Diagnosing osteomyelitis in diabetic foot by diffusion-weighted imaging and dynamic contrast material-enhanced magnetic resonance imaging: a systematic review and meta-analysis.

AIM: To evaluate the diagnostic performance of diffusion-weighted imaging (DWI) and dynamic contrast enhanced (DCE), for diagnosing osteomyelitis in the diabetic foot. MATERIALS AND METHODS: A thorough search was carried out to identify suitable studies published up to September 2023. The quality of the studies involved was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The diagnostic sensitivity and specificity of each imaging modality/method for each specific cut point were summarized. The summary receiver operating characteristic (SROC) curve was calculated using bivariate mixed effects models. RESULTS: Five studies investigating 187 patients and 234 bone lesions with 110 diagnosed osteomyelitis were enrolled. Four studies used DWI (172 lesions), three studies used DCE techniques (140 lesions) and two studies presented results of conventional MRI (66 lesions). The sensitivity ranges using conventional MRI, DWI and DCE were 65%-100%, 65%-100% and 64%-100%, respectively. The specificity ranges were 50%-61%, 56%-95%, and 66%-93%, respectively. The SROC curve of DWI and DCE was 0.89 (95% CI, 0.86-0.92) and 0.90 (95% CI, 0.87-0.92), respectively. CONCLUSION: Combining DWI and DCE methods, alongside conventional MRI, can improve the reliability and accuracy of diabetic foot osteomyelitis diagnosis. However, the study recognizes result variability due to varying protocols and emphasizes the need for well-designed studies with standardized approaches. To optimize diagnostic performance, the study recommends considering low ADC values, Ktrans or rapid wash-in rate from DCE such as iAUC60, along with using large ROIs that cover the entire lesion while excluding normal bone marrow.

Anti-RANKL Antibody For Active Charcot Foot Neuro-Osteoarthropathy in Patients with Diabetes and Chronic Kidney Disease.

BACKGROUND: Charcot neuroosteoarthropathy (CNO) is characterized with increased osteoclastic activity that can be curbed with antiresorptive agents. Chronic kidney disease (CKD) precludes bisphosphonates but anti-receptor activator of nuclear factor-B ligand (anti-RANKL) antibody, denosumab, can be contemplated in CKD. We investigated denosumab for active CNO of foot in CKD for CNO remission. METHODS: During the study period, 446 persons of diabetes with unilateral, active CNO of foot and CKD were identified and 78 were finally enrolled. Patients received either 60 mg denosumab (single-dose, subcutaneous) along with standard of care (SoC) as total contact cast (TCC) (group A; n = 26) or SoC (group B; n = 52) only. Patients were followed every 4 weeks until CNO remission and subsequently every 8 weeks until 48 weeks following remission. Remission was defined as temperature difference <2 °C between 2 feet confirmed twice (4 weeks apart) with clinical resolution of signs of inflammation. The primary outcome studied was proportion of patients achieving remission within 48 weeks and the time to remission. RESULTS: Median age was 56.5 (48.8-65) and 57 (48.5-61.2) years, P = .57; duration of diabetes 16 (10-25.3) and 14.9 (10-19) years, P = .151; and estimated glomerular filtration rate 44.8 (21.1-65.6) and 45.7 (32.9-55.7) mL/min/1.73 m2, P = .771, in group A and B, respectively. Median temperature difference at presentation between the affected and opposite foot was 3.4 °C (2.7-6.9) and 3.2 °C (2.2-4.0), P = .119, respectively. All patients achieved remission in group A (100%) compared with 42 (80.8%) in group B (P = .006) (hazard ratio 0.52, 95% CI: 0.32-0.87; P = .012). The median time to remission was similar in the 2 groups (15 [11-25] and 17.5 [14-31.5] weeks, P = .229, respectively). 25-Hydroxyvitamin D3 >14 ng/mL was significantly associated (OR 9.5, 95% CI 1.04-87.5, P = .045) with remission. CONCLUSION: Anti-RANKL antibody added to SoC (TCC) induces remission of active foot CNO in greater proportions of patients with diabetes and CKD.

Outcomes Following Surgical Correction of Talocalcalcaneal Joint Dislocation in Diabetes Associated Charcot Foot Arthropathy.

