Lower Limb Chronic Ischaemia Presenting Exclusively as Fungal Toenail Infection: Case Report and Brief Literature Review.

BACKGROUND/AIM: 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. CASE REPORT: 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. CONCLUSION: 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.

Patient experience of the process to diagnosis of chronic limb-threatening ischaemia: A qualitative study.

INTRODUCTION: Delays exist at each stage of the chronic limb-threatening ischaemia (CLTI) care pathway, but there is little known about patient factors influencing delay to diagnosis of CLTI. This study explores the experiences and perceptions of patients recently diagnosed with CLTI. METHODS: A qualitative interview study was conducted. Sixteen participants underwent semi-structured interviews. Reflexive thematic analysis was performed on the data, aiming to understand factors which can influence delay in the CLTI care pathway. RESULTS: Five interrelated themes were developed: CLTI is a devastating condition; Reluctance to ask for help; When we are empowered we get better care; Luck plays a role in the process to diagnosis; and Vascular units can do better, comprising sub-themes of information transfer-consider communication and arterial versus non-arterial centres-proximity isn't everything. CONCLUSIONS: The five themes generated from the interview data describe factors relevant to delay given meaning by participants who have lived experience of CLTI. Theme content should be noted by clinicians, commissioners and providers looking to improve care pathways for patients with CLTI. The importance of awareness for the public, patients and clinicians linked ideas in some themes and interventions to raise awareness should be considered.

The Modified Albumin-Bilirubin (ALBI) Grade Reflect the Fate of Limb Prognosis in Patients with Chronic Limb-Threatening Ischemia.

BACKGROUND: To examine the influence of liver function on patients with chronic limb-threatening ischemia (CLTI), we classified patients with CLTI after revascularization according to their modified albumin-bilirubin (ALBI) grades. METHODS: We retrospectively analyzed single-center data of patients who underwent revascularization for CLTI between 2015 and 2020. Patients were classified with ALBI grades 1, 2a, and 2b and 3 according to the ALBI score, which was calculated, based on serum albumin and total bilirubin levels. The endpoints were the 2-year amputation-free survival (AFS) and 1-year wound healing rates. RESULTS: We included 190 limbs in 148 patients, and 50, 54, and 86 cases were assigned as grade 1, 2a, and 2b and 3, respectively. The 2-year AFS rates for the grade 1, 2a, and 2b and 3 groups were 79 ± 6%, 66% ± 7%, and 45 ± 6%, respectively (P < 0.01). One-year cumulative wound healing rates for grade 1, 2a, and 2b and 3 groups were 68 ± 7%, 69% ± 6%, and 48% ± 5%, respectively (P = 0.01). Multivariate Cox proportional hazard analyses identified age (≥75 years), dependent ambulatory status, and modified ALBI grades 2b and 3 compared with grades 1 and 2a as significant independent predictors of AFS. The dependent ambulatory status and Wound, Ischemia, and foot Infection classification stage 4 were significant negative predictors of wound healing. CONCLUSIONS: Many patients with CLTI had high modified ALBI grades, and impaired liver function classified as modified ALBI grade 2b and 3 is a robust negative predictor of AFS.

The treatment effect of endovascular therapy for chronic limb-threatening ischemia with systemic sclerosis.

Systemic sclerosis (SSc) is a collagen disease with immune abnormalities, vasculopathy, and fibrosis. Ca blockers and prostaglandins are used to treat peripheral circulatory disturbances. Chronic limb-threatening ischemia (CLTI) is a disease characterized by extremity ulcers, necrosis, and pain due to limb ischemia. Since only a few patients present with coexistence of CLTI and SSc, the treatment outcomes of revascularization in these cases are unknown. In this study, we evaluated the clinical characteristics and treatment outcomes of seven patients with CLTI and SSc, and 35 patients with uncomplicated CLTI who were hospitalized from 2012 to 2022. A higher proportion of patients with uncomplicated CLTI had diabetes and male. There were no significant differences in the age at which ischemic ulceration occurred, other comorbidities, or in treatments, including antimicrobial agents, revascularization and amputation, improvement of pain, and the survival time from ulcer onset between the two subgroups. EVT or amputation was performed in six or two of the seven patients with CLTI and SSc, respectively. Among those who underwent EVT, 33% (2/6) achieved epithelialization and 67% (4/6) experienced pain relief. These results suggest that the revascularization in cases with CLTI and SSc should consider factors such as infection and general condition, since revascularization improve the pain of these patients.

