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Little is known regarding outcomes of talus fracture management among patients with diabetes mellitus. This study aimed to compare post-operative outcomes after open reduction and internal fixation for talus fracture in patients with complicated diabetes, uncomplicated diabetes, and patients without diabetes. We used the PearlDiver database to identify patients who underwent operative repair of talus fractures from 2009 to 2021. Complications were evaluated at 30-days, 90-days, and 1 year of surgery. As we performed multiple separate analyses, to minimize the risk of type 1 error we employed the Bonferroni correction for statistical significance (p< 0.017). The PearlDiver identified 5,232 patients with talus fracture that underwent open reduction internal fixation. Stratified by diabetes status, the "complicated diabetes," "uncomplicated diabetes," and "no diabetes" groups contained 223, 418, and 4591 patients, respectively. Reoperation, acute kidney injury, and myocardial infarction were increased among diabetes patients compared to non-diabetes patients, irrespective of diabetes severity within 3 months of surgery. Furthermore, patients with complicated diabetes were more likely to develop sepsis and wound disruption compared to their non-diabetes counterparts within 3 months. While not statistically significant, complicated diabetes patients were diagnosed with talar non-union at higher rates compared with non-diabetes patients. Further analysis may reveal a clinically significant discrepancy in non-union between these groups. Complicated diabetes is associated with significantly higher risk of multiple adverse events following talus fracture repair., (Copyright © 2024 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Diabetic foot ulcers (DFUs) are a severe complication for diabetic patients, significantly impacting patient quality of life and healthcare system efficiency. Traditional standard of care (SOC) treatments are inadequate for many patients, necessitating the use of advanced wound care products, such as human placental membranes. We studied a real-world population of large, hard-to-heal and complicated wounds, otherwise under-studied in the wound care literature. To this end, we conducted a retrospective cohort analysis to compare the effectiveness of a human placental amnion/chorion membrane product using retention-based processing (RE-AC) and SOC in managing chronic DFUs. During the study period of September 2021 through April 2024, we collected retrospective observational data from electronic health records of 21 patients treated with RE-AC at three outpatient wound care centres. Additionally, 21 control SOC patients were matched from a wound registry using Coarsened Exact Matching. Patients were categorized into two cohorts based on whether they received RE-AC or SOC. Key metrics included wound size progression and wound closure. The analysis employed Bayesian regression and Hurdle Gamma Analysis of Covariance models. Despite their rather large size (average of 13.8 cm 2 ), our results indicated that RE-AC achieved almost a 10% higher expected wound closure rate compared to SOC at 12 weeks (8.53% [credible interval: 5.60%-10.7%]). Further, for wounds that did not close, RE-AC resulted in a 93.6% (credible interval: 147.7%-41.6) improvement in expected Percent Area Reduction over the SOC group at 12 weeks. We noted that on average, SOC wounds stalled or grew larger. In terms of a risk ratio comparing the study group with SOC, we found a 52% benefit in the RE-AC group (RR = 1.52). The findings suggest that even with larger DFUs, R-AC is superior to SOC for wound closure and expected Percent Area Reduction by 12 weeks. This benefit likely leads to reduced treatment costs, optimized resource utilization and improved outcomes in the DFU patient population; ultimately resulting in improved patient care., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Treatment of calcaneal fractures in patients with diabetes mellitus (DM) is challenging. The purpose of this study was to compare post-operative outcomes after open reduction and internal fixation (ORIF) for calcaneus fracture in patients with complicated DM, uncomplicated DM, and patients without DM. A commercially available de-identified database was queried for all calcaneus fracture diagnoses undergoing ORIF from 2010 to 2021. The patients were separated into three groups for analysis: patients without DM (10,951, 82.6%), uncomplicated DM (1,500, 11.3%) and complicated DM (802, 6.1%). At 1 year, post-operative adverse events were assessed among the three groups. The odds of adverse event(s) for each group were compared between the three groups with and without characteristic matching. In the unmatched cohorts, patients with complicated DM, when compared with patients without DM and patients with uncomplicated DM, had significantly higher rates of all adverse events with exception of DVT. Rates of CNA were significantly higher in patients with complicated DM compared with no DM (OR 107.7 (CI 24.83-467.6) p < 0.0001) and uncomplicated DM (OR 44.26 (CI 3.86-507.93) p = 0.0002). After matching, non-union, AKI, sepsis, surgical site infection, and wound disruption were higher in patients with complicated DM compared with patients without DM. There were no significant differences in the three groups with regard to reoperation, DVT, MI, pneumonia, or below the knee amputation. Patients with DM who underwent ORIF for calcaneus fracture experienced higher rates of post-operative adverse events compared with those patients without DM., (© 2024 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Background: Diabetic foot ulcers are a severe complication in diabetic patients, significantly impact healthcare systems and patient quality of life, often leading to hospitalization and amputation. Traditional Standard of Care (SOC) treatments are inadequate for many patients, necessitating advanced wound care products (AWCPs) like human placental membranes. This study conducts a retrospective analysis to compare the effectiveness of two human placental membrane products, retention-processed amnion chorion (RE-AC) and lamination-processed amnion chorion (L-AC) in managing chronic diabetic foot ulcers (DFUs)., Methods: The study collected retrospective observational data from electronic health records (EHRs) of patients treated for DFU at three outpatient wound care centers. Patients were categorized into two cohorts based on the treatment received. Key metrics included wound size progression and the number of product applications. The analysis employed Bayesian estimation, utilizing an analysis of covariance model with a Hurdle Gamma likelihood., Results: We found that RE-AC achieved a marginally higher expected Percent Area Reduction (xPAR) in DFUs compared to L-AC at 12 weeks (67.3% vs. 52.6%). RE-AC also required fewer applications, suggesting greater efficiency in general wound closure. Probability of full wound closure was similar in both groups (0.738 vs 0.740 in RE-AC and L-AC, respectively)., Conclusion: The findings suggest that while L-AC might be slightly more effective in complete ulcer healing, RE-AC offers overall better treatment efficiency, especially in reducing the frequency of applications. This efficiency can lead to improved patient comfort, reduced treatment costs, and optimized resource utilization in healthcare settings., Competing Interests: RGF and ZT received no direct funding other than support in the preparation of this manuscript. Neither RGF nor ZT have any formal relationship, past or present, with BioStem Technologies. Both authors have read and approved the final version of the manuscript. RGF had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