BACKGROUND: Growing clinical interest in the treatment of acquired foot deformity due to diabetes-associated Charcot foot arthropathy has led to multiple reports of favorable clinical outcomes in patients when their acquired deformity is at the midfoot level. Clinical failures and less than optimal clinical outcomes are achieved when the deformity is at the hindfoot or ankle levels. METHODS: A retrospective review was performed of all patients who underwent surgical correction of diabetes-associated Charcot foot arthropathy with talocalcaneal dislocation over an 18-year period. Reduction of the talocalcaneal dislocation, and maintenance of the correction with percutaneous pins and circular external fixation after subtalar joint preparation for fusion, was used as the method of surgically achieving a clinically plantigrade foot. Clinical outcomes were based on resolution of infection, limb salvage, and the ability to ambulate with commercially available therapeutic footwear. RESULTS: Forty-three feet in 39 patients were included. A favorable clinical outcome was achieved in 32 of 43 feet (74%) with 26 (60%) considered to have an "excellent" result with minimal shoeing issues and 6 (14%) considered to have a "good" outcome based on their need for a custom shoe modification and/or some form of short ankle-foot orthosis. Eleven feet (26%) were judged to have a "poor" clinical outcome and among those 11 feet, 6 underwent partial, or whole-foot amputation, 2 had persistent wounds, and 5 required the use of a standard ankle foot orthosis or Charcot Restraint Orthotic Walker (CROW). CONCLUSION: Subtalar dislocation in Charcot arthropathy is a complex clinical problem. In our series, reduction and maintenance of the reduction after subtalar dislocation was essential for a favorable clinical outcome.

Painful Nonunion in Patients With Clinically Plantigrade Diabetes-Associated Charcot Foot Arthropathy.

BACKGROUND: It has been assumed that diabetic patients with peripheral neuropathy should not have pain associated with Charcot foot arthropathy. METHODS: During a 19-year period, 14 diabetic patients (15 feet) presented for treatment with pain following resolution of the acute phases of midfoot Charcot foot arthropathy. All were clinically plantigrade with plain radiographic evidence of bony union without deformity. Pain did not resolve with the use of appropriate therapeutic footwear. When used, CT scans uniformly demonstrated nonunion. RESULTS: All 14 patients had resolution of their presenting pain following successful arthrodesis. Nonunion was confirmed at surgery in all of the patients. One patient developed a fatal pulmonary embolus following removal of the external fixator. Two required late exostectomy for bony overgrowth at the surgical site of fusion for nonunion. CONCLUSION: This small series of patients would suggest that nonunion of the Charcot neuroarthropathy process was responsible for complaints of pain not able to be managed with therapeutic footwear. Successful arthrodesis resolved the pain. CT imaging may help identify a treatable source of pain in this population.

[18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography and conventional imaging modalities in the diagnosis of diabetic foot osteomyelitis: a meta-analysis.

AIM: This meta-analysis aimed to evaluate the comparative diagnostic efficacy of [18F]Fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and conventional imaging, MRI, and white blood cell (WBC) scintigraphy in detecting foot osteomyelitis among diabetic patients. MATERIALS AND METHODS: An exhaustive search was conducted within the PubMed and Embase databases to identify publications available up until February 2024. Studies were included if they evaluated the diagnostic efficacy of [18F]FDG PET or the comparative diagnostic performance between PET and (MRI or WBC scintigraphy). Two researchers independently assessed the quality of the included studies, utilizing the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. RESULTS: Nine retrospective or prospective studies involving 605 patients were included in the meta-analysis. For [18F]FDG PET, the overall sensitivity was 0.83(95% CI: 0.69-0.94), while the overall specificity was 0.92(95% CI: 0.86-0.97). In the head-to-head comparison, no significant difference of sensitivity was found between [18F]FDG PET and MRI (0.72 vs. 0.68, P=0.81), as well as between [18F]FDG PET and WBC scintigraphy (0.57 vs. 0.66, P=0.64). In addition, specificity was also found to be no significant difference between [18F]FDG PET and MRI (0.90 vs. 0.82, P=0.27), as well as [18F]FDG PET and WBC scintigraphy (0.81 vs. 0.93, P=0.09). CONCLUSION: [18F]FDG PET demonstrates similar sensitivity and specificity to MRI and WBC scintigraphy in detecting foot osteomyelitis among diabetic patients. MRI, often cited as a primary choice in guidelines, might be preferred due to its lower cost and lower dose. Further larger sample prospective studies are needed to confirm these findings.

