Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This is the first guideline on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes published by the IWGDF. We followed the GRADE Methodology to devise clinical questions in the PACO (Population, Assessment, Comparison, Outcome) and PICO (Population, Intervention, Comparison, Outcome) format, conducted a systematic review of the medical literature, and developed recommendations with the rationale. The recommendations are based on the evidence from our systematic review, expert opinion when evidence was not available, and also taking into account weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to an intervention. We here present the 2023 Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus and also suggest key future topics of research.

Diagnosis and treatment of active charcot neuro-osteoarthropathy in persons with diabetes mellitus: A systematic review.

BACKGROUND: There are uncertainties regarding the diagnostic criteria, optimal treatment methods, interventions, monitoring and determination of remission of Charcot neuro-osteoarthropathy (CNO) of the foot and ankle in people with diabetes mellitus (DM). The aims of this systematic review are to investigate the evidence for the diagnosis and subsequent treatment, to clarify the objective methods for determining remission and to evaluate the evidence for the prevention of re-activation in people with CNO, DM and intact skin. METHODS: We performed a systematic review based on clinical questions in the following categories: Diagnosis, Treatment, Identification of Remission and Prevention of Re-Activation in people with CNO, DM and intact skin. Included controlled studies were assessed for methodological quality and key data from all studies were extracted. RESULTS: We identified 37 studies for inclusion in this systematic review. Fourteen retrospective and observational studies relevant to the diagnosis of active CNO with respect to clinical examination, imaging and blood laboratory tests in patients with DM and intact skin were included. We identified 18 studies relevant to the treatment of active CNO. These studies included those focused on offloading (total contact cast, removable/non-removable knee high devices), medical treatment and surgical treatment in the setting of active CNO. Five observational studies were identified regarding the identification of remission in patients who had been treated for active CNO. We did not identify any studies that met our inclusion criteria for the prevention of re-activation in patients with DM and intact skin who had been previously treated for active CNO and were in remission. CONCLUSIONS: There is a paucity of high-quality data on the diagnosis, treatment, and prognosis of active CNO in people with DM and intact skin. Further research is warranted to address the issues surrounding this complex disease.

Postoperative healing in the diabetic foot is impacted by discharge destination.

The aim of this study was to evaluate the impact of discharge destination on diabetes-related limb salvage surgery outcomes post-hospitalisation. This was a single-centre, observational, descriptive study of 175 subjects with diabetes who underwent limb salvage surgery of a minor foot amputation or wide incision and debridement for an acutely infected diabetic foot ulcer (DFU). Comparisons were made between subjects discharged home vs a skilled nursing facility (SNF) for 12 months postoperatively. Univariate, multivariate, and time-to-event analyses were performed. The SNF discharge group (n = 40) had worse outcomes with longer healing time (P = .022), more rehospitalisations requiring a podiatry consult (P = .009), increase of subsequent ipsilateral major lower-extremity amputation (P = .028), and a higher mortality rate (P = .012) within the 12-month postoperative period. There was no significant difference between the cohorts in surgically cleared osteomyelitis (P = .8434). The Charlson Comorbidity Index values for those discharged home and those in a short-term nursing facility were similar (P = .3819; home x ¯ =5.33 ± 2.84 vs SNF x ¯ =5.75 ± 2.06). The planned discharge destination after limb salvage surgery among people with an acutely infected DFU should be an added risk factor for healing outcomes. Patients discharged to SNFs experience additional morbidity and mortality compared with patients discharged home post-hospitalisation.

Updates on Diabetic Foot and Charcot Osteopathic Arthropathy.

PURPOSE OF REVIEW: Diabetes mellitus affects approximately 30.8 million people currently living in the USA. Chronic diabetes complications, including diabetic foot complications, remain prevalent and challenging to treat. We review clinical diagnosis and challenges providers may encounter when managing diabetic foot ulcers and Charcot neuroarthropathy. RECENT FINDINGS: Mechanisms controlling these diseases are being elucidated and not fully understood. Offloading is paramount to heal and manage diabetic foot ulcers and Charcot neuroarthropathy. Diabetic foot ulcers recur and the importance of routine surveillance and multidisciplinary approach is essential. Several predictors of failure in Charcot foot include a related diabetic foot ulcer, midfoot or rearfoot location of the Charcot event, and progressive bony changes on interval radiographs. Patients with diabetic foot ulcer and/or Charcot neuroarthropathy are in need of consistent and regular special multidisciplinary care. If not diagnosed early and managed effectively, morbidity and mortality significantly increase.

