RATIONALE AND OBJECTIVES:Sarcopenia is a significant predictor of adverse outcomes in cardiovascular diseases. However, most prior studies have focused on lumbar muscle indices and have overlooked the prognostic relevance of site-specific muscle loss in peripheral artery disease (PAD). This study aimed to evaluate whether machine learning (ML) models incorporating the lower-leg muscle index (LMI) provide superior prediction of long-term mortality in PAD patients undergoing revascularization. MATERIALS AND METHODS:A retrospective cohort of 208 consecutive PAD patients hospitalized for planned lower-extremity revascularization was analyzed. Preoperative clinical data and CT angiography-derived muscle indices were collected. Feature selection employed LASSO, mRMR, random forest, and gradient boosting; the number of variables was limited by the 10 events per variable rule. Multivariate Cox regression assessed associations between muscle indices and all-cause mortality. Eight ML models were validated, and performance was evaluated with C-index and AUC. Calibration and decision curve analysis were also performed. RESULTS:During a mean follow-up of 29.5 ± 15.5 months, 44 deaths were recorded. Non-survivors had more comorbidities, inflammation, and lower-limb muscle loss. Among muscle indices, LMI showed the highest discrimination for mortality (AUC 0.71), outperforming abdominal indices. Higher LMI was associated with lower mortality risk (HR = 0.94, 95 % CI 0.92-0.97, p = 0.004) across all subgroups. Gradient boosting yielded the best predictive performance, with C-indexes of 0.847, 0.809, and 0.823 at 1, 3, and 5 years, respectively. Calibration and decision curve analysis demonstrated model robustness and clinical utility. CONCLUSIONS:Lower-leg muscle index is a superior and accessible predictor of long-term mortality in PAD, exceeding conventional abdominal muscle indices. ML models using LMI enable individualized risk stratification and may improve post-revascularization management.
Peripheral artery disease (PAD) confers elevated risk for major adverse cardiovascular events (MACE), yet accurate risk stratification remains a challenge, particularly among patients with advanced disease necessitating endovascular revascularization. This study aimed to improve the prediction of MACE in a clearly defined high-risk PAD population (hospitalized patients undergoing endovascular intervention) by identifying novel protein biomarkers and developing a robust risk model. We prospectively analyzed blood samples from 164 hospitalized PAD patients scheduled for endovascular revascularization, employing untargeted plasma proteomics and metabolomics. Differential protein and metabolite profiles were compared between patients with and without subsequent MACE. Several proteins, including MMP3, MMP19, and PRB2, were markedly elevated in patients who developed MACE. A proteomics-based risk model incorporating these biomarkers achieved high discriminative accuracy (area under the curve > 0.80) for identifying individuals at increased risk. Metabolomic profiling revealed additional pathway alterations, notably involving tryptophan and glycogen metabolism, which provided mechanistic insights into cardiovascular complications but were not directly incorporated into the prediction model. This study demonstrates that integrating protein biomarkers markedly improves risk stratification in advanced PAD patients undergoing surgical intervention. The findings offer promising tools for early detection and enable more personalized management for this high-risk subgroup, while also deepening understanding of disease pathophysiology. However, further validation in larger and more diverse prospective cohorts is warranted before these findings can be broadly applied in clinical practice.
