Objective:The long-term prognosis and optimal management for Takayasu arteritis (TA) patients with severe stenosis of the descending thoracic and abdominal aorta remain undefined. We compared the clinical outcomes of surgical intervention and medical management. Methods:Between January 2011 and January 2022, 78 TA patients with severe descending thoracic and abdominal aortic stenosis were enrolled at Peking Union Medical College Hospital. The cohort included the surgical group (n = 62) and the conservative treatment group (n = 16). Baseline characteristics were assessed to reduce selection bias. The primary outcome was all-cause mortality. Secondary outcomes were defined as the event-free survival and quality of life. Long-term follow-up of the clinical outcomes was also performed. Results:Surgical intervention significantly reduced all-cause mortality compared to conservative management (P < 0.001). Patients who underwent surgeries also exhibited improved quality of life regardless of their physical condition (P < 0.01) or psychological condition (P = 0.006). Postoperative reductions in systolic blood pressure (P = 0.033) and antihypertensive medication requirements (P = 0.015) were observed compared to medical management. In the surgical group, different surgical approaches presented with other complications, with the open surgical group having higher comorbidities within 30 days and a lower rate of long-term restenosis (P = 0.038). Conclusion:Surgical intervention significantly improves long-term outcomes in TA patients with severe stenosis of the descending thoracic and abdominal aorta.

BACKGROUND:Benign prostatic hyperplasia (BPH) is prevalent among aging men. Whether exposure to internet-derived health information is associated with disease awareness and symptom burden at initial diagnosis remains unclear. METHODS:We conducted a cross-sectional study of 400 newly diagnosed BPH outpatients. Participants were classified by prior exposure to internet-derived BPH content. BPH awareness and International Prostate Symptom Scores (IPSS) were compared using the Mann-Whitney U test and multivariate linear regression adjusted for age, education, and disposable income. Stratified analyses were performed according to educational attainment, disposable income, and content format. RESULTS:Exposure to internet-derived BPH content was independently associated with higher awareness and lower IPSS. Compared with unexposed participants, exposed participants had higher awareness (median 1.5 vs. 0) and lower IPSS (median 7.0 vs. 10.5) (both p < 0.001). In multivariable models, being unexposed was associated with a 1.39-point lower awareness score and a 2.20-point higher IPSS (both p < 0.001). In stratified analyses, the associations remained significant across education and income strata. Among exposed participants, those accessing text-based or mixed-format content had higher awareness and lower IPSS than those exposed to videos only (both p < 0.001). CONCLUSIONS:This study shows that exposure to internet-derived health content is significantly associated with higher BPH awareness and a lower symptom burden at initial presentation. Text-based or mixed-format content may be more effective than video-only formats.

To evaluate the association of sodium-glucose cotransporter 2 inhibitors (SGLT2i) with diabetic ketoacidosis (DKA) in type 2 diabetes mellitus (T2DM) patients across different subgroups, we searched randomized controlled trials (RCTs) comparing SGLT2i with the control groups among T2DM patients and including DKA as a safety outcome. Pooled risk ratios (RRs) were calculated using random or fixed-effects models, as appropriate. An inverse-variance-weighted Mendelian randomization (MR) analysis was performed to estimate the genetic correlation. Twenty-two trials involving 80,235 patients were included. SGLT2i increased the risk of DKA compared to the control groups (RR 2.32, 95% CI 1.64-3.27). The risk was significantly increased in patients with higher HbA1c levels (> 7.9%) (RR 2.24, 95% CI 1.59-3.14), but not in those with lower HbA1c levels (≤ 7.9%) (RR 1.05, 95% CI 0.49-2.26; interaction P = 0.034). SGLT2i increased DKA risk in chronic kidney disease (CKD) (RR 2.70, 95% CI 1.55-4.71) and high atherosclerotic cardiovascular disease (ASCVD) risk trials (RR 2.46, 95% CI 1.47-4.11) but not significantly in heart failure (HF) trials (RR 1.23, 95% CI 0.51-2.96). Moreover, in the HF trials, SGLT2i consistently did not increase the risk of DKA in any clinical subgroups. Nevertheless, MR analysis still confirmed a genetic association between SGLT2i and the risk of DKA among overall T2DM patients. SGLT2i may increase the risk of DKA in T2DM patients, particularly in patients with higher levels of HbA1c and those with comorbid CKD or at high-risk ASCVD. However, the increased risk was not significant in patients with HF.

