OBJECTIVE: Chronic lower limb ischaemia is a peripheral arterial disease (PAD) which is typically instigated by atherosclerotic plaques in the peripheral vasculature. This article reports on a unique case of chronic ischaemia in the lower limb, presenting in a distinctive manner as a fungal toenail infection.
METHODS: An 82-year-old frail woman with multimorbidity presented with toenail symptoms in her right foot. While initial examination had shown onychomycosis, further investigation was unexpectedly consistent with chronic ischaemia in the lower limb. We explored the clinical presentation, diagnostic challenges encountered, and the subsequent management of this unique manifestation in the context of the patient\'s multimorbidity.
CONCLUSIONS: This case report highlights the need to consider chronic limb ischemia as a differential diagnosis in toenail infections when no alternative causes or predisposing factors are identified.

Chronic limb threatening ischemia (CLTI) poses a significant treatment challenge for vascular surgeons, interventionalists, podiatrists, and associated medical specialists. The evidence for what constitutes appropriate care is rapidly evolving and new treatment options are in constant development. This review examines the current guidelines for CLTI care, as well as reported outcomes for multiple care strategies in this patient population, including revascularization and medical optimization. We performed a literature review of the PubMed database, reviewing articles that reported outcomes for CLTI care between 2000 and 2023, and described these outcomes as they relate to the current state of CLTI treatment. Significant data are still forthcoming regarding CLTI care, but widespread adoption of appropriate CLTI care is essential for the treatment of this vulnerable population.

Peripheral arterial disease (PAD) represents one of the most prevalent cardiovascular disease processes and carries a high burden of morbidity and mortality. Patients with chronic limb-threatening ischemia (CLTI), the most severe manifestation of PAD, have the highest rates of cardiovascular morbidity and mortality of the overall PAD population. Patients with below-the-knee (BTK) PAD have an increased propensity toward CLTI due to small-vessel caliber and the frequently comorbid conditions of end-stage renal disease and diabetes mellitus, which tend to affect small artery beds preferentially. For those with BTK PAD with CLTI, the standard of care is revascularization. Early revascularization was performed using surgical bypass. However, endovascular techniques, starting with percutaneous transluminal angioplasty and expanding to the modern armamentarium of adjunctive devices and therapies, have become standard of care for most patients with CLTI due to BTK PAD. In this review, we will discuss the modern surgical and endovascular approaches to revascularization, as well as devices that are currently in development or preapproval study for the treatment of BTK PAD.

BACKGROUND: Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI.
METHODS: A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it.
RESULTS: We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients.
CONCLUSIONS: All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

The Society for Vascular Surgery Wound, Ischemia, and foot Infection\'s (WIfI\'s) threatened limb classification system serves to comprehensively assess the severity of disease in patients with chronic limb-threatening ischemia by identifying and grading the main factors that place the threatened limb at greatest risk: wound severity, ischemic burden, and presence of infection. Each of these 3 factors is graded and the limb placed into a clinical stage, with increasing stage associated with severity of limb threat and predicted risk of major limb amputation at 1 year. Globally, there is a growing body of evidence reported from multiple institutions that has assessed amputation rates and wound-healing outcomes following revascularization in patients with WIfI clinical staging. Risk of major amputation at 1 year is low in clinical stage 1, moderate in stages 2 and 3, and high in stage 4. Higher clinical stages are associated with prolonged time to wound healing, while 1-year wound healing rates consistently decrease with increasing clinical stage. Additional avenues of investigation utilizing WIfI as an objective clinical staging tool have yielded new insights into which patients benefit from revascularization, complexity of care, hospital length of stay, quality of life, ethnic and socioeconomic disparities, as well as spurred interest in other modalities of assessing limb perfusion and their possible clinical utility. Ongoing study and refinement of WIfI grading and clinical staging will continue to improve its prognostic utility.