New Horizons in Peripheral Artery Disease.

Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams.

Dual-pathway inhibition in patients with chronic limb-threatening ischemia requiring reintervention for infrapopliteal occlusions.

Our study aimed to assess the influence of incorporating new oral anticoagulant (NOAC) therapy on clinical outcomes among patients who underwent endovascular intervention for below-the-knee (BTK) occlusions necessitating reintervention. The inclusion criteria encompassed patients with chronic limb-threatening ischemia (CLTI) and had undergone a successful endovascular intervention for BTK artery occlusion, necessitating reintervention. Patients who underwent endovascular interventions for BTK reocclusion were compared to those who received dual-pathway inhibition with NOAC (rivaroxaban 2.5 mg 2 × 1) and clopidogrel (NOAC group), or dual-antiplatelet therapy with clopidogrel and aspirin (DAPT group). The primary endpoints were target vessel reocclusion and target lesion revascularization (TLR) at the 1-year follow-up, while major and minor amputations served as the secondary endpoint. Additionally, a one-year comparison was conducted between the two groups for major bleeding events. 64 patients in our clinic treated with endovascular reintervention (NOAC = 28, DAPT = 34). The TLR rate is 10.7% in NOAC group (N = 3) and 32.4% in DAPT group (N = 11, p = 0.043). The target vessel reocclusion rate is 17.8% in NOAC group (N = 5) and 41.2% in DAPT group (N = 14, p = 0.048). Minor or major amputation rate at 1-year follow-up was 3.6% in NOAC group (N = 1) and 11.7% in DAPT group (N = 4, p = 0.245). The patency rate is significantly higher, and the TLR rate is significantly lower in the NOAC group compared to the DAPT group, with no significant difference in major bleeding between the two groups. Although no statistically significant difference exists in amputation rates, a numerical distinction is evident.

The Impact of Mental Health on Patient Outcomes in Peripheral Arterial Disease and Critical Limb Threatening Ischemia and Potential Avenues to Treatment.

The physical consequences of peripheral artery disease (PAD) are well established; however, the impact of comorbid mental health disorders such as depression and anxiety are not well understood. The impact of psychological stress is not only associated with worse perioperative morbidity and mortality but also with a physiologic cascade that accelerates plaque formation. Increasing screening to identify and subsequently treat comorbid mental health disorders is an integral next step in improving outcomes in PAD management. Failure to adequately address social and psychological impact on PAD patients will further widen the gap in disparities faced by high-risk and disenfranchised populations. Integration of mental health professionals, addiction specialists, and community navigators into multidisciplinary care teams can bolster support for PAD patients and improve outcomes.

A Systematic Review of the Quality of Clinical Practice Guidelines for Chronic Limb-Threatening Ischemia.

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.

A single center's 15-year experience with palliative limb care for chronic limb threatening ischemia in frail patients.

