Immunodominant MHC-II (Major Histocompatibility Complex II) Restricted Epitopes in Human Apolipoprotein B.

BACKGROUND: CD (cluster of differentiation) 4+ T-cell responses to APOB (apolipoprotein B) are well characterized in atherosclerotic mice and detectable in humans. CD4+ T cells recognize antigenic peptides displayed on highly polymorphic HLA (human leukocyte antigen)-II. Immunogenicity of individual APOB peptides is largely unknown in humans. Only 1 HLA-II-restricted epitope was validated using the DRB1*07:01-APOB3036-3050 tetramer. We hypothesized that human APOB may contain discrete immunodominant CD4+ T-cell epitopes that trigger atherosclerosis-related autoimmune responses in donors with diverse HLA alleles. METHODS: We selected 20 APOB-derived peptides (APOB20) from an in silico screen and experimentally validated binding to the most commonly occurring human HLA-II alleles. We optimized a restimulation-based workflow to evaluate antigenicity of multiple candidate peptides in HLA-typed donors. This included activation-induced marker assay, intracellular cytokine staining, IFNγ (interferon gamma) enzyme-linked immunospot and cytometric bead array. High-throughput sequencing revealed TCR (T-cell receptor) clonalities of APOB-reactive CD4+ T cells. RESULTS: Using stringent positive, negative, and crossover stimulation controls, we confirmed specificity of expansion-based protocols to detect CD4+ T cytokine responses to the APOB20 pool. Ex vivo assessment of AIM+CD4+ T cells revealed a statistically significant autoimmune response to APOB20 but not to a ubiquitously expressed negative control protein, actin. Resolution of CD4+ T responses to the level of individual peptides using IFNγ enzyme-linked immunospot led to the discovery of 6 immunodominant epitopes (APOB6) that triggered robust CD4+ T activation in most donors. APOB6-specific responding CD4+ T cells were enriched in unique expanded TCR clonotypes and preferentially expressed memory markers. Cytometric bead array analysis detected APOB6-induced secretion of both proinflammatory and regulatory cytokines. In clinical samples from patients with angiographically verified coronary artery disease, APOB6 stimulation induced higher activation and memory phenotypes and augmented secretion of proinflammatory cytokines TNF (tumor necrosis factor) and IFNγ, compared with patients with low coronary artery disease. CONCLUSIONS: Using 3 cohorts, each with ≈20 donors, we discovered and validated 6 immunodominant, HLA-II-restricted APOB epitopes. The immune response to these APOB epitopes correlated with coronary artery disease severity.

Topical pravibismane as adjunctive therapy for moderate or severe diabetic foot infections: A phase 1b randomized, multicenter, double-blind, placebo-controlled trial.

This Phase 1b study was designed to evaluate the safety and efficacy of pravibismane, a novel broad-spectrum topical anti-infective, in managing moderate or severe chronic diabetic foot ulcer (DFU) infections. This randomized, double-blind, placebo-controlled, multicenter study consisted of 39 individuals undergoing pravibismane treatment and 13 individuals in the placebo group. Assessment of safety parameters included clinical observations of tolerability and pharmacokinetics from whole blood samples. Pravibismane was well-tolerated and exhibited minimal systemic absorption, as confirmed by blood concentrations that were below the lower limit of quantitation (0.5 ng/mL) or in the low nanomolar range, which is orders of magnitude below the threshold of pharmacological relevance for pravibismane. Pravibismane treated subjects showed approximately 3-fold decrease in ulcer size compared to the placebo group (85% vs. 30%, p = 0.27). Furthermore, the incidence of ulcer-related lower limb amputations was approximately 6-fold lower (2.6%) in the pooled pravibismane group versus 15.4% in the placebo group (p = 0.15). There were no treatment emergent or serious adverse events related to study drug. The initial findings indicate that topical pravibismane was safe and potentially effective treatment for improving recovery from infected chronic ulcers by reducing ulcer size and facilitating wound healing in infected DFUs (ClinicalTrials.gov Identifier NCT02723539).

