Intact Fish Skin Graft to Treat Deep Diabetic Foot Ulcers.

BACKGROUND: Diabetic foot ulcers are chronic, difficult to heal, and potentially life-threatening. Few medical devices have been studied in diabetic ulcers penetrating to bone or tendon. METHODS: We conducted an international, open-label randomized controlled trial, randomly assigning patients with diabetic ulcers penetrating to bone, joint, or tendon 1:1 to intact fish skin graft or standard wound care, with assigned treatment applied through 14 weeks. The primary end point was the proportion of ulcers healed at 16 weeks, defined as reepithelization as identified by the investigator, and confirmed 14 days later. A blinded adjudication committee confirmed healing at both time points. Healing was also assessed at 20 and 24 weeks. RESULTS: Between July 2020 and November 2022, 255 patients were randomly assigned to intact fish skin graft (n=129) or standard of care (n=126). Healing was achieved in 44% of patients at 16 weeks with intact fish skin graft compared with 26% for standard of care (P<0.001, unadjusted), with additional healing at 20 weeks (46% vs. 32%) and 24 weeks (55% vs. 38%). Mean (SD) time to healing was 17.3 (0.69) weeks (95% confidence interval [CI], 15.5 to 18.7) for the intact fish skin graft group and 19.4 (0.66) weeks (95% CI, 18.1 to 20.7) for the standard of care group. In a Cox regression, intact fish skin graft was associated with faster time to healing (hazard ratio, 1.59; 95% CI, 1.07 to 2.36). Primary wound infections were the most common adverse event, occurring in 39 (30.2%) of patients in the intact fish skin graft group and 31 (24.6%) of patients in the standard of care group. CONCLUSIONS: Among patients with deep diabetic foot ulcers, treatment with intact fish skin graft was superior to standard of care in proportion of wounds healed at 16 weeks and was associated with faster time to healing. (Funded by European Commission Fast Track to Innovation Horizon 2020, and Kerecis Ltd. ClinicalTrials.gov NCT04257370.).

Update on Nutritional Advice Post-Heart Transplant: A Cross-Sectional Study across French-Speaking European Centers.

INTRODUCTION: Heart transplantation is the standard treatment for severe heart failure. Graft preservation and infectious risk secondary to immunosuppressive drugs lead healthcare teams to offer nutritional advice to patients upon discharge from the hospital. However, no consensus or recommendation is available. METHOD: We conducted a study to review the practices in all 26 centers providing heart transplantation in French-speaking Europe. We requested and analyzed the written documents these centers provided to their patients. The same two dieticians categorized the highlighted pieces of advice into distinct, autonomous categories. RESULTS: We identified 116 pieces of advice, categorized into three areas: dietary restrictions for immunosuppressant/food interaction; environmental and food preparation guidelines and prevention of foodborne infections; and healthy and active lifestyle recommendations. Except for advice on immunosuppressant/food interaction, over one-third of the centers suggest discontinuing advice within 2 years post-transplant. General dietary advice covers lipids, carbohydrates, protein, calcium, sodium, and fiber but offers limited guidance on fatty acids despite their importance in cardiovascular risk prevention. CONCLUSION: This study represents a pioneering exploration of the nutritional advice provided to patients following cardiac transplantation. It underscores the critical necessity of establishing consensus-based clinical guidelines in this domain.

Attainment of LDL-cholesterol target in high cardiovascular risk type 1 diabetic French people.

AIMS: As people with type 1 diabetes have increased risk of cardiovascular morbi-mortality, management of cardiovascular risk factors is of crucial importance. We assessed the prevalence and factors associated with LDL-cholesterol (LDL-c) target achievement in patients with type 1 diabetes at high and very-high cardiovascular risk. METHODS: In this observational multicenter study, we included hospitalized patients with type 1 diabetes who had a fasting blood lipid analysis at admission. Cardiovascular risk level and LDL-c target values were defined according to ESC/EAS guidelines into force at admission: LDL-c target for very-high risk (VHR) and high risk (HR) patients was 1.4 and 1.8 mmol/l respectively for patients included from September 2019 (2019 guidelines) and 1.8 and 2.6 mmol/l respectively for patients included in 2016-2019 (2016 guidelines). LDL-c target attainment was assessed in HR and VHR patients, and factors associated with attainment were identified with multivariable analysis. RESULTS: We included 85 HR patients (median age 37y [interquartile range: 27;45], 64 % females) and 356 VHR patients (49 [35;61] years, 42 % females). In HR patients, 7 % were treated with statins, and 35.3 % achieved the LDL-c target. Increasing age (odds ratio 0.58 [95 % confidence interval: 0.38;0.89]), body mass index (0.86 [0.75;0.98]), and HbA1c (0.69 [0.50;0.94]) were independently associated with lower odds of attaining LDL-c target. In VHR patients, 36 % were treated with statins, and 17.4 % achieved LDL-c target. Statin treatment (2.33 [1.22;4.43]), secondary prevention (2.33 [1.21;4.48]) and chronic renal failure (2.82 [1.42;5.61]) were associated with higher odds of attaining LDL-c target. CONCLUSION: Control of LDL-c is highly insufficient in both HR and VHR patients. Cardiovascular risk evaluation and better control of risk factors may help decrease cardiovascular morbi-mortality in patients with type 1 diabetes. REGISTRATION NUMBER: NCT03449784.