BACKGORUND:Peripheral arterial disease (PAD) is a chronic vascular disease with high morbidity, often accompanied by sarcopenia. However, the prognostic value and mechanistic relevance of computed tomography (CT)-defined sarcopenia in PAD remain unclear. This study aims to assess the independent impact of sarcopenia on all-cause mortality and major adverse cardiovascular events in PAD patients, and to determine optimal third lumbar vertebra skeletal muscle index (L3-SMI) cutoffs for risk stratification. METHODS:In this retrospective cohort study, 208 PAD patients were grouped by L3-SMI into sarcopenia (n = 110) and nonsarcopenia (n = 98). Multivariate Cox regression evaluated associations with mortality and major adverse cardiovascular events (MACE), while restricted cubic spline (RCS) models explored dose-response patterns. Kaplan-Meier and log-rank tests compared survival, and Spearman correlation analyzed functional and metabolic associations. RESULTS:The sarcopenia group exhibited significantly higher age (71.5 ± 9.38 vs. 65.81 ± 10.25 years, P < 0.001), while lower L3-SMI (36.48 ± 5.67 vs. 47.31 ± 7.88 cm2/m2, P < 0.001), lower body mass index (22.31 ± 2.96 vs. 25.77 ± 2.72 kg/m2, P < 0.001), lower albumin (37 vs. 39 g/L, P = 0.005), and lower serum phosphate (1.14 vs. 1.23 mmol/L, P = 0.009). Over a 36-month median follow-up, sarcopenia was associated with increased all-cause death (27% vs. 14%, P = 0.034) and MACE incidence (28% vs. 14%, P = 0.024). Multivariate Cox regression revealed that each 1-unit decrease in L3-SMI elevated death risk by 7% (adjusted hazard ratio [HR] = 0.93, 95% confidence interval [CI]: 0.88-0.98, P = 0.009) and MACE risk by 9% (adjusted HR = 0.92, 95% CI: 0.86-0.96, P = 0.008). RCS analysis identified nonlinear dose-response relationships: L3-SMI <40.97 cm2/m2 sharply increased death risk (HR = 3.3), while L3-SMI <48.78 cm2/m2 significantly amplified MACE risk (HR = 7.89). Correlations between L3-SMI and Barthel index (r = 0.56, P < 0.001), serum phosphate (r = 0.53, P = 0.002), and Fontaine stage (r = -0.39, P = 0.007) suggested sarcopenia might exacerbate disease progression via metabolic dysregulation, immune suppression, and functional decline. CONCLUSION:CT-defined sarcopenia independently predicts poor outcomes in PAD. L3-SMI thresholds enable early risk stratification and support targeted interventions to improve prognosis. These findings underscore the importance of incorporating body composition assessment into routine risk evaluation for PAD patients.
In middle-aged and older atherosclerotic renal artery stenosis (ARAS), the anatomical severity of stenosis is a poor surrogate for microvascular competence, and the renal benefit of revascularization is unpredictable. We developed Renal-Video-AI, a self-supervised deep learning framework (Video Swin Transformer with VideoMAE pretraining) that extracts spatiotemporal hemodynamic features from contrast-enhanced ultrasound, and applied it to a multi-center Discovery Cohort (N = 1,226), an independent External Validation Cohort (N = 122), a prospective Multimodal Cohort with paired 10x Visium spatial transcriptomics (N = 57), and an aged two-kidney-one-clip (2K1C) murine model. Unsupervised phenomapping identified 3 intrinsic hemodynamic phenotypes—Preserved, Delayed, and Rarefied. The Rarefied phenotype predicted major adverse renal events (MAREs) independently of anatomical stenosis [hazard ratio (HR) 4.82, 95% confidence interval (CI) 3.10 to 6.50; Fine–Gray subdistribution HR (sHR) 5.1], and adding the phenotype to a standard clinical model improved the C-statistic from 0.72 to 0.88. A significant phenotype-by-treatment interaction (P < 0.01) showed that stenting reduced events only in the Delayed phenotype (HR 0.52, 95% CI 0.35 to 0.78), not in the Preserved (HR 0.98) or Rarefied (HR 1.05) phenotypes. In absolute terms, stenting reduced the 3-year cumulative incidence of MARE in the Delayed phenotype from 25.4% to 13.2% (absolute risk reduction 12.2%; number needed to treat = 8, 95% CI 6 to 13), with no benefit in the Preserved (8.4% versus 8.0%) or Rarefied (38.6% versus 39.4%) phenotypes. Spatial transcriptomics localized a hypoxia and pyroptosis signature to rarefied tissue, and the aged 2K1C model revealed a mitochondrial reactive oxygen species (ROS)–NLRP3–pyroptosis axis whose pharmacological inhibition (MCC950) restored microvascular perfusion. AI video-phenomapping thus reframes the revascularization decision around microvascular competence rather than anatomy, identifying both therapeutic futility (Rarefied) and a treatable window (Delayed), and nominates NLRP3-driven pyroptosis as a therapeutic target.