OBJECTIVE: Our institution's multidisciplinary Prevention of Amputation in Veterans Everywhere (PAVE) program allocates veterans with critical limb threatening ischemia (CLTI) to immediate revascularization, conservative care, primary amputation, or palliative limb care according to previously reported criteria. These four groups align with the approaches outlined by the global guidelines for the management of CLTI. In the present study, we have delineated the natural history of the palliative limb care group of patients and quantified the procedural risks and outcomes. METHODS: Veterans prospectively enrolled into the palliative limb cohort of our PAVE program from January 2005 to January 2020 were analyzed. The primary outcome was mortality. The secondary outcomes included overall and limb-related readmissions, limb loss, and wound healing. The clinical frailty scale (CFS) score was calculated, and the 5-year expected mortality was estimated using the Veterans Affairs Quality Enhancement Research Initiative tool. Regression analysis was performed to establish associations among the following variables: mortality, wound, ischemia, and foot infection (WIfI) score, CFS score, overall admissions, and limb-related admissions. RESULTS: The PAVE program enrolled 1158 limbs during 15 years. Of the 1158 limbs, 157 (13.5%) in 145 patients were allocated to the palliative limb care group. The overall mortality of the group was 88.2% (median interval, 3.5 months; range, 0-91 months). Of the 128 patients who had died, 64 (50%) had died within 3 months of enrollment. The predicted 5-year mortality for the group was 66%. The average CFS score for the group was 6.2, denoting persons moderately to severely frail. Using the CFS score, 106 patients were considered frail and 39 were considered not frail. No differences were found in mortality between the frail and nonfrail patients. However, a statistically significant difference was found in early (<3 months) mortality (56.2% vs 37.5%; P = .032). The 30-day limb-related readmission rate was 4.7%. Eventual major amputation was necessary for 18 limbs (11.5%). Wound healing occurred in 30 patients (20.6%). Regression analysis demonstrated no association between the CFS score and mortality (r = 0.55; P = .159) or between the WIfI score and mortality (r = 0.0165; P = .98). However, a significant association was found between the WIfI score and limb-related admissions (r = 0.97; P < .001). CONCLUSIONS: Frail patients with CLTI had high early mortality and a low risk of limb-related complications. They also had a low incidence of deferred primary amputation or limb-related readmissions. In our cohort, the vast majority of patients had died within a few months of enrollment without requiring an amputation. A comprehensive approach to the treatment of CLTI patients should include a palliative limb care option because a significant proportion of these patients will have limited survival and can potentially avoid unnecessary surgery and major amputation.

Safety and Effectiveness of Paclitaxel Drug-Coated Devices in Peripheral Artery Revascularization: Insights From VOYAGER PAD.

BACKGROUND: Paclitaxel drug-coated devices (DCDs) were developed to improve lower extremity revascularization (LER) patency in peripheral artery disease (PAD) but have been associated with long-term mortality. OBJECTIVES: This study assessed DCD safety and effectiveness in LER for PAD. METHODS: VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) randomized patients with PAD who underwent LER to rivaroxaban or placebo. The primary VOYAGER PAD study efficacy and safety outcomes were composite cardiovascular and limb events and Thrombolysis In Myocardial Infarction major bleeding. For prespecified DCD analyses, primary safety and effectiveness outcomes were mortality and unplanned index limb revascularization (UILR). Major adverse limb events (MALE) were a secondary outcome. Inverse probability treatment weighting was used to account for each subject's propensity for DCD treatment. Effects of rivaroxaban were assessed with Cox proportional hazards models. RESULTS: Among 4,316 patients who underwent LER, 3,478 (80.6%) were treated for claudication, and 1,342 (31.1%) received DCDs. Median follow-up was 31 months, vital status was ascertained in 99.6% of patients, and there were 394 deaths. After weighting, DCDs were not associated with mortality (HR: 0.95; 95% CI: 0.83-1.09) or MALE (HR: 1.08; 95% CI: 0.90-1.30) but were associated with reduced UILR (3-year Kaplan-Meier: 21.5% vs 24.6%; HR: 0.84; 95% CI: 0.76-0.92). Irrespective of DCD use, consistent benefit of rivaroxaban for composite cardiovascular and limb events (Pinteraction = 0.88) and safety of rivaroxaban with respect to bleeding (Pinteraction = 0.57) were observed. CONCLUSIONS: In >4,000 patients with PAD who underwent LER, DCDs were not associated with mortality or MALE but were associated with persistent reduction in UILR. These findings provide insight into the safety and effectiveness of DCDs in PAD. (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD [VOYAGER PAD]; NCT02504216).

Prevalence of elevated serum fatty acid synthase in chronic limb-threatening ischemia.