Definitive single-stage surgery for treating diabetic foot osteomyelitis: a protocolized pathway including antibiotic bone graft substitute use.

BACKGROUND: Diabetic foot ulcers (DFUs) are a challenging complication of diabetes mellitus, often leading to poor clinical outcomes and significant socioeconomic burdens. We evaluated the effectiveness of a definitive single-stage protocolized surgical management pathway, including the use of local antibiotic bone graft substitute, for the treatment of infected DFUs with associated osteomyelitis. METHODS: A retrospective cohort study was conducted. Medical records were extracted (from January 2017 to December 2020) to establish a database consisting of patients who underwent surgical intervention for the treatment of an infected DFU with osteomyelitis. Patients were divided into conventional (control) and protocolized (intervention) surgical groups depending on the treatment received. Clinical outcomes were assessed over a 12-month follow-up period. RESULTS: A total of 136 consecutive patients were included (conventional = 33, protocolized = 103). The protocolized group demonstrated a statistically significant reduction in the mean number of operations performed per patient (1.2 vs. 3.5) (P < 0.001) and a shorter accumulative hospital length of stay (12.6 vs. 25.1 days) (P < 0.001) compared to the conventional group. Major amputation rates were significantly lower in the protocolized group (2% vs. 18%) (P < 0.001). Within 12 months of surgical intervention, the protocolized group exhibited an ulcer healing rate of 89%, with a low rate of recurrence (3%). CONCLUSION: The protocolized surgical pathway, including local antibiotic bone graft substitute use, demonstrated superior outcomes compared to conventional management for the treatment of infected DFUs with osteomyelitis. Further research is needed to evaluate the cost-effectiveness and generalizability of this approach.

Effect of Buerger-Allen exercise on wound healing in patients with diabetic foot ulcers: a randomised controlled trial.

OBJECTIVE: A diabetic foot ulcer (DFU) is a complication of type 2 diabetes that is difficult to treat. Buerger-Allen exercise has shown effectiveness in improving foot circulation and neuropathy in several studies; however, to the best of our knowledge, no randomised controlled study has investigated its effectiveness for DFU healing. Therefore, this study aimed to assess the effects of Buerger-Allen exercise on the healing of DFUs in patients with type 2 diabetes. METHOD: This is a parallel-group randomised controlled trial (RCT). Of 50 patients with neuropathic DFUs, 41 completed the study. They were assigned randomly to a study group (n=21) and a control group (n=20). Patients in the study group received the standard medical treatment and semi-supervised Buerger-Allen exercise for three sessions per week for four weeks, while patients in the control group only received the standard medical treatment. The outcome measures were: ankle-brachial pressure index (ABPI); ulcer size; ulcer depth; SINBAD score; and ulcer risk for poor outcomes (based on the SINBAD score). RESULTS: The study group's mean age was 49.48±6.45 years and the control group's mean age was 49.15±5.85. The study group's ABPI increased significantly compared to the baseline (1.17±0.04 versus 1.11±0.05, respectively; p<0.001) and the control group (1.17±0.04 versus 1.14±0.05, respectively; p=0.04) post-intervention. Ulcer size also reduced significantly in the study group compared to the baseline (2.63±2.0 versus 7.48±5.55cm2, respectively; p<0.001) and the control group (2.63±2.0 versus 6.43±4.45cm2, respectively; p<0.001) post-intervention. Ulcer depth decreased significantly in the study group compared to the baseline (1.71±1.05 versus 4.19±1.74mm, respectively; p<0.001) and the control group (1.71±1.05 versus 2.80±1.57mm, respectively; p=0.01) post-intervention. Furthermore, the SINBAD score in the study group decreased significantly compared to the baseline (1.38±0.86 versus 2.14±1.06, respectively; p<0.001) and the control group (1.38±0.86 versus 2.0±0.79, respectively; p=0.02) post-intervention. Moreover, the ulcer risk for poor outcomes, based on the SINBAD score, reduced significantly only in the study group, compared to the baseline (p=0.041). The control group showed non-significant changes compared to the baseline in all outcome measures (p>0.05). CONCLUSION: From the findings of this RCT, Buerger-Allen exercise, in combination with standard wound care, may help accelerate the healing of neuropathic DFUs in patients with type 2 diabetes, and could be suggested as part of the management plan for such conditions as an easy-to-perform offloading exercise intervention.