BackgroundsPeripheral artery disease (PAD) frequently causes to persistent functional impairment in skeletal muscle even after successful revascularization, implicating non-ischemic pathological mechanisms. Sarcopenia, a myopathy characterized by progressive loss of muscle mass, strength, and function—shares these non-ischemic features and affects approximately one-third of PAD patients, yet the molecular basis of their comorbidity remains poorly defined.MethodsThree transcriptome datasets (GSE120642, GSE181930, and GSE226151) were included in the analysis, covering skeletal muscle samples from peripheral artery disease (PAD) and sarcopenia. Weighted gene co-expression network analysis (WGCNA) was performed independently for each disease cohort, followed by parallel feature selection using three machine learning algorithms (LASSO, Random Forest, and Boruta) to identify shared diagnostic biomarkers. Immune cell infiltration was deconvoluted using CIBERSORT. Drug-gene interaction analysis was conducted via DGIdb. The functional role of the lead candidate S100A9 was validated by untargeted metabolomic profiling of C2C12 myoblasts treated with recombinant S100A9.ResultsSeventy-six overlapping disease-associated genes were identified from WGCNA, and five core diagnostic biomarkers—BCKDHB, PIM1, JAML, NFE2, and S100A9 — were selected through three-way machine learning consensus. Enrichment analyses revealed shared involvement of innate immune activation, granulocyte infiltration, and branched-chain amino acid (BCAA) catabolism. CIBERSORT deconvolution confirmed elevated neutrophil abundance as a convergent immune feature of both diseases. Metabolomic profiling demonstrated that recombinant S100A9 disrupted nucleotide and energy homeostasis, induced mitophagy dysregulation, and promoted oxidative stress in C2C12 myoblasts. DGIdb screening identified Paquinimod, a selective S100A9 inhibitor with Phase II clinical safety data, as a candidate for therapeutic repositioning.ConclusionThis study reveals that upregulation of skeletal muscle inflammation and abnormal branched-chain amino acid metabolism may be common features of PAD and sarcopenia. BCKDHB, PIM1, JAML, NFE2, and S100A9 were identified as common diagnostic biomarkers, and metabolomics further confirmed that S100A9 may be a potential intervention target.
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the cellular images shown in Fig. 7A on p. 995 were strikingly similar to data in a paper that had previously been published in the journal Molecular Cancer that was written by different authors at different research institutes. Furthermore, an independent analysis of the data in this paper performed by the Editorial Office revealed that flow cytometric data in Fig. 2A, the cell migration and invasion assay data in Fig. 3A and D and the control western blot data in Fig. 5A were also strikingly similar to data that had either previously been published in articles written by different authors at different research institutes, or which were submitted for publication at around the same time. Given that the abovementioned data had already been published before the receipt of this paper at International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 988‑997, 2018; DOI: 10.3892/ijmm.2018.3685].