Comparison of two donor-derived cell-free DNA tests and a blood gene-expression profile test in heart transplantation.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) testing is an emerging screening modality for noninvasive detection of acute rejection (AR). This study compared the testing accuracy for AR of two commercially available dd-cfDNA and gene-expression profiling (GEP) testing in heart transplant (HTx) recipients. METHODS: This is a retrospective, observational study of HTx only patients who underwent standard and expanded single nucleotide polymorphism (SNP) dd-cfDNA between October 2020 to January 2022. Comparison with GEP was also performed. Assays were compared for correlation, accurate classification, and prediction for AR. RESULTS: A total of 428 samples from 112 unique HTx patients were used for the study. A positive standard SNP correlated with the expanded SNP assay (p < .001). Both standard and expanded SNP tests showed low sensitivity (39%, p = 1.0) but high specificity (82% and 84%, p = 1.0) for AR. GEP did not improve sensitivity and showed worse specificity (p < .001) compared to standard dd-cfDNA. CONCLUSION: We found no significant difference between standard and expanded SNP assays in detecting AR. We show improved specificity without change in sensitivity using dd-cfDNA in place of GEP testing. Prospective controlled studies to address how to best implement dd-cfDNA testing into clinical practice are needed.

Topical Oxygen Therapy for Wound Healing: A Critical Evaluation.

Oxygen is an undisputed key factor in wound healing. Adequate oxygen pressure in tissues allows for cell growth and proliferation, necessary for wound healing. In the case of peripheral arterial disease leading to hypoxemia, oxygen supplementation is beneficial. The roles and validity of topical and systemic oxygen therapy in wound healing is debated. Topical oxygen therapy (TOT) is delivered at 100% oxygen saturation and has been demonstrated to increase the pO2 levels within the wound base center, decrease the size of the wound, and decrease the time to wound healing compared to patients that did not undergo topical oxygen therapy. Alternatives to topical oxygen therapy are systemic oxygen therapy including hyperbaric oxygen therapy and inspired oxygen therapy. Systemic oxygen therapy carries the risk of oxygen organ toxicity as the result of an oxidative stress and genotoxicity state. Topical O2 therapy is a viable option for chronic wounds, with its demonstrated effects on decrease in wound size and time to healing. Adjunctive clinical wound debridement's decrease the necrotic debris and therefore the topical oxygen diffusion distance optimizing the therapy effect.

Double Versus Triple Arthrodesis Fusion Rates: A Systematic Review.

Hindfoot arthrodesis is often required for end-staged deformities, such as posterior tibial tendon dysfunction, osteoarthritis, or rheumatoid arthritis. Although the need for hindfoot arthrodesis is generally accepted in severe deformities, there is a debate whether a double or triple arthrodesis should be performed. The aim of our systematic review is to review the fusion rates and mean time to fusion in double and triple arthrodesis. A total of 184 articles were identified using the keyword search through the database of articles published from 2005 to 2017. After review by 3 physicians, a total of 13 articles met the eligibility criteria. The reason for double or triple arthrodesis within the studies were posterior tibial tendon dysfunction, tarsal coalition, degenerative joint disease, osteoarthritis, rheumatoid arthritis, Charcot Marie Tooth, Multiple Sclerosis, Polio, neuromuscular disorder, cerebral palsy, acrodystrophic neuropathy, clubfoot, post-traumatic, and seronegative arthropathy (spondyloarthritis). Within these 13 studies, there were a total of 343 (6-95) subjects extremities operated on. The overall fusion rate for double arthrodesis was 91.75% (289/315) compared to 92.86% (26/28) triple arthrodesis fusion rate, p value .8370. The mean time to fusion for double arthrodesis was 17.96 ± 7.96 weeks compared to 16.70 ± 8.18 weeks for triple arthrodesis, p value = .8133. There are risks associated with triple arthrodesis including increased surgical times, lateral wound complications, residual deformity, surgical costs and peri-articular arthritis. Given the benefits of double arthrodesis over triple arthrodesis and the nearly equivalent fusion rates and time to fusion, double arthrodesis is an effective alternative to triple arthrodesis. The authors of this systematic review recommend double arthrodesis as the hindfoot fusion procedure of choice.

Evaluation of Polymerase Chain Reaction in the Identification and Quantification of Clinically Relevant Bacterial Species in Lower Extremity Wound Infections.