Semaglutide as a potential treatment for obesity in Smith-Kingsmore syndrome (SKS) patients: A mosaic mutation case report.

We present for the first-time efficacy and tolerability of GLP-1-RA (Semaglutide) in Smith-Kingsmore syndrome (SKS). SKS is a rare genetic disorder characterized by intellectual disability, macrocephaly, seizures and distinctive facial features due to MTOR gene mutation. We present a 22-year-old woman with mosaic SKS and severe obesity (Body Mass Index ≥40 kg/m²), treated with semaglutide. She achieved a 9 kg (7.44%) weight loss over 12 months without adverse effects.This case highlights semaglutide's potential in managing obesity in SKS patients, emphasizing the need for further research in this rare genetic disorder.

Weight suppression at lowest weight as an indicator of eating disorder clinical severity: A retrospective cohort study.

OBJECTIVES: Weight suppression (WS) defines the difference between the highest weight in adulthood and the current weight. WS at lowest weight is the difference between the highest and the lowest ever weight. Weight rebound is the difference between the past lowest weight and current weight. The distinction in the capacities of WS, weight rebound, and WS at the lowest weight remains unclear regarding their efficacy in forecasting clinical endpoints. This study assessed the relationship between WS, WS at lowest weight and/or weight rebound and eating disorder (ED) clinical severity. METHODS: In this retrospective cohort study, adult participants were selected at the Outpatient Unit for multidisciplinary assessment of ED, Montpellier, France, between February 2012 and October 2014 and May 2017 and January 2020. ED clinical severity was evaluated using the Eating Disorder Examination Questionnaire (EDE-Q). RESULTS: The sample included 303 patients: 204 with anorexia nervosa (AN) and 99 with bulimia nervosa (BN). The EDE-Q total score was positively correlated with WS at lowest weight in patients with AN (Spearman's rho = 0.181, p = 0.015) and with BN (Spearman's rho = 0.377; p < 0.001). It was also positively correlated with weight rebound (Spearman's rho = 0.319; p = 0.003) in patients with BN. In the multivariate analysis, EDE-Q total score was associated with WS at lowest weight only in patients with BN (ß = 0.265; p = 0.03). CONCLUSION: WS at lowest weight seems to be a good measure of ED clinical severity. More research is needed for better understanding WS at lowest weight in assessment and treatment of patients with ED.

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery.

OBJECTIVE: This retrospective cohort study aimed to assess the effectiveness of semaglutide 2.4 mg in patients with severe obesity (BMI ≥ 40 kg/m2 ) who had previously undergone bariatric surgery (BS) but failed to achieve satisfactory weight loss or experienced weight regain compared with patients without a history of BS with similar BMI. METHODS: The authors analyzed data from 129 patients with a BMI ≥ 40 kg/m2 , including 39 with (BS+) and 90 without (BS-) a history of BS. The patients received semaglutide treatment for 24 weeks starting at 0.25 mg/wk and gradually increasing to reach a final dose of 2.4 mg/wk. The treatment outcomes were assessed based on the percentage of weight loss, changes in BMI, and waist circumference. RESULTS: Semaglutide treatment resulted in significant 9.1% weight loss in the BS+ group, with no significant difference in weight loss between the BS+ and BS- groups. CONCLUSIONS: This study is the first, to the authors' knowledge, to compare the effectiveness of semaglutide treatment in patients with versus those without a history of BS, providing valuable evidence of its efficacy. By focusing on individuals with severe obesity (BMI > 40 kg/m2 and associated comorbidities), it fills a gap in the current literature and highlights the potential of semaglutide 2.4 mg as a treatment option for this specific population.

