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.

A Wound Environment Control System to Avoid Major Amputation in Diabetic Foot Ulcers.

We report the case of a 58-year-old patient with a diabetic foot lesion at high risk of major amputation successfully treated by a new innovative wound environment control system.

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 The EPICHAR study is as yet an unpublished cohort of people living with diabetes complicated by CN (in active or chronic phase).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.

Evaluation of the Use of Antibiofilmogram Technology in the Clinical Evolution of Foot Ulcers Infected by Staphylococcus aureus in Persons Living with Diabetes: A Pilot Study.

Infected diabetic foot ulcers (DFUs) represent a serious threat to public health because of their frequency and the severity of their consequences. DFUs are frequently infected by bacteria in biofilms, obstructing antibiotic action. Antibiofilmogram was developed to assess the impact of antibiotics to inhibit biofilm formation. This pilot study aimed to determine the benefits of this technology in predicting antibiotic activity on the outcome of 28 patients with Grade 2 DFUs that were infected by a monomicrobial Staphylococcus aureus. Patients with diabetes were followed during the antibiotic treatment (day 14) and the follow-up period of the study (day 45). The contribution of Antibiofilmogram was compared between patients with non-concordant results (n = 13) between antibiogram and Antibiofilmogram versus concordant results (n = 15). The clinical improvement of wounds (80.0% vs. 38.5%, p = 0.0245) and the absence of exudates (0% vs. 33.3%, p = 0.0282) were observed in concordant vs. discordant groups. This pilot study provides promising results for the interest of Antibiofilmogram in the prescription of antibiotics to prevent biofilm formation in infected DFUs.

Characteristics of new patient referrals to specialised diabetic foot units across Europe and factors influencing delays.

OBJECTIVE: Foot ulcers are a common complication of diabetes and are associated with an increase in lower limb amputation and death. Early referral to a specialised unit is recommended. The aim of this study was to assess the characteristics of new-patient referrals to specialised diabetes foot care units across Europe and to determine the factors involved in delayed referral. METHOD: In this prospective observational study, consecutive patients with a new foot ulcer presenting to nine diabetic foot centres in five European countries (France, Germany, Italy, Spain and the UK) were included. RESULTS: Some 25% of the 332 patients included had presented with a foot ulcer >3 months before referral to the participating foot clinic. Compared with patients referred earlier, patients with a long time to referral (>3 months) were older (p=0.006) and had a less severe wound according to Infectious Diseases Society of America (IDSA) classification (p=0.003) and University of Texas classification (grade D=infection + peripheral artery disease, p=0.004). CONCLUSION: The proportion of patients with a diabetic foot ulcer (DFU) referred to a specialised unit >3 months after the beginning of the ulcer remained high throughout Europe. Patients with severe DFU were, however, referred more quickly by front line health professionals. Primary care professionals need to be made aware of the importance of early referral to a specialised unit in order to improve the management of foot disease in patients with diabetes. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.

Effectiveness of fast-track pathway for diabetic foot ulcerations.

AIM: To investigate the effectiveness of fast-track pathway (FTP) in the management of diabetic foot ulceration (DFU) after 2 years of implementation. METHODS: The study group was composed of patients who referred to a specialized DF centre due to DFUs. Those were divided in two groups: early referral (ER) and late referral (LR) patients. According to FTP, ER were considered patients who referred after 2 weeks in the case of uncomplicated non-healing ulcers (superficial, not infected, not ischemic), within 4 days in the case of complicated ulcers (ischemic, deep, mild infection) and within 24 h in the case of severely complicated ulcers (abscess, wet gangrene, fever). Healing, healing time, minor and major amputation, hospitalization, and survival were evaluated. The follow-up was 6 months. RESULTS: Two hundred patients were recruited. The mean age was 70 ± 13 years, 62.5% were male, 91% were affected by type 2 diabetes with a mean duration of 18 ± 11 years. Within the group, 79.5% had ER while 20.5% had LR. ER patients showed increased rates of healing (89.9 vs. 41.5%, p = 0.001), reduced healing time (10 vs. 16 weeks, p = 0.0002), lower rates of minor (17.6 vs. 75.6%, p < 0.0001) and major amputation (0.6 vs. 36.6%, p < 0.0001), hospitalization (47.1 vs. 82.9%, p = 0.001), and mortality (4.4 vs. 19.5%, p = 0.02) in comparison to LR. At multivariate analysis, ER was an independent predictor of healing, while LR was an independent predictor for minor and major amputation and hospitalization. CONCLUSION: After the FTP implementation, less cases of LR were reported in comparison to ER. ER was an independent predictor of positive outcomes such as healing, healing time, limb salvage, hospitalization, and survival.