Risk factors for erectile dysfunction in diabetes mellitus: a systematic review and meta-analysis.

Background: Previous studies have established that diabetes mellitus (DM) markedly raises the risk of developing erectile dysfunction (ED). Despite extensive investigations, the risk factors associated with ED in diabetic men have yet to be unequivocally determined, owing to incongruent and inconclusive results reported in various studies. Objective: The objective of this systematic review and meta-analysis was to assess the risk factors for ED in men with DM. Methods: A comprehensive systematic review was conducted, encompassing studies published in the PubMed, Scopus and Embase databases up to August 24th, 2023. All studies examining the risk factors of ED in patients with DM were included in the analysis. To identify significant variations among the risk factors, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were employed. The risk of bias was evaluated using the Newcastle-Ottawa Scale(NOS) for longitudinal studies and the Agency for Healthcare Research and Quality Scale(AHRQ) for cross-sectional studies. Results: A total of 58 studies, including a substantial participant pool of 66,925 individuals diagnosed with DM, both with or without ED, were included in the meta-analysis. Mean age (OR: 1.31, 95% CI=1.24-1.37), smoking status (OR: 1.32, 95% CI=1.18-1.47), HbA1C (OR: 1.44, 95% CI=1.28-1.62), duration of DM (OR: 1.39, 95% CI=1.29-1.50), diabetic neuropathy (OR: 3.47, 95% CI=2.16-5.56), diabetic retinopathy (OR: 3.01, 95% CI=2.02-4.48), diabetic foot (OR: 3.96, 95% CI=2.87-5.47), cardiovascular disease (OR: 1.92, 95% CI=1.71-2.16), hypertension (OR: 1.74, 95% CI=1.52-2.00), microvascular disease (OR: 2.14, 95% CI=1.61-2.85), vascular disease (OR: 2.75, 95% CI=2.35-3.21), nephropathy (OR: 2.67, 95% CI=2.06-3.46), depression (OR: 1.82, 95% CI=1.04-3.20), metabolic syndrome (OR: 2.22, 95% CI=1.98-2.49), and diuretic treatment (OR: 2.42, 95% CI=1.38-4.22) were associated with increased risk factors of ED in men with DM. Conclusion: Our study indicates that in men with DM, several risk factors for ED have been identified, including mean age, HbA1C, duration of DM, diabetic neuropathy, diabetic retinopathy, diabetic foot, cardiovascular disease, hypertension, microvascular disease, vascular disease, nephropathy, depression, metabolic syndrome, and diuretic treatment. By clarifying the connection between these risk factors and ED, clinicians and scientific experts can intervene and address these risk factors, ultimately reducing the occurrence of ED and improving patient management.

Second Metatarsal Length and Transfer Ulcers After First Metatarsal Amputation in Diabetic Foot Infections.

BACKGROUND: Plantar transfer ulcers (TUs) underneath the second metatarsal head are frequent after first metatarsal ray amputations due to diabetic foot infections. Whether the second metatarsal length (2ML) is associated with TU occurrence in these patients is unclear. This study evaluated whether 2ML is associated with TU occurrence after first-ray amputations and whether ulcer-free survival is shorter in patients with "excess" 2ML. METHODS: Forty-two patients with a mean age of 67 (range 33-93) years, diabetes, and first metatarsal ray amputation (first amputation at the affected foot) were included. Two independent readers measured the 2ML using the Coughlin method. A protrusion of more than 4.0 mm of the second metatarsal was defined as "excess" 2ML. The effect of 2ML on ulcer occurrence was analyzed using a multivariate Cox regression model. A Kaplan-Meier curve for TU-free survival was constructed comparing the 2 groups of "normal" (n = 21) and "excess" 2ML (n = 21). RESULTS: Interrater reliability was excellent. TUs underneath the second metatarsal occurred in 15 (36%) patients. In agreement with our hypothesis, 2ML was nonsignificantly different in patients with TUs, recording a mean of 5.3 (SD 2.5) mm, compared to patients without 4.0 (SD 2.3) mm (hazard ratio [HR] 1.12, 95% CI 0.89-1.41), whereas insulin dependence was associated with ulcer occurrence (HR 0.33, 95% CI 0.11-0.99). CONCLUSION: In our relatively small study population with a cutoff level of 4 mm for excess 2ML, ulcer-free survival was similar in patients with "normal" and "excess" 2ML. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance.