The aim of this paper is to review the recent literature regarding the epidemiology and surgical management of Charcot neuro-osteoarthropathy (CNO). We propose that a fundamental change in the approach and assumptions regarding the historical treatment of active CNO should be considered. Although the true incidence and prevalence of CNO in the US population with diabetes are not known, we estimated the incidence to be 27,602 per year and the prevalence to be 208,880 persons. In persons with diabetes, the incidence of CNO is higher than that of prostate, lung, kidney, and thyroid cancer, and in the entire US population, the incidence of CNO is higher than that of multiple myeloma, soft tissue sarcoma, and primary bone sarcoma. In persons with diabetes, the incidence of CNO is higher than fractures of the femoral shaft, distal femur, tibia, talus, calcaneus and Lisfranc ligament injuries. Surgical techniques have evolved over the past half century, and surgery is the standard for treating displaced fractures and intra-articular injuries. Since CNO is a fracture, dislocation, or fracture dislocation in patients with neuropathy, why do we treat CNO differently? Elsewhere in the skeleton displaced osseous and ligament injuries are treated surgically. Based on the information presented in this manuscript, we suggest that it is time for a paradigm shift in the treatment of persons with CNO. While uncommon, CNO in persons with diabetes is not rare. Given the advances in surgical techniques, surgical intervention should be considered earlier in persons with CNO who are at risk for developing deformity related foot ulceration., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Aims: Contralateral temperature difference (CTD) is a frequently used marker of healing in Charcot neuro-osteoarthropathy (CN). We aimed to determine whether there is a consistent approach to CTD measurement during healing and the decision-making process around cessation of immobilisation., Materials and Methods: Medline, Scopus, and Web of Science were searched until February 2022 for peer-reviewed studies using keywords, including (('arthropathy' OR 'osteoarthropathy' OR 'osteopathy' OR 'neuroarthropathy') AND 'Charcot' AND ('temperature')), which returned 789 results excluding duplicates. Included studies monitored CTD in those with active CN to (i) assess the healing process and (ii) assist in determining the transition from immobilisation., Results: Thirty four studies in total (n = 677 participants) were shortlisted and 19 were included after full paper review. Average CTD at presentation varied from 1.6 to 8.0°C with insufficient data to determine if CTD was proportional to severity of Charcot. Evidence of a relationship between CTD and radiographic or scintigraphy-based markers of healing varied depending on the methodology employed. Threshold CTD for the cessation of immobilisation ranged from <1°C to <2°C. Most frequently it was <2°C sustained for 2-3 visits. Temperature was monitored typically every 2-6 weeks using handheld thermometry at CN site(s) after resting the feet for 15 min. Device type, accuracy/reliability, and ambient temperature were rarely reported., Conclusions: Further research on CTD and radiographic and radiotracer markers is needed involving larger cohorts. Standardisation in reporting of thermometry device type, accuracy and reliability, foot resting times, and ambient temperature controls is essential to facilitate the comparison of studies, meta-analysis, and evaluation of different immobilisation interventions., (© 2023 John Wiley & Sons Ltd.)