Relationship between Lean Tissue Mass and Muscle Function in Women with Obesity.

It is well documented that lean tissue mass (LTM) decreases with aging in patients with obesity, but there is no information available regarding muscle strength changes, a parameter that may be better associated with sarcopenic obesity (SO). The objectives of this study were to analyze the changes in LTM and fat mass (FM), muscle strength and muscle function with aging in women with obesity and to determine the prevalence of SO. LTM and FM were determined by DXA, muscle strength with the hand-grip test and muscle function with the 6 min walk test (6MWT) in 383 women with obesity. A redistribution of the LTM and FM occurred with age, characterized by a gain at the trunk to the detriment of the lower limbs, thus reducting in appendicular LTM indices. The physical performances evaluated by the muscle strength and muscle function decreased concomitantly, and the prevalence of low values for both these parameters was 22.8% and 13.4%, respectively, in the older patients. In summary, although a reduction in appendicular LTM and muscle performances occurred with age and resulted in an increase in the prevalence of SO, the number of women with obesity affected by SO remained low (n ≤ 15), even in those older than 60 years.

Renal function is highly associated with podiatric risk in diabetic patients.

Background: Chronic kidney disease (CKD) is correlated with the incidence of diabetic foot ulcer (DFU). Furthermore, the International Working Group on the Diabetic Foot (IWGDF) has proposed a classification of the risk factors for DFU. The purpose of this study was to investigate the relationship between the IWGDF risk classification and the glomerular filtration rate level estimated by the CKD Epidemiology Collaboration formula (eGFR). Methods: We conducted a prospective multicentric study. Patients were recruited from either diabetology or nephrology departments. The secondary objectives were to determine this relationship after excluding people on dialysis and to identify the factors associated with podiatric risk. Results: Four hundred and eighty-six patients were included, with a mean age of 64.2 years (±15.7) and a mean diabetes duration of 15.7 years (±12.1). Based on the IWGDF classification, 53.5% of the population were in podiatric stage 0, 11.7% in stage 1 and 34.8% in stage 2 or 3. The mean eGFR level was significantly lower in patients with podiatric risk ≥2 (36.8 ± 33.9 mL/min/1.73 m2 vs 71.9 ± 35.3 mL/min/1.73 m2, P < .0001) and a significant association was found between the eGFR and the podiatric risk. This association remained significant after the exclusion of the hemodialysis patients. After receiver operating characteristic analysis, a cutoff of 45 ± 11 mL/min/1.73 m2 (area under the curve 0.76) was found discriminant to define a group of CKD patients at higher risk for podiatric stage ≥2. Conclusion: eGFR levels are linked to podiatric stages in diabetes mellitus. Patients with eGFR <45 mL/min/1.73 m2 and dialysis patients should be carefully managed in collaboration with diabetic foot specialized centers.

Global healthcare pathway of people living with diabetes prior to wounding is associated with a decreased risk of amputation.

AIMS: Diabetic foot ulcer (DFU) has a poor prognosis and high amputation rate. We previously used the French National Health Data System (Système National des Données de Santé: SNDS) to analyze the impact of deprivation and healthcare access on DFU prognosis. The purpose of this ancillary study was to explore the relationship between the global care pathway (care consumption) the year before and after DFU and the risk of amputation. METHODS: We conducted a study based on a cohort from the SNDS. The data came from a region of France and subjects living with a complication of DFU. We looked at care consumption one year before and one year after wound onset. Risk of amputation was calculated one year after DFU onset. RESULTS: Data were extracted for 6,642 patients. Subjects with DFU had a better prognosis regarding amputation risk when they are taking cardiovascular, antibiotic, neurological, drugs. A consultation with an ophthalmologist was also linked to a better prognosis: HR = 0.71 IC95 (0.499-0.995) (p = 0.04). CONCLUSION: People with the best diabetes follow-up, even with several comorbidities, appear to have a better prognosis for their DFU. This highlights the importance of global healthcare and the care pathway in this chronic disease.

Definition of thermal indicators for the study of thermoregulation alterations in the foot of people living within diabetic peripheral neuropathy: A proof of concept.

