A case of pseudo-Kaposi sarcoma with chronic limb-threatening ischemia.

BACKGROUND: Pseudo-Kaposi sarcoma (PKS) is a rare vascular proliferative disease, caused by arteriovenous malformation (AVM) and chronic venous insufficiency. The lesions are characterized by purple or reddish-brownish papules, plaques, and nodules. Although benign, it is clinically similar to Kaposi's sarcoma (KS), a malignant disease, and must be differentiated by histopathological examination. We report a rare case of PKS with chronic limb-threatening ischemia (CLTI). CASE PRESENTATION: An 83-year-old man with diabetes mellitus (DM) presented to a local dermatology department with a complaint of a right second toe ulcer and was, thereby, referred to our department due to arterial bleeding during skin biopsy to exclude malignant diseases. Although the pulsation of dorsalis pedis artery of the affected limb was palpable, the skin perfusion pressure was only 20 and 30 mmHg on the dorsum and planter surface, respectively, indicating severe ischemia of toe and forefoot. Ultrasonography and computed tomography revealed an AVM around the right second metatarsophalangeal joint and occlusion of the right dorsalis pedis artery in the middle, indicating CLTI in the background. Pathological findings of the skin biopsy found capillary blood vessel proliferation, hemosiderin deposition, and extravascular red blood cell leakage in the dermal layer, which could be found in KS. However, CD34 was normally stained in the vascular endothelium, and human herpesvirus-8 staining was negative, resulting in the pathological diagnosis of PKS, a proliferative vascular lesion associated with AVM. The ulcer was spontaneously epithelialized, but 2 years later the ulcer recurred and infection developed, necessitating treatment for abnormal blood flow. Transarterial embolization using N-butyl 2-cyanoacrylate for the AVM controlled abnormal perfusion once; however, the procedure exacerbated perfusion of the toe, resulting in foot ulcer progression. Forefoot amputation with surgical excision of AVM was performed, and thereby, wound healing was achieved. CONCLUSION: This is a rare case of PKS with CLTI complicated with AVM. As there is currently no established consensus on the treatment of PKS, the approach to treatment strategy should be tailored to the specific condition of each patient.

Prognostic factors after open and endovascular repair for infected native aneurysms of the abdominal aorta and common iliac artery.

OBJECTIVE: Infected native aneurysms (INAs) of the abdominal aorta and iliac arteries are uncommon, but potentially fatal. Endovascular aneurysm repair (EVAR) has recently been introduced as a durable treatment option, with outcomes comparable to those yielded by conventional open repair. However, owing to the rarity of the disease, the strengths and limitations of each treatment remain uncertain. The present study aimed to separately assess post-open repair and post-EVAR outcomes and to clarify factors affecting the short-term and late prognosis after each treatment. METHODS: Using a nationwide clinical registry, we investigated 600 patients treated with open repair and 226 patients treated with EVAR for INAs of the abdominal aorta and/or common iliac artery. The relationships between preoperative or operative factors and postoperative outcomes, including 90-day and 3-year mortality and persistent or recurrent aneurysm-related infection, were examined. RESULTS: Prosthetic grafts were used in >90% of patients treated with open repair, and in situ and extra-anatomic arterial reconstruction was performed in 539 and 57 patients, respectively. Preoperative anemia and imaging findings suggestive of aneurysm-enteric fistula were independently associated with poor outcomes in terms of both 3-year mortality (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.01-2.62; P = .046, and HR, 2.24; 95% CI, 1.12-4.46; P = .022, respectively) and persistent or recurrent infection (odds ratio [OR], 2.16; 95% CI, 1.04-4.49; P = .039, and OR, 4.96; 95% CI, 1.81-13.55; P = .002, respectively) after open repair, whereas omental wrapping or packing and antibiotic impregnation of the prosthetic graft for in situ reconstruction contributed to improved 3-year survival (HR, 0.60; 95% CI, 0.39-0.92; P = .019, and HR, 0.53; 95% CI, 0.32-0.88; P = .014, respectively). Among patients treated with EVAR, abscess formation adjacent to the aneurysm was significantly associated with the occurrence of persistent or recurrent infection (OR, 2.24; 95% CI, 1.06-4.72; P = .034), whereas an elevated preoperative white blood cell count was predictive of 3-year mortality (HR, 1.77; 95% CI, 1.00-3.13; P = .048). CONCLUSIONS: Profiles of prognostic factors differed between open repair and EVAR in the treatment of INAs of the abdominal aorta and common iliac artery. Open repair may be more suitable than EVAR for patients with concurrent abscess formation.