Objective: To conduct a systematic review and meta-analysis of recently published randomized controlled trials (RCTs) that employed the use of topical oxygen therapy (TOT) as an adjunct therapy in the treatment of Wagner 1 and 2 diabetic foot ulcers. Approach: Following a literature search of eligible studies from 2010 onward, four RCTs were included. Studies were analyzed for patient and wound characteristics, outcomes, risk of bias, and quality of the evidence assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. A random-effects meta-analysis for complete wound healing was carried out due to statistical heterogeneity of included studies. Results: Risk of bias judgment (RoB2 analysis) resulted in one low-risk trial and three trials with some risk. One study was determined to be the origin of the statistical heterogeneity. Pooled results showed statistical significance with a risk ratio (RR) of 1.59 (95% confidence interval [CI]: 1.07-2.37; p  = 0.021). Sensitivity analysis, based on imputed values for missing outcomes, demonstrated that both the RR and 95% CIs changed little. The GRADE ratings for each domain were as follows: (a) risk of bias: moderate (3); (b) imprecision: moderate (2), high (1); (c) inconsistency: low (2), high (1); (d) indirectness: moderate (2), high (1); and (e) publication bias: moderate (1), high (2). Overall, the evidence was moderate. Innovation: Our study shows that TOT is a viable diabetic foot ulcer therapy. Conclusions: These data support the use of TOT for the treatment of chronic Wagner 1 or 2 diabetic foot ulcers in the absence of infection and ischemia.

Background: This study sought to examine the real-world impact of multimodality cyclical-pressure topical wound oxygen therapy (TWO2) on hospitalizations and amputations in patients with diabetic foot ulcer (DFU) compared with patients without TWO2. Methods: We conducted a retrospective review of deidentified patient medical records at 2 U.S. Veterans Affairs hospitals between January 2012 and January 2020. DFU patients were assigned to TWO2 or NO TWO2 cohorts based on their treatment records. Patients received appropriate standard of care and may have received other advanced wound treatments, including skin substitutes, negative pressure wound therapy, and growth factors. Primary study outcomes were patients requiring hospitalization and/or amputation within 360 days of initial wound documentation. Findings: Among unmatched cohorts of 202 patients with DFU (91 TWO2, 111 NO TWO2), 6.6% and 12.1% of TWO2 patients had hospitalizations and amputations, respectively, compared with 54.1% and 41.4% of NO TWO2 patients within 360 days ( p  < 0.0001, p  < 0.0001), representing 88% and 71% reductions. Among propensity score-matched cohorts of 140 DFU patients (70 TWO2, 70 NO TWO2), compared with NO TWO2, 82% fewer TWO2 patients were hospitalized (7.1% vs. 40.0%, p  < 0.0001) and 73% fewer TWO2 patients had amputations (8.6% vs. 31.4%, p  = 0.0007). Logistic regression among matched cohorts demonstrated nearly ninefold and fivefold higher risk of hospitalization and amputation, respectively, for NO TWO2 versus TWO2. Interpretation: This retrospective cohort study demonstrates that treating patients with DFU with TWO2 is associated with significant reductions in hospitalizations and amputations in the real-world setting.

Oxygen is a critical component of many biological processes and is essential for wound healing. Chronic wounds are typically characterized as being hypoxic in that the partial pressure of oxygen (pO 2 ) in the center of the wound is often below a critical threshold necessary to fully support those enzymatic processes necessary for tissue repair. Providing supplemental oxygen can effectively raise pO 2 levels to better optimize functioning of these essential enzymes. While hyperbaric oxygen therapy has been well studied in this regard, comparative clinical studies have fallen short of providing clear evidence in support of this modality for healing chronic diabetic foot ulcers (DFU). Topical oxygen therapy (TOT) has been in clinical use for over 50 years with encouraging pre-clinical and clinical studies that have shown improved healing rates when compared to standard care. Nonetheless, TOT has heretofore been discounted as an unproven wound healing modality without theoretical or clinical evidence to support its use. This review shall provide a brief summary of the role of oxygen in wound healing and, specifically, discuss the different types of topical oxygen devices and associated studies that have convincingly shown their efficacy in healing chronic DFUs. The time has come for topical oxygen therapy to be embraced as a proven adjunctive modality in this regard.

Prevention of amputation has become a key objective of clinicians providing care to patients with high-risk diabetic foot problems. In this regard, the multidisciplinary diabetic foot team (MDFT) has been embraced as the most effective way to manage patients with foot ulcers, infections, and Charcot feet. Importantly, such specialized teams have also integrated various surgical specialties to enable more expedient management of these often complex conditions. Experienced diabetic foot surgeons over the last three or four decades have contributed much to this discipline, whereby foot-sparing reconstructive procedures or minor amputations have become fundamental strategies for limb preservation teams. Central to limb salvage, of course, is the recognition of underlying vascular insufficiency and the importance of prompt (endo)vascular intervention. Restoration of adequate perfusion is essential to allow the podiatric, orthopaedic, or plastic surgeon to perform indicated functional reconstructive or minor amputation procedures. This evidence-based overview discusses the various indications and surgical principles inherent in modern concepts aimed at preventing amputation in the high-risk diabetic foot., Competing Interests: All authors report no conflicts of interest in the writing of this manuscript., (© 2021 Delhi Orthopedic Association. All rights reserved.)

In the last 15 years an abundance of literature has demonstrated that angiosome-targeted revascularization, either endovascular or open, can lead to better clinical results in patients with chronic limb-threatening ischemia. According to this literature, the angiosome concept should guide our treatment strategy in every chronic limb-threatening ischemia patient. However, in our daily practice, its application is often difficult or impossible. Most foot wounds spread over multiple angiosomes and, moreover, the value of an angiosome-guided revascularization approach can vary according to vascular anatomy, collateral vessel network, type of revascularization, and wound. The aim of this article is to explore values and limits of the angiosome concept, and to propose some "instructions for use" regarding its application in our daily practice.

Surgery for acute and chronic diabetic foot problems has long been an integral component of care. While partial foot amputations remain as important diabetic limb-salvaging operations, foot-sparing reconstructive procedures have become equally important strategies to preserve the functional anatomy of the foot while addressing infection, chronic deformities, and ulcerations. A classification of types of diabetic foot surgery is discussed in accordance with the soft tissue status and acuity of the presenting foot problem. This brief overview from the Association for Diabetic Foot Surgeons describes common conditions best treated by surgical interventions, as well as specific indications. While techniques and indications continue to evolve, effective surgical management of the diabetic foot remains an integral component of care as well as for the prevention of recurrent ulceration., (© 2019 John Wiley & Sons, Ltd.)