PURPOSE: Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings. METHODS: This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem-Intervention/Indicator-Comparator-Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria. RESULTS: Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [18F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [18F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [18F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [18F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [18F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging. CONCLUSION: These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications.

Surgical Management of Diabetic Foot Burns Is Associated With Poor Outcomes: A Systematic Review and Meta-Analysis.

There is no consensus on the optimal management of diabetic foot burn injuries. Here, we systematically identify studies reporting on diabetic foot burns and evaluate outcomes among patients managed operatively vs nonoperatively. PubMed, Embase, and Web of Science were searched. Screening was performed by independent reviewers. Primary research studies with English full texts published between 1980 and 2023 that discussed outcomes of foot burns in adults with diabetes were included and critically appraised using validated tools. Results are presented using descriptive statistics of aggregated data. The search yielded 2402 nonduplicate papers, of which 35 met the inclusion criteria. Nine papers were included for meta-analysis, including 7 retrospective comparative analyses, 1 cross-sectional study, and 1 retrospective chart review. There were 1798 diabetic foot burn patients. The mean age was 58.2 years (SD 4.12), and 73.1% (n = 1314) were male. A total of 15.7% (n = 283) of patients were surgically managed, including debridement (3.7%, n = 66), grafting (8.2%, n = 147), flap (0.2%, n = 3), and primary amputation (7.1%, n = 127). The secondary amputation rate, defined as amputation following initial surgery, was 4.9% (n = 14). The overall amputation rate was 7.8% (n = 141). Other complications included infection (4.0%, n = 72), osteomyelitis (1.9%, n = 34), and graft failure (8.2%, n = 12). One study reported functional status at the last visit. Diabetic foot burns are highly morbid. The surgical management of these complex injuries is high risk, as amputation results in poorer quality of life and functional outcomes.

[National expert consensus on the diagnosis and surgical treatment of diabetic foot ulcers complicated with lower extremity vasculopathy (2024 version)].

Diabetic foot ulcers complicated with lower extremity vasculopathy possess the characteristics of high incidence, slow healing, and poor prognosis, which may eventually lead to amputation or even life-threatening if not treated properly. The treatment of complicated lower extremity vasculopathy is vital to improve the healing process of diabetic foot ulcers, which has gradually received attention in clinical practice. Recently, a number of clinical trials on diabetic foot ulcers complicated with lower extremity vasculopathy were reported. In order to further standardize the clinical diagnosis and treatment of diabetic foot ulcers complicated with lower extremity vasculopathy, an expert group headed by Burns and Trauma Branch of Chinese Geriatrics Society, Chinese Burn Association, and Wound Repair Professional Committee of Chinese Medical Doctor Association deliberated and compiled the National expert consensus on the diagnosis and surgical treatment of diabetic foot ulcers complicated with lower extremity vasculopathy (2024 version) together. This consensus is based on evidences from the literature, covers the disease characteristics, evidence-based evidence of clinical diagnosis and treatment, as well as the application of new technologies and new treatment approaches of diabetic foot ulcers complicated with lower extremity vasculopathy. The goal of this consensus is to provide clear guidance to practitioners on the best approaches for screening, diagnosing, and treating diabetic foot ulcers complicated with lower extremity vasculopathy in individuals, hoping to provide a normative clinical practice basis for medical staff engaged in the treatment of diabetic foot wounds.

Extended-Spectrum Beta-Lactamase Escherichia coli Diabetic Foot Osteomyelitis Causing Sausage Toe Deformity: Successful Therapy with Ertapenem in the Outpatient Setting.