The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes and a foot ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this guideline the IWGDF, the European Society for Vascular Surgery and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development, and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications.

Current status of surgical treatment for acute aortic dissection in Japan: Nationwide database analysis.

OBJECTIVE: To clarify the current status of surgical treatment of acute aortic dissection (AAD) in Japan through the Japan Cardiovascular Database analysis. METHODS: In total, 7194 patients who underwent surgical treatment for AAD in 2021, including type A (TAAAD) (n = 6416) and type B (TBAAD) (n = 778), were investigated. RESULTS: The median age was 70 years, with patients older than age 80 years constituting 21.7% and 23.4% of TAAAD and TBAAD cases. Emergency admission was 88.5% and 78.5%. Shock was found in 11.8% and 6.0%. Rupture/impending rupture occurred in 10.7%/6.0% and 24.0%/11.1%, respectively. Branch malperfusion was complicated in 10.4% and 25.2%. Open repairs were performed in 97.7% and 20.3%, whereas endovascular repairs were performed in 2.3% and 79.7%, respectively. In the increased prevalence of endografting procedures, neurological complications and renal failure occurred frequently after open repair with frozen elephant trunk for 29.9% and 50.3%. The operative mortality rate was 9.8% and 11.5% for open repair and 8.1% and 10.0% for endovascular repair. In patients with TAAAD, age older than 80 years, preoperative critical comorbidities, classical dissection, and coexisting chronic vital organ diseases were independent risk factors for mortality. In frozen elephant trunk procedures, neurologic complications and renal failure were frequent. The operative mortality was higher during the superacute phase within 1 or 2 hours from onset to arrival and between arrival and surgery. CONCLUSIONS: The current status of surgical treatments for AAD including the increased prevalence of endografting of thoracic endovascular aortic repair and frozen elephant trunk were demonstrated with favorable outcomes in the Japan Cardiovascular Database analyses.

The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot Ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis, and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this updated guideline, the IWGDF, the European Society for Vascular Surgery, and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications.

The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes mellitus and a foot ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis, and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this updated guideline, the IWGDF, the European Society for Vascular Surgery, and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications.

Surgical Treatment for Popliteal Artery Entrapment Syndrome in Japan: a Retrospective, Multicentre Study Using a National Clinical Registry.

OBJECTIVE: Surgical treatment is an established method for popliteal artery entrapment syndrome (PAES), which, however, mainly derives from single centre experiences where PAES cases are centralised and treated periodically. This study evaluated clinical outcomes of surgical treatment for PAES in a clinical setting where PAES cases were not centralised. METHODS: Multicentre, retrospective cohort study using a national clinical registry. From a Japanese nationwide clinical registry, data for patients who underwent surgical treatment for PAES between 2013 and 2018, including 58 limbs from 41 institutes, were retrieved and evaluated. Patency was analysed using Kaplan-Meier curves. RESULTS: The mean patient age was 36 ± 19 years, 78% were male, and the incidence of PAES was 0.24 limbs/centre/year, reflecting a clinical setting where PAES cases are not centralised. The most frequent arterial symptom was intermittent claudication (90%). Computed tomography was performed in 57 limbs (98%) for the diagnosis, however active manoeuvres such as dorsiflexion and plantarflexion during the examination was performed in only 13 limbs (22%), and occlusion of the popliteal artery was present in 38 limbs (66%) at diagnosis. Regarding surgical treatment, myotomy alone was performed in only seven limbs (12%), and other limbs were revascularised. Mean follow up was 26 ± 20 months, and surgical treatment was effective as it relieved symptoms in > 96% of limbs, with five year primary and secondary patency of the surgical treatment for PAES of 72% and 93%, respectively. CONCLUSION: Results of surgical treatment were acceptable even in a clinical setting where PAES cases were not centralised. However, a low incidence of active manoeuvres performed during the examination and a high incidence of occlusion at diagnosis suggests there may be delayed or underdiagnosis of PAES in Japan, and increased awareness for PAES is warranted.

