Cardiovasc Diabetol

Lower-extremity arterial disease (LEAD) is a major endemic disease with an alarming increased prevalence worldwide. It is a common and severe condition with excess risk of major cardiovascular events and death. It also leads to a high rate of lower-limb adverse events and non-traumatic amputation. The American Diabetes Association recommends a widespread medical history and clinical examination to screen for LEAD. The ankle brachial index (ABI) is the first non-invasive tool recommended to diagnose LEAD although its variable performance in patients with diabetes. The performance of ABI is particularly affected by the presence of peripheral neuropathy, medial arterial calcification, and incompressible arteries. There is no strong evidence today to support an alternative test for LEAD diagnosis in these conditions. The management of LEAD requires a strict control of cardiovascular risk factors including diabetes, hypertension, and dyslipidaemia. The benefit of intensive versus standard glucose control on the risk of LEAD has not been clearly established. Antihypertensive, lipid-lowering, and antiplatelet agents are obviously worthfull to reduce major cardiovascular adverse events, but few randomised controlled trials (RCTs) have evaluated the benefits of these treatments in terms of LEAD and its related adverse events. Smoking cessation, physical activity, supervised walking rehabilitation and healthy diet are also crucial in LEAD management. Several advances have been achieved in endovascular and surgical revascularization procedures, with obvious improvement in LEAD management. The revascularization strategy should take into account several factors including anatomical localizations of lesions, medical history of each patients and operator experience. Further studies, especially RCTs, are needed to evaluate the interest of different therapeutic strategies on the occurrence and progression of LEAD and its related adverse events in patients with diabetes

Spatial investigation of congenital malformations in Reunion Island (2008-2012)

International audienceBackground: Reunion Island is a French territory located in the south- western Indian Ocean. The Reunion Registry of congenital malformations is in charge of monitoring cases. Overall prevalence (289 cases per 10,000 births) is close to the average reported by mainland French registries (315 cases). However, the prevalence of spina bifida is almost twice (10 cases per 10,000 births) the one reported in mainland France (5 cases). This study aims to describe the spatial distribution of different birth defects and identifying clusters.Methods: The analysis specifically tackles three groups being potentially related to environmental exposure. Each case recorded between 2008 and 2012 was geolocated according to its home address: 492 cases of congenital heart defects, 108 cases of cleft lip and palate and 69 cases of spina bifida. Four statistical methods were applied at different administrative scales: Standardized Prevalence Ratio (SPR), Hierarchical Clus- ter Analysis (HCA), Kulldorff method and Geographic epicenter method.Results: The resulting clusters differ depending on the method. Combining the observation at different administrative scales helps to identify the most affected areas for each pathology.Conclusions: These initial observations allow considering case-control studies to identify exposure factors in the most affected areas, including environmental, socio-economic and healthcare factors

Spatial investigation of congenital malformations in Reunion Island (2008-2012)

International audienceBackground: Reunion Island is a French territory located in the south- western Indian Ocean. The Reunion Registry of congenital malformations is in charge of monitoring cases. Overall prevalence (289 cases per 10,000 births) is close to the average reported by mainland French registries (315 cases). However, the prevalence of spina bifida is almost twice (10 cases per 10,000 births) the one reported in mainland France (5 cases). This study aims to describe the spatial distribution of different birth defects and identifying clusters.Methods: The analysis specifically tackles three groups being potentially related to environmental exposure. Each case recorded between 2008 and 2012 was geolocated according to its home address: 492 cases of congenital heart defects, 108 cases of cleft lip and palate and 69 cases of spina bifida. Four statistical methods were applied at different administrative scales: Standardized Prevalence Ratio (SPR), Hierarchical Clus- ter Analysis (HCA), Kulldorff method and Geographic epicenter method.Results: The resulting clusters differ depending on the method. Combining the observation at different administrative scales helps to identify the most affected areas for each pathology.Conclusions: These initial observations allow considering case-control studies to identify exposure factors in the most affected areas, including environmental, socio-economic and healthcare factors

Spatial investigation of congenital malformations in Reunion Island (2008-2012)

International audienceBackground: Reunion Island is a French territory located in the south- western Indian Ocean. The Reunion Registry of congenital malformations is in charge of monitoring cases. Overall prevalence (289 cases per 10,000 births) is close to the average reported by mainland French registries (315 cases). However, the prevalence of spina bifida is almost twice (10 cases per 10,000 births) the one reported in mainland France (5 cases). This study aims to describe the spatial distribution of different birth defects and identifying clusters.Methods: The analysis specifically tackles three groups being potentially related to environmental exposure. Each case recorded between 2008 and 2012 was geolocated according to its home address: 492 cases of congenital heart defects, 108 cases of cleft lip and palate and 69 cases of spina bifida. Four statistical methods were applied at different administrative scales: Standardized Prevalence Ratio (SPR), Hierarchical Clus- ter Analysis (HCA), Kulldorff method and Geographic epicenter method.Results: The resulting clusters differ depending on the method. Combining the observation at different administrative scales helps to identify the most affected areas for each pathology.Conclusions: These initial observations allow considering case-control studies to identify exposure factors in the most affected areas, including environmental, socio-economic and healthcare factors

Risk Factors for a First Episode of Ventilator