No consensus or guideline has been established regarding the optimal timing of tissue resection after revascularization in patients with chronic limb-threatening ischemia (CLTI). This study aimed to compare early tissue resection and watchful waiting after revascularization regarding the outcomes of patients with CLTI. We searched PubMed, the Cochrane Library, and EMBASE for relevant randomized trials and observational studies published from their inception to May 1, 2024. In total, five articles were analyzed. The results showed that the early tissue resection group had a higher wound healing rate than the watchful waiting group (I2 = 26%, odds ratio [OR] = 2.80, 95% confidence interval [CI] 1.32 to 5.92, P = 0.007). However, the rate of major amputation was significantly higher in the early tissue resection group than in the watchful waiting group (I2 = 5%, OR = 1.48, 95% CI 1.18 to 1.86, P < 0.001), and wound recurrence rate in the early tissue resection group was relatively higher than that in the watchful waiting group (I2 = 0%, OR = 2.42, 95% CI: 0.99 to 5.93, P = 0.05). No statistical significance was found in the rate of postoperative mortality (I2 = 2%, OR = 0.99, 95% CI: 0.69 to 1.41, P = 0.94) and wound healing time (I2 = 97%, standardized mean difference = -105.92, 95% CI -232.96 to 21.13, P = 0.10) between the early tissue resection and watchful waiting groups. For patients without signs of infection, a watchful waiting strategy could reduce the risk of major amputation.

This study aimed to evaluate the long-term clinical outcomes of drug-coated drug (DCB) angioplasty for long femoropopliteal lesions in older patients with chronic limb-threatening ischemia (CLTI). In this multi-center retrospective study, we enrolled 119 patients with CLTI due to Trans-Atlantic Inter-Society Consensus (TASCII) C/D femoropopliteal lesions who underwent DCB angioplasty. A total of 119 patients with 122 limbs (TASCII C = 67, 54.9%; TASCII D = 55, 45.1%) were enrolled. At 36-month follow-up, primary patency, assisted primary patency, secondary patency, and freedom from target lesion revascularization were 47.3%, 49.8%, 59.5%, and 62.7%, respectively, and there was a significant improvement over baseline in Rutherford class (P < .001) and ankle-brachial index measurements (P < .001). Complex target lesions (P = .017) and 1 stenosis-free outflow vessel (P = .001) were risk predictors of freedom from clinically driven target lesion revascularization. Complex target lesions (P = .044), diabetes (P = .007), and 1 stenosis-free outflow vessel (P = .003) were risk predictors of restenosis. At 2 months, the ulcer healing rate was 96.3% (26/27). At 36 months, the limb salvage and survival rates were 85.8% and 83.3%, respectively. DCB angioplasty were safe and effective for older patients with CLTI attributable to femoropopliteal TASCII C/D lesions.

OBJECTIVE: This study aimed to validate the correlation between the Global Limb Anatomic Staging System (GLASS) and primary limb-based patency (LBP) and to identify the risk factors associated with LBP loss.
METHODS: A single-center retrospective analysis was performed on patients with chronic limb-threatening ischemia (CLTI) who underwent endovascular therapy (EVT) between January 2018 and May 2022. All lesions were categorized into three groups (GLASS I, II, and III). The primary LBP rates were analyzed and compared across the GLASS stages. The risk factors for the loss of primary LBP were identified using Cox regression analysis.
RESULTS: In total, 236 limbs from 231 patients were included, with 52 (22%) limbs stratified as GLASS I, 59 (25%) limbs as GLASS II, and 125 (53%) limbs as GLASS III. The one-year LBP rates for limbs classified as GLASS I, II, and III were 78.8%, 69.5%, and 41.6%, respectively (P <0.001). The long-term LBP rate was 54.2% in GLASS I, 38.6% in GLASS II, and 10.5% in, GLASS III (P < 0.001). Multivariate analysis revealed that GLASS stages (GLASS Ⅰ vs GLASS Ⅲ: Hazard Ratio [HR]: 0.36; 95% Confidence Interval [CI]: 0.18-0.72; P = 0.004, GLASS Ⅱ vs GLASS Ⅲ: HR: 0.47; 95%CI: 0.25-0.86; P = 0.02), diabetes, smoking, and sex were independently associated with LBP.
CONCLUSIONS: GLASS stage III was associated with lower LBP rates in patients with CLTI who underwent EVT. The GLASS stages may serve as prognostic indicators for patients with CLTI after intervention.