99mTc-white blood cell SPECT/CT to assess diabetic foot osteomyelitis remission: contribution of semi-quantitative scoring system.

AIMS: We previously reported that 99mTc-White blood cell (WBC) single-photon emission computed tomography (SPECT/CT) could be a useful tool to assess diabetic foot osteomyelitis (DFO) remission and guide the duration of antibiotic treatment. The aim of the present study was to evaluate the performance and reproducibility of two analysis methods to diagnose DFO remission using 99mTc-WBC-SPECT/CT. METHODS: 99mTc-WBC-SPECT/CT performed for patients with DFO at the end of antibiotic treatment were retrospectively read by two nuclear physicians (one senior and one junior). Assessment by conventional visual analysis and by the use of a semi-quantitative scoring system, the composite score index (CSI), was performed. The performance and reproducibility of methods were compared between the two nuclear physicians. Successful treatment of DFO was defined by the absence of DFO relapse at the same site within 1 year. RESULTS: A total of 68 patients with 74 DFO were included. Three were excluded from the analysis due to the low quality of SPECT/CT; among the 71 DFO analyzed, 11 (15.5%) had a relapse during follow-up. Performances of 99mTc-WBC-SPECT/CT to predict DFO remission with conventional visual assessment were significantly lower for junior than for senior nuclear physician with moderate inter-rater agreement (Kappa: 0.417). Performances with the use of CSI were similar between the two readers with good inter-rater agreement (Kappa: 0.756). CONCLUSION: The study found that conventional visual assessment of 99mTc-WBC-SPECT/CT to assess DFO remission requires experience, and supported that CSI could be useful for junior nuclear physician to discriminate residual infections and inflammatory post-treatment uptake.

Referral of patients with diabetic foot ulcers in four European countries: patient follow-up after first GP visit.

OBJECTIVE: This study aimed to analyse the characteristics of patients, including demographics, medical history and treatment, with a diabetic foot ulcer (DFU) during their first follow-up visit to a general practitioner (GP). METHODS: A two-part quantitative online questionnaire was distributed among GPs in France, UK, Germany and Spain. Part one entailed a survey of GPs' perceptions of referrals for DFU. Part two collected data on recently managed DFU cases. The percentage of responses was compared for each question and across the four countries for significant differences. RESULTS: In part one of the study, 600 questionnaires were collected (150 per country) and 1188 patients managed for a DFU were included in the second part. About 88% of patients had type 2 diabetes, with a significant proportion of suboptimal control (average HbA1c: 10.64mmol/l). A patient complaint led to diagnosis in 60% of the cases. Wounds were found to be more frequently located in the toes and midfoot, and were superficial (according to the Texas Wound Classification system) in 80% of the cases. More than two-thirds of patients developed small wounds (<5cm2); more than half of them had infected wounds. Approximately 50% of wounds were ischaemic, which triggered the onset of a DFU. Follow-up wound examinations before and after hospitalisation were performed by nurses, except in Germany where GPs undertook this role, including prescribing offloading devices and in the UK where follow-up was managed by podiatrists. Ischaemia, wound necrosis, suspected osteomyelitis and absence of wound healing were the primary reasons for hospital admission during the first month after diagnosis. CONCLUSION: Delay in specialised foot care is a recurring topic in the treatment of DFUs, even with different health-care structures across Europe. Knowledge and education on DFUs should be reinforced among GPs and nurses to establish a global DFU care network between primary and specialised care, avoid hospitalisation and adequately manage high-risk patients.

The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors.

Immune checkpoint inhibitors (CPI) are increasingly being used in oncology, and many autoimmune side effects have been described. Diabetes mellitus (DM) has been reported in approximately 1% of subjects treated with programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors, alone or in association with CTLA-4 inhibitors. In the present mini-review, we aimed to describe different clinical pictures and pathophysiology associated with these forms of diabetes. Data on CPI-related DM was gathered from the largest case series in the literature and from our centre dedicated to immunotherapy complications (ImmuCare-Hospices Civils de Lyon). Most cases are acute autoimmune insulin-dependent diabetes which are similar to fulminant diabetes (extremely acute onset with concomitant near-normal HbA1c levels). Other cases, however, have a phenotype close to type 2 diabetes or appear as a decompensation of previously known type 2 diabetes. The occurrence of diabetes can also be a complication of autoimmune pancreatitis induced by CPI use. Finally, two cases of diabetes in a context of autoimmune lipoatrophy have recently been described. Regarding the wide variety of CPI-induced diabetes, the discovery of a glucose disorder under CPI should motivate specialised care for aetiological diagnosis and appropriate treatment.