A case of lymphoma mimicking infected internal iliac artery aneurysm.

BACKGROUND: Malignant lymphoma rarely mimics an infected arterial aneurysm and a ruptured arterial aneurysm because of similar imaging findings, leading to misdiagnosis. The hematomas of ruptured aneurysms are radiologically difficult to distinguish from those of malignant lymphoma in emergency settings. Hence, a definitive diagnosis is crucial to avoid unnecessary surgery. CASE PRESENTATION: A man in his 80s with hematuria and shock vital had right internal iliac artery aneurysm (IIAA) and perianeurysmal fluid retention, which appeared to be a ruptured or an infected aneurysm. Treatment was initiated for infected IIAA instead of for ruptured IIAA. Systemic inflammatory response syndrome developed, and the infectious sources were assessed. Pacemaker lead and urinary tract infections were identified and treated; however, blood pressure was unstable. The aneurysm was treated with endovascular aortic aneurysm repair following antibiotic therapy; however, fluid retention increased, and inflammatory status and hematuria deteriorated. Open surgical conversion was performed to manage the infected lesions. Although an iliopsoas abscess was detected during surgery and nephrectomy and ureterectomy were performed to control the hematuria, analysis of the removed tissues led to the pathological diagnosis of diffuse large B-cell lymphoma (DLBCL). CONCLUSIONS: We encountered a case of DLBCL with imaging findings mimicking an infected internal iliac artery aneurysm, and definitive diagnosis was made more than 2 months after the initial examination. Definitively diagnosing malignant lymphoma around an iliac artery aneurysm based merely on symptoms and imaging findings is extremely difficult. Thus, histological examination should be actively performed in atypical infected aneurysms.

Regenerative Effect of Umbilical Cord-Derived Mesenchymal Stromal Cells in a Rat Model of Established Limb Ischemia.

BACKGROUND: Although regenerative cell therapy is expected to be an alternative treatment for peripheral artery disease (PAD), many regenerative cell therapies have failed to show sufficient efficacy in clinical trials. Most preclinical studies have used acute ischemia models, despite PAD being a chronic disease. In addition, aging and atherosclerosis decrease the quality of a patient's stem cells. Therefore, using a non-acute ischemic preclinical model and stem cells with high regenerative potency are important for the development of effective regenerative therapy. In this study, we assessed the tissue regenerative potential of umbilical cord-derived mesenchymal stromal cells (UCMSCs), which could potentially be an ideal cell source, in a rat model of established ischemia.Methods and Results: The regenerative capacity of UCMSCs was analyzed in terms of angiogenesis and muscle regeneration. In vitro analysis showed that UCMSCs secrete high amounts of cytokines associated with angiogenesis and muscle regeneration. In vivo experiments in a rat non-acute ischemia model showed significant improvement in blood perfusion after intravenous injection of UCMSCs compared with injection of culture medium or saline. Histological analysis revealed UCMSCs injection enhanced angiogenesis, with an increased number of von Willebrand factor-positive microcapillaries, and improved muscle regeneration. CONCLUSIONS: These results suggest that intravenous administration of UCMSCs may be useful for treating patients with PAD.

Endovascular versus open repair in patients with abdominal aortic aneurysm: a claims-based data analysis in Japan.