BACKGROUND:Infective endocarditis (IE) is a serious infectious disease with a rising incidence rate and high mortality rate. While lactate dehydrogenase (LDH) is a sensitive and accessible biomarker of inflammation, tissue damage and metabolic alteration, its prognostic value in IE remains unexplored. OBJECTIVE:This study aims to investigate the prognostic value of admission serum LDH levels for 28-day mortality in critically ill IE patients. METHODS:The data used in this retrospective cohort study was extracted from the MIMIC-IV database. Restricted cubic spline analysis, Cox regression, Kaplan-Meier survival analysis, and receiver operating characteristic analysis were performed to evaluate the predictive value of serum LDH in critically ill IE patients. Key clinical confounders for the adjusting Cox models were filtered by LASSO regression. RESULTS:A total of 215 critically ill patients with diagnosed IE were included during their first intensive care unit admission. LDH was one of the most significant confounders identified by LASSO analysis. The crude and adjusted Cox models revealed a consistently independent and dose-response relationship between high serum LDH and higher mortality. The fully adjusted model showed each standard deviation increase in LDH (log2) was associated with a hazard ratio of 2.37 (95% CI: 1.51-3.71, p < 0.001). Kaplan-Meier curves demonstrated significantly different survival patterns across LDH levels (p = 0.0032). The area under the curve (AUC) of LDH was higher than SOFA score (AUC=0.637 v.s. 0.573, p=0.251). CONCLUSION:This study identified serum LDH as an independent predictor of mortality in critically ill IE patients.

OBJECTIVE:This study aims to evaluate the role of antiphospholipid antibodies (aPLs) in patients with SLE with heart valve diseases (HVDs). METHODS:This prospective study included consecutive patients with SLE who visited Peking Union Medical College Hospital between April 1999 and December 2024. Echocardiography was performed based on clinical indications. Clinical characteristics, aPL profiles and echocardiographic findings were collected. Logistic regression was used to evaluate associations between aPLs and HVD. RESULTS:Among 508 patients with SLE, 27.4% had HVD. The most frequently affected valves were aortic (17.3%) and mitral (11.2%) valves, with thickening (19.5%) and regurgitation (15.9%) as the leading lesion types. aPLs positive patients with SLE had higher rates of HVD (35.1% vs 24.0%, p=0.010), including valve thickening (25.3% vs 16.9%, p=0.028), regurgitation (24.7% vs 12.1%, p<0.001), vegetations (9.1% vs 0.8%, p<0.001) and stenosis (1.9% vs 0.0%, p=0.008). Anticardiolipin-IgG was associated with HVD (OR=2.484, p=0.003), mitral lesions (OR=4.156, p<0.001), valve thickening (OR=2.255, p=0.011) and regurgitation (OR=2.121, p=0.014). Anti-β2 glycoprotein I-IgG showed similar associations and was also linked to valve stenosis (OR=11.209, p=0.022). Lupus anticoagulant (LA) was associated with valve vegetations (OR=8.659, p<0.001) and interventional/surgical indications (OR=6.868, p=0.005). CONCLUSION:aPLs, especially IgG isotype and LA, are independently associated with diverse HVD in SLE. Echocardiographic monitoring is warranted in aPL-positive patients.

Right ventricular failure as a severe consequence of pulmonary arterial hypertension (PAH) is an independent risk factor for poor prognosis, although the pathogenesis of right ventricular remodeling (RVR) remains unclear. Exploring the shared molecular pathways and key molecules in the right ventricle in monocrotaline (MCT) and pulmonary artery banding (PAB) rat models may reveal critical RVR mechanisms. Untargeted proteome and metabolome analysis were performed on the right ventricular myocardium of two RVR models (MCT-induced PAH rats and PAB-operated rats) to identify the altered proteins and metabolites, followed by validation using parallel reaction monitoring analysis and quantitative real-time polymerase chain reaction (qPCR). The multi-omics profiles of MCT and PAB rat models were compared to explore the key dysregulated molecules and pathways in RVR. Our proteomics study identified 25 shared RVR-altered differentially expressed proteins. Multiple common biological pathways were identified between PAB and MCT rat models, encompassing myocardial remodeling and energy metabolism alternation, etc. Various molecules and pathways related to vesicle transport and autophagy were identified, including nidogen-1, the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) signaling pathway, and the microautophagy pathway (all previously unreported in RVR). Glycerophospholipid metabolism was the sole statistically significant common metabolic pathway enriched by metabolomics. Underreported biological processes, including vesicle transport and autophagy, may contribute to the pathophysiology of PAH-induced RVR.