Aspirin in people with diabetes: Time to clean up the prescription list?

The effect of aspirin in primary cardiovascular (CV) prevention in people with diabetes is still a matter of debate. Recent results of ASCEND trial suggest that the absolute benefit on CV events is largely counter-balanced by the bleeding risk. However, one crucial question is whether aspirin should be maintained or withdrawn from the prescription list of those who are already under this therapy since a while ago. Indeed, large epidemiological data reported that the aspirin discontinuation was associated to an increased risk of CV events. Moreover, besides the CV outcome, potential positive impact of aspirin on cancer is still under investigation. To conclude, there is no more systematic indication for aspirin in people with diabetes free of CV disease, especially when diabetes and all other CV risk factors are optimally controlled. For those already on aspirin, data are not conclusive enough for a systematic approach and benefit/risk balance must be discussed with patients to take a shared decision.

Neurovascular Response to Pressure in Patients With Diabetic Foot Ulcer.

Diabetic foot ulcer (DFU) is a problem worldwide, and prevention is crucial. We hypothesized that the inability of the skin to respond to pressure is involved in DFU pathogenesis and could be an important predictive factor to take into account. We included 29 patients with DFU and 30 patients with type 2 diabetes without DFU. Neuropathy and skin blood flow at rest were assessed in response to acetylcholine, sodium nitroprusside, local heating (42°C), and to nonnoxious locally applied pressure. Results were compared with those obtained from 10 healthy age-matched control subjects. Vasodilatation in response to pressure was significantly impaired in both groups with diabetes compared with healthy subjects. The vasodilator capacity to pressure was significantly lower in patients with DFU compared with those without DFU, despite the absence of significant difference in cutaneous pressure perception threshold and vascular reactivity to acetylcholine, sodium nitroprusside, and heat. This pronounced alteration of neurovascular response to pressure in patients with DFU is a good marker of skin vulnerability and could be used to better predict individuals at risk.

Vascular Events and Carotid Atherosclerosis: A 5-Year Prospective Cohort Study in Patients with Type 2 Diabetes and a Contemporary Cardiovascular Prevention Treatment.

BACKGROUND AND AIMS: European recommendations on cardiovascular prevention suggest that carotid atherosclerosis assessment by duplex ultrasonography could help in some cases to better assess CV risk. We investigated whether the presence of carotid atherosclerosis determined by duplex ultrasonography is associated with cardiovascular events in patients with type 2 diabetes and could therefore help to reclassify cardiovascular risk. METHODS: Among 624 consecutive patients with type 2 diabetes and carotid atherosclerosis assessment by duplex ultrasonography between January and December 2012, 583 (93%) were included and followed up prospectively. The primary endpoint was the occurrence of cardiovascular events. The rate of new cardiovascular events was compared between patients with (n = 104) and those without (n = 479) prior cardiovascular events. RESULTS: A total of new 104 cardiovascular events occurred in 72 patients (12.5%) during a mean ± SD follow-up period of 5.1 ± 1.6 years. At baseline, for 202 patients (34.6%), carotid evaluation was normal; 381 (65.4%) had a carotid atherosclerosis lesion. The presence of carotid atherosclerosis at baseline was not significantly associated with an increased risk of new cardiovascular events in both groups. The rate of new cardiovascular events was more than twice as high in patients with prior cardiovascular event than those without. CONCLUSION: Systematic carotid atherosclerosis assessment by duplex ultrasonography in patients with type 2 diabetes and a contemporary cardiovascular prevention treatment does not offer additional information as to the risk of cardiovascular events. This trial is registered with ClinicalTrials.gov (ID: NCT02929355).

Diabetes mellitus induced by PD-1 and PD-L1 inhibitors: description of pancreatic endocrine and exocrine phenotype.