AIMS: This study investigates how diabetic peripheral neuropathy is linked to impairment of thermoregulatory mechanisms using a thermal camera, spectral thermal analysis and a physical test. METHODS: The plantar skin temperature of all participants was measured using a thermal camera following a 6-min walking exercise. The data were subjected to frequency decomposition, resulting in two frequency ranges corresponding to endothelial and neurogenic mechanisms. Then, 40 thermal indicators were evaluated for each participant. ROC curve and statistical tests allowed to identify indicators able to detect the presence or absence of diabetic peripheral neuropathy. RESULTS: The study included 33 participants living with diabetes. The results revealed that a 6-min walk exercise increased plantar foot temperature and highlighted a significant difference between people living with diabetes with and without peripheral neuropathy (p < 0.01). The results also revealed the advantages of using thermal images rather than single point measurements. CONCLUSIONS: Diabetic peripheral neuropathy is linked to impairment of thermoregulatory mechanisms. This link can be highlighted after a dedicated 6-min walk exercise, enabling to activate these mechanisms, and measuring with a thermal camera the temporal plantar skin temperature. Assessment of this link gave best results by filtering the thermal signal in the neurogenic range.

High prevalence of malnutrition in systemic sclerosis: Results from a French monocentric cross-sectional study.

OBJECTIVES: Systemic sclerosis (SSc) can cause malnutrition due to frequent gastrointestinal involvement. However, prevalence of malnutrition in SSc is poorly known. The aim of this study was to evaluate the prevalence of malnutrition in SSc and its potential associations with disease features in patients from a tertiary referral center. METHODS: All patients meeting American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for SSc followed between January 1, 1985, and January 1, 2019, at the Department of Internal Medicine, Saint Eloi University Hospital, were included. Malnutrition was assessed using the 2020 French recommendations for SSc and the malnutrition universal screening tool score. Severe malnutrition was defined via the French Haute Autorité de Santé (National Health Authority) 2007 criteria. RESULTS: A total of 120 patients were included, with mean age 64 (± 15) y and a female-to-male sex ratio of 5:1. According to 2020 French recommendations, 71 patients (59.2%) were malnourished and 30 (25%) had at least one criterion of severe malnutrition. With the malnutrition universal screening tool score, 41.7%, 20%, and 38.3%, respectively, had low, medium, and high risk of malnutrition. Multivariate analysis revealed the following results: 1) malnutrition was associated with cardiac involvement (P < 0.01); 2) a high malnutrition universal screening tool score was also associated with specific cardiac involvement (P < 0.01); and 3) severe malnutrition was strongly correlated with interincisal distance <35 mm (P = 0.02). CONCLUSIONS: Malnutrition affects more than half of SSc patients and is associated with specific cardiac involvement. Interincisal distance <35 mm could be a red flag for severe malnutrition in SSc.

Use of the SINBAD score as a predicting tool for major adverse foot events in patients with diabetic foot ulcer: A French multicentre study.

OBJECTIVE: To assess the relationship between the site, ischaemia, neuropathy, bacterial infection, area, depth (SINBAD) score and major adverse foot events in patients with diabetes and foot ulcers. METHODS: For this retrospective ancillary study, patients (n = 537) followed for a diabetic foot ulcer (DFU) in six French hospitals were included between 1 February 2019 and 17 March 2019, and between 1 February 2020 and 17 March 2020. The SINBAD score was assessed at inclusion. The frequency of a composite outcome consisting of eight major adverse foot events (MAFE) was assessed after 5-6 months of follow-up: hospitalisation for DFU, septic surgery, revascularisation, minor amputation, major amputation, death, secondary infection and ulcer recurrence. A logistical regression explored the link between the SINBAD score and MAFE and each of its component. RESULTS: A low SINBAD score (from 0 to 3) was observed in 61% of patients and a high (from 4 to 6) in 39%. MAFE occurred in, respectively, 24% and 28% of these patients. Multivariate analyses showed a significant relationship between the SINBAD score and MAFE, with the continuous SINBAD score: odds ratio (OR) 1.72 [95% CI (1.51-1.97)] or dichotomic SINBAD score (values: 0-3 and 4-6): OR 3.71 [95% CI (2.54-5.42)]. The SINBAD score (continuous or dichotomic) at inclusion was also significantly associated with six out of the eight components of the MAFE. CONCLUSIONS: The SINBAD score is a useful tool for predicting major adverse foot events.

Furan fatty acid extracted from Hevea brasiliensis latex increases muscle mass in mice.

