Charcot neuroarthropathy in persons with diabetes: It's time for a paradigm shift in our thinking.

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.

Outcomes of open reduction and internal fixation of calcaneus fractures: A database study comparing patients with and without diabetes.

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.

Contralateral foot temperature monitoring during Charcot immobilisation: A systematic review.

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.

Topical Wound Oxygen Therapy in the Treatment of Chronic Diabetic Foot Ulcers.

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 (pO2) 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 pO2 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.

Surgery for the diabetic foot: A key component of care.

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.

A prospective, multicentre, open-label, single-arm clinical trial for treatment of chronic complex diabetic foot wounds with exposed tendon and/or bone: positive clinical outcomes of viable cryopreserved human placental membrane.

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 cm2 , 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.

Safety and efficacy of intramuscular human placenta-derived mesenchymal stromal-like cells (cenplacel [PDA-002]) in patients who have a diabetic foot ulcer with peripheral arterial disease.

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 × 106 , 10 × 106 , 30 × 106 and 100 × 106 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.

A systematic review and meta-analysis of débridement methods for chronic diabetic foot ulcers.

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.

A systematic review and meta-analysis of off-loading methods for diabetic foot ulcers.

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.

The incidence of lower-extremity amputation and bone resection in diabetic foot ulcer patients treated with a human fibroblast-derived dermal substitute.

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.

Limb salvage using advanced technologies: a case report.

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.

Assessing placental membrane treatment efficiency in diabetic foot ulcers: Processing for retention versus lamination.

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.

Efficacy of Topical Wound Oxygen Therapy in Healing Chronic Diabetic Foot Ulcers: Systematic Review and Meta-Analysis.

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.

Ankle and hindfoot fusions: comparison of outcomes in patients with and without diabetes.

BACKGROUND: Patients with diabetes mellitus (DM) are believed to have higher complication rates when undergoing ankle and hindfoot fusions, but data is lacking. The purpose of this study was to compare the postoperative outcomes of major foot and ankle arthrodeses in patients with and without DM. Another goal was to evaluate what effect glycemic control had on the outcomes of patients with diabetes. METHODS: A retrospective review of charts from operative years 2005 to 2010 was performed. Inclusion criteria encompassed patients requiring major hindfoot and/or ankle fusion. Exclusion criteria included any patient who did not have at least 6-month followup. Seventy four patients with DM were matched with 74 non-DM patients based on age, gender, and length of surgery. Significance was set at p < 0.05 with associated 95% confidence intervals. RESULTS: The overall complication rate was found to be significantly higher in patients with DM, a history of tobacco use, and peripheral neuropathy. The postoperative infection rate was found to be significantly higher in patients with DM, poor long-term glucose control (Hgb A1c levels greater than or equal to 7%), a history of tobacco use, peripheral artery disease, and peripheral neuropathy. Our rate of noninfectious complications was found to be significantly higher in patients with DM, poor short-term glucose control (a preoperative glucose greater than 200 mg/dL), a history of tobacco use, and previous solid organ transplantation. Patients greater than or equal to 65 years of age were significantly associated with fewer overall complications and postoperative infections. CONCLUSION: This study confirmed our hypothesis that patients with DM were at increased risk for postoperative complications after foot and/or ankle arthrodesis when compared to patients without DM. A secondary finding of this study demonstrated patients with poor short- and long-term glucose control experienced more complications.

Reduced Hospitalizations and Amputations in Patients with Diabetic Foot Ulcers Treated with Cyclical Pressurized Topical Wound Oxygen Therapy: Real-World Outcomes.

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.

Surgical strategies for prevention of amputation of the diabetic foot.

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.

Surgical off-loading of the diabetic foot.

Surgical intervention for chronic deformities and ulcerations has become an important component in the management of patients with diabetes mellitus. These patients are no longer relegated to wearing cumbersome braces or footwear for deformities that might otherwise be easily corrected. Although surgical intervention in these often high-risk individuals is not without risk, the outcomes are fairly predictable when patients are properly selected and evaluated. In this brief review, we discuss the rationale and indications for diabetic foot surgery, focusing on the surgical decompression of deformities that frequently lead to foot ulcers.

Foot Angiosomes: Instructions for Use.

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.

A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study.

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.

Intra-osseous gout in a diabetic patient.

UNLABELLED: The following case is an interesting presentation of gout and its long-term affects in a diabetic individual. The patient initially presented with ankle pain and, after radiographic examination, a suspicious lytic lesion in the talus and a fracture of the medial malleolus were identified. A full workup with bone biopsy was undertaken and, although the patient did not present in the typical fashion, gout was ultimately diagnosed. Based on our experience with this patient, we recommend that gout be included in the list of differential diagnoses in diabetic patients with ankle pain and radiographic evidence of articular and bone destruction. The diagnosis and treatment of gout are addressed in this paper as well. LEVEL OF CLINICAL EVIDENCE: 4.