BACKGROUND: Percutaneous deep vein arterialization (pDVA) is considered a treatment modality in patients with no-option critical limb ischemia. However, there is still a paucity of evidence regarding its safety and efficacy.
METHODS: MEDLINE (via PubMed), Embase and Web of Science databases as well as the CENTRAL registry up to the end of June 2023.
METHODS: This review adhered to the PRISMA guidelines (PROSPERO registration no. CRD42023445171). The risk of bias was assessed using the methodological index for non-randomized studies (MINORS). Primary endpoints included technical success, overall survival and limb salvage during the follow-up. Amputation-free survival at 30 days, 6 months and 1 year as well as complete wound healing, major adverse limb events and reintervention were investigated as secondary outcomes.
RESULTS: Five observational studies, comprising 208 patients (142 Rutherford class 5/77 Rutherford class 6), were included. MINORS revealed a low risk of bias. The meta-analysis reached a pooled technical success rate of 96.2% (95% CI: 91.5-98.4), an overall survival of 82.8% (95% CI: 70.5-95.2) and a limb salvage rate of 77.2% (95% CI: 65.2-89.1) during the follow-up. The amputation-free survival at 30 days, 6 months and 1 year was 87.8%, 68.7% and 65.6%, respectively. Furthermore, pDVA resulted in a complete wound healing rate of 53.4% (95% CI: 30.3-76.5). The pooled reintervention rate was as high as 46.7% (37.1-56.3%).
CONCLUSIONS: PDVA seems a feasible bail-out strategy for patients with no option for routine treatment of CLTI. However, due to the small number of studies, the strength of the evidence is low.

BACKGROUND: To assess the quality of clinical practice guidelines (CPGs) for chronic limb-threatening ischemia (CLTI) using the Appraisal of Guidelines for Research and Evaluation II instrument.
METHODS: A systematic review of Medline, Embase, and online CPG databases was carried out. Four CPGs on CLTI were identified: Global Vascular Guidelines (GVG), European Society of Cardiology (ESC), American College of Cardiology, and National Institute for Health and Care Excellence guidelines on lower limb peripheral arterial disease. Two independent appraisers analyzed the 4 CPGs using the Appraisal of Guidelines for Research and Evaluation II instrument. CPGs were ranked across 6 domains with 23 items that ranged from 1 (strongly disagree) to 7 (strongly agree). A scaled domain score was calculated as a percentage of the maximum possible score achievable. A domain score of ≥50% and an overall average domain score of ≥80% reflected a CPG of adequate quality recommended for use.
RESULTS: GVG had the highest overall score (82.9%), as an average of all domains, and ESC had the lowest score (50.2%). GVG and National Institute for Health and Care Excellence guidelines had all domains scoring >50%, while American College of Cardiology had 5 and ESC had 3. Two domains, rigor of development and applicability, scored the lowest among the CPGs. There was a lack of detail in describing systematic methods used in the literature review, how guidelines were formulated with minimal bias, and the planned procedure for updating the guidelines. Implications of guideline application and monitoring of outcomes after implementations were not explicitly discussed.
CONCLUSIONS: The GVG guideline published in 2019 discussing CLTI is assessed to be of high quality and recommended for use. This review helps to improve clinical decision-making and quality of future CPGs for CLTI.

Peripheral arterial disease (PAD) is on the rise, with a growing prevalence in an aging population and increasing rates of diabetes. Chronic limb-threatening ischemia poses a significant risk of limb loss. PAD is common in females, particularly after menopause, with a 35% prevalence rate in females older than 65 years. Studies have suggested that females have inferior outcomes compared with men after endovascular revascularization for PAD. With the rising utilization of endovascular interventions for the treatment of PAD, we sought to perform a review of sex-based outcomes of peripheral endovascular interventions for the treatment of symptomatic PAD. A scoping literature review was conducted to evaluate outcomes in females patients undergoing endovascular peripheral interventions for PAD. Eligibility criteria included studies focusing on adult females with lifestyle-limiting claudication or chronic limb-threatening ischemia who underwent endovascular intervention. Various endovascular procedures were considered and outcomes of interest included mortality, amputations, reinterventions, bleeding complications, and major adverse cardiac events. A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane Library databases. Sixteen studies were included in the review. Females patients undergoing endovascular interventions were associated with bleeding complications, higher rates of reintervention, and a risk of nonfatal strokes. However, females sex was not linked to higher rates of amputation or conclusively higher mortality rates post intervention. The comprehensive scoping review reveals important sex-related disparities in outcomes after endovascular procedures for symptomatic PAD. Females patients have been reported to experience worse outcomes in terms of reinterventions and bleeding complications. These findings emphasize the need for future trials focusing specifically on females patients to develop sex-inclusive treatment recommendations for advanced PAD.