Identification of bacteria by polymerase chain reaction (PCR) is known to be more sensitive than culture, which brings to question the clinical applicability of the results. In this study, we evaluate the ability of PCR to detect clinically relevant bacterial species in lower extremity wound infections requiring operative debridement, as well as the quantitative change in biodiversity and bacterial load reflected by PCR during the course of treatment. Thirty-four infected lower extremity were examined by analysis of 16S ribosomal RNA subunit and by culture. McNemar's test was used to measure the concordance of clinically relevant bacterial species identified by PCR compared to culture during each debridement. Change in wound biodiversity from initial presentation to final closure was evaluated by Wilcoxon signed-rank test. Kaplan-Meier survival curve was used to characterize change in measured bacterial load over the course of operative debridement. A total of 15 and 12 clinically relevant bacterial species were identified by PCR and culture, respectively. The most common bacterial species identified were Coagulase-negative Staphylococcus, Staphylococcus aureus, and Enterococcus spp. PCR was less likely to detect Enterococcus spp. on initial debridement and Coagulase-negative Staphylococcus on closure in this study population. A significant decrease in mean number of clinically relevant species detected from initial debridement to closure was reflected by culture (p = .0188) but not by PCR (p = .1848). Both PCR (p = .0128) and culture (p = .0001) depicted significant reduction in mean bacterial load from initial debridement to closure. PCR is able to identify common clinically relevant bacterial species in lower extremity surgical wound infections. PCR displays increased sensitivity compared to culture with relation to detection of biodiversity, rather than bacterial load. Molecular diagnostics and conventional culture may serve a joint purpose to assist with rendering clinical judgment in complex wound infections.

Risks Factors Associated With Major Lower Extremity Amputation After Vertical Contour Calcanectomy.

The primary aim of the study is to determine risks for major lower extremity amputation after undergoing Vertical Contour Calcanectomy. Subanalysis was performed comparing patients who underwent Vertical Contour Calcanectomy who were fully ambulatory to those who were partially or nonambulatory postoperatively. Within the cohort of 63 patients included in the Vertical Contour Calcanectomy 85.71% (54/63) of patients had diabetes mellitus, 53.97% (34/63) had peripheral arterial disease, and 19.05% (12/63) had Charcot Neuroarthropathy. Multivariate logistic regression, found that (1) patients that underwent primary closure at the time of the Vertical Contour Calcanectomy, were 79.9% more likely (odds ratio [OR] 0.20; 95% confidence interval [CI] 0.04-0.96) to have limb salvage and that (2) female patients were 85.4% less likely compared to male patients (OR 0.15; 95% CI 0.02-0.99) to undergo major lower extremity amputation. Patients with coronary artery disease were 5.2 times more likely (OR 5.18; 95% CI 1.120-23.94) and patients that were nonambulatory preoperatively, were 10.3 times more likely (OR 10.28; 95% CI 1.60-66.26), to be partially or nonambulatory after Vertical Contour Calcanectomy. Primary closure at time of Vertical Contour Calcanectomy significantly decreases the risk of major lower extremity amputation, and diminished preoperative ambulatory status as well as coronary artery disease makes it less likely that patients return to full ambulation after Vertical Contour Calcanectomy.

The Impact of Hospitalization for Diabetic Foot Infection on Health-Related Quality of Life: Utilizing PROMIS.

Diabetic foot infections (DFI) are an increasingly common cause of hospitalizations. Once hospitalized with DFI, many patients require some level of amputation, often undergoing multiple operations. With increasing importance on patient-centered metrics, self-reported health-related quality of life (HRQOL) tools have been developed. This prospective cohort study aimed assessed the impact of DFI on HRQOL. Two hundred twenty-four patients completed the 29-item Patient-Reported Outcome Measurement Information System (PROMIS) and 12-Item Short Form (SF-12) survey. Secondary outcomes using the Foot and Ankle Ability Measures survey were obtained and included in the analysis. The study group was comprised of hospitalized patients with DFIs (n = 120), and the control group was comprised of patients with diabetes who were evaluated for routine outpatient foot care (n = 104); diabetic foot screening, wound care, onychomycosis, and/or callosities. Using this cohort, a propensity score-matched sample of hospitalized patients with DFI (n = 35) and control group patients (n = 35) was created for comparative analysis. The 2-independent sample t test was used to test for group differences on each of the PROMIS subscale outcomes. Using PROMIS, we found that hospitalized patients with DFI reported significantly worse HRQOL in 6 of 7 subscales (physical function, anxiety, depression, fatigue, social role, pain intensity; p value range: .0001-.02) compared to outpatients with diabetes evaluated for routine foot care. There was no significant difference between the 2 groups on sleep disturbance (p = .22). Patients hospitalized for DFI report lower HRQOL compared to patients with diabetes receiving routine outpatient foot care.