Objective: Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone., Research Design and Methods: Patients with diabetes and chronic DFUs were randomized (double-blind) to either active TWO2 therapy or sham control therapy-both in addition to optimal SOC. The primary outcome was the percentage of ulcers in each group achieving 100% healing at 12 weeks. A group sequential design was used for the study with three predetermined analyses and hard stopping rules once 73, 146, and ultimately 220 patients completed the 12-week treatment phase., Results: At the first analysis point, the active TWO2 arm was found to be superior to the sham arm, with a closure rate of 41.7% compared with 13.5%. This difference in outcome produced an odds ratio (OR) of 4.57 (97.8% CI 1.19, 17.57), P = 0.010. After adjustment for University of Texas Classification (UTC) ulcer grade, the OR increased to 6.00 (97.8% CI 1.44, 24.93), P = 0.004. Cox proportional hazards modeling, also after adjustment for UTC grade, demonstrated >4.5 times the likelihood to heal DFUs over 12 weeks compared with the sham arm with a hazard ratio of 4.66 (97.8% CI 1.36, 15.98), P = 0.004. At 12 months postenrollment, 56% of active arm ulcers were closed compared with 27% of the sham arm ulcers ( P = 0.013)., Conclusions: This sham-controlled, double-blind randomized controlled trial demonstrates that, at both 12 weeks and 12 months, adjunctive cyclical pressurized TWO2 therapy was superior in healing chronic DFUs compared with optimal SOC alone., (© 2019 by the American Diabetes Association.)

Background : Foot complications such as ulceration and neuropathy are common complications of diabetes mellitus (DM). Previous reports have demonstrated a possible increased risk of these complications in diabetic patients with low levels of serum vitamin D. Objectctive : The purpose of this study is to compare serum vitamin D levels in diabetic patients with and without Charcot neuroarthropathy (CN), peripheral arterial disease (PAD), infection (DFI), ulceration (DFU), and peripheral neuropathy (DPN). Design : A retrospective chart review of all patients undergoing foot and ankle surgery with a history of DM over a 13 month period was performed. From this cohort, fifty subjects with CN were matched with 50 without CN and preoperative lab values were compared. A secondary evaluation was performed on the subjects' other comorbidities including PAD, DFI, DFU, and DPN. Results : Seventy-eight percent of our patients had vitamin D deficiency or insufficiency. Preoperative serum vitamin D levels were not significantly different between diabetic patients with and without CN (p = 0.55). Diabetic patients with PAD (p = 0.03), DFI (p = 0.0006), and DFU (p = 0.04) were all found to have significantly lower serum vitamin D levels than diabetic patients without these complications. Lower levels of serum albumin and higher serum creatinine were also noted with subjects with PAD, DFI, DPN, and DFU. While seasonal serum vitamin D level fluctuation was noted, this difference did not reach statistical significance with the numbers available. Conclusion : We found various lower extremity complications to be associated with low serum vitamin D including PAD, DFI, and DFU. While other studies have questioned the role of vitamin D and CN, we were unable to identify any significant difference between diabetic patients with and without Charcot neuroarthropathy. Level of evidence : Level 2.

The objective of this study was to examine the safety of cenplacel (PDA-002) in patients with peripheral arterial disease (PAD) and a diabetic foot ulcer (DFU). Cenplacel is a mesenchymal-like cell population derived from full-term human placenta. This phase 1, dose-escalation study investigated cenplacel in diabetic patients with chronic DFUs (Wagner grade 1 or grade 2) and PAD [ankle-brachial index (ABI) >0·5 and ≤0·9], enrolled sequentially into each of four dose cohorts (3 × 10 6 , 10 × 10 6 , 30 × 10 6 and 100 × 10 6 cells; administered intramuscularly on study days 1 and 8 in combination with standard of care). Overall, cenplacel was well tolerated in all 15 patients in the study. Before enrollment, nine patients had an ulcer for ≥6 months and 11 had an ABI of 0·7-0·85. No patient met dose-limiting toxicity criteria and no treatment-related serious adverse events were reported. There was preliminary evidence of ulcer healing in seven patients (five complete; two partial) within 3 months of cenplacel treatment, and circulating endothelial cell levels (a biomarker of vascular injury in PAD) were decreased within 1 month. Cenplacel was generally safe and well tolerated in patients with chronic DFUs and PAD. Outcomes from this study informed the doses, endpoints, biomarkers and patient population for an ongoing phase 2 trial., (© 2017 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: We conducted a multicenter evaluation of a novel remote foot-temperature monitoring system to characterize its accuracy for predicting impending diabetic foot ulcers (DFU) in a cohort of patients with diabetes with previously healed DFU., Research Design and Methods: We enrolled 132 participants with diabetes and prior DFU in this 34-week cohort study to evaluate a remote foot-temperature monitoring system (ClinicalTrials.gov Identifier NCT02647346). The study device was a wireless daily-use thermometric foot mat to assess plantar temperature asymmetries. The primary outcome of interest was development of nonacute plantar DFU, and the primary efficacy analysis was the accuracy of the study device for predicting the occurrence of DFU over several temperature asymmetry thresholds., Results: Of the 129 participants who contributed evaluable data to the study, a total of 37 (28.7%) presented with 53 DFU (0.62 DFU/participant/year). At an asymmetry of 2.22°C, the standard threshold used in previous studies, the system correctly identified 97% of observed DFU, with an average lead time of 37 days and a false-positive rate of 57%. Increasing the temperature threshold to 3.20°C decreased sensitivity to 70% but similarly reduced the false-positive rate to 32% with approximately the same lead time of 35 days. Approximately 86% of the cohort used the system at least 3 days a week on average over the study., Conclusions: Given the encouraging study results and the significant burden of DFU, use of this mat may result in significant reductions in morbidity, mortality, and resource utilization., (© 2017 by the American Diabetes Association.)

