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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.)

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.

Background: There are no conclusive data to support the contention that diabetic patients have an increased frequency of ankle equinus compared with their nondiabetic counterparts. Additionally, a presumed contributing cause of foot ulceration is ankle joint equinus. Therefore, we sought to determine whether persons with diabetes have a higher prevalence of ankle joint equinus than do nondiabetic persons., Methods: A prospective pilot survey of 102 outpatients (43 diabetic and 59 nondiabetic) was conducted. Demographic and historical data were obtained. Each patient underwent a standard lower-extremity examination, including the use of a biplane goniometer to measure ankle joint range of motion., Results: Equinus, defined as ankle dorsiflexion measured at 0° or less, was found in 24.5% of the overall population. In the diabetes cohort, 16 of 43 patients (37.2%) were affected compared with 9 of 59 nondiabetic participants (15.3%) (P = .011). There was a threefold risk of equinus in the diabetic population (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.28-8.44; P < .013). The equinus group had a history of ulceration in 52.0% compared with 20.8% of the nonequinus group (P = .003). Equinus, therefore, imparted a fourfold risk of ulceration (OR, 4.13; 95% CI, 1.58-10.77; P < .004). We also found a 2.8 times risk of equinus in patients with peripheral neuropathy (OR, 2.8; 95% CI, 1.11-7.09; P < .029)., Conclusions: Equinus may be more prevalent in diabetic patients than previously reported. Although we cannot prove causality, we found a significant association between equinus and ulceration.

Objective: This prospective study was designed to evaluate the rate of surgical site infection (SSI) after foot and ankle surgery in patients with and without diabetes., Research Design and Methods: The study prospectively evaluated 1,465 consecutive foot and ankle surgical cases performed by a single surgeon., Results: The overall SSI rate in this study was 3.5%, with significantly more infections occurring in individuals with diabetes than in those without (9.5 vs. 2.4%, P < 0.001). Peripheral neuropathy, Charcot neuroarthropathy, current or past smoking, and increasing length of surgery were significantly associated with SSI on multivariate analysis., Conclusions: This study demonstrates significant associations between the development of SSI and chronic complications of diabetes. We confirm previous findings that it is peripheral neuropathy and not diabetes itself that most strongly determines the development of postoperative infections in these surgical patients.

Background: Patients with diabetes mellitus may be at increased risk for infection following foot and ankle surgery. This study aimed to determine whether patients with a diagnosis of diabetes mellitus have an increased rate of infection following foot and ankle surgery compared with a cohort of patients without diabetes. Furthermore, our study sought to demonstrate whether patients with complicated diabetes are at greater risk of postoperative wound infection than are patients with uncomplicated diabetes or patients without diabetes., Methods: We conducted a retrospective review of the charts of 1000 patients who had orthopaedic foot and ankle surgery. The following data were extracted: patient age, sex, history of diabetes mellitus, development of postoperative infection, severity of infection, inpatient or outpatient surgery, use of internal or external fixation, tobacco use, history of organ transplantation, history of rheumatoid arthritis, length of surgery, follow-up time in weeks, and comorbid conditions., Results: The overall infection rate in this study was 4.8%. Fifty-two percent of all infections occurred in our diabetic study group, which represented only 19% of the patient population. Postoperative infections occurred in significantly more persons with diabetes (13.2%) than in those without diabetes (2.8%). Diabetic patients were five times more likely to experience a severe infection requiring hospitalization compared with patients without diabetes. After removing the patients with neuropathy from the analysis, there was no longer a significant association between diabetes and infection. The presence of complicated diabetes increased the risk of postoperative infection by a factor of ten compared with the risk for patients without diabetes and by a factor of six compared with the risk for patients with uncomplicated diabetes. We did not identify a significantly increased risk of infection in patients with uncomplicated diabetes compared with that in patients without diabetes., Conclusions: Patients with diabetes mellitus are at increased risk of severe infection compared with those without diabetes. Patients with uncomplicated diabetes did not have an increased risk of postoperative infection compared with patients without diabetes, whereas patients with complicated diabetes had a significantly higher rate of postoperative infection.