Inflammation as a Therapeutic Target for Diabetic Neuropathies.

Diabetic neuropathies (DNs) are one of the most prevalent chronic complications of diabetes and a major cause of disability, high mortality, and poor quality of life. Given the complex anatomy of the peripheral nervous system and types of fiber dysfunction, DNs have a wide spectrum of clinical manifestations. The treatment of DNs continues to be challenging, likely due to the complex pathogenesis that involves an array of systemic and cellular imbalances in glucose and lipids metabolism. These lead to the activation of various biochemical pathways, including increased oxidative/nitrosative stress, activation of the polyol and protein kinase C pathways, activation of polyADP ribosylation, and activation of genes involved in neuronal damage, cyclooxygenase-2 activation, endothelial dysfunction, altered Na(+)/K(+)-ATPase pump function, impaired C-peptide-related signaling pathways, endoplasmic reticulum stress, and low-grade inflammation. This review summarizes current evidence regarding the role of low-grade inflammation as a potential therapeutic target for DNs.

The NIDDK Diabetic Foot Consortium.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetic Foot Consortium (DFC) was established in September 2018 by the NIDDK to build an organization to facilitate the highest quality of clinical research on diabetic foot ulcers (DFUs) that will answer clinically significant questions to improve DFU healing and prevent amputations. The initial focus of the DFC is to develop and validate biomarkers for DFUs that can be used in clinical care and research. The DFC consists of a data coordinating center (DCC) for operational oversight and statistical analysis, clinical sites for participant recruitment and evaluation, and biomarker analysis units (BAUs). The DFC is currently studying biomarkers to predict wound healing and recurrence and is collecting biosamples for future studies through a biorepository. The DFC plans to address the challenges of recruitment and eligibility criteria for DFU clinical trials by taking an approach of "No DFU Patient Goes Unstudied." In this platform approach, clinical history, DFU outcome, wound imaging, and biologic measurements from a large number of patients will be captured and the in-depth longitudinal data set will be analyzed to develop a computational-based DFU risk factor profile to facilitate scientifically sound clinical trial design. The DFC will expand its platform to include studies of the role of social determinants of health, such as food insecurity, housing instability, limited health literacy, and poor social support. The DFC is starting partnerships with the broad group of stakeholders in the wound care community.

A Family-Based Mental Health Navigator Intervention for Youth in the Child Welfare System: Protocol for a Randomized Controlled Trial.

BACKGROUND: Youth in the child welfare system (child welfare-involved [CWI] youth) have high documented rates of mental health symptoms and experience significant disparities in mental health care services access and engagement. Adolescence is a developmental stage that confers increased likelihood of experiencing mental health symptoms and the emergence of disorders that can persist into adulthood. Despite a high documented need for evidence-based mental health services for CWI youth, coordination between child welfare and mental health service systems to increase access to care remains inadequate, and engagement in mental health services is low. Navigator models developed in the health care field to address challenges of service access, fragmentation, and continuity that affect the quality of care provide a promising approach to increase linkage to, and engagement in, mental health services for CWI youth. However, at present, there is no empirically supported mental health navigator model to address the unique and complex mental health needs of CWI youth and their families. OBJECTIVE: Using a randomized controlled trial, this study aims to develop and test a foster care family navigator (FCFN) model to improve mental health service outcomes for CWI adolescents (aged 12-17 years). METHODS: The navigator model leverages an in-person navigator and use of adjunctive digital health technology to engage with, and improve, care coordination, tracking, and monitoring of mental health service needs for CWI youth and families. In total, 80 caregiver-youth dyads will be randomized to receive either the FCFN intervention or standard of care (clinical case management services): 40 (50%) to FCFN and 40 (50%) to control. Qualitative exit interviews will inform the feasibility and acceptability of the services received during the 6-month period. The primary trial outcomes are mental health treatment initiation and engagement. Other pre- and postservice outcomes, such as proportion screened and time to screening, will also be evaluated. We hypothesize that youth receiving the FCFN intervention will have higher rates of mental health treatment initiation and engagement than youth receiving standard of care. RESULTS: We propose enrollment of 80 dyads by March 2024, final data collection by September 2024, and the publication of main findings in March 2025. After final data analysis and writing of the results, the resulting manuscripts will be submitted to journals for dissemination. CONCLUSIONS: This study will be the first to produce empirically driven conclusions and recommendations for implementing a family mental health navigation model for CWI youth with long-standing and unaddressed disparities in behavioral health services access. The study findings have potential to have large-scale trial applicability and be feasible and acceptable for eventual system implementation and adoption. TRIAL REGISTRATION: ClinicalTrials.gov NCT04506437; https://www.clinicaltrials.gov/study/NCT04506437. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49999.