PURPOSE:To explore the function of cyclopamine in corneal neovascularization and subsequent fibrosis after cornea alkali-burn injury. METHODS:In vivo, mice cornea were injured by NaOH, and then treated with cyclopamine, clodronate liposomes (CLO-LPS), and vehicle of cyclopamine separately by subconjunctival injections. Clinical features were observed and pathological characteristics were examined. In vitro, M1 macrophages (M1φ) and human umbilical vein endothelial cells (HUVECs) were co-cultured, and the abilities of proliferation, migration, and tube formation of HUVECs were detected under different interventions of M1φ. RESULTS:Alkali-burn injury induced massive angiogenesis and decreased transparency of the cornea, along with numerous macrophages infiltration and Shh protein expression in the cornea. However, corneal neovascularization, macrophage infiltration, and Shh expression could suppressed by cyclopamine and CLO-LPS significantly. In addition, treatment with cyclopamine also reduced the expression of inflammatory factors (TNF-α, IL-6) and fibrosis factors (VIM, α-SMA). In vitro, M1φ promotes migration and tube formation of HUVECs by secreting Shh protein, which could be inhibited by cyclopamine. CONCLUSION:Cyclopamine could suppress inflammation and angiogenesis of alkali-burned cornea, as well as subsequent fibrosis. The study reveals that cyclopamine suppresses corneal neovascularization in a dual mechanism of inhibiting macrophage infiltration and suppressing Shh signaling.

Background Culture-negative infective endocarditis (CNIE) presents significant diagnostic and therapeutic challenges due to the absence of identifiable pathogens, leading to empirical antibiotic treatment and potentially worse clinical outcomes. This study aims to compare the clinical characteristics, surgical outcomes, and long-term prognoses of patients with CNIE and culture-positive infective endocarditis.Methods A total of 698 patients who underwent surgery for infective endocarditis between 2013 and 2024 were included, with 154 (22.1%) classified as CNIE. Baseline, intraoperative, and postoperative factors were analyzed in several ways including multivariate Cox regression and structural equation modeling.Results Patients with CNIE had worse preoperative cardiac and renal function and a higher incidence of postoperative renal replacement therapy. While overall long-term survival did not differ significantly between CNIE and culture-positive infective endocarditis, female patients with CNIE showed a significantly worse prognosis (hazard ratio, 2.13 [95% CI, 1.02-4.43]; P=0.04). Mediation analysis indicated that reduced renal function (estimated glomerular filtration rate) partially mediated the relationship between culture status and death, highlighting a potential mechanism.Conclusions Although the survival rates of patients with CNIE and culture-positive infective endocarditis are similar, the prognosis of female patients with CNIE is significantly worse.

OBJECTIVE:Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with high mortality. The ratio of pulmonary to systemic vascular resistance (SVR) (Rp : Rs) may increase with disease progression. However, the prognostic value of Rp : Rs in predicting the outcomes of patients with SLE-PAH remains to be elucidated. METHODS:Between 1 February 2012, and 30 June 2022, consecutive patients with a diagnosis of SLE-PAH and minimum one follow-up were enrolled prospectively. The end points were all-cause mortality and lung transplantation. The predictive values of baseline clinical characteristics and hemodynamic parameters, including Rp : Rs, were analyzed using Cox proportional hazard analyses. C-statistics were used to compare the predictive ability between the models. RESULTS:A total of 285 patients were included and followed up for a median duration of 3.41 (interquartile range 1.81-5.72), during which 58 (20.4%) patients reached the endpoint. Multivariable Cox regression analysis revealed that in addition to the 6-minute walk distance (6MWD), the Rp : Rs was an independent predictor of the endpoint [hazard ratio 24.72; 95% confidence interval (CI) 5.59-109.29, P  < 0.001] in predicting the endpoint. The concordance index for a model incorporating the Rp : Rs and the 6MWD yielded a value of 0.75 (95% CI 0.68-0.82), which showed better predictive accuracy than the simplified risk stratification strategy. Introducing the Rp : Rs ratio to the 2022 ESC/ERS four-stratum model significantly improved its predictive performance for these patients. CONCLUSION:The Rp : Rs serves as an independent predictor of adverse prognosis in patients with SLE-PAH and could provide additional value over current risk-assessment tools.