BACKGROUND Diabetic foot osteomyelitis is a high-morbidity and debilitating complication of diabetic foot ulcers that contributes to significantly worse quality of life in the affected population and higher cost of healthcare services. One of the clinical presentations of diabetic foot osteomyelitis is the 'sausage' toe deformity, which affects the phalanges (local soft tissue infection and underlying bony changes). This deformity is highly suggestive of the presence of osteomyelitis. Unfortunately, during recent years, the emergence of antibiotic-resistant bacteria have created great difficulties in choosing appropriate empirical antibiotics for the treatment of diabetic foot infections. Multidrug-resistant pathogens have been strongly related to higher morbidity and mortality compared with infections caused by their antibiotic-susceptible counterparts. CASE REPORT We describe a case of a 74-year-old woman with long-standing insulin-treated type 2 diabetes, who experienced extended-spectrum beta-lactamase-producing Escherichia coli infection that caused diabetic foot osteomyelitis with 'sausage' deformity in her second right toe. She was successfully treated with surgical debridement combined with the administration of ertapenem in the outpatient setting, completing, in total, a 6-week course of antibiotic therapy. CONCLUSIONS 'Sausage' toe deformity is one of the clinical presentations of diabetic foot osteomyelitis, and should be an alarming sign in everyday clinical practice. Ertapenem is an excellent option for the treatment of diabetic foot infections caused by extended-spectrum beta-lactamase E. coli in the outpatient setting. Early diagnosis and proper therapeutic approach are of great importance to reduce the risk of amputations, overall mortality, total cost, and the surge of antimicrobial resistance in the community.

Diabetic Foot Infections and Amputations Are All Too Common-Here's What Could Move the Needle.

This Medical News article discusses how multidisciplinary care teams, new drugs and devices, and practical solutions to socioeconomic factors could reduce diabetic foot infections and amputations.

L-arginine supplementation abrogates hypoxia-induced virulence of Staphylococcus aureus in a murine diabetic pressure wound model.

Diabetic foot ulcers (DFUs) are the most common complications of diabetes resulting from hyperglycemia leading to ischemic hypoxic tissue and nerve damage. Staphylococcus aureus is the most frequently isolated bacteria from DFUs and causes severe necrotic infections leading to amputations with a poor 5-year survival rate. However, very little is known about the mechanisms by which S. aureus dominantly colonizes and causes severe disease in DFUs. Herein, we utilized a pressure wound model in diabetic TALLYHO/JngJ mice to reproduce ischemic hypoxic tissue damage seen in DFUs and demonstrated that anaerobic fermentative growth of S. aureus significantly increased the virulence and the severity of disease by activating two-component regulatory systems leading to expression of virulence factors. Our in vitro studies showed that supplementation of nitrate as a terminal electron acceptor promotes anaerobic respiration and suppresses the expression of S. aureus virulence factors through inactivation of two-component regulatory systems, suggesting potential therapeutic benefits by promoting anaerobic nitrate respiration. Our in vivo studies revealed that dietary supplementation of L-arginine (L-Arg) significantly attenuated the severity of disease caused by S. aureus in the pressure wound model by providing nitrate. Collectively, these findings highlight the importance of anaerobic fermentative growth in S. aureus pathogenesis and the potential of dietary L-Arg supplementation as a therapeutic to prevent severe S. aureus infection in DFUs.IMPORTANCES. aureus is the most common cause of infection in DFUs, often resulting in lower-extremity amputation with a distressingly poor 5-year survival rate. Treatment for S. aureus infections has largely remained unchanged for decades and involves tissue debridement with antibiotic therapy. With high levels of conservative treatment failure, recurrence of ulcers, and antibiotic resistance, a new approach is necessary to prevent lower-extremity amputations. Nutritional aspects of DFU treatment have largely been overlooked as there has been contradictory clinical trial evidence, but very few in vitro and in vivo modelings of nutritional treatment studies have been performed. Here we demonstrate that dietary supplementation of L-Arg in a diabetic mouse model significantly reduced duration and severity of disease caused by S. aureus. These findings suggest that L-Arg supplementation could be useful as a potential preventive measure against severe S. aureus infections in DFUs.

Effect of denosumab on inflammation and bone health in active Charcot foot: A phase II randomised controlled trial.

AIMS: We aimed to investigate the effect of denosumab on pedal bone health and clinical resolution in active Charcot foot (CN). METHODS: This multicentre open-label phase 2 randomised controlled trial recruited adults with diabetes mellitus and active CN within 3 months of onset. Participants were randomised to standard care alone, or with denosumab 60 mg subcutaneously. Denosumab was administered at baseline and again at 6 months, unless foot temperature had normalised (i.e. <2 °C compared to contralateral foot). Co-primary outcomes were change in calcaneal Stiffness Index and foot temperature normalisation over 18 months. RESULTS: Twelve participants per group were analysed; mean age 58 ± 11 years, 83 % male and 92 % had type 2 diabetes. Active CN duration was median 8 (IQR 7-12) weeks. Ninety-two percent were Eichenholtz stage 1 and 96 % involved the midfoot. After 1-month, median decline in Stiffness Index was less in the denosumab verses standard care group (0.5 [IQR -1.0 to 3.9] vs -2.8 [-8.5 to -1.0], p = 0.008). At 18-months, 92 % of the denosumab group attained foot temperature normalisation versus 67 % of the standard care group (p = 0.13). CONCLUSIONS: Denosumab ameliorated the early decline in calcaneal Stiffness Index associated with active CN. However, no difference in normalisation of foot temperature was observed.