Objective: The purpose of this study was to compare mortality risks of patients with Charcot arthropathy with those of patients with diabetic foot ulcer and those of patients with diabetes alone (no ulcer or Charcot arthropathy)., Research Design and Methods: A retrospective cohort of 1,050 patients with incident Charcot arthropathy in 2003 in a large health care system was compared with patients with foot ulcer and those with diabetes alone. Mortality was determined during a 5-year follow-up period. Patients with Charcot arthropathy were matched to individuals in the other two groups using propensity score matching based on patient age, sex, race, marital status, diabetes duration, and diabetes control., Results: During follow-up, 28.0% of the sample died; 18.8% with diabetes alone and 37.0% with foot ulcer died compared with 28.3% with Charcot arthropathy. Multivariable Cox regression shows that, compared with Charcot arthropathy, foot ulcer was associated with 35% higher mortality risk (hazard ratio 1.35 [95% CI 1.18-1.54]) and diabetes alone with 23% lower risk (0.77 [0.66-0.90]). Of the patients with Charcot arthropathy, 63% experienced foot ulceration before or after the onset of the Charcot arthropathy. Stratified analyses suggest that Charcot arthropathy is associated with a significantly increased mortality risk independent of foot ulcer and other comorbidities., Conclusions: Charcot arthropathy was significantly associated with higher mortality risk than diabetes alone and with lower risk than foot ulcer. Patients with foot ulcers tended to have a higher prevalence of peripheral vascular disease and macrovascular diseases than patients with Charcot arthropathy. This finding may explain the difference in mortality risks between the two groups.

Objective: We have compared the hyperemic response to heat and the endothelium-dependent and endothelium-independent vasodilatation between the dorsum of the foot and the forearm in diabetic neuropathic and non-neuropathic patients and healthy control subjects., Research Design and Methods: We studied the cutaneous microcirculation in the forearm and foot in 15 diabetic patients with neuropathy, in 14 diabetic patients without neuropathy, and in 15 control subjects matched for age, sex, BMI, and in the case of diabetic patients, for the duration of diabetes. Patients with peripheral vascular disease and/or renal impairment were excluded. The cutaneous microcirculation of the dorsum of the foot and the flexor aspect of the forearm was tested in all subjects. Single-point laser Doppler was employed to measure the maximal hyperemic response to heating of the skin to 44 degrees C and laser Doppler imaging scanner was used to evaluate the response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent response) and 1% sodium nitroprusside (NaNP) (endothelium-independent response)., Results: The transcutaneous oxygen tension was lower in the neuropathic group at both foot and forearm level, while the maximal hyperemic response to heat was similar at the foot and forearm level in all three groups. The endothelium-dependent vasodilation (percent increase over baseline) was lower in the foot compared to the forearm in the neuropathic group (23 +/- 4 vs. 55 +/- 10 [mean +/- SEM]; P < 0.01)], the non-neuropathic group (33 +/- 6 vs. 88 +/- 14; P < 0.01), and the control subjects (43 +/- 6 vs. 93 +/- 13; P < 0.001). Similar results were observed during the iontophoresis of NaNP (P < 0.05). No differences were found among the three groups when the ratio of the forearm:foot response was calculated for both the endothelium-dependent (neuropathic group, 2.25 +/- 0.24; non-neuropathic group, 2.55 +/- 0.35; and control subjects, 2.11 +/- 0.26; P = NS) and endothelium-independent vasodilation (neuropathic group, 1.54 +/- 0.27; non-neuropathic group, 2.08 +/- 0.33; and control subjects, 2.77 +/- 1.03; P = NS). The vasodilatory response, which is related to the C nociceptive fiber action, was reduced at the foot level during iontophoresis of Ach in the neuropathic group. In contrast, no difference was found during the iontophoresis of NaNP at the foot and forearm level and of Ach at the forearm level among all three groups., Conclusions: In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm.