Real-world treatment patterns and diagnosis of charcot foot in franco-belgian diabetic foot expert centers (The EPiChar Study).

AIM: To evaluate the real-life diagnosis and therapeutic means of Charcot Neuroosteoarthropathy (CN) in French-Belgian diabetic foot expert centers. METHODS: We collected clinical characteristics, results of exams and therapeutic pathways of consecutive adult patients with diabetic osteoarthropathy seen in consultation or hospitalization from January 1 to December 31, 2019 in 31 diabetic foot expert centers. The primary outcome was to describe the diagnostic and management methods for CN according to patient clinical characteristics, the clinical-radiological characteristics of acute and chronic CN and discharge means. RESULTS: 467 patients were included: 364 with chronic CN and 103 in the acute phase. 101 patients had bilateral chronic CN. Most patients were male (73.4%), treated with insulin (73.3%), and with multicomplicated diabetes. In the acute phase, edema and increased foot temperature were present in 75% and 58.3% of cases, respectively. Diagnosis confirmation was usually by MRI and the mode of discharge was variable. In the chronic phase, orthopedic shoes were prescribed in 81.5% of cases. CONCLUSIONS: This observational study highlights the diagnostic and therapeutic practices in 31 diabetic foot centers. Our results highlight that the use of MRI and the modalities of offloading, an essential treatment in the acute phase, need to be better standardized. Centers were highly encouraging about creating a patient registry.

Intact Fish Skin Graft vs. Standard of Care in Patients with Neuroischaemic Diabetic Foot Ulcers (KereFish Study): An International, Multicentre, Double-Blind, Randomised, Controlled Trial Study Design and Rationale.

BACKGROUND: Cell and/or tissue-based wound care products have slowly advanced in the treatment of non-healing ulcers, however, few studies have evaluated the effectiveness of these devices in the management of severe diabetic foot ulcers. METHOD: This study (KereFish) is part of a multi-national, multi-centre, randomised, controlled clinical investigation (Odin) with patients suffering from deep diabetic wounds, allowing peripheral artery disease as evaluated by an ankle brachial index equal or higher than 0.6. The study has parallel treatment groups: Group 1 treatment with Kerecis® Omega3 Wound™ versus Group 2 treatment with standard of care. The primary objective is to test the hypothesis that a larger number of severe diabetic ulcers and amputation wounds, including those with moderate arterial disease, will heal in 16 weeks when treated with Kerecis® Omega3 Wound™ than with standard of care. CONCLUSION: This study has received the ethics committee approval of each participating country. Inclusion of participants began in March 2020 and ended in July 2022. The first results will be presented in March 2023. The study is registered in ClinicalTrials.gov as Identifier: NCT04537520.

Trends in the relation between hyperglycemia correction and active Charcot neuroarthropathy: results from the EPICHAR study.

INTRODUCTION: The pathophysiology of Charcot neuroarthropathy (CN) remains unclear. There are a number of hypotheses but these are not exclusive. In its clinical presentation, this complication intersects with the semiology of diabetic-induced neuropathy, such as peripheral hypervascularization and the appearance of arteriovenous shunt. The EPICHAR study is as yet an unpublished cohort of people living with diabetes complicated by CN (in active or chronic phase). Based on the findings of the EPICHAR study, this study aimed to investigate whether a reduction in the rate of hyperglycemia accompanies the onset of an active phase of CN. RESEARCH DESIGN AND METHODS: Hemoglobin A1c (HbA1c) levels were assessed 3 months (M3) and 6 months (M6) before the diagnosis of active CN (M0). RESULTS: 103 patients living with diabetes and presenting active CN were included between January and December 2019 from the 31 centers participating in this study (30 in France and 1 in Belgium). The mean age of the participants was 60.2±12.2 years; the vast majority were men (71.8%) living with type 2 diabetes (75.5%). Mean HbA1c levels significantly declined between M6 (median 7.70; Q1, Q3: 7.00, 8.55) and M3 (median 7.65; Q1, Q3: 6.90, 8.50) (p=0.012), as well as between M6 and M0 (median 7.40; Q1, Q3: 6.50, 8.50) (p=0.014). No significant difference was found between M3 and M0 (p=0.072). CONCLUSIONS: A significant reduction in HbA1c levels seems to accompany the onset of the active phase of CN. TRIAL REGISTRATION NUMBER: NCM03744039.

Insulin allergy: a diagnostic and therapeutic strategy based on a retrospective cohort and a case-control study.

AIMS/HYPOTHESIS: Insulin allergy is a rare but significant clinical challenge. We aimed to develop a management workflow by (1) validating clinical criteria to guide diagnosis, based on a retrospective cohort, and (2) assessing the diagnostic performance of confirmatory tests, based on a case-control study. METHODS: In the retrospective cohort, patients with suspected insulin allergy were classified into three likelihood categories according to the presence of all (likely insulin allergy; 26/52, 50%), some (possible insulin allergy; 9/52, 17%) or none (unlikely insulin allergy; 17/52, 33%) of four clinical criteria: (1) recurrent local or systemic immediate or delayed hypersensitivity reactions; (2) reactions elicited by each injection; (3) reactions centred on the injection sites; and (4) reactions observed by the investigator (i.e. in response to an insulin challenge test). All underwent intradermal reaction (IDR) tests. A subsequent case-control study assessed the diagnostic performance of IDR, skin prick and serum anti-insulin IgE tests in ten clinically diagnosed insulin allergy patients, 24 insulin-treated non-allergic patients and 21 insulin-naive patients. RESULTS: In the retrospective cohort, an IDR test validated the clinical diagnosis in 24/26 (92%), 3/9 (33%) and 0/14 (0%) likely, possible and unlikely insulin allergy patients, respectively. In the case-control study, an IDR test was 80% sensitive and 100% specific and identified the index insulin(s). The skin prick and IgE tests had a marginal diagnostic value. Patients with IDR-confirmed insulin allergy were treated using a stepwise strategy. CONCLUSIONS/INTERPRETATION: Subject to validation, clinical likelihood criteria can effectively guide diabetologists towards an insulin allergy diagnosis before undertaking allergology tests. An IDR test shows the best diagnostic performance. A progressive management strategy can subsequently be implemented. Continuous subcutaneous insulin infusion is ultimately required in most patients. CLINICALTRIALS: gov: NCT01407640.

Rapid glycemic regulation in poorly controlled patients living with diabetes, a new associated factor in the pathophysiology of Charcot's acute neuroarthropathy.

OBJECTIVE: Aggressive antidiabetic therapy and rapid glycemic control are associated with diabetic neuropathy. Here we investigated if this is also the case for Charcot neuroarthropathy. RESEARCH DESIGN AND METHODS: HbA1c levels and other relevant data were extracted from medical databases of 44 cases of acute Charcot neuroarthropathy. RESULTS: HbA1c levels significantly declined from 8.25% (67mmol/mol) [7.1%-9.4%](54-79mmol/mol), at -6 months (M-6), to 7.40%(54mmol/mol) [6.70%-8.03%] (50-64 mmol/mol) during the six months preceding the diagnosis of Charcot neuroarthropathy (P <0.001). CONCLUSIONS: HbA1c levels significantly declined during the six months preceding the onset of Charcot neuroarthropathy. This decline seems to be a associated factor with the appearance of an active phase of Charcot neuroarthropathy in poorly controlled patients with diabetic sensitive neuropathy.

Skin collagen pentosidine and fluorescence in diabetes were predictors of retinopathy progression and creatininemia increase already 6years after punch-biopsy.

OBJECTIVE: Advanced glycation end products (AGEs) of collagens appear to contribute to microvascular complications in diabetes. Do high concentrations of AGEs in skin collagen predict accelerated progression of these complications after 6 years and indicate the need for tighter anti-diabetic treatment? DESIGN AND METHODS: We measured two AGE parameters in collagen extracted from skin punch-biopsies: pentosidine and fluorescence at 370/440nm, as markers and predictors of microvascular complications, in 30 patients with diabetes (14 type-1, 16 type-2) without renal insufficiency, and in age- and gender-matched normoglycemic controls, followed at Hôtel-Dieu in Paris. RESULTS: At the time of biopsy, marked increases in pentosidine (p=0.0014) and fluorescence (p=0.0001) expressed per collagen hydroxyproline, were found in the patients with diabetes versus the controls. A significant effect of age was found for pentosidine, but not fluorescence, measurements in the normoglycemic controls. Therefore pentosidine but not fluorescence results were corrected for age in the patients. Pentosidine and fluorescence were correlated with diabetes duration. Fluorescence was significantly dependent on retinopathy presence and score in type-1 and type-2 diabetes, whereas pentosidine was not. Fluorescence was correlated with microalbuminuria only in type-1 diabetes. Neither fluorescence nor pentosidine were correlated with creatininemia. Already six years after biopsy, retinopathy score progression and creatininemia increase were significantly correlated with initial pentosidine and fluorescence measurements. CONCLUSIONS: These AGEs are good predictors of progression of microvascular complications and appear to be pathogenic. High skin concentrations of AGEs should induce tighter anti-diabetic treatment.

Diagnosing diabetic foot osteomyelitis in patients without signs of soft tissue infection by coupling hybrid 67Ga SPECT/CT with bedside percutaneous bone puncture.

OBJECTIVE: Successful treatment of osteomyelitis is more likely with accurate diagnosis and identification of the causative pathogens. This typically requires obtaining a specimen of bone, usually by image-guided biopsy. We sought to develop a simpler bedside method for definitively diagnosing osteomyelitis. RESEARCH DESIGN AND METHODS: Over 2 years, we enrolled consecutive patients presenting to our diabetic foot clinic with a foot ulcer and clinically suspected osteomyelitis but without soft tissue infection. Each underwent hybrid (67)Ga single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) imaging; those with a positive scan underwent bedside percutaneous bone puncture. Patients with a positive bone culture received culture-guided antibiotic therapy. Patients with negative (67)Ga SPECT/CT imaging or with positive imaging but negative bone culture were not treated with antibiotics. All patients were followed up for ≥ 1 year. RESULTS: Among 55 patients who underwent (67)Ga SPECT/CT imaging, 13 had negative results and all of their foot ulcers resolved without antibiotic therapy. Among 42 with positive imaging, 2 were excluded (for recent antibiotic therapy) and 40 had bone punctures (3 punctured twice): 19 had negative results, 3 of which were likely false negatives, and 24 had positive results (all gram-positive cocci). At follow-up, 3 patients had died, 3 had undergone amputation, and 47 had no evidence of foot infection. The sensitivity and specificity of this combined method were 88.0 and 93.6%, respectively, and the positive and negative predictive values were 91.7 and 90.7%, respectively. CONCLUSIONS: Coupling of (67)Ga SPECT/CT imaging and bedside percutaneous bone puncture appears to be accurate and safe for diagnosing diabetic foot osteomyelitis in patients without signs of soft tissue infection, obviating the need for antibiotic treatment in 55% of suspected cases.