Complex diabetic foot ulcers (DFUs) with exposed tendon or bone remain a challenge. They are more susceptible to complications such as infection and amputation and require treatments that promote rapid development of granulation tissue and, ultimately, reepithelialisation. The clinical effectiveness of viable cryopreserved human placental membrane (vCHPM) for DFUs has been established in a level 1 trial. However, complex wounds with exposed deeper structures are typically excluded from randomised controlled clinical trials despite being common in clinical practice. We report the results of a prospective, multicentre, open-label, single-arm clinical trial to establish clinical outcomes when vCHPM is applied weekly to complex DFUs with exposed deep structures. Patients with type 1 or type 2 diabetes and a complex DFU extending through the dermis with evidence of exposed muscle, tendon, fascia, bone and/or joint capsule were eligible for inclusion. Of the 31 patients enrolled, 27 completed the study. The mean wound area was 14·6 cm 2 , and mean duration was 7·5 months. For patients completing the protocol, the primary endpoint, 100% wound granulation by week 16, was met by 96·3% of patients in a mean of 6·8 weeks. Complete wound closure occurred in 59·3% (mean 9·1 weeks). The 4-week percent area reduction was 54·3%. There were no product-related adverse events. Four patients (13%) withdrew, two (6·5%) for non-compliance and two (6·5%) for surgical intervention., (© 2016 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: Chronic hard-to-heal wounds generate high costs and resource use in western health systems and are the focus of intense efforts to improve healing outcomes. Here, we introduce a novel native collagen (90 %):alginate (10 %) wound dressing and compare it with the established oxidised dressings Method: Matrices were analysed by atomic force microscopy (AMF), scanning electron microscopy (SEM), and immunoelectron microscopy for collagen types I, III and V. Viability assays were performed with NIH-3T3 fibroblasts. Matrix metalloproteinase (MMP) binding was analysed, and the effect of the wound dressings on platelet-derived growth factor B homodimer (PDGF-BB) was investigated., Results: Unlike oxidised regenerated cellulose (ORC)/collagen matrix and ovine forestomach matrix (OFM), the three-dimensional structure of the native collagen matrix (NCM) was found to be analogous to intact, native, dermal collagen. Fibroblasts seeded on the NCM showed exponential growth whereas in ORC/collagen matrix or OFM, very low rates of proliferation were observed after 7 days. MMP sequestration was effective and significant in the NCM. In addition, the NCM was able to significantly stabilise PDGF-BB in vitro., Conclusion: We hypothesise that the observed microstructure of the NCM allows for an effective binding of MMPs and a stabilisation and protection of growth factors and also promotes the ingrowth of dermal fibroblasts, potentially supporting the re commencement of healing in previously recalcitrant wounds., Declaration of Interest: This work was supported by BSN Medical, Hamburg, Germany.