BACKGROUND: Tibial artery calcification (TAC) is correlated with an increased risk of amputation and mortality in patients with chronic limb-threatening ischemia (CLTI). The association between calcification characteristics and adverse limb events of CLTI. However, it has not been assessed. This study aims to assess the relationship between the characteristics of TAC based on computed tomography angiography (CTA) scans and postoperative outcomes in patients with CLTI undergoing infrapopliteal endovascular therapy.
METHODS: This was a retrospective study of patients who underwent infrapopliteal endovascular revascularization for CLTI and had a preoperative CTA scan. Based on CTA, TAC was divided into the following categories: annularity, thickness, continuity and severity. Cox regression models using generalized estimating equations were performed to assess the relationship between calcification characteristics and postoperative outcomes. The outcomes evaluated were the occurrence of all cause mortality (ACM) and unplanned amputation.
RESULTS: Among the 148 patients undergoing endovascular, there were 50 (33.8%) patients died and 26 (17.6%) patients underwent unplanned amputation. Annular calcification was more common in the ACM group than in the non-ACM group. No significant differences were found between the two groups with regard to the probability of calcification in the thickness and the continuity (P>0.05). Patients in the unplanned amputation group had significantly annular, thin and continuity calcifications (P<0.05) than those in the non-unplanned amputation group. The presence of annular calcification was an independent predictor of ACM (hazard ratio (HR), 3.186; 95% confidence interval (CI), 1.781-5.702; P<0.001) and unplanned amputation (HR, 3.739; 95% CI, 1.707-8.191; P<0.05).
CONCLUSIONS: Among patients with CLTI, the occurrence of annular calcification in the tibial artery are related to a greater chance of ACM and unplanned amputation in the postoperative period. The circumferential degree of TAC of the operated limb can be considered as a marker of clinical prognosis in this group of patients.

Critical limb ischemia (CLI) is a common complication of diabetes mellitus that typically occurs in the later stages of the disease. Vascularization is indeed an important physiological process involving the formation of new blood vessels from existing ones. It occurs in response to various normal and pathophysiological conditions, and one of its critical roles is to compensate for inadequate oxygen supply, which is often seen in situations like chronic limb ischemia (CLI). Histidine triad nucleotide-binding protein 1 (Hint1) is a member of the Hint family that has been shown to attenuate cardiac hypertrophy, but its role in vascularization still needs to be clarified. In this study, we investigated the role of Hint1 in CLI. We found that Hint1 is significantly reduced in the muscle tissue of STZ-induced diabetic mice and high-glucose (HG)-treated endothelial cells (ECs). Hint1 deletion impaired blood flow recovery and vascularization, whereas Hint1 overexpression promoted these processes. In addition, our in vitro study showed that Hint1 deficiency aggravated mitochondrial dysfunction in ECs, as evidenced by impaired mitochondrial respiration, decreased mitochondrial membrane potential, and increased reactive oxygen species. Our findings suggest that Hint1 deficiency impairs blood perfusion by damaging mitochondrial function and that Hint1 may represent a potential therapeutic target for treating CLI.

UNASSIGNED: To evaluate 6-month outcomes of drug-coated balloon (DCB) angioplasty of infrapopliteal lesions in patients with chronic limb-threatening ischemia (CLTI).
UNASSIGNED: We analyzed 6-month follow-up data from the 10-center PRIME-WIFI prospective registry on 300 consecutive patients (33.000% female) with CLTI who underwent DCB angioplasty for infrapopliteal arterial lesions. The primary outcome was freedom from major adverse event (MAE), a composite of major amputation, all-cause death, and clinically-driven target limb reintervention (CD-TLR). Secondary outcomes included amputation-free survival (AFS), freedom from each primary outcome component, primary sustained clinical improvement, and quality of life (QOL) score. Independent risk factors of MAE were determined using Cox proportional hazards regression analysis.
UNASSIGNED: A total of 409 infrapopliteal lesions in 312 limbs were treated with DCB, with 54.167% of the limbs being treated for isolated infrapopliteal lesions. By Kaplan-Meier analysis, at 6 months post- procedure (follow-up rate, 85.000%), freedom from MAE was 86.353%; AFS was 90.318%; and freedom from major amputation, all-cause death, and CD-TLR were 96.429%, 93.480%, and 95.079%, respectively. At 6-month follow-up, 83.590% of patients showed primary sustained clinical improvement, and QOL score (4.902±1.388) improved compared with that before procedure (2.327±1.109; p<0.001). Chronic renal insufficiency, chronic obstructive pulmonary disease, Rutherford grade, and postoperative infrapopliteal runoff score were independent risk factors for MAE within 6 months.
UNASSIGNED: In CLTI, DCB angioplasty of infrapopliteal lesions yields acceptable early efficacy and safety.
CONCLUSIONS: This study evaluated the 6-month outcomes of DCB angioplasty in infrapopliteal lesions in CLTI patients by analyzing multicenter prospective data, showing that infrapopliteal DCB angioplasty can be performed with acceptable freedom from MAE rate, amputation-free survival rate, freedom from major amputation rate, survival rate, and freedom from CD-TLR rate. No patient experienced DCB-related intraoperative distal embolism. Chronic renal insufficiency, chronic obstructive pulmonary disease, Rutherford grade and postoperative infrapopliteal runoff score were independent risk factors for MAE within 6 months. Comparative real-world studies are needed.