UNASSIGNED: Chronic limb-threatening ischemia (CLTI) is known for its high rates of major amputation and mortality. Conventional revascularization techniques often fail in CLTI patients due to the heavily diseased arteries. Foot vein arterialization (FVA) has been proposed as an alternative technique to provide arterial blood to the foot by using the disease-free venous bed.
UNASSIGNED: This systematic review and meta-analysis aimed to determine outcomes of surgical FVA (sFVA) and percutaneous FVA (pFVA) at 6 and 12 months post-procedure.
UNASSIGNED: PubMed, Scopus, Web of Science, and the Cochrane Library databases were searched to identify papers reporting clinical outcomes of sFVA and pFVA published between January 1966 and March 2023.
UNASSIGNED: Databases were searched for eligible studies. A meta-analysis was performed to evaluate the limb salvage rate, overall survival rate, and wound healing rate at 6 and 12 months.
UNASSIGNED: A total of 27 studies were included, with 753 patients and 793 limbs. Of the included studies, 16 analyzed the sFVA technique and 11 the pFVA technique. Of the included patients, 86.3% were Rutherford 5/6 in the sFVA group versus 98.4% in the pFVA group. The pooled limb salvage rate at 6 and 12 months was 78.1% and 74.1% in the sFVA group and 81.7% and 78.6% in the pFVA group, respectively. Wound healing rates were not reported in the sFVA group. In the pFVA group, the pooled wound healing rates were 48.1% and 64.5% at 6 and 12 months, respectively.
UNASSIGNED: This study showed promising results after FVA among a large population of CLTI patients. In high-risk patients, pFVA is a feasible option with favorable limb salvage and wound healing rates.

UNASSIGNED: Percutaneous transluminal angioplasty (PTA) remains the mainstay of endovascular therapy for infrapopliteal chronic limb-threatening ischemia (CLTI), but outcomes have not been well characterized using high-quality data. The aim of this meta-analysis was to provide an updated benchmark for rates of primary patency and binary restenosis after PTA using prospectively collected, predominantly core-lab adjudicated randomized controlled trial (RCT) data.
UNASSIGNED: MEDLINE, EMBASE, Cochrane Central, and ClinicalTrials.gov were queried for RCTs published through November 2022 using PTA as a control arm and including patients with infrapopliteal CLTI. Studies were excluded if >25% of patients had intermittent claudication, other vessels were included, or primary patency or binary restenosis were not outcomes. Outcomes were analyzed using random effects models. This analysis was publicly registered (PROSPERO ID#394543). No funding was utilized.
UNASSIGNED: Seventeen RCTs were included (1048 patients, 1279 lesions). Pooled primary patency rates using data from 6 RCTs were 68% at 6 months (95% confidence interval [CI]=45%-84%) and 66% at 12 months (95% CI=51%-79%). Pooled binary restenosis rates using data from 11 RCTs were 54% at 6 months (95% CI=33%-73%) and 60% at 9 to 12 months (95% CI=39%-78%). Significant heterogeneity was present in all outcomes (I2>50%, p<0.0001). Publication bias was not observed (Egger\'s p>0.1).
UNASSIGNED: This meta-analysis provides estimates for binary restenosis and primary patency following PTA utilizing prospectively collected, predominantly core-lab adjudicated data. Results demonstrate 1-year primary patency rates that are 10% to 20% higher than what has been historically used in power calculations. These new estimates will help facilitate more accurate power analysis for future RCTs.
CONCLUSIONS: Rates of primary patency and binary restenosis after percutaneous transluminal angioplasty (PTA) have not been well-described using high-quality data, and investigators have been utilizing estimates of 40% to 50% and 45% to 65%, respectively, when performing power calculations for trials. This meta-analysis demonstrates using high-quality, prospectively collected, and predominantly core-lab adjudicated randomized controlled trial data that actual rates of primary patency are closer to 60% up to 1 year following PTA and provides the first meta-analysis estimate of binary restenosis rates up to 1 year after PTA. These estimates will help facilitate more accurate power calculations for future RCTs in this space.