Objectives: Endovascular aortic repair (EVAR) evolved through competition with open aortic repair (OAR) as a safe and effective treatment option for appropriately selected patients with abdominal aortic aneurysm (AAA). Although endoleaks are the most common reason for post-EVAR reintervention, compliance with lifelong regular follow-up imaging remains a challenge. Design: Retrospective data analysis. Setting: The Japan Medical Data Center (JMDC), a claims database with anonymous data linkage across hospitals, consists of corporate employees and their families of ≤75 years of age. Participants: The analysis included participants in the JMDC who underwent EVAR or OAR for intact (iAAA) or ruptured (rAAA) AAA. Patients with less than 6 months of records before the aortic repair were excluded. Main outcome measures: Overall survival and reintervention rates. Results: We identified 986 cases (837 iAAA and 149 rAAA) from JMDC with first aortic repairs between January 2015 and December 2020. The number of patients, median age (years (IQR)), follow-up (months) and post-procedure CT scan (times per year) were as follows: iAAA (OAR: n=593, 62.0 (57.0-67.0), 26.0, 1.6, EVAR: n=244, 65.0 (31.0-69.0), 17.0, 2.2), rAAA (OAR: n=110, 59.0 (53.0-59.0), 16.0, 2.1, EVAR: n=39, 62.0 (31.0-67.0), 18.0, 2.4). Reintervention rate was significantly higher among EVAR than OAR in rAAA (15.4% vs 8.2%, p=0.04). In iAAA, there were no group difference after 5 years (7.8% vs 11.0%, p=0.28), even though EVAR had initial advantage. There were no differences in mortality rate between EVAR and OAR for either rAAA or iAAA. Conclusions: Claims-based analysis in Japan showed no statistically significant difference in 5-year survival rates of the OAR and EVAR groups. However, the reintervention rate of EVAR in rAAA was significantly higher, suggesting the need for regular post-EVAR follow-up with imaging. Therefore, international collaborations for long-term outcome studies with real-world data are warranted.

Lateral approach to distal peroneal artery without fibular resection.

Bypass to the peroneal artery has sometimes been effective for pedal gangrene. However, the difficulty of approaching the terminal segment of the peroneal artery because of its anatomic features has been a clinical issue. Surgical access to this area can be achieved via a lateral approach with fibular resection. Although severe complications associated with fibular resection have rarely been reported, a less invasive surgical procedure would enable faster postoperative recovery and reduce the incidence of wound-related complications. We have described our experience with successful terminal peroneal artery bypass via a lateral approach without fibular resection in a 38-year-old male patient with chronic limb-threatening ischemia.

Prediction Models for Two Year Overall Survival and Amputation Free Survival After Revascularisation for Chronic Limb Threatening Ischaemia.

OBJECTIVE: The aim of this study was to create prediction models for two year overall survival (OS) and amputation free survival (AFS) after revascularisation in patients with chronic limb threatening ischaemia (CLTI). METHODS: This was a retrospective analysis of prospectively collected multicentre registry data (JAPAN Critical Limb Ischaemia Database; JCLIMB). Data from 3 505 unique patients with CLTI who had undergone revascularisation from 2013 to 2017 were extracted from the JCLIMB for the analysis. The cohort was randomly divided into development (2 861 patients) and validation cohorts (644 patients). In the development cohort, multivariable risk models were constructed to predict two year OS and AFS using Cox proportional hazard regression analysis. These models were applied to the validation cohort and their performances were evaluated using Harrell's C index and calibration plots. RESULTS: Kaplan-Meier estimates of two year OS and AFS post-revascularisation in the whole cohort were 69% and 62%, respectively. Strong predictors for OS consisted of age, activity, malignant neoplasm, chronic kidney disease (CKD), congestive heart failure (CHF), geriatric nutritional risk index (GNRI), and sex. Strong predictors for AFS included age, activity, malignant neoplasm, CKD, CHF, GNRI, body temperature, white blood cells, urgent revascularisation procedure, and sex. Prediction models for two year OS and AFS showed good discrimination with Harrell's C indexes of 0.73 (95% confidence interval [CI] 0.69 - 0.77) and 0.72 (95% CI 0.68 - 0.76), respectively CONCLUSION: Prediction models for two year OS and AFS post-revascularisation in patients with CLTI were created. They can assist in determining treatment strategies and serve as risk adjustment modalities for quality benchmarking for revascularisation in patients with CLTI at each facility.