AIMS: Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors restore antitumor immunity, but many autoimmune side-effects have been described. Diabetes mellitus is a rare complication, and little data concerning its pathophysiology and phenotype have been published. This study aimed to describe both pancreatic endocrine and exocrine functions, immunological features and change in pancreas volume in subjects with diabetes mellitus induced by PD-1 and PD-L1 inhibitors. METHODS: We analyzed the data of six subjects treated with immunotherapy who presented acute diabetes. RESULTS: There were five men and one woman. Median age was 67 years (range 55-83). Three subjects were treated with nivolumab, two with pembrolizumab and one with durvalumab. Median time to diabetes onset after immunotherapy initiation was 4 months (range 2-13). Four patients presented fulminant diabetes (FD); none of these had type 1 diabetes (T1D)-related autoantibodies, none of them had T1D or FD-very high-risk HLA class II profiles. The bi-hormonal endocrine and exocrine pancreatic failure previously reported for one FD patient was not found in other FD subjects, but glucagon response was blunted in another FD patient. Pancreas volume was decreased at diabetes onset in 2 FD patients, and all patients presented a subsequent decrease of pancreas volume during follow-up. CONCLUSIONS: In the patients presented herein, immunotherapy-induced diabetes was not associated with T1D-related autoantibodies. The hormonal and morphological analysis of the pancreatic glands of these six cases contributes to the understanding of the underlying and probably heterogeneous mechanisms. There is a need to find biomarkers to identify patients at risk to develop these new forms of diabetes at early stages of the process to prevent ketoacidosis and to evaluate preventive strategies.

Perception of diabetic foot ulcers among general practitioners in four European countries: knowledge, skills and urgency.

OBJECTIVE: Diabetic foot ulcers (DFU) have the potential to deteriorate rapidly, in the absence of prompt assessment and treatment. The aim of this study was to analyse the awareness and perception of DFU among general practitioners (GPs) from four European countries, and to find possible differences between these countries in terms of management. METHOD: A two-part, quantitative, online questionnaire was distributed to GPs across four countries in Europe-the UK, France, Germany and Spain. The first part entailed a survey on the perception and knowledge of the pathogenesis and management of DFU, among GPs. The second part of the questionnaire was used for the collection of data on recently-managed DFU cases. RESULTS: For the first part of the study, 600 questionnaires were collected (150 per country) and 1188 patient cases of DFU management were included in the second part. In France, only 49% of GPs mentioned neuropathy as the main causative process in DFU development. However, in Germany and the UK, 82% and 83% of GPs, respectively, considered neuropathy as an important causative factor. DFU care in Spain and the UK is thought to be organised by multidisciplinary teams (MDT) (83% and 84% of GPs, respectively, completely agreed with this statement). In France and Germany, GPs are responsible for follow-up and management. Only UK physicians have clearly identified specialised podiatrists to refer patients to, if needed. Approximately 29-40% of GPs in all countries did not feel they were sufficiently trained in the DFU treatment protocol. Almost 30% of GPs in France and Germany thought that DFU treatment was not well-established due to the absence of clinical guidelines and protocols. CONCLUSION: The intra-country and inter-country management of the complex aspects of DFU is quite heterogeneous. The cause of this finding is multifactorial. Although there are international guidelines, it would be beneficial to establish clear and specific competencies for the different health professionals involved in DFU management. As a minimum, intra-country heterogeneity should improve with their development.

Delayed referral of patients with diabetic foot ulcers across Europe: patterns between primary care and specialised units.

OBJECTIVE: Diabetic foot ulceration (DFU) has the potential to deteriorate rapidly without prompt assessment and treatment. The aim of this study was to assess the referral patterns for DFU, from primary care to specialised diabetes foot care units. METHOD: A two-part, quantitative, online questionnaire was administered to GPs across four countries in Europe: France, the UK, Germany and Spain. The first part entailed a survey of GPs' perceptions of referrals for DFU. The second part of the questionnaire collected data on recently managed DFU cases. RESULTS: There were 600 questionnaires collected in the first part of the study (150 per country), and 1188 patient cases of DFU management were included in the second part. Up to 95% of patients had type 2 diabetes. Patients' complaints led to diagnosis, on average, 60% of the time, and the diagnosis was an incidental finding during a consultation 13-28% of the time. On average, only 40% of GPs completely agreed that they have clearly identified DFU clinical practitioners working in a hospital facility. In 55-66% of cases, the duration of DFU was unknown or DFU diagnosis was delayed more than three weeks from the onset of the wound. On average, 48% of patients were referred after an unknown duration or more than one month from the onset of DFU. CONCLUSION: Despite differences in health-care structures across Europe, delays in referral to specialist foot care teams seems to be a common theme. There is an ongoing need to educate GPs, nurses and patients to be more aware of the risk of DFU, and the need for prompt referral to specialist diabetic foot teams.