Background Right ventricular dysfunction (RVD) is a common complication of idiopathic dilated cardiomyopathy linked to poor outcomes. However, reliable noninvasive biomarkers for RVD remain lacking. This study aimed to identify urinary proteomic markers using mass spectrometry and machine learning. Methods In this prospective cohort, patients with idiopathic dilated cardiomyopathy were classified by cardiac magnetic resonance imaging into groups with RVD (RV ejection fraction <45%) and without RVD groups. Baseline urine samples were profiled by data‐independent acquisition mass spectrometry. Differentially expressed proteins were identified and selected by least absolute shrinkage and selection operator regression to build a diagnostic model, developed in a training set, and validated in a test set. The primary end point was a composite of cardiovascular death, heart failure rehospitalization, left ventricular assist device implantation, or heart transplantation. Results The study enrolled 147 patients with idiopathic dilated cardiomyopathy (64 with RVD, 83 without), with a median follow‐up of 19.3 months. Of 3579 quantified urinary proteins, 46 were differentially expressed between groups. A 3‐protein panel (RARRES1 [retinoic acid receptor responder protein 1], MVB12B [multivesicular body subunit 12B], GSK3A [glycogen synthase kinase 3 alpha]) was identified and showed excellent diagnostic accuracy (training area under the curve 0.946; validation area under the curve0.935), outperforming both NT‐proBNP (N‐terminal pro–brain natriuretic peptide) and tricuspid annular plane systolic excursion. The risk score derived from this panel effectively stratified patients, with the high‐risk group exhibiting significantly worse outcomes than the low‐risk group (hazard ratio, 3.24 [95% CI, 1.56–6.71], P=0.002). Conclusions The urinary proteomic panel developed in this study demonstrates diagnostic and prognostic potential for identifying RVD in idiopathic dilated cardiomyopathy, providing a promising noninvasive tool for precise detection and clinical risk stratification.

BACKGROUND:Right ventricular (RV) maladaptive remodeling has been demonstrated to be more severe in males than in females under similar afterload, with androgen potentially involved. However, the mechanism remains unknown. METHODS:We performed RV proteomics and metabolomics in male and castrated rats with pulmonary artery banding (PAB) or sham surgery. The core pathway was tested in other sets of male, castrated male, and testosterone-replaced rats with and without pathway inhibitors administration and in RV remodeling patients. Metabolite verification was carried out by matching secondary spectra. RESULTS:With the same extent of increases in RV afterload, male PAB rats exhibited more pronounced RV hypertrophy and fibrosis than castrated PAB rats (p < 0.05). The omics analysis indicated that pathways and functions related to oxidative stress were exhibited in the male group, with the platelet-derived growth factor (PDGF) pathway being among them. More proteins and metabolites associated with fatty acid metabolism were downregulated in males. Correlation analysis showed that PDGF receptor beta (PDGFRB) and signal transducer and activator of transcription 3 (STAT3) were negatively correlated with carnitine and reactive oxygen species scavenging metabolites only in male rats. The activation of the PDGF pathway was verified in testosterone-replaced PAB rats and male patients with RV remodeling. Treatments with PDGFRB inhibitor and STAT3 inhibitor could reverse RV maladaptive remodeling in male and testosterone-replaced PAB rats but not in castrated ones. CONCLUSIONS:Androgen might exacerbate RV maladaptive remodeling via intensified oxidative stress and insufficient energy supply, with activating the PDGFRB-STAT3 signaling being one of the possible pathways.