Skeletal muscle is essential for locomotion and plays a crucial role in energy homeostasis. It is regulated by nutrition, genetic factors, physical activity and hormones. Furan fatty acids (FuFAs) are minor fatty acids present in small quantities in food from plants and animals origin. Recently, we showed that a preventive nutritional supplementation with furan fatty acid in a DIO mouse model reduces metabolic disorders. The present study was designed to determine the influence of FuFA-F2 extracted from Hevea brasiliensis latex on skeletal muscle phenotype. In C2C12 myotubes we found that FuFA-F2 whatever the concentration used increased protein content. We revealed that in C2C12 myotubes FuFA-F2 (10 µM) increases protein synthesis as shown by the stimulation of mTOR phosphorylation. Next, to confirm in vivo our results C57Bl6 mice were supplemented by oral gavage with vehicle or FuFA-F2 (20 mg/kg) for 3 and a half weeks. We found that mice supplemented with FuFA-F2 had a greater lean mass than the control mice. In line with this observation, we revealed that FuFA-F2 increased muscle mass and promoted more oxidative muscle metabolism in mice as attested by cytochrome c oxidase activity. In conclusion, we demonstrated that FuFA-F2 stimulates muscle anabolism in mice in vitro and in vivo, mimicking in part physical activity. This study highlights that in vivo FuFA-F2 may have health benefits by increasing muscle mass and oxidative metabolism.

Preventive nutritional supplementation with furan fatty acid in a DIO mouse model increases muscle mass and reduces metabolic disorders.

The increase in obesity has become a major global health problem and is associated with numerous metabolic dysfunctions. Furan fatty acids (FuFAs) are minor lipids present in our diet. Recently we showed that FuFA-F2 extracted from Hevea brasiliensis latex stimulates muscle anabolism in mice in vitro and in vivo, mimicking in part physical activity. While skeletal muscle is essential for energy metabolism and is the predominant site of insulin-mediated glucose uptake in the post prandial state, our results suggested that FuFA-F2 could have favorable effects against obesity. The aim of this work was therefore to study whether a preventive nutritional supplementation with FuFA-F2 (40 mg or 110 mg/day/kg of body weight) in a diet-induced obesity (DIO) mouse model may have beneficial effects against obesity and liver and skeletal muscle metabolic dysfunction. We showed that 12 weeks of FuFA-F2 supplementation in DIO mice decreased fat mass, increased lean mass and restored normal energy expenditure. In addition, we found that FuFA-F2 improved insulin sensitivity. We revealed that FuFA-F2 increased muscle mass but had no effect on mitochondrial function and oxidative stress in skeletal muscle. Furthermore, we observed that FuFA-F2 supplementation reduced liver steatosis without impact on mitochondrial function and oxidative stress in liver. Our findings demonstrated for the first time that a preventive nutritional supplementation with a furan fatty acid in DIO mice reduced metabolic disorders and was able to mimic partly the positive effects of physical activity. This study highlights that nutritional FuFA-F2 supplementation could be an effective approach to treat obesity and metabolic syndrome.

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.

Omega-3 to omega-6 fatty acid oxidation ratio as a novel inflammation resolution marker for metabolic complications in obesity.

BACKGROUND AND AIMS: The oxidative metabolism of polyunsaturated fatty acids (PUFAs) leads to bioactive isoprostanoids. The aim was to establish the associations of a complete urinary isoprostanoid profiling in a cohort study of carefully phenotyped obese subjects to determine possible potential differential implications for omega-6 PUFA- and omega-3 PUFA-derived isoprostanoids for obesity, metabolic indicators, and inflammation. METHODS AND RESULTS: PUFA peroxidation compounds were determined in urine samples from obese human subjects (n = 46) by liquid chromatography coupled to tandem mass spectrometry. Increased omega-6 arachidonic acid (AA) oxidation, mainly represented by 5-F2c isoprostane (5-F2c-IsoP) and metabolites of 15-F2t-IsoP, was associated with body mass index, glycated hemoglobin (HbA1c) and mean arterial blood pressure. In addition, we identified the omega-3 PUFA-derived urinary metabolites 14-F4t-NeuroP from docosahexaenoic acid (DHA) and 5-F3t-IsoP from eicosapentaenoic acid (EPA), which declined with age. The omega-3 to omega-6 oxidation ratio was a significant predictor of inflammation in obesity. CONCLUSION: The findings point to full urinary isoprostanoid profiling as a more sensitive measure of PUFA oxidative stress in obesity-induced metabolic complications compared with individual isoprostanoid measures. Furthermore, the results suggest the balance between the omega-3 and omega-6 PUFA oxidation as determinative for the consequences of oxidative stress on inflammation in obesity.