Background The neutrophil–monocyte-to-lymphocyte ratio (NMLR), calculated as (neutrophil count + monocyte count) / lymphocyte count, is a composite inflammatory marker reflecting innate immune activation and disruption of immune homeostasis. Previous studies have suggested the prognostic value of NMLR in patients with acute myocardial infarction, after cardiopulmonary resuscitation, and after mechanical thrombectomy for stroke. However, its role in predicting amputation risk among patients with peripheral artery disease (PAD) remains unclear. Methods This multicenter retrospective cohort study included 1,445 patients with peripheral artery disease from four centers in China between 2016 and 2025. We evaluated whether preoperative NMLR independently predicted long-term amputation risk. Kaplan–Meier curves, Cox proportional hazards models, restricted cubic splines, competing-risk models, landmark analysis, propensity score matching, and mediation analysis were used to validate the association. External validation was performed in a UK Biobank PAD cohort (n = 9,113). Results During a median follow-up of 25.3 months, 108 amputation events occurred (7.5%). The risk of amputation increased progressively across NMLR quartiles, with a markedly higher incidence in the highest quartile than in the lowest quartile (14.3% vs. 2.8%; log-rank P < 0.001). In the fully adjusted Cox model, NMLR remained significantly associated with amputation risk when analyzed as a continuous variable (HR = 1.083, 95% CI: 1.007–1.164; P = 0.032). Compared with patients in Q1, those in Q4 had a significantly higher risk of amputation (HR = 2.29, 95% CI: 1.03–5.07; P = 0.041), with a statistically significant trend across quartiles (P for trend = 0.020). Restricted cubic spline analysis did not reveal a significant nonlinear association after full adjustment. The results of competing-risk analysis, propensity score matching, and landmark analysis were generally consistent. Mediation analysis showed that NMLR explained only a small proportion of the association between Rutherford classification and amputation risk, with a mediation proportion of 8.1%, supporting that NMLR was largely independent of anatomical disease severity. In the external validation cohort from the UK Biobank, patients in the highest NMLR quartile still had a higher risk of amputation than those in the lowest quartile (HR = 1.569, 95% CI: 1.102–2.233; P = 0.013). Conclusions Elevated preoperative NMLR was independently associated with an increased long-term risk of amputation in patients with PAD, and this association was validated in an external cohort. As a low-cost and readily available inflammatory marker derived from routine blood tests, NMLR may provide complementary risk information beyond the traditional Rutherford classification and may be particularly useful for preoperative risk stratification in patients with early-stage disease. Prospective studies are warranted to further validate its clinical utility.
Background: This systematic review/meta-analysis investigated the risks of fluoroquinolones (FQs) for aortic aneurysms (thoracic/abdominal) and Stanford A/B dissections. Methods: We searched EMBASE, Ovid, PubMed, Web of Science, and Scopus databases in February 2024. Eligible observational studies were those that presented adjusted risk estimates for aortic aneurysm or dissection (AAD) incidence, aortic-specific mortality, or all-cause mortality in FQ-treated versus untreated unexposed populations. Results: A total of 13 studies were included (36,224,419 participants), eight of which were cohort studies, two were nested case-control studies, and three were case-crossover designs. FQ exposure was associated with significantly elevated de novo AAD risk within 30 days (relative risk (RR) = 3.40, 95% confidence interval (CI) = [2.72, 4.24]; heterogeneity: I2 = 41.5%, p = 0.11) and 60 days (RR = 3.53, 95% CI = [2.78, 4.49]; heterogeneity: I2 = 87.0%, p < 0.0001). The analysis also revealed a higher all-cause mortality risk for FQs versus non-exposed controls (odds ratio (OR) = 1.44, 95% CI = [1.08, 1.93]; heterogeneity: I2 = 0%, p = 0.80). Subgroup analysis demonstrated comparable aortic dissection (AD) and aortic aneurysm (AA) risks, except for a significantly increased de novo AA risk at 30 days (RR = 9.13, 95% CI = [6.05, 13.78]; heterogeneity: I2 = 68.7%, p = 0.07) and 60 days (OR = 1.69, 95% CI = [1.27, 2.26]; heterogeneity: I2 = 52%, p = 0.10). Conclusion: This meta-analysis found a significant association between FQ use and short-term AAD risk. These results suggest that clinicians should weigh the risks of AAD before prescribing FQs, especially in patients with aortic vulnerability or pre-existing aortic pathology, considering alternative treatments when feasible. The PROSPERO Registration: CRD42024509853 (https://www.crd.york.ac.uk/PROSPERO/view/CRD42024509853).