BACKGROUND: The effectiveness of excimer laser atherectomy (ELA) combined with drug-coated balloon (DCB) for de novo femoropopliteal artery disease (FPAD) is currently unknown. This case series evaluated the clinical outcomes of ELA combined with DCB in de novo FPAD from a real-world clinical perspective.
METHODS: We conducted a retrospective study of patients treated with ELA + DCB for de novo FPAD between November 2016 and January 2020. The primary efficacy endpoint was the initial patency rate; secondary endpoints included target lesion revascularization without clinically driven target lesion revascularization (CD-TLR) and technical success. Primary safety endpoints included all-cause death, unplanned major amputation, and postoperative complications.
RESULTS: The mean follow-up was 37.8 ± 25.3 months and included 56 consecutive patients (68.23 ± 8.01 years, 41 men). Forty-three patients had lifestyle-restricted claudication, and 13 patients had critical limb-threatening ischemia. The mean length of the lesion was 178.41 mm in all patients. The total lesion occlusion rate was 48.2 (n = 27), and the overall technical success rate was 100%. The 12-month, 24-month, 36-month, and 48-month primary patency rates of the ELA + DCB group were 75%, 66.1%, 58.9%, and 42.8%, respectively. Freedom from CD-TLR at 12, 24, 36, and 48 months was 83.9%, 80.3%, 76.8%, and 57.1%, respectively.
CONCLUSIONS: In real-world clinical practice, ELA + DCB appears to be a safe and effective endovascular treatment for de novo FPAD, with a low rate of freedom from CD-TLR and a good patency rate.

Critical limb ischemia, the final course of peripheral artery disease, is characterized by an insufficient supply of blood flow and excessive oxidative stress. H2 S molecular therapy possesses huge potential for accelerating revascularization and scavenging intracellular reactive oxygen species (ROS). Moreover, it is found that BMP6 is the most significantly up-expressed secreted protein-related gene in HUVECs treated with GYY4137, a H2 S donor, based on the transcriptome analysis. Herein, a UIO-66-NH2 @GYY4137@BMP6 co-delivery nanoplatform to strengthen the therapeutic effects of limb ischemia is developed. The established UIO-66-NH2 @GYY4137@BMP6 nanoplatform exerts its proangiogenic and anti-oxidation functions by regulating key pathways. The underlying molecular mechanisms of UIO-66-NH2 @GYY4137@BMP6 dual-loading system lie in the upregulation of phosphorylated YAP/TAZ and Jun to promote HUVECs proliferation and downregulation of phosphorylated p53/p21 to scavenge excessive ROS. Meanwhile, laser-doppler perfusion imaging (LDPI), injury severity evaluation, and histological analysis confirm the excellent therapeutic effects of UIO-66-NH2 @GYY4137@BMP6 in vivo. This work may shed light on the treatment of critical limb ischemia by regulating YAP, Jun, and p53 signaling pathways based on gas-protein synergistic therapy.

This paper presents the challenges faced by a patient undergoing limb-sparing treatment due to chronic limb-threatening ischemia (CLTI) complicated with long-standing nonhealing foot ulcer and intense pain. However, after multiple vascular surgeries, the foot wound continued to worsen, which could lead to transfemoral amputation and even death. We report a case of an aged male patient admitted after complaining of \"pain and ulceration in his left foot for ten months\". The patient was diagnosed with arteriosclerosis obliterans of the lower limbs with critical limb ischemia, which improved little after the drug therapy. This patient had undergone three endovascular procedures with a medical history of myocardial infarction and stenting. The main artery could not be directly connected to the foot by open or endovascular surgery due to severe vascular occlusion below the knee. In addition, foot ulcers made it impossible to walk, which induced angina pectoris. After coordination and discussion, we determined to perform a 2-week lateral tibial periosteum distraction (LTPD). The procedure significantly improved the foot wound and relieved the pain. After the two-week personalized wound management, the wound healed, and the pain disappeared. Consequently, the patient was able to walk independently, without recurrence during the 3-month follow-up period. Periosteal distraction has rarely been reported in previous literature and is mainly used to treat patients with diabetic foot, rather than those who have undergone repeated percutaneous transluminal angioplasty (PTA) for CLTI combined with foot ulcers. As most CLTI patients are suffering from cardiac, cerebral, and renal diseases, their blood vessels are difficult to open, with high re-occlusion and recurrence rates and low limb salvage rate. Therefore, we present our case herein so that the CLTI patients whose inferior genicular arteries cannot be opened due to severe infrapopliteal arterial occlusion complicated with nonhealing foot ulcers or intractable pain can be treated with LTPD, thus providing them with the \"last kilometer\" bloodstream towards the foot.

Botulinum toxin type A (BoNT/A) is a potent neurotoxin with widely use range, for the good outcomes in the treatment of pain, it was considered as an unique analgesic drugs with the feature of sustained efficacy after a single application, but up to now, treating chronic limb-threatening ischemia (CLTI) with BoNT/A was rarely reported. We present a 91-year-old man with CLTI, the main clinical manifestations were left foot rest pain, intermittent claudication and toe necrosis, the patient refused invasive treatments, and the pain failure to respond to conventional analgesic drugs, the subcutaneous injections of BoNT/A was performed to the patient. The pain score on the visual analog scale (VAS), decreased from 5-6 (before treatment) to 1 within days after infiltration, and keep in 1-2 of VAS during follow-up. Our case report demonstrated that BoNT/A may be an unique minimally invasive solution for treating rest pain in CLTI.