Economic model to estimate cost of negative pressure wound therapy with instillation vs control therapies for hospitalised patients in the United States, Germany, and United Kingdom.

An economic model was developed to estimate the cost of negative pressure wound therapy with instillation and dwelling of a topical wound solution vs control therapies. Economic model inputs were means derived from the results of a recently published systematic review and meta-analysis of 13 comparative studies of negative pressure wound therapy with instillation. Means across studies comprising complex acute and chronic wounds for negative pressure wound therapy-instillation vs control (negative pressure wound therapy without instillation, gauze dressings, or gentamicin polymethylmethacrylate beads) groups were 1.77 vs 2.69 operating room visits (P = .008) and 9.88 vs 21.80 therapy days (P = .02), respectively. These inputs plus hospital cost data were used to model costs for the United States, Germany, and the United Kingdom. For the United States, Germany, and United Kingdom, respectively, economic model estimates of total potential per patient savings were $33 338, €8467, and £5626 for negative pressure wound therapy-instillation group vs control, based on assumed number of OR visits during therapy, cost of therapy system, and length of therapy. Model results showed an overall potential cost-savings with negative pressure wound therapy-instillation vs control, based on fewer OR visits and shorter therapy duration as reported in the published systematic review and meta-analysis.

A Systematic Review of Angular Deformities in Charcot Neuroarthropathy.

Charcot neuroarthropathy of the foot and ankle is associated with periarticular deformities and progressive radiographic changes. There have been studies analyzing the radiographic angulations and deformity progression in Charcot neuroarthropathy deformity. The aim of this paper is to provide systematic review of studies that evaluate foot and ankle radiographic parameters in patients with Charcot neuroarthropathy. A multidatabase search including, medline, EMBASE, Google Scholar, Cochrane Library, Clinicaltrials.gov and reference lists of included studies, was performed from 1980 to 2020. A total of 7 articles were included that analyzed radiographic angulations in Charcot neuroarthropathy deformity. The articles could be categorized into nonoperative angulation measurements, and pre- versus postoperative angulation measurements. The presence of ulcerations and the severity of the Charcot neuroarthropathy deformity were found to result from predominantly sagittal plane deformity. The deformity initiates with medial column collapse and progresses to continual lateral column collapse. Surgical intervention resulting in immediate postoperative improvement in angular measurements, however, without beaming of both the medial and lateral column, there was recurrence of the lateral column deformity. This systematic review of articles analyzing angular deformities in Charcot neuroarthropathy patients, demonstrates the progressive sagittal plane breakdown patterns of Charcot as well as the benefits of surgical intervention.

Complications of Charcot Reconstruction in Patients With Peripheral Arterial Disease.

The primary aim was to determine the rate of complications in patients with peripheral arterial disease and diabetic Charcot neuroarthropathy who underwent osseous reconstruction. Complications included delayed healing, dehiscence, and major lower extremity amputation. A review of patients with Charcot neuroarthropathy requiring reconstruction secondary to ulceration or acute infection was performed. Descriptive analysis compared outcomes between those with and without peripheral arterial disease. Bivariate analysis and multivariate logistic regression were analyzed for delayed healing, dehiscence, and major amputation. In a cohort of 284 patients with diabetic Charcot neuroarthropathy who underwent osseous reconstruction, the rate of peripheral arterial disease was 20.8% (59/284). Bivariate analysis for delayed healing found hypertension (p = .0352), peripheral arterial disease (p = .0051), and smoking history (p = .0276) to be statistically significant factors. Delayed healing was 2.012 times more likely in the presence of peripheral arterial disease [OR 2.012 (95% CI 1.088-3.720)]. Bivariate analysis for major lower extremity amputation found renal disease (0.0003) (renal disease: ESRD and CKD) and peripheral arterial disease (0.0001) to be statistically significant factors. Major amputation was 4.414 times more likely in the presence of peripheral arterial disease [OR 4.414 (95% CI 2.087-9.334)]. Peripheral arterial disease was identified in 20.8% (59/284) of diabetic patients who underwent Charcot osseous reconstruction. Peripheral arterial disease increased the risk of delayed healing by 2.012 fold, and increased the risk of major lower extremity amputation by 4.414 fold. The rates of complications in patients with peripheral arterial disease were significantly higher than those without peripheral arterial disease who underwent osseous reconstruction.