BACKGROUND:Abdominal aortic endograft infection (AAEI) is a rare but life-threatening complication following endovascular aneurysm repair. This study aimed to report surgical outcomes of AAEI from 2 specialized Chinese vascular centers and analyze prognostic risk factors. METHODS:A dual-center retrospective cohort study enrolled 41 patients who underwent complete infected graft excision and revascularization for AAEI between February 2018 and September 2025. Clinical data were collected and analyzed via Kaplan-Meier survival analysis and univariate COX regression. RESULTS:This cohort included 40 males and 1 female (mean age: 64.22 ± 9.12 years). Complete removal of the infected graft was performed in all cases, with revascularization achieved via extra-anatomical bypass (EAB, n = 39) or in situ reconstruction (n = 2). Median follow-up time was 12 months. All-cause mortality was 29.3%, nonfatal complication rate was 39.0% and reintervention rate was 17.1% (7/41). Elevated white blood cell (WBC) (P = 0.01, hazard ratio [HR] = 3.90) and enteric fistula (P = 0.04, HR = 3.21) worsened survival; advanced age showed a trend toward significance (P = 0.09). C-reactive protein level and renal artery stent coverage had no significant prognostic impact (P > 0.05). CONCLUSION:EAB is a feasible and practical option for high-risk AAEI patients, particularly at centers lacking biological grafts. Enteric fistula, elevated preoperative WBC, and advanced age predict poor survival. Large prospective multicenter trials are needed to refine individualized treatments for AAEI.
BACKGROUND:An increasing number of patients with abdominal aortic aneurysms (AAAs) are opting for endovascular aneurysm repair (EVAR), and predicting postoperative survival is important for patient management. The development of a postoperative prognostic model using machine learning (ML) can be effective in predicting postoperative survival, and research on this issue needs to be further enhanced. This study aims to establish predictive models for prognosis in AAA patients after EVAR. METHODS:Perioperative and follow-up information of 163 AAA patients were collected in Beijing Hospital who underwent EVAR from January 2016 to April 2023. The patients were divided into a training set and a test set in a ratio of 7:3. ML methods such as least absolute shrinkage and selection operator (LASSO) regression, random forests, linear discriminant analysis, naive Bayes, K-nearest neighbor algorithm, support vector machines, and decision trees were selected to build prediction models, and these models were evaluated by the receiver operating characteristic curves (ROC). RESULTS:The study cohort comprised 163 patients with a mean age of 72 ± 8.4 years, 33 (20.2%) patients died during the follow-up period, and the majority were male (88.3%). Patients were categorized into survivors (n = 130) and nonsurvivors (n = 33). LASSO regression selected chronic obstructive pulmonary disease (COPD), maximum diameter of aneurysm to body mass index ratio (DBR), and stroke history. The area under the ROC (AUC) for the training and test sets of nomogram was 0.77 and 0.75, respectively. K-Nearest Neighbors (KNN) was the most effective ML algorithm, with the AUC of 0.85 and 0.81 superlatively for the training and test sets. CONCLUSION:Stroke, DBR, and COPD can predict prognosis after EVAR in AAA patients. KNN is better than other algorithms in the study.
Objective To share the diagnosis and treatment outcomes of brucellar aortoiliac aneurysms (BIAAs) from two large vascular surgery centres in China, and to describe the clinical characteristics and prognosis of different treatment regimens. Methods A retrospective analysis was performed on the demographic, clinical, and follow up data of 15 patients with BIAAs admitted to the Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University, and Beijing Hospital between May 2019 and June 2025. Results Among the 15 patients, 14 were men and one was a woman; 12 had a history of contact with sheep or their faeces. Lumbar/abdominal pain and fever were the most common clinical manifestations. The positive rate of Brucella Rose Bengal Test (RBT) was 100% (15 of 15), the positive rate of blood culture was 40% (6 of 15), and the positive rate of intra-operative tissue culture was 11% (1 of 9). All 15 patients completed follow up with a mean follow up duration of 32.93 ± 22.61 months, and the survival rate was 93% (14 of 15). Five patients who received endovascular treatment had a good prognosis, five patients who underwent open surgery achieved satisfactory curative effects, one patient who received conservative treatment remained stable, and four patients who received endovascular treatment developed severe complications and infection recurrence, among whom one died despite rescue efforts. Conclusion BIAAs are clinically rare and highly dangerous. Open surgery based on anti-Brucella therapy remains the preferred radical treatment option in clinical practice, and endovascular treatment can be used as an alternative in specific emergency cases. It should be noted that this study had a small sample size, and the comparison of different treatment methods was mainly descriptive, with certain limitations.