The Impact of Chronic Limb-Threatening Ischemia on Cardiac Surgery.

Purpose: The effect of chronic limb threatening ischemia (CLTI) on advanced cardiac disease, which requires surgical treatment, has rarely been reported. The purpose of this study was to review the outcomes of cardiac surgery in patients with CLTI and determine the risk factors, with a particular focus on the severity of CLTI. Patients: The baseline characteristics and outcomes of 33 patients who were treated for CLTI and underwent cardiac surgery were retrospectively analyzed. The states of CLTI were evaluated based on the Wound, Ischemia, and foot Infection (WIfI) classification system, and 33 patients were divided into the low-WIfI group (stages 1-2, n = 13) and high-WIfI group (stages 3-4, n = 20). Results: The in-hospital mortality rate was 0% in low-WIfI group and 35% in high-WIfI group (p = 0.027). Postoperative complications, particularly severe infections, occurred more frequently among high-WIfI group than low-WIfI group (70.0% vs. 23.1%, p < 0.01). Multivariable analysis identified foot infection grade as a WIfI classification factor and lower albumin levels as factors significantly associated with postoperative complications. The 1-year and 2-year survival rates were 84.6% and 67.7% in low-WIfI group and 45% and 28.1% in high-WIfI group, respectively (p = 0.011). Conclusions: Cardiac surgery in patients with high WIfI stage was an extremely high-risk procedure. In such patients, lowering the WIfI stage by lower extremity revascularization and/or debridement of diseased parts prior to cardiac surgery can be considered.

Successful endovascular therapy involving direct puncture for spontaneous internal iliac artery aneurysm rupture.

Neurofibromatosis type 1 (NF-1) is associated with fatal vascular complications. A 40-year-old woman with NF-1 who had previously undergone left iliac artery ligation and femorofemoral bypass grafting for internal iliac artery (IIA) aneurysm rupture was transported to our hospital for the treatment of a newly developed IIA aneurysm. Although endovascular therapy was difficult owing to the previous surgery, we successfully performed embolization of the aneurysm and its feeding vessels via direct percutaneous puncture under ultrasound guidance. Aneurysm enhancement had completely disappeared at 2 months postoperatively. We have reported a novel approach of direct percutaneous puncture for IIA aneurysm embolization in a patient with NF-1.

NT5E mutation in sisters who underwent aortic valve replacements for aortic stenosis.

Mutations of the NT5E gene encoding the cluster of differentiation 73 (CD73) protein have been found in patients with characteristic calcification of joints and arteries (CALJA). CD73 plays a protective role against aortic valve calcification; therefore, its deletion results in aortic valve calcification. However, to date, there are no reports of a patient with CALJA with aortic stenosis. In this study, we describe 2 extremely rare cases of sisters with identical NT5E gene mutation patterns, both of whom developed late-onset severe aortic stenosis and limb ischaemia. Both patients underwent aortic valve replacement and bilateral distal arterial bypass surgeries successfully. They were genetically diagnosed with CALJA based on the NT5E mutation. Our report suggests that NT5E mutations should be considered in patients requiring aortic valve replacement for a calcified aortic valve and bypass surgery for specific calcified and occluded arteries.

Challenges for the Development of Extracellular Vesicle-Based Nucleic Acid Medicines.

Nucleic acid drugs, such as siRNAs, antisense oligonucleotides, and miRNAs, exert their therapeutic effects by causing genetic changes in cells. However, there are various limitations in their delivery to target organs and cells, making their application to cancer treatment difficult. Extracellular vesicles (EVs) are lipid bilayer particles that are released from most cells, are stable in the blood, and have low immunogenicity. Methods using EVs to deliver nucleic acid drugs to target organs are rapidly being developed that take advantage of these properties. There are two main methods for loading nucleic acid drugs into EVs. One is to genetically engineer the parent cell and load the target gene into the EV, and the other is to isolate EVs and then load them with the nucleic acid drug. Target organ delivery methods include passive targeting using the enhanced permeation and retention effect of EVs and active targeting in which EVs are modified with antibodies, peptides, or aptamers to enhance their accumulation in tumors. In this review, we summarize the advantages of EVs as a drug delivery system for nucleic acid drugs, the methods of loading nucleic acid drugs into EVs, and the targeting of EVs to target organs.