Objective: The objective of this prospective, multicentre clinical study is to assess the application of MatriStem MicroMatrix (MSMM) and MatriStem Wound Matrix (MSWM) (porcine urinary bladder derived extracellular matrix) compared with Dermagraft (DG) (human fibroblast-derived dermal substitute) for the management of non-healing diabetic foot ulcers (DFUs)., Method: A randomised, multicentre study was conducted at thirteen centers throughout the US. It was designed to evaluate the incidence of ulcer closure, rate of ulcer healing, wound characteristics, patient quality of life, cost-effectiveness, and recurrence. Those subjects whose DFUs decreased in size by ≤30% or increased by ≤50% during the standard of care (SOC) phase were randomised into the treatment phase of the study. The study evaluated complete wound closure by eight weeks with weekly device application. A two-week post treatment SOC phase followed the treatment phase for any wounds that did not heal by the end of eight weeks, and wound closure was also evaluated at the end of that period. Ulcer recurrence at 6 months post-treatment was evaluated in the subjects that showed wound healing by the end of the post-treatment SOC phase. Standard adjunctive therapy, including debridement, saline irrigation and foot off-loading, was provided to both arms during the four-week screening period, after which eligible subjects were randomised in a 1:1 ratio, to either the MatriStem (MS) or DG treatment arm. This study was developed to evaluate the hypothesis that the wound outcomes observed after wound management with MS were non-inferior to those of DG after eight weeks. The authors present the planned interim results of this study after one half of the projected enrolment was completed., Results: There were 95 subjects consented and entered into the SOC four-week screening phase of the trial and 56 were randomised into the treatment phase. At the planned interim analysis, there was a significantly lower cost per subject and significant improvement in patient quality of life for the subjects treated with MS compared with those managed with DG. However, there was not a statistically significant difference found during the analysis of the interim data between the two study groups for rate of wound healing or number of subjects with complete wound closure., Conclusion: The data from this interim analysis show that MSMM and MSWM provide results for healing DFUs that are similar to the results obtained for DG at a significant quality of life and economic advantage., Declaration of Interest: The opinions expressed are those of the authors and not necessarily those of the Department of Veterans Affairs or the United States Government. T.W. Gilbert is employed as the Chief Science Officer and is a stockholder in ACell, Inc., which commercializes MatriStem Wound Matrix and MicroMatrix. None of the other authors have a conflict of interest to declare.

Background: Several methods of débridement of diabetic foot ulcers are currently used. The relative efficacy of these methods is not well established., Methods: This systematic review and meta-analysis was conducted to find the best available evidence for the effect of débridement on diabetic foot wound outcomes. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011 for randomized controlled studies (RCTs) and observational comparative studies., Results: We identified 11 RCTs and three nonrandomized studies reporting on 800 patients. The risk of bias was moderate overall. Meta-analysis of three RCTs showed that autolytic débridement significantly increased the healing rate (relative risk [RR], 1.89; 95% confidence interval [CI] 1.35-2.64). Meta-analysis of four studies (one RCT) showed that larval débridement reduced amputation (RR, 0.43; 95% CI, 0.21-0.88) but did not increase complete healing (RR, 1.27; 95% CI, 0.84-1.91). Surgical débridement was associated with shorter healing time compared with conventional wound care (one RCT). Insufficient evidence was found for comparisons between autolytic and larval débridement (one RCT), between ultrasound-guided and surgical débridement, and between hydrosurgical and surgical débridement., Conclusions: The available literature supports the efficacy of several débridement methods, including surgical, autolytic, and larval débridement. Comparative effectiveness evidence between these methods and supportive evidence for other methods is of low quality due to methodologic limitations and imprecision. Hence, the choice of débridement method at the present time should be based on the available expertise, patient preferences, the clinical context and cost., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Increased plantar foot pressure is one of several key factors that lead to diabetic foot ulcers. Multiple methods have been proposed to relieve this pressure and thus enhance wound healing and potentially prevent relapse. We aimed in this systematic review to find the best available evidence for off-loading methods., Methods: We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest included complete wound healing, time to complete wound healing, amputation, infection, and relapse rates., Results: We identified 19 interventional studies, of which 13 were randomized controlled trials, including data from 1605 patients with diabetic foot ulcers using an off-loading method. The risk of bias in the included studies was moderate. This analysis demonstrated improved wound healing with total contact casting over removable cast walker, therapeutic shoes, and conventional therapy. There was no advantage of irremovable cast walkers over total contact casting. There was improved healing with half-shoe compared with conventional wound care. Therapeutic shoes and insoles reduced relapse rate in comparison with regular footwear. Data were sparse regarding other off-loading methods., Conclusions: Although based on low-quality evidence (ie, evidence warranting lower certainty), benefits are demonstrated for use of total contact casting and irremovable cast walkers in the treatment of diabetic foot ulcers. Reduced relapse rate is demonstrated with various therapeutic shoes and insoles in comparison with regular footwear., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Early diagnosis and a multidisciplinary team approach to managing comorbidities are essential in treating foot ulcerations., Competing Interests: Author disclosures Dr. Frykberg has received research support from Osiris Therapeutics, Advanced BioHealing, AOTI, KCI, Smith & Nephew, Tissue Regenix, and ACell. All other authors report no actual or potential conflicts of interest with regard to this article.

Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients. Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing. Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based. Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use.

Linezolid, a mild monoamine oxidase inhibitor, is a commonly used antibiotic drug for the treatment of complicated skin and skin structure infections, including diabetic foot infections. Use of linezolid has been associated with serotonin syndrome, a potentially life-threatening condition typically caused by the combination of two or more medications with serotonergic properties, due to increased serotonin release. The goals of this article are to highlight the risk factors associated with the development of serotonin syndrome related to the use of linezolid and to aid in its prevention and early diagnosis. In this case series we report on two hospitalized patients who, while being treated with linezolid for pedal infections, developed serotonin syndrome. Both individuals were also undergoing treatment with at least one serotonergic agent for depression and had received this medication within 2 weeks of starting the antibiotic drug therapy. In these individuals, we noted agitation, confusion, tremors, and tachycardia within a few days of initiation of linezolid therapy. Owing to the risk of serotonin toxicity, care should be taken when prescribing linezolid in conjunction with any other serotonergic agent. Although serotonin syndrome is an infrequent complication, it can be potentially life threatening. Therefore, risks and benefits of therapy should be weighed before use.

Patients with severe acute and chronic lower extremity wounds often present a significant challenge in terms of limb salvage. In addition to control of infection, assuring adequate perfusion and providing standard wound care, advanced modalities are often required to facilitate final wound closure. We herein present a case study on a diabetic patient with gangrene and necrotising soft-tissue infection who underwent a forefoot pedal amputation to control the sepsis. Despite his non invasive vascular studies demonstrating poor healing potential at this level, he was not deemed suitable for revascularisation by our vascular surgeons and ankle-level amputation was recommended. Nonetheless, over a 5-month period using multiple advanced wound care therapies, wound closure was ultimately achieved., (Published 2013. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: Diabetic foot ulcers (DFUs) are frequently recalcitrant and at risk for infection, which may lead to lower-extremity amputation or bone resection. Reporting the incidence of amputations/bone resections may shed light on the relationship of ulcer healing to serious complications. This study aimed to evaluate the incidence of amputations/bone resections in a randomized controlled trial comparing human fibroblast-derived dermal substitute plus conventional care with conventional care alone for the treatment of DFUs., Design: Ulcer-related amputation/bone resection data were extracted from data on all adverse events reported for the intent-to-treat population (N = 314), and amputations were categorized by type: below the knee, Syme, Chopart, transmetatarsal, ray, toe, or partial toe. Data were analyzed retrospectively for the incidence of amputation/bone resection by treatment., Setting: Randomized controlled trial., Patients: Patients with full-thickness DFUs greater than 6 weeks' duration., Interventions: Standard wound care plus human fibroblast-derived dermal substitute versus standard wound care alone., Main Results: The incidence of amputation/bone resection in the study was 8.9% (28/314) overall, 5.5% (9/163) for patients receiving human fibroblast-derived dermal substitute, and 12.6% (19/151) for patients receiving conventional care (P = .031). Of the 28 cases of amputation/bone resection, 27 were preceded by ulcer-related infection., Conclusion: There were significantly fewer amputations/bone resections in patients who received human fibroblast-derived dermal substitute versus conventional care, likely related to the lower incidence of infection adverse events observed in the human fibroblast-derived dermal substitute treatment group.