On diabetic foot ulcer knowledge gaps, innovation, evaluation, prediction markers, and clinical needs.

Diabetic foot ulcers (DFUs) remain a very prevalent and challenging complication of diabetes worldwide due to high morbidity, high risks of lower extremity amputation and associated mortality. Despite major advances in diabetes treatment in general, there is a paucity of FDA approved technologies and therapies to promote successful healing. Furthermore, accurate biomarkers to identify patients at risk of non-healing and monitor response-to-therapy are significantly lacking. To date, research has been slowed by a lack of coordinated efforts among basic scientists and clinical researchers and confounded by non-standardized heterogenous collection of biospecimen and patient associated data. Novel technologies, especially those in the single and 'multiomics' arena, are being used to advance the study of diabetic foot ulcers but require pragmatic study design to ensure broad adoption following validation. These high throughput analyses offer promise to investigate potential biomarkers across wound trajectories and may support information on wound healing and pathophysiology not previously well understood. Additionally, these biomarkers may be used at the point-of-care. In combination with national scalable research efforts, which seek to address the limitations and better inform clinical practice, coordinated and integrative insights may lead to improved limb salvage rates.

Strategies to reduce severe diabetic foot infections and complications during epidemics (STRIDE).

AIMS: Patients with diabetes, including those with foot complications, are at highest risk for severe outcomes during the COVID-19 pandemic. Diabetic foot ulcers (DFU) present additional challenges given their superimposed risk for severe infections and amputations. The main objectives were to develop a triage algorithm to effectively risk-stratify all DFUs for potential complications, complying with social distancing regulations, preserving personal protective equipment, and to assess feasibility of virtual care for DFU. METHODS: Longitudinal study during the COVID-19 pandemic performed at a large tertiary institution evaluating the effectiveness of a targeted triage protocol developed using a combined approach of virtual care, electronic medical record data mining, and tracing for rapid risk stratification to derive optimal care delivery methods. 2868 patients with diabetes at risk for foot complications within last 12 months were included and rates of encounters, hospitalizations, and minor amputations were compared to one year prior. RESULTS: The STRIDE protocol was implemented in 1-week and eventually included 2600 patients (90.7%) demonstrating effective triage. During normal operations, 40% (938 of 2345) of all visits were due to DFUs and none were performed virtually. After implementation, 98% face-to-face visits were due to DFU, and virtual visits increased by 21,900%. This risk stratified approach led to similar low rates of DFU-related-hospitalization and minor amputation rates 20% versus 24% (p > 0.05) during and prior the pandemic, respectively. CONCLUSIONS: Implementation of STRIDE protocol was effective to risk-stratify and triage all patients with diabetic foot complications preventing increase in hospitalization and amputations while promoting both social and physical distancing.

Influence of Patient Setting and Dedicated Limb Salvage Efforts on Outcomes in Charcot-Related Foot Ulcer.