Unique Challenges in Diabetic Foot Science.

In the past 30 years, there has been a rapid influx of information pertaining to the diabetic foot (DF) coming from numerous directions and sources. This article discusses the current state of the DF literature and challenges it presents to clinicians with its associated increase in knowledge on their derivations, complications, and interventions. Further, we attempt to provide tips on how to navigate and criticize the current literature to encourage and maximize positive outcomes in this challenging patient population.

Diagnosis and treatment of diabetic foot ulcer complicated with lower extremity vasculopathy: Consensus recommendation from the Chinese Medical Association (CMA), Chinese Medical Doctor Association (CMDA).

Diabetic foot ulcer complicated with lower extremity vasculopathy is highly prevalent, slow healing and have a poor prognosis. The final progression leads to amputation, or may even be life-threatening, seriously affecting patients' quality of life. The treatment of lower extremity vasculopathy is the focus of clinical practice and is vital to improving the healing process of diabetic foot ulcers. Recently, a number of clinical trials on diabetic foot ulcers with lower extremity vasculopathy have been reported. A joint group of Chinese Medical Association (CMA) and Chinese Medical Doctor Association (CMDA) expert representatives reviewed and reached a consensus on the guidelines for the clinical diagnosis and treatment of this kind of disease. These guidelines are based on evidence from the literature and cover the pathogenesis of diabetic foot ulcers complicated with lower extremity vasculopathy and the application of new treatment approaches. These guidelines have been put forward to guide practitioners on the best approaches for screening, diagnosing and treating diabetic foot ulcers with lower extremity vasculopathy, with the aim of providing optimal, evidence-based management for medical personnel working with diabetic foot wound repair and treatment.

Implementing a contextually appropriate foot-ankle exercise programme in primary care for the prevention of modifiable risk factors for ulcers in people with diabetes: protocol for a hybrid type 2 study.

INTRODUCTION: Diabetes is a highly prevalent disease that negatively impacts people's health and quality of life. It can result in diabetic peripheral neuropathy (DPN) and foot complications, which in turn lead to ulcers and amputations. The international guidelines on diabetic foot included specific foot-ankle exercises as preventive strategy capable of modifying the risk factors for ulcers. Our aim is to test the effectiveness and to implement a contextually appropriate preventive intervention-a foot-ankle exercises programme alongside educational strategies-in a primary care setting to improve range of motion (ROM), strength, functionality of foot-ankle, and quality of life in people with diabetes. METHODS AND ANALYSIS: This is a hybrid type 2 implementation-effectiveness study organised in four phases, being undertaken in Limeira, São Paulo. Phase 1, preimplementation, aims to gather information about the contextual characteristics, barriers, and facilitators and to form the implementation team. In phase 2, the implementation team will structure the foot-ankle programme, adapting it to the context of primary healthcare, and develop the training for health professionals. In phase 3, effectiveness of the 12 week group-based intervention will be tested by a cluster randomised controlled trial. Primary care units (18 clusters) will be randomly allocated to a control or intervention group, with a total sample of 356 people. Primary outcomes will be DPN symptoms and ankle and first metatarsal phalangeal joint ROM. Reach, adoption, and implementation will be evaluated by Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. In phase 4, maintenance and expansion of the programme in the municipality will be assessed. ETHICS AND DISSEMINATION: This protocol and the informed consent to be signed by the participants were approved by the Ethics Committee of the School of Medicine of the University of São Paulo (CAAE:63457822.0.0000.0068, 29 November 2022). The project will generate and share data in a public repository. Results will be disseminated through peer-reviewed journals, conference proceedings, and electronic communications for health professionals. TRIAL REGISTRATION NUMBER: NCT05639478.