担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Vascular Surgery  

Objective: Chronic limb-threatening ischemia often requires toe amputation. However, the extent of tissue loss varies according to the procedure and is not fully captured by conventional wound-grading systems. This study compared wound healing after toe amputation following endovascular therapy (EVT) and bypass surgery, stratified by the number of toes amputated. Methods: This retrospective multicenter cohort study included consecutive patients with chronic limb-threatening ischemia who underwent infrainguinal revascularization with concomitant toe amputation between 2015 and 2023. Tissue loss was defined by the number of toes amputated at the initial procedure, and patients were subsequently classified into single- and multiple-toe amputation cohorts. Wound healing was evaluated using cumulative incidence functions, with death and major amputation treated as competing risks. Clinical outcomes between EVT and bypass surgery were compared using inverse probability of treatment weighting. Factors associated with wound healing were assessed using multivariate Fine-Gray regression models. Results: In total, 412 patients were analyzed. In the single-toe cohort, bypass surgery was associated with faster wound healing compared with EVT, and this difference remained significant at 1 year (84.4% vs 72.7%, respectively). Conversely, limb salvage did not differ significantly between the two treatment modalities. In the multiple-toe cohort, early wound-healing trajectories were similar; however, the bypass surgery group demonstrated a trend toward better 1-year wound-healing rates (73.6% vs 53.4%) and improved limb salvage. Multivariate Fine-Gray analysis identified bypass surgery as an independent predictor of wound healing. Meanwhile, hemodialysis, higher inframalleolar disease, and greater tissue loss severity were associated with delayed healing. Conclusions: Bypass surgery was associated with improved wound healing following toe amputation. These findings highlight the importance of considering the number of toes amputated when evaluating wound-healing outcomes after different revascularization strategies.

DOI： 10.1016/j.jvs.2026.06.153

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Jvs Vascular Insights  

Objective: Achieving complete healing of ischemic wounds is a central therapeutic goal in the clinical management of patients with chronic limb-threatening ischemia (CLTI). This study aimed to develop a machine-learning (ML) model to predict 1-year wound healing and identify its predictors in patients with CLTI. Methods: This multicenter retrospective study analyzed 772 patients with CLTI and ischemic wounds who underwent infrainguinal revascularization between 2015 and 2022. Patients were randomly divided into the training (n = 579) and test (n = 193) cohorts. A random forest model was developed using 15 variables encompassing demographics, clinical, and limb-related factors, such as Wound, Ischemia, foot Infection and Global Limb Anatomic Staging System (GLASS) stages. Model performance was evaluated using the area under the receiver-operating characteristic curve (AUCROC) and accuracy. Feature importance was assessed and compared with the results of the multivariable logistic regression analysis. Results: The model exhibited excellent performance in the training subset [AUCROC = 1.00, true-positive rate (TPR) = 1.00, false-positive rate (FPR) = 0.12] and maintained acceptable discrimination in the internal validation (AUCROC = 0.72, TPR = 0.89, FPR = 0.63) and independent test cohorts (AUCROC = 0.78, TPR = 0.93, FPR = 0.70). The corresponding accuracies were 0.96, 0.72, and 0.77, respectively, indicating robust generalizability across datasets. In the ML model, serum albumin, hemoglobin, and age were identified as the most influential features, followed by treatment modality, GLASS inframalleolar stage, and Wound, Ischemia, foot Infection wound grade. In contrast, multivariable logistic regression analysis indicated that low serum albumin levels, advanced GLASS inframalleolar stage, and endovascular therapy were independently associated with poorer 1-year wound healing outcomes. Conclusions: The ML-based model showed acceptable predictive performance for 1-year wound healing in patients with CLTI. Systemic factors, including low albumin, anemia, and advanced age, were identified as key determinants, underscoring the importance of comprehensive systemic management in addition to revascularization.

DOI： 10.1016/j.jvsvi.2026.100454

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Annals of Vascular Surgery  

Background: Patients with chronic limb-threatening ischemia (CLTI) and inframalleolar (IM) P1 disease present a substantial challenge, and the impact of dialysis on revascularization outcomes remains unclear. This study aimed to compare wound healing and limb salvage after bypass surgery (BSX) and endovascular therapy (EVT) in dialysis-dependent and dialysis-independent patients with CLTI and IM P1. Methods: We retrospectively analyzed the multicenter data from patients undergoing infrainguinal revascularization for CLTI with IM P1 between 2015 and 2023. Patients were categorized into 4 cohorts based on dialysis dependence and Wound, Ischemia, and foot Infection (WIfI) stages 3 and 4. Results: We reviewed collected data from 690 patients with CLTI and IM P1. After propensity score matching, we analyzed 42 dialysis-dependent patients with WIfI 3, 54 dialysis-dependent patients with WIfI 4, 41 dialysis-independent patients with WIfI 3, and 56 dialysis-independent patients with WIfI 4. In the dialysis-dependent cohort, BSX was associated with significantly higher wound healing rates than EVT in WIfI stages 3 and 4. In the dialysis-independent cohort, no significant difference in wound healing was observed between the groups in either WIfI stage. Overall survival did not significantly differ between BSX and EVT in any subgroup. Conclusion: In summary, BSX may lead to better wound healing than EVT in dialysis-dependent patients with IM P1 disease and WIfI stages 3 and 4. No significant differences were observed between treatment strategies in dialysis-independent patients. Thus, BSX might be a preferable revascularization strategy in selected dialysis-dependent patients, although prospective studies are needed to confirm this result.

DOI： 10.1016/j.avsg.2025.05.038

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PubMed

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Vascular Surgery  

Objective: We examined the influence of heart failure (HF) on patients with chronic limb-threatening ischemia (CLTI) and the negative predictors of limb and life prognosis among patients with CLTI and HF, the clinical outcomes of patients with CLTI after infrainguinal revascularization were compared. Methods: Multicenter data of patients who underwent infrainguinal revascularization for CLTI between 2015 and 2022 were analyzed retrospectively. The end point was amputation-free survival (AFS) among patients with HF or without HF. Subgroup analyses among patients with HF were performed grouped by revascularization procedures or ejection fraction (EF) classification: HF with reduced EF (HFrEF) (EF of <40%), HF with mildly reduced EF (HFmrEF) (40% ≤ EF < 50%), and HF with preserved EF (HFpEF) (EF ≥50%). Results: Of the 772 patients included, 186 (24%) had HF. No differences were found in the Wound, Ischemia, foot Infection (WIfI) stage, Global Limb Anatomic Staging System stage, or treatment procedures between the HF and non-HF groups. The 2-year AFS rates of the HF and non-HF groups were 63% ± 2% vs 50% ± 4%, respectively (P < .01). Among the HF group, the AFS of the bypass group was significantly higher than that of the endovascular therapy (EVT) group (59% ± 7% vs 46% ± 5%; P = .04). Then, the AFS rates of the HFpEF, HFmrEF, and HFrEF groups were 61% ± 6%, 50% ± 8%, and 35% ± 7%, respectively (P < .01). Multivariate Cox proportional hazard analyses identified age ≥80 years, nonambulatory status, hypoalbuminemia (<3.5 g/dL), end-stage renal disease, EVT, WIfI stage 4, and HF as negative predictors of AFS among all patients. In the HF group, age ≥80 years, nonambulatory status, EVT, WIfI stage 4, and reduced EF (<40%) were significant negative predictors. Conclusions: HF is a robust negative predictor of AFS among patients with CLTI who underwent infrainguinal revascularization. HFrEF was a negative predictor of AFS.

DOI： 10.1016/j.jvs.2025.04.002

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PubMed

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Physiological Reports  

Macrophages play crucial roles in abdominal aortic aneurysm (AAA) formation through the inflammatory response and extracellular matrix degradation; therefore, regulating macrophages may suppress AAA formation. Interleukin-38 (IL-38) is a member of the IL-1 family, which binds to IL-36 receptor (IL1RL2) and has an anti-inflammation effect. Because macrophages express IL1RL2, we hypothesized that IL-38 suppresses AAA formation by controlling macrophages. We assessed a C57BL6/J mouse angiotensin II-induced AAA model with or without IL-38 treatment. RAW 264.7 cells were cultured with tumor necrosis factor-α and treated with or without IL-38. Because p38 has important roles in inflammation, we assessed p38 phosphorylation in vitro and in vivo. To clarify whether the IL-38 effect depends on the p38 pathway, we used SB203580 to inhibit p38 phosphorylation. IL1RL2⁺ macrophage accumulation along with matrix metalloproteinase (MMP)-2 and -9 expression was observed in mouse AAA. IL-38 reduced the incidence of AAA formation along with reduced M1 macrophage accumulation and MMP-2 and -9 expression in the AAA wall. Macrophage activities including inducible nitric oxide, MMP-2, and MMP-9 production and spindle-shaped changes were significantly suppressed by IL-38. Furthermore, we revealed that inhibition of p38 phosphorylation diminished the effects of IL-38 on regulating macrophages to reduce AAA incidence, indicating the protective effects of IL-38 depend on the p38 pathway. IL-38 plays protective roles against AAA formation through regulation of macrophage accumulation in the aortic wall and modulating the inflammatory phenotype. Using IL-38 may be a novel therapy for AAA patients.

DOI： 10.14814/phy2.15581

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