Charcot neuroarthropathy is a devastating consequence of diabetes mellitus and peripheral neuropathy. Because of its rarity, the condition is often misdiagnosed or poorly managed. When misadventure occurs, patients with Charcot neuroarthropathy can suffer ulceration, infection, amputation, and death. When patients have Charcot-related foot ulcers, the risks are amplified. Utilizing advanced electronic medical record analysis, a 30-month investigation was undertaken to determine if patients with diabetes mellitus and a concomitant diagnosis of Charcot-related foot ulcer were at greater risk of complications because of location setting of initial treatment for their condition. Charcot foot-related ulcers that are diagnosed in the outpatient setting had established foot specialist care. The outpatient management of the condition lead to a significant reduction in the amount of admissions to a higher acuity setting. However, patient outcomes did not vary once established and dedicated limb salvage efforts were employed. In this large contemporary population managed in a tertiary health system, patients with Charcot-related foot ulcer had negative outcomes when they were initially treated in an inpatient setting and had a significantly greater likelihood of readmission as compared with individuals who had established focused limb salvage care.

Vehicle ergonomics contributing to a diabetic foot ulcer.

BACKGROUND: Diabetes mellitus continues to be a rising concern in the United States. It affects an estimated 9.4% of the population and approximately 1.5 million Americans are diagnosed annually. Approximately 85% of diabetic foot ulcers are associated with diabetic peripheral neuropathy and an infected diabetic foot ulcer is often the first sign of diabetes. There are countless studies within the literature that investigate how insensate feet and the manifestation of a foot ulcer further decrease quality of life and increase risk for mortality. Literature focuses on gait and kinematics that contribute to the formation of a diabetic foot ulcer. While pressure and shear forces are etiologic factors that may lead to the formation of diabetic foot ulcers, the position of the foot while driving an automobile has been ignored as a possible risk factor. CASE PRESENTATION: The clinical case will describe the events of healing a neuropathic diabetic foot ulcer beyond the standard of care treatment plan. It is one of the first case reports to describe vehicle ergonomics as an etiologic factor contributing to a diabetic foot ulcer. Once the patient becomes aware of the unnecessary source of pressure, education and care is provided to manage this likely source of daily pressure to the neuropathic foot. CONCLUSION: The article emphasizes the importance of a complete assessment, including nontraditional factors, which may lead to diabetic complications.

A Tale of Two Eras: Mining Big Data from Electronic Health Records to Determine Limb Salvage Rates with Podiatry.

AIMS/HYPOTHESIS: Diabetic foot complications remain very prevalent in the US and worldwide, and a major risk for devastating amputations. We evaluated the impact of establishing a fully integrated and specialized Podiatry service into a large tertiary academic health system to implement structured and targeted preventative foot care on limb salvage rates. METHODS: Cross-sectional cohorts' data mining analysis was conducted of all encounters for diabetes and any foot complications between 2000-2005 and 2010-2015, preceding and after full implementation of podiatry service, respectively. The primary outcome was the change in major non-traumatic lower extremity amputations. Secondary outcomes included minor non-traumatic lower extremity amputations, other diabetic foot complications, limb salvage procedures as documented by procedural coding, and location (outpatient, inpatient, ED) of service rendered. RESULTS: We analyzed 100 million patient encounters that met the above criteria. Compared with the initial cohort, integration of specialized podiatry services resulted in a significant decrease in the number of major amputations from 127 to 85/year (p<0.05), and halved the amputations rate from 0.004% to 0.002% (p<0.05). Rates of minor lower extremity amputations remained unchanged (p>0.10), while the rates of preventative procedures including foot ulcer debridement doubled (0.0002% to 0.0004% ; p<0.03). Diagnoses of diabetic foot complications increased significantly (p<0.05) and shifted toward the outpatient setting. CONCLUSION: Full integration of specialized Podiatry service led to a significant decrease in major amputation rates, supporting teamwork between podiatry and diabetes health-care providers is essential to performing timely diabetic foot complications management, preventative procedures leading to limb salvage, and a shift in the care location.