Are the Sanders-Frykberg and Brodsky-Trepman Classifications Reliable in Diabetic Charcot Neuroarthropathy?

The purpose of this study was to assess the intra- and inter-reader reliability of the 2 Charcot neuroarthropathy classifications (Sanders-Frykberg and Brodsky-Trepman), as well as Eichenholtz staging. We hypothesized that the inter-reader reliability, with respect to these 3 classification systems, would be moderate at best. Digital radiographic images were organized in a digital slide presentation without clinical information. All 5 reviewers underwent a standard training session administered by the principal investigator, reviewing 5 cases of Charcot neuroarthropathy. Images of 55 cases of Charcot neuroarthropathy and 5 normal cases were distributed to each of the 5 physicians electronically, who independently rated all 60 cases according to the 3 classification systems. The 95% confidence interval of the intraclass correlation coefficient estimate for Sanders-Frykberg was 0.9601 to 0.9833 at week 0 and 0.9579 to 0.9814 at week 8, which can be regarded as "excellent" reliability. For Trepman-Brodsky, the 95% confidence interval of the intraclass correlation coefficient estimate was 0.8463 to 0.9327 at week 0 and 0.8129 to 0.9226 at week 8, which can be regarded as "good" to "excellent" reliability. For Eichenholtz, the 95% confidence interval of the intraclass correlation coefficient estimate was 0.6841 to 0.8640 and 0.6931 to 0.8730 at weeks 0 and 8, respectively, which can be regarded as "moderate" to "good" reliability. The classification systems of Charcot neuroarthropathy are an important tool for communication among physicians. Based on the results at our institution, the Sanders-Frykberg classification exhibited the best inter-reader performance. The Trepman-Brodsky classification exhibited good to excellent reliability as well. The intraclass correlation coefficient of the Eichenholtz classification was moderate to good.

Glove and instrument changing to prevent bacterial contamination in infected wound debridement and closure procedures: A prospective observational study.

Many surgeons use a single table of instruments for both excisional debridement and coverage/closure of infected wounds. This study investigates the effectiveness of a two-table set-up of sterile instruments, in addition to glove exchange, to reduce instrument cross-contamination during these procedures. This is a prospective, single-site, institutional review board-approved observational study of surgical debridements of infected wounds over a 17-month period. Two separate sterile surgical tables were used for each case: Table A for initial wound debridement (debridement set-up) and Table B for wound coverage/closure (clean set-up). Swabs of each table and its respective instruments were taken after debridement but prior to coverage/closure. The primary outcome of interest was bacterial growth at 48 hours. There were 72 surgical cases included in this study. Culture results of Table A demonstrated bacterial growth in 23 of 72 (32%) cases at 48 hours compared with 5of 72 (7%) from Table B (P = .001). These data suggest that there is significant bacterial contamination of surgical instruments used for debridement of infected wounds. Use of a two-table set-up reduced instrument cross-contamination by 78%, suggesting avoidable re-contamination of the wound.

Increased Risk of Nonunion and Charcot Arthropathy After Ankle Fracture in People With Diabetes.

The aim of this study was to evaluate the frequency of complications after an ankle fracture in patients with and without diabetes and to evaluate risk factors for nonunion. We conducted a retrospective study of 439 patients with ankle fractures (31.7% had diabetes) and followed them for 1 year or until the fracture healed. The fracture severity and determination of nonunion and Charcot arthropathy were determined from independent evaluation of radiographs by 2 members of the research team. Nonunion was defined as a fracture that did not heal within 6 months of the fracture. The majority of patients were women (67% in each group). The risk of complications was significantly higher in patients with diabetes compared with those without diabetes. The odds ratio (OR) and 95% confidence interval (CI) for nonunion was 6.5 (3.4 to 12.8); for Charcot arthropathy, 7.6 (2.3 to 21.0); for wounds, 1.8 (1.1 to 2.9); for infection, 2.8 (1.4 to 5.7); and for amputation, 6.6 (0.98 to 80.0). In the logistical regression analysis, 6 factors were associated with fracture nonunion: dialysis (7.7; 1.7 to 35.2), diabetes (3.3; 1.5 to 7.4), fracture severity (bi- and trimalleolar fractures) (4.9; 1.4 to 18.0), beta blockers (2.5; 1.1 to 5.4), steroids (3.1; 1.2 to 7.7), and infection (3.7; 1.2 to 11.3). The results of the study demonstrate the increased risk of complications after an ankle fracture among patients with diabetes, dialysis, or open fractures and those using steroids and beta blockers. Further work is needed to identify areas for risk reduction.