Health Related Quality of Life Over Time After Revascularisation in Patients With Chronic Limb Threatening Ischaemia.

OBJECTIVE: Chronic limb threatening ischaemia (CLTI) decreases life expectancy and impairs health related quality of life (HR-QOL). Revascularisation is needed to relieve ischaemia and salvage limbs. Although a major goal of CLTI treatment is maintaining QOL, little information is available about changes of HR-QOL over time after revascularisation. HR-QOL with survival after revascularisation for CLTI was assessed. METHODS: The clinical database of the Surgical reconstruction versus Peripheral INtervention in pAtients with critical limb isCHemia (SPINACH), a prospective multicentre observational study, was analysed. Outcome measures were disease specific QOL per the Vascular Quality of Life (VascuQOL) questionnaire and the Short Form (SF) 36 evaluated generic QOL, which were assessed at baseline and three, 12, 24, and 36 months. The outcome measure was change of QOL from baseline. The minimally important difference (half a standard deviation from baseline) was used as the cut off point for improved, worsened, and unchanged QOL. RESULTS: Overall QOL was improved in 61% of patients for the VascuQOL and approximately 40% for the SF-36 component summaries at three months. However, these proportion gradually decreased to 21% - 31% at three years. In contrast, the proportion of deceased patients gradually increased over the three year follow up. Multivariable analysis revealed that pre-operative non-ambulatory status was inversely associated with improved QOL for the three month VascuQOL and SF-36 mental component summary, and surgical reconstruction was positively associated with these measurements. Advanced age and renal failure were inversely associated with improved QOL for the SF-36 mental component summary and VascuQOL at one to three years. CONCLUSION: Revascularisation improved QOL. However, patients with non-ambulatory status exhibited a negative association with improved QOL at three months, and advanced age and renal failure limited benefits one to three years after revascularisation. Accumulating QOL data will be essential for post-revascularisation QOL estimation. Pre-operative assessment, including estimated QOL, is important in shared decision making for patient oriented outcomes in the treatment of CLTI patients.

Impact of homocysteine levels on mortality risk in patients with chronic limb-threatening ischemia undergoing revascularization.

The current study aimed to reveal the clinical impact of plasma homocysteine levels in chronic limb-threatening ischemia (CLTI) patients undergoing revascularization. This was a sub-analysis of a prospective multicenter registry of CLTI patients, named the Surgical reconstruction versus Peripheral INtervention in pAtients with critical limb isCHemia (SPINACH) study. The current analysis included 192 non-dialysis-dependent CLTI patients who underwent revascularization for CLTI, and whose plasma homocysteine levels at baseline were available. The association of clinical characteristics with homocysteine levels was evaluated with the linear regression model. The association of homocysteine levels with the mortality risk was investigated using the Cox proportional hazards regression model. Cystatin C-based estimated glomerular filtration rate (eGFR) was independently associated with log-transformed homocysteine levels; the adjusted standardized regression coefficient (95% confidence interval) was - 0.432 (- 0.657 to - 0.253; P < 0.001). Homocysteine levels were significantly associated with the mortality risk in the univariate model (P = 0.017); the unadjusted hazard ratio was 1.71 (1.13-2.50) per twofold increase. The association was significantly attenuated when adjusted for cystatin C-based eGFR (P < 0.001); the hazard ratio adjusted for cystatin C-based eGFR was 1.28 (0.80-1.90; P = 0.29). An apparent association of homocysteine levels with an increased risk of mortality could be explained by renal dysfunction. Future studies will be needed to validate the current findings.