There are currently no serum-based evaluations that can corroborate the severity of peripheral artery disease (PAD). In this cross-sectional study, we assessed the prevalence of elevated serum fatty acid synthase (cFAS) in patients with chronic limb-threatening ischemia (CLTI) and evaluated the accuracy of its use in detecting this condition. Preoperative fasting serum samples from 87 patients undergoing vascular intervention were collected between October 2014 and September 2016. Median age was 62 years, with 56 (64%) men, and 32 (37%) with CLTI. We found that elevated cFAS content (OR 1.17; 95% CI 1.04-1.31), type 2 diabetes (T2D; OR 5.22; 95% CI 1.77-15.4), and smoking (OR 3.53; 95% CI 1.19-10.5) were independently associated with CLTI and could detect the presence of CLTI with 83% accuracy (95% CI 0.74-0.92). Furthermore, serum FAS content was positively correlated with FAS content in femoral artery plaque in patients with severe PAD ([Formula: see text] = 0.22; P = 0.023). Finally, significantly higher co-localization of FAS and ApoB were observed within lower extremity arterial media (P < .001). Our findings indicate that serum FAS content is a marker for disease severity in patients with PAD, independent of concomitant T2D and smoking, and may play a key role in FAS and ApoB peripheral plaque progression.

Detection of asymptomatic carotid stenosis in patients with lower-extremity arterial disease: development and external validations of a risk score.

BACKGROUND: Recommendations for screening patients with lower-extremity arterial disease (LEAD) to detect asymptomatic carotid stenosis (ACS) are conflicting. Prediction models might identify patients at high risk of ACS, possibly allowing targeted screening to improve preventive therapy and compliance. METHODS: A systematic search for prediction models for at least 50 per cent ACS in patients with LEAD was conducted. A prediction model in screened patients from the USA with an ankle : brachial pressure index of 0.9 or less was subsequently developed, and assessed for discrimination and calibration. External validation was performed in two independent cohorts, from the UK and the Netherlands. RESULTS: After screening 4907 studies, no previously published prediction models were found. For development of a new model, data for 112 117 patients were used, of whom 6354 (5.7 per cent) had at least 50 per cent ACS and 2801 (2.5 per cent) had at least 70 per cent ACS. Age, sex, smoking status, history of hypercholesterolaemia, stroke/transient ischaemic attack, coronary heart disease and measured systolic BP were predictors of ACS. The model discrimination had an area under the receiver operating characteristic (AUROC) curve of 0.71 (95 per cent c.i. 0.71 to 0.72) for at least 50 per cent ACS and 0.73 (0.72 to 0.73) for at least 70 per cent ACS. Screening the 20 per cent of patients at greatest risk detected 12.4 per cent with at least 50 per cent ACS (number needed to screen (NNS) 8] and 5.8 per cent with at least 70 per cent ACS (NNS 17). This yielded 44.2 and 46.9 per cent of patients with at least 50 and 70 per cent ACS respectively. External validation showed reliable discrimination and adequate calibration. CONCLUSION: The present risk score can predict significant ACS in patients with LEAD. This approach may inform targeted screening of high-risk individuals to enhance the detection of ACS.

Effects of PCSK9 Inhibitor on Favorable Limb Outcomes in Patients with Chronic Limb-Threatening Ischemia.

AIM: The aim of this study was to examine the effects of evolocumab on favorable limb events in patients with chronic limb-threatening ischemia (CLTI). METHODS: A single-center, prospective observational study was performed on 30 patients with CLTI. The subjects were divided into 2 groups based on evolocumab administration: evolocumab-treated (E) group ( n=14) and evolocumab non-treated (non-E) group (n=16). The primary outcome was 12-month freedom from major amputation. The secondary outcomes were 12-month amputation-free survival (AFS), overall survival (OS), and wound-free limb salvage. The mean follow-up period was 18±11 months. RESULTS: No significant difference was detected between the two groups for the 12-month freedom from major amputation (log-rank p=0.15), while the 12-month AFS rate was significantly higher in the E group than that in the non-E group (log-rank p=0.02). The 12-month OS rate in the E group was shown a tendency for improvement, as compared with that in the non-E group (log-rank p=0.056). Evolocumab administration was not associated with a significant change in freedom from major amputation (HR, 0.23, 95% CI, 0.03-2.07, p=0.19). However, evolocumab administration was related to a tendency for improvement of AFS and OS (HR, 0.13, 95% CI, 0.02-1.06, p=0.056; HR, 0.16, 95% CI, 0.02-1.37, p=0.09, respectively). Moreover, The E group had a higher proportion of wound-free limb salvage at 12 months (92% vs. 42%, p=0.03). CONCLUSION: Evolocumab administration was associated with a better AFS outcome in patients with CLTI. Long-term administration of evolocumab over 12 months contributed to improving proportion of wound-free limb salvage.