Retrospective Cohort Analysis of Pedal Procedures in the Thrombocytopenic Patient.

Thrombocytopenia is an important medical condition to understand prior to performing procedures in the foot and ankle. We have set forth to highlight factors a physician should take into consideration before performing procedures in the thrombocytopenic patient. A retrospective cohort analysis at a large academic institution was undertaken utilizing a cohort discovery tool to discover incidence and management strategies for patients with foot-related conditions that require in-office procedures. We demonstrate that a full history and physical are important to guide treatment along with complete blood count testing prior to intervention. We included all patients at the institution that underwent a foot and ankle procedure in-office with podiatric surgery over 10 years where thrombocytopenia was demonstrable via complete blood count within 3 months of the procedure. Patients' charts were reviewed for 1 year following podiatric intervention and outcomes were recorded. The cohort reveals that patients with thrombocytopenia have many advanced comorbidities but performing procedures in this cohort is safe. Complications from procedures included erythrocyte transfusion, ulcer recurrence, need for formal surgical intervention, infection, falls, and death. We then provide a brief discussion about the etiology and management options available for thrombocytopenia.

Malignant Transformation of a Site of Prior Diabetic Foot Ulceration to Verrucous Carcinoma: A Case Report.

The case of a 62-year-old Caucasian man with type 1 diabetes who developed malignant transformation of an area of prior diabetic foot ulceration (DFU) is reported. He had significant hallux valgus deformity, multiple episodes of healing and breakdown, and eventual transformation to verrucous carcinoma (VC). This case report highlights the malignant transformation of a site of previous DFU to VC, which, to the best of the authors' knowledge, has not yet been described in the literature. There has been little research performed that examines VC in the diabetic population. This case report also highlights the importance of clinical suspicion for malignant transformation as well as the use of subsequent biopsy when necessary.

Physician knowledge of a rare foot condition - influence of diabetic patient population on self-described knowledge and treatment.

BACKGROUND: Charcot neuroarthopathy (CN), a rare foot and ankle condition usually complicating diabetes mellitus, leads to deformity, poor quality of life, and increased mortality and morbidity. The prevalence of this condition in the diabetic patient population is not currently known but has been reportedly misdiagnosed in up to 95% of cases. METHODS: We sought to evaluate general knowledge regarding CN in non-foot specialist clinical faculty at a large academic institution and to understand their practice habits. Our survey emphasizes the necessity of better education surrounding CN to improve outcomes in a preventative fashion. This will enable us to determine how to focus educational forums surrounding this topic in the future. RESULTS: Seven hundred eighty-nine faculty members were sent the survey while 400 completed the survey for a response rate of 50.7%. The respondents were representative of academic rank at the institution and were comprised of endocrinologists, internal medicine physicians and family medicine physicians. We found that 67.6% of responders had a self-described poor or complete lack of knowledge of this condition. Clinicians with self-described better knowledge of CN were more likely to provide a correct initial management of CN (p < 0.001; r = 0.3639). CONCLUSIONS: In this large tertiary institution, a majority of providers among internal medicine, endocrinologists, and family medicine physicians demonstrated minimal or no knowledge of this rare, but potentially devastating diabetes complication. However, those providers who are knowledgeable of CN, performed better in the initial management of this condition. Also, respondents who treated more diabetic patients demonstrated an association with correct management. Education, and the development of better understanding amongst clinicians, is crucial to limit the devastating effects of this condition in the future.

Podiatry impact on high-low amputation ratio characteristics: A 16-year retrospective study.