Acute myocardial infarction (AMI) can be divided into myocardial infarction with coronary artery disease (MICAD) or with nonobstructive coronary arteries (MINOCA) according to the severity of artery stenosis. Antiphospholipid syndrome (APS) can present with AMI, but the subtype and prognosis are not fully understood. The study was conducted based on the APS cohort in Peking Union Medical College Hospital. According to coronary angiography, AMI patients were classified as MICAD or MINOCA. Thrombotic APS (tAPS) patients were enrolled to explore the risk factors of AMI. The study enrolled 36 APS-AMI patients, 26 (72

Immunotherapy plays an important role in the treatment of bladder cancer (BLCA), with outcomes influenced by the tumor microenvironment (TME). Angiogenesis, a hallmark of cancer progression, shapes the TME and impacts immunotherapy efficacy. However, its specific role in BLCA remains underexplored. We analyzed 268 angiogenesis-related genes (ARGs) across ten gene sets using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Through unsupervised clustering, we identified ARG-based subtypes and developed an ARG scoring system to quantify angiogenesis activity. The ARG score was correlated with clinical outcomes, immune cell infiltration, and immunotherapy response. Functional validation was performed using in vitro assays. Two distinct ARG clusters exhibited significant differences in immune profiles, clinical outcomes, and functional characteristics. Patients in the high ARG cluster had poorer survival but showed enhanced responsiveness to immune checkpoint inhibitors (ICIs). The novel ARG score demonstrated strong predictive power for immunotherapy efficacy and survival outcomes. ARG expression patterns profoundly impact the TME, clinical outcomes, and immunotherapy response in BLCA. The ARG score is a novel biomarker for stratifying patients and optimizing treatment strategies. These findings may contribute to clarifying the characteristics of TME and enable the exploration of more potent immunotherapy strategies.

Brain abscess is a severe infection characterized by the accumulation of pus within the brain parenchyma. Accurate identification of the causative pathogens is crucial for effective treatment and improved patient outcomes. This 10-year retrospective, single-center study aimed to compare the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) in brain abscess. We reviewed 612 patients diagnosed with brain abscess and identified 174 cases with confirmed etiology. The median age was 52 years, with 69.5% males. Culture tests predominately identified gram-positive bacteria, particularly Streptococcus spp. Gram-negative bacteria, including Klebsiella spp., were also detected. However, mNGS revealed a more diverse pathogen spectrum, focusing on anaerobes (e.g., Fusobacterium spp., Parvimonas spp., Porphyromonas spp., Prevotella spp., and Tannerella spp.). mNGS exhibited significantly higher overall pathogen-positive rates in pus samples (85.0% vs 50.0%, P = 0.0181) and CSF samples (84.2% vs 7.9%, P < 0.0001) compared to culture. Furthermore, the detection rates for anaerobes displayed a notable disparity, with mNGS yielding significantly higher positive detections in both pus samples (50.0% vs 10%, P = 0.0058) and CSF samples (18.4% vs 0%, P = 0.0115) when compared to culture methods. The assistance of mNGS in pathogen detection, particularly anaerobes in brain abscess, was evident in our findings. mNGS demonstrated the ability to identify rare and fastidious pathogens, even in culture-negative cases. These results emphasize the clinical value of mNGS as a supplement for brain abscess, enabling more comprehensive and accurate pathogen identification.IMPORTANCEThe accurate identification of pathogens causing brain abscess is crucial for effective treatment and improved patient outcomes. In this 10-year retrospective study, the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) was compared. The study analyzed 612 patients with brain abscess and confirmed etiology in 174 cases. The results showed that culture tests predominantly identified gram-positive bacteria, while mNGS unveiled a broader diverse pathogen spectrum, particularly anaerobes. The mNGS method exhibited significantly higher overall rates of pathogen positivity both in pus and cerebrospinal fluid (CSF) samples, surpassing the culture methods. Notably, mNGS detected a significantly higher number of anaerobes in both pus and CSF samples compared to culture methods. These findings underscore the clinical value of mNGS as a supplement for brain abscess diagnosis, enabling more comprehensive and accurate pathogen identification, particularly for rare and fastidious pathogens that evade detection by conventional culture methods.

The crucial pathophysiological and prognostic roles of the right ventricle in various diseases have been well-established. Nonetheless, conventional cardiovascular imaging modalities are frequently associated with intrinsic limitations when evaluating right ventricular (RV) morphology and function. The integration of artificial intelligence (AI) in multimodality imaging presents a promising avenue to circumvent these obstacles, paving the way for future fully automated imaging paradigms. This review aimed to address the current challenges faced by clinicians and researchers in integrating RV imaging and AI technology, to provide a comprehensive overview of the current applications of AI in RV imaging, and to offer insights into future directions, opportunities, and potential challenges in this rapidly advancing field.