Risk Stratification for 2-Year Mortality in Patients with Chronic Limb-Threatening Ischemia Undergoing Endovascular Therapy.

AIM: The latest Global Vascular Guidelines (GVG) recommend assessing the 2-year mortality risk in patients with chronic limb-threatening ischemia (CLTI) before revascularization. This study aimed to reveal whether the Wound, Ischemia and foot Infection (WIfI) classification, developed originally as a risk assessment tool for limb prognosis, would be useful in predicting the 2-year mortality risk in patients with CLTI in the era of GVG and WIfI. METHODS: We retrospectively analyzed 849 patients with CLTI who were primarily treated with endovascular therapy (EVT) between April 2010 and December 2016. The impact of baseline characteristics, including the WIfI classification on mortality risk, was investigated using the Cox proportional hazards regression model. RESULTS: During a mean follow-up of 19.3 months, 243 deaths were observed. The 2-year mortality rate was 32.3%. Multivariate analysis demonstrated that WIfI classification stages (p=0.037), in addition to male sex (p=0.010), age (p＜0.001), non-ambulatory status (p＜0.001), body mass index (p=0.002), and hemodialysis (p＜0.001), were independent predictors for an increased risk of mortality, while the Rutherford classification was not. CONCLUSIONS: WIfI classification stages were independently associated with mortality risk in patients with CLTI undergoing EVT, while the Rutherford classification was not. The WIfI classification would be a practical tool for planning the revascularization strategy in CLTI treatment.

Classificação WifI: o novo sistema de classificação da Society for Vascular Surgery para membros inferiores ameaçados, uma revisão de literatura / WIfI classification: the Society for Vascular Surgery lower extremity threatened limb classification system, a literature review

Resumo A Society for Vascular Surgery propôs nova classificação para o membro inferior ameaçado, baseada nos três principais fatores influenciadores do risco de amputação do membro: ferida (Wound, W), isquemia (Ischemia, I) e infecção do pé (foot Infection, fI): a classificação WIfI. Esta abrange também os diabéticos, anteriormente excluídos do conceito de isquemia crítica do membro devido a seu quadro clínico complexo. O objetivo da classificação era fornecer estratificação de risco precisa e precoce ao paciente com membro inferior ameaçado; auxiliar no manejo clínico, permitindo comparar terapias alternativas; e predizer o risco de amputação em 1 ano e a necessidade de revascularização. O objetivo deste estudo é reunir os principais pontos abordados sobre a classificação WIfI no meio científico. A maior parte dos estudos de validação da classificação demonstram sua associação à predição de salvamento do membro, eventos de reintervenção, amputação e estenose, taxas de amputação maior e menor, sobrevida livre de amputação, e cicatrização de feridas.

Abstract The Society for Vascular Surgery has proposed a new classification system for the threatened lower limb, based on the three main factors that have an impact on limb amputation risk: Wound (W), Ischemia (I) and foot Infection ("fI") - the WIfI classification. The system also covers diabetic patients, previously excluded from the concept of critical limb ischemia because of their complex clinical condition. The classification's purpose is to provide accurate and early risk stratification for patients with threatened lower limbs; assisting with clinical management, enabling comparison of alternative therapies; and predicting risk of amputation at 1 year and the need for limb revascularization. The objective of this study is to collect together the main points about the WIfI classification that have been discussed in the scientific literature. Most of the studies conducted for validation of this classification system prove its association with factors related to limb salvage, such as amputation rates, amputation-free survival, prediction of reintervention, amputation, and stenosis (RAS) events, and wound healing.