Plantar Foot Ulcer Recurrence in Neuropathic Patients Undergoing Percutaneous Tendo-Achilles Lengthening.

Equinus contracture carries 3- and 4-fold associations with diabetes and plantar foot ulceration, respectively. Percutaneous tendo-Achilles lengthening is a useful method to alleviate peak plantar pressure resulting from equinus. We aimed to evaluate the effectiveness of percutaneous tendo-Achilles lengthening and estimate the relative longevity of the approach in reducing ulcer recurrence. The medical records of patients with equinus contracture who underwent percutaneous tendo-Achilles lengthening from 2010 to 2017 were reviewed. Included patients presented with plantar ulcers and a gastroc-soleus equinus of any angle <10° of ankle dorsiflexion with the affected knee extended and flexed. Patients who received concomitant tendon lengthening procedures (including anterior tibial tendon or flexor digitorum longus) were excluded. Outcome measures included time to wound healing, time to ulcer recurrence, and development of transfer lesion. Ninety-one patients underwent percutaneous tendo-Achilles lengthening with subsequent pedal ulceration without concomitant procedures. A total of 69 (75.8%) patients had a plantar forefoot ulcer, 7 (7.7%) had midfoot ulcers, 5 (5.5%) had hindfoot ulcers, and 3 (3.3%) had ulcers in multiple locations. Seven patients received prophylactic tendo-Achilles lengthening. At a mean follow-up of 31.6 months (±26), 66 (78.6%) wounds healed at a median 12.9 weeks. A total of 29 patients (43.9%) experienced ulcer recurrence at a mean of 12 months. Twelve patients (13%) experienced a transfer lesion at a mean of 16.6 months. Tendo-Achilles lengthening can be an effective adjunctive approach to achieve wound healing and reduce long-term ulcer recurrence in patients with equinus contracture and neuropathic plantar foot ulcers. A relengthening procedure may be needed within approximately 12 months from index surgery.

Charcot Reconstruction: Outcomes in Patients With and Without Diabetes.

The objective of this study is to compare risk adjusted matched cohorts of Charcot neuroarthropathy patients who underwent osseous reconstruction with and without diabetes. The 2 groups were matched based on age, body mass index, hypertension, history of end-stage renal disease, and peripheral arterial disease. Bivariate analysis was performed for preoperative infection, location of Charcot breakdown, and post reconstruction outcomes, in patients with a minimum of 1 year follow-up period. Through bivariate analysis, presence of preoperative ulceration (p = .0499) was found to be statistically more likely in the patients with diabetes; whereas, delayed osseous union (p = .0050) and return to ambulation (p ≤ .0001) was statistically more likely in patients without diabetes. The nondiabetic Charcot patients were 17.6 folds more likely to return to ambulation (odds ratio [OR] 17.6 [95% confidence interval {CI} {3.5-87.6}]), and 16.4 folds more likely to have delayed union (OR 16.4 [95% CI {1.9-139.6)]). Subanalysis compared well-controlled diabetic and nondiabetic Charcot neuroarthropathy patients for same factors. Multivariate analysis, in the subanalysis, found return to ambulation was 15.1 times likely to occur in the nondiabetic CN cohort (OR 15.1 [95% CI 1.3-175.8]) compared to the well-controlled diabetic CN cohort.

Long Term Outcomes of Split-Thickness Skin Grafting to the Plantar Foot.

The most common consequence of neuropathy is a diabetic foot ulcer, which usually occurs on the plantar surface of the foot. Split-thickness skin grafting (STSG) has been shown in numerous studies to be an effective treatment for rapid coverage of diabetic ulcers. The purpose of this study is to retrospectively examine the outcomes of STSG to the plantar foot and determine the durability of this treatment compared to non-plantar surface STSG. This is a retrospective, single-center, institutional review board approved, case-control study of all patients who received STSG to their lower extremity for chronic ulcers from November 2013 to February 2017. Patients with ulcers on the plantar surface were considered cases, and non-plantar surface ulcers were considered controls. There were 182 patients who received STSG to the lower extremity, 52 to the plantar surface foot and 130 to non-plantar surface locations. Healing at 30 days was not significantly different between plantar and nonplantar ulcers (19% versus 28%, p = .199) but did become significant at 60, 90, and 365 days (21% versus 45%, p = .003; 33% versus 49%, p = .043; 38% versus 64%, p = .002, respectively). However, time to full healing was not significantly different between plantar and nonplantar groups (18.2 ± 19.5 versus 17.4 ± 21.6 weeks, mean ± standard deviation, p = .84). Recurrence was low for both groups (17% versus 10%, respectively), and there was no significant difference between groups (p = .17). Patients with plantar surface ulcers can achieve a durable coverage/closure of their wounds with STSG. When combined with appropriate patient selection and postoperative offloading, acceptable recurrence rates can be achieved.