The prevalence of Peripheral Artery Disease (PAD) is rising globally, yet early risk stratification remains challenging due to the limitations of traditional obesity metrics. TyG–ABSI, an index combining Triglyceride-Glucose (TyG) with A Body Shape Index (ABSI), is a novel marker reflecting both functional insulin resistance and structural visceral adiposity. However, its predictive value for PAD remains unexplored in large prospective cohorts. We included 390,274 adults from the UK Biobank. Baseline characteristics were analyzed across TyG–ABSI quartiles and PAD status. Associations between TyG-related indices and incident PAD were assessed using multivariable-adjusted Cox regression, Kaplan–Meier survival curves, and restricted cubic splines. Robustness was evaluated via Fine-Gray competing risk models, propensity score matching, subgroup analyses, and external validation in the NHANES database. Consensus k-means clustering, integrating biochemical and insulin resistance markers, identified metabolic phenotypes and stratified PAD risk. Feature selection (LASSO, Boruta, and Minimum Redundancy Maximum Relevance [mRMR]) guided the development of six machine learning models (logistic regression, GBM, XGBoost, AdaBoost, LightGBM, and neural network) for PAD prediction, with interpretability assessed via SHAP analysis. Higher TyG–ABSI and related indices were strongly associated with increased PAD incidence (cumulative incidence at 15 years: 4.16
Sulodexide is a highly purified glycosaminoglycan with multiple pharmacological effects, including endothelial glycocalyx repair, endothelial cell protection, anti-inflammatory and antithrombotic actions, promotion of fibrinolysis, reduction of blood viscosity, lipid regulation, and anti-oxidative activity. It serves as a potentially effective foundational therapeutic agent for the prevention and treatment of vascular diseases. This consensus integrates current scientific knowledge on the clinical application of sulodexide in vascular diseases, aiming to provide guidance and reference for rational drug use among clinicians. The consensus statements first elaborate on the pharmacological mechanisms and pharmacokinetic profiles of sulodexide. Through a structured review and integration of published basic and clinical research evidence from China and abroad, it summarizes clinical efficacy and safety data for sulodexide in chronic venous disease, venous thromboembolism, peripheral arterial disease, and microangiopathy, highlighting the importance of rational use of sulodexide in vascular disease management. Additionally, based on evidence-based medicine and existing medical guidelines, specific clinical application recommendations are proposed.
Objective Type V Takayasu arteritis (TAK) is the most extensive form of this large-vessel vasculitis, frequently necessitating complex surgical management due to its multiterritory arterial involvement. This study aims to evaluate the clinical efficacy and safety of 1-stage supra-aortic and aortovisceral artery (SAVA) bypass in patients with Numano type V TAK. Methods We retrospectively reviewed all patients diagnosed with type V TAK undergoing simultaneous SAVA bypass at 6 tertiary centers in China between February 2017 and April 2024. These patients were selected from a multicenter surgical database of 264 patients with TAK. Demographics and characteristics were collected. The primary end point was mortality within 30 days after surgery; secondary end points included graft patency, major surgery-related complications, and overall survival. All patients were prospectively followed, and outcomes were analyzed. Results A total of 12 patients, with 115 SAVA segments affected by TAK, underwent reconstruction of 42 arteries. These reconstructions utilized 14 autologous great saphenous vein grafts and 28 prosthetic grafts with a mean operative time of 514 ± 101 minutes. The 30-day survival rate was 100%. During a mean follow-up duration of 47.4 ± 28.5 months, 4 cases of graft restenosis were detected, of which 1 was successfully resolved via surgical thrombectomy and 3 were managed conservatively. No late mortality or major complications was observed. Postoperatively, systolic blood pressure decreased significantly, and patients achieved sustained symptom relief with improved health-related quality of life. Conclusions With appropriate perioperative management and surgical planning, the simultaneous reconstruction of SAVA in type V TAK can be performed safely and effectively.
[This corrects the article DOI: 10.1016/j.bioactmat.2024.03.013.].