PURPOSE: Complications from diabetes mellitus including major lower extremity amputation may have significant impact on a patient's mortality. This study determined what impact the addition of a limb salvage and diabetic foot program involving podiatry had at an academic institution over 16years by analyzing high-low amputation ratio data. METHODS: The high-low amputation ratio in the diabetic population who underwent non-traumatic amputation of the lower extremity was retrospectively evaluated at an academic institution via cohort discovery of the electronic medical record and analysis of billing over 16years. RESULTS: We directly compared two eras, one without podiatry and one with a podiatry presence. It was found that with the addition of a podiatry program, limb salvage rates significantly increased (R2 (without podiatry)=0.45, R2 (with podiatry)=0.26), with a significant change in both the rate of limb salvage per year (-0.11% per year versus -0.36% per year; p<0.01) and an overall decrease in high-low amputation ratio (0.89 without podiatry to 0.60 with podiatry). Of note, approximately 40 major lower extremity amputations were avoided per year with the addition of a podiatry program (p<0.05). CONCLUSIONS: Our findings signify the importance of podiatric care in the diabetic population. With an established podiatry program present at an academic institution, major lower extremity amputations can be avoided and more limbs can be salvaged, thus preventing some of the moribund complications from this condition.

Classic Solitary Kaposi Sarcoma of the Foot in an Immunocompetent Patient: A Case Report.

Kaposi sarcoma (KS) is a tumor derived from endothelial cell lineage caused by Kaposi sarcoma-associated virus or human herpesvirus-8. The authors have set forth to describe a unique presentation of the classical form of KS in a homosexual individual. The authors demonstrate that a full history and physical are important in determining how to guide treatment along with ancillary tests, which can prove vital to determine management strategy. The authors then provide a brief discussion about variants of KS, biopsy techniques, and current treatment options available to patients diagnosed with this condition. The patient described is a 60-year-old male of Eastern European descent, who is immunocompetent in a monogamous homosexual relationship with a new onset and rapidly progressing skin lesion on the plantar aspect of his foot. Surgical excision of the tumor was performed and surveillance was determined to be the treatment of choice.

Bizarre parosteal osteochondromatous proliferation: a novel case report of recurrence in the toe.

Bizarre parosteal osteochondromatous proliferation (BPOP) is an uncommon reactive mesenchymal lesion mainly affecting the small bones of the hands and feet. They frequently occur in young adults. It is important to understand and differentiate BPOP from other lesions, especially because of its atypical microscopic features and tendency to recur. We present a case of a recurrent lesion involving the toe and discuss management options. To our knowledge, our current case report is the first in the literature to report a recurring BPOP lesion of the toe.

Charcot stage 0: A review and consideratons for making the correct diagnosis early.

Charcot neuropathic osteoarthropathy (CN) is a rare disease (NIDDK, NIH Summary Report Charcot Workshop, 2008) that causes significant morbidity and mortality for affected patients. The disease can result in severe deformities of the foot and ankle that contribute to the development of ulcerations and amputations. Medical advances have failed to find ways to stop the progression of the disease. However, it is known that early detection of the CN has a substantial impact on patient outcomes. CN in the earliest stage is very difficult to recognize and differentiate from other similar presenting diseases. We intend to outline clinical considerations practitioners can use when evaluating a patient with early stage suspected CN.

Data mining for identifying novel associations and temporal relationships with Charcot foot.

INTRODUCTION. Charcot foot is a rare and devastating complication of diabetes. While some risk factors are known, debate continues regarding etiology. Elucidating other associated disorders and their temporal occurrence could lead to a better understanding of its pathogenesis. We applied a large data mining approach to Charcot foot for elucidating novel associations. METHODS. We conducted an association analysis using ICD-9 diagnosis codes for every patient in our health system (n = 1.6 million with 41.2 million time-stamped ICD-9 codes). For the current analysis, we focused on the 388 patients with Charcot foot (ICD-9 713.5). RESULTS. We found 710 associations, 676 (95.2%) of which had a P value for the association less than 1.0 × 10⁻5 and 603 (84.9%) of which had an odds ratio > 5.0. There were 111 (15.6%) associations with a significant temporal relationship (P < 1.0 × 10⁻³). The three novel associations with the strongest temporal component were cardiac dysrhythmia, pulmonary eosinophilia, and volume depletion disorder. CONCLUSION. We identified novel associations with Charcot foot in the context of pathogenesis models that include neurotrophic, neurovascular, and microtraumatic factors mediated through inflammatory cytokines. Future work should focus on confirmatory analyses. These novel areas of investigation could lead to prevention or earlier diagnosis.