Evaluation of Peripheral Perfusion in the Presence of Plantar Heel Ulcerations Status After Transmetatarsal Amputation With Achilles Tendon Lengthening.

The objective of this study is to evaluate peripheral perfusion in patients who developed plantar heel ulcerations status after transmetatarsal amputation and Achilles tendon lengthening. Peripheral perfusion was assessed via contrast angiography of the 3 crural vessels (anterior tibial, posterior tibial, and peroneal arteries), as well as intact heel blush and plantar arch. The secondary objective is to correlate the arterial flow to time to develop heel ulceration and incidence of minor and major lower-extremity amputation. Diagnostic angiography without intervention was performed on 40% of patients (4/10), and interventional angiography was performed on 60% of patients (6/10). In-line flow was present in 0% (0/10) of the peroneal arteries, 60% (6/10) of the anterior tibial arteries, and 70% (7/10) of the posterior tibial arteries. Heel angiographic contrast blush was present in 60% (6/10), and intact plantar arch was present in 60% (6/10). Patients developed heel ulcerations at a mean time of 7.6 months (range 0.7 to 41.2) postoperatively. The incidence of major lower-extremity amputation was 30% (3/10), with a mean time of 5.2 months (range 3.5 to 8.3) from time of heel wound development. No amputation occurred in 6 patients (60%). Among them, intact anterior tibial inline arterial flow was present in 3, intact posterior tibial inline arterial flow was present in 6, and heel blush was present in 5. Our results demonstrate that an open calcaneal branch of the posterior tibial artery is sufficient to heal plantar heel ulcerations to potentially increase rates of limb salvage.

Quantitative Results of Perfusion Utilising Hyperspectral Imaging on Non-diabetics and Diabetics: A Pilot Study.

There is a paucity of quantitative measures of microvascular perfusion values in the skin. Newly developed, handheld hyperspectral imaging devices identify unique spectral fingerprints of oxygenated and deoxygenated haemoglobin in the superficial microvasculature. Establishing value ranges for healthy patients without vascular complications will subsequently help standardise assessments for perfusion defects. In particular, diabetics who are prone to vascular calcifications and lower extremity wounds may benefit. A total of 73 subjects were enrolled in the study and split in two cohorts: 36 'non-diabetic' non-vascularly compromised patients and 37 'diabetic' patients with a formal diagnosis of diabetes but without history of pedal ulceration. Values of oxygenated haemoglobin (HT-Oxy) and deoxygenated haemoglobin (HT-DeOxy) from both devices are analysed.

The impact of negative-pressure wound therapy with instillation on wounds requiring operative debridement: Pilot randomised, controlled trial.

Presence of bacteria in wounds can delay healing. Addition of a regularly instilled topical solution over the wound during negative-pressure wound therapy (NPWT) may reduce bioburden levels compared with standard NPWT alone. We performed a prospective, randomised, multi-centre, post-market trial to compare effects of NPWT with instillation and dwell of polyhexamethylene biguanide solution vs NPWT without instillation therapy in wounds requiring operative debridement. Results showed a significantly greater mean decrease in total bacterial counts from time of initial surgical debridement to first dressing change in NPWT plus instillation (n = 69) subjects compared with standard NPWT (n = 63) subjects (-0.18 vs 0.6 log10 CFU/g, respectively). There was no significant difference between the groups in the primary endpoint of required inpatient operating room debridements after initial debridement. Time to readiness for wound closure/coverage, proportion of wounds closed, and incidence of wound complications were similar. NPWT subjects had 3.1 times the risk of re-hospitalisation compared with NPWT plus instillation subjects. This study provides a basis for exploring research options to understand the impact of NPWT with instillation on wound healing.