patients undergoing HR, which will provide significant guidance for surgeons. Firstly, this study design is practical and feasible in clinical practice. Secondly, this RCT will encompass various types of HR procedures (including laparoscopic or open HR, as well as minor or major hepatectomy), ensuring a representative clinical application. Thirdly, to our knowledge, this is the first RCT to compare the effects of 15- and 25-min IPM on early recurrence of HCC. TRIAL REGISTRATION:This trial was registered on April 29, 2024, in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), under the registration number ChiCTR2400083647. The protocol version is V1.0 (20,240,429).

The debate between off-pump coronary artery bypass grafting (OPCAB) and on-pump coronary artery bypass grafting (ONCAB) in diabetic patients remains. This meta-analysis aimed to investigate outcomes after OPCAB versus ONCAB for patients with diabetes. Literature research was conducted up to December 2023 using Ovid Medline, EMBASE, and the Cochrane Library. Eligible studies were observational studies with a propensity-score analysis of OPCAB versus ONCAB. The primary outcomes were early mortality and mid-term survival. The secondary outcomes were cerebrovascular accidents, reoperation for bleeding, incomplete revascularization, myocardial infarction, low cardiac output, and renal replacement therapy. Our research identified seven observational studies with a propensity-score analysis enrolling 13,085 patients. There was no significant difference between OPCAB and ONCAB for early mortality, mid-term survival, myocardial infarction, low cardiac output, and renal replacement therapy. OPCAB was associated with a lower risk of cerebrovascular accidents (OR 0.43; 95

Blood pressure dipping patterns have long been considered to be associated with adverse events. We aimed to investigate whether dipping patterns of postoperative MAP were related to 90-day and hospital mortality in patients undergoing CABG. Four thousand three hundred ninety-one patients were classified into extreme dippers (night-to-day ratio of MAP ≤ 0.8), dippers (0.8 < night-to-day ratio of MAP ≤ 0.9), non-dippers (0.9 < night-to-day ratio of MAP ≤ 1), and reverse dippers (> 1). Compared with non-dippers, reverse dippers were at a higher risk of 90-day mortality (aHR = 1.58; 95

Aim Mitral valve repair (MVr) is associated with more favourable long-term outcomes than mitral valve replacement (MVR) in cases of isolated mitral valve disease suitable for repair. However, there is debate regarding whether the superiority of MVr extends to patients with concomitant aortic and mitral valve disease. Therefore, this meta-analysis was conducted to compare the survival benefits between aortic valve replacement (AVR) plus MVr with a double valve replacement (DVR). Method A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane until 20 October 2022. Studies comparing MVr and MVR in patients undergoing concomitant AVR were included. The primary outcome was long-term survival. The secondary outcomes were early mortality, mitral valve reoperation, and valve-related adverse events. Results Sixteen studies with a total of 140,638 patients were included in this analysis. Patients undergoing AVR plus MVr exhibited a favourable trend in long-term survival (HR 0.85; 95% CI 0.71–1.03; p=0.10; I2=58%). The reconstructed Kaplan–Meier curve revealed that the long-term survival at 5, 10, and 15 years was higher in the AVR plus MVr (80.95%, 67.63%, and 51.18%, respectively) than in the DVR group (76.62%, 61.36%, 43.21%, respectively). Aortic valve replacement plus MVr had a lower risk of early mortality (RR 0.67; 95% CI 0.58–0.79; p<0.001; I2=77%), thromboembolic events (RR 0.81; 95% CI 0.67–0.98; p=0.03; I2=5%), and haemorrhagic events (RR 0.87; 95% CI 0.78–0.98; p=0.01; I2=59%). Moreover, both groups displayed comparable rates of mitral valve reoperation (HR 1.73; 95% CI 0.86–3.48; p=0.13; I2=60%) and infective endocarditis (RR 1.60; 95% CI 0.65–3.93; p=0.31; I2=0%). However, the rate of reoperation for AVR plus MVr significantly increased in rheumatic heart disease patients (HR 3.30, 95% CI 1.66–6.59; p<0.0001). Conclusions Compared with DVR, AVR plus MVr was associated with favourable long-term survival, reduced early mortality risk, and a lower incidence of thromboembolic and haemorrhagic events without increasing the risk of mitral valve reoperation or infective endocarditis in unselected patients. However, higher reoperation rates were observed in rheumatic heart disease patients undergoing AVR plus MVr.