Association between End-Stage Renal Disease and Major Adverse Limb Events after Peripheral Vascular Intervention.

PURPOSE: To examine the effect of end-stage renal disease (ESRD) on the likelihood of major adverse limb events (MALEs) in patients with Rutherford Category 4-6 critical limb ischemia (CLI) who underwent percutaneous vascular intervention (PVI). MATERIALS AND METHODS: Two contemporaneous cohorts of patients who underwent PVI for symptomatic CLI from 2012 to 2022, differing in ESRD status, were matched using propensity score methods. This database identified 628 patients who underwent 1,297 lower extremity revascularization procedures; propensity score matching yielded 147 patients (180 limbs, 90 limbs in each group). Kaplan-Meier and Cox proportional hazard analyses were used to assess the effect of ESRD status on MALEs, stratified into major amputation (further stratified into above-knee amputation and below-knee amputation [BKA]) and reintervention (PVI or bypass). RESULTS: After PVI, 31.3% of patients in the matched cohorts experienced a MALE (45.7% ESRD vs 18.2% non-ESRD), and 15.6% experienced a major amputation (27.1% ESRD vs 5.2% non-ESRD). Cox proportional hazards analysis revealed that ESRD was an independent predictor of MALE (hazard ratio [HR], 3.15; 95% CI, 1.58-6.29; P = .001), major amputation (HR, 7.00; 95% CI, 2.06-23.79; P = .002), and BKA (HR, 7.56; 95% CI, 1.71-33.50; P = .008). CONCLUSIONS: ESRD is strongly predictive of MALE and major amputation risk, specifically BKA, in patients undergoing PVI for Rutherford Category 4-6 CLI. These patients warrant closer follow-up, and new methods may become necessary to predict and further reduce their amputation risk.

Prediction of Limb Salvage Following Percutaneous Vascular Intervention Using a Composite Tibial Artery Perfusion Score.

PURPOSE: To assess a novel tibial artery perfusion score (TPS) for predicting limb salvage in critical limb ischemia (CLI) patients undergoing percutaneous vascular intervention (PVI). PATIENTS AND METHODS: A consecutive cohort of 115 CLI patients undergoing PVI in 144 limbs from 2011 to 2016 was analyzed. TPS comprised a 27-point scale based on: (1) patent tibial vessels following PVI, (2) severity of calcification of the tibial arteries, (3) presence of an intact pedal arch following intervention, (4) whether or not revascularization was direct or indirect based on the target angiosome, (5) presence of angiosome blush at the completion of index intervention. Limbs were stratified into (1) High [21-27 points], (2) Medium [13-20 points], and (3) Low [0-12 points] TPS. Predictive value of TPS was evaluated using logistic regression and Cox proportional hazards models. RESULTS: The median follow-up was 15.7 months (range 0.4-69.9 months). Limb salvage in High, Medium, and Low TPS groups was 90.6%, 85.9%, and 55.6%, respectively, as freedom from the composite outcome: (1) limb complication resulting in death, (2) tibial bypass surgery, (3) above-the-knee amputation, or (4) below-the-knee amputation in patients without supratibial disease at the time of PVI. TPS was significantly associated with limb salvage defined as freedom from both the composite outcome and major amputation. CONCLUSIONS: Based on this preliminary investigation, TPS was associated with limb salvage in CLI limbs, particularly in high-risk limbs. Further validation in a prospective cohort may identify patients with high-risk limbs in need of closer surveillance and earlier reintervention. LEVEL OF EVIDENCE: Level IV, case series.

NOS1AP genetic variation is associated with impaired healing of diabetic foot ulcers and diminished response to healing of circulating stem/progenitor cells.

It is unclear why many with diabetes develop foot ulcers (DFU) and why some do not heal. It could be associated with genetic variation. We have previously shown that NOS1AP variation is associated with lower extremity amputation in those with diabetes and that circulating stem progenitor cell concentration (SPC) is associated with impaired foot ulcer healing in those with diabetes. The goal of this study was to determine if NOS1AP variation is associated with impaired wound healing and with SPC mobilization in those with DFU. In longitudinal cohort study we demonstrate that NOS1AP variants rs16849113 and rs19649113 are associated with impaired wound healing and with SPC mobilization in those with DFU. We believe that further study of NOS1AP is merited and that it NOS1AP might be associated with a functional impairment.

Measurements of CD34+/CD45-dim Stem Cells Predict Healing of Diabetic Neuropathic Wounds.

Management of neuropathic foot ulcers in patients with diabetes (DFUs) has changed little over the past decade, and there is currently no objective method to gauge probability of successful healing. We hypothesized that studies of stem/progenitor cells (SPCs) in the early weeks of standard wound management could predict who will heal within 16 weeks. Blood and debrided wound margins were collected for 8 weeks from 100 patients undergoing weekly evaluations and treatment. SPC number and intracellular content of hypoxia-inducible factors (HIFs) were evaluated by flow cytometry and immunohistochemistry. More SPCs entered the bloodstream in the first 2 weeks of care in patients who healed (n = 37) than in those who did not (n = 63). Logistic regression demonstrated that the number of blood-borne SPCs and the cellular content of HIFs at study entry and the first-week follow-up visit predicted healing. Strong correlations were found among week-to-week assessments of blood-borne SPC HIF factors. We conclude that assays of SPCs during the first weeks of care in patients with DFUs can provide insight into how well wounds will respond and may aid with decisions on the use of adjunctive measures.

Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy.

Diabetic patients undergoing hyperbaric oxygen therapies (HBO(2)T) for refractory lower extremity neuropathic ulcers exhibit more than a twofold elevation (p=0.004) in circulating stem cells after treatments and the post-HBO(2)T CD34(+) cell population contains two- to threefold higher levels of hypoxia inducible factors-1, -2, and -3, as well as thioredoxin-1 (p<0.003), than cells present in blood before HBO(2)T. Skin margins obtained from 2-day-old abdominal wounds exhibit higher expression of CD133, CD34, hypoxia inducible factor-1, and Trx-1 vs. margins from refractory lower extremity wounds and expression of these proteins in all wounds is increased due to HBO(2)T (p<0.003). HBO(2)T is known to mobilize bone marrow stem cells by stimulating nitric oxide synthase. We found that nitric oxide synthase activity is acutely increased in patients' platelets following HBO(2)T and remains elevated for at least 20 hours. We conclude that HBO(2) T stimulates vasculogenic stem cell mobilization from bone marrow of diabetics and more cells are recruited to skin wounds.

The evolving paradigm of revascularization for wound healing: which intervention for which wound?

Chronic limb ischemia (CLI) presents a therapeutic challenge. A collaborative multidisciplinary model utilizes the collective skills of the vascular surgeon, podiatrist, and plastic surgeon to achieve optimal outcomes. As treatment paradigms continue to evolve toward minimally invasive approaches, a thoughtful comparison of the available options is essential for wound care specialists. Minimally invasive, catheter-based options offer less morbidity with reduced patency compared to traditional, open bypass. Individualized selection of the most appropriate revascularization option should be made after careful consideration of the wound severity, anatomic location of occlusive disease and patient comorbidities.

Biologic resurfacing of the ankle and first metatarsophalangeal joint: case studies with a 2-year follow-up.

The goal of biologic resurfacing is to provide a smooth joint surface with a low coefficient of friction, which allows the joint to function with near normal biomechanics, as well as provide intermittent pressure, to the subchondral and cancellous bone. This unique combination often results in the formation of a "neocartilage-like" structure that can reduce pain and restore biomechanics. As well as giving a brief history of cutis arthroplasty, this article describes cases in which the ankle and first metatarsophalangeal joint underwent biologic resurfacing, with a 2-year postoperative follow up.

Use of a small bilateral external fixator for ankle fusion.

A variety of methods are available for surgeons to use in an effort to achieve fusion ankle arthrodesis. Among these, external fixation devices have proven to be effective. In this article, we describe the use of a small external fixation frame that is affixed to the medial and lateral aspects of transfixation pins, and used to compress the arthrodesis interface.

Diagnostic and prognostic value of erythrocyte sedimentation rate in contiguous osteomyelitis of the foot and ankle.

This is a 95-patient prospective study evaluating diagnostic and prognostic efficacy of erythrocyte sedimentation rate (ESR) for contiguous pedal osteomyelitis. ESRs, bone and soft tissue microbiologic cultures, and pathologic examination of the suspected bone involved were obtained. ESRs were drawn within 48 hours before surgically obtaining the bone specimen. A subset of 16 patients, determined by pathology to have osteomyelitis, had intermittent erythrocyte sedimentation rates drawn for at least 56 days to determine trends based on the patient being healed or not healed. Pathology resulted in diagnosis of osteomyelitis in 66 patients. A statistical significance of ESR was found when comparing those with and without osteomyelitis. Seventy-four had a secondary diagnosis of diabetes mellitus. No statistical significance was found in regards to ESR in absence or presence of osteomyelitis when considering the variable of diabetes mellitus. Negative and positive predictive values were calculated at different ESR levels to determine the diagnostic value of ESR. Eight patients with osteomyelitis, determined to be healed over 56 days of treatment, showed a decline of ESRs. No trend of declination was seen in 8 patients determined not healed after 56 days. A statistically significant difference in average ESR between patients with osteomyelitis who had no bacterial growth of bone and those with one or more organisms growing in bone was found. ESR as a diagnostic tool for contiguous pedal osteomyelitis has been found in this study to be both valuable and significant. The comorbidity of diabetes mellitus did not significantly change the ESR values in patients with or without osteomyelitis. ESR as a modality to document the success of treatment for those with osteomyelitis proved valuable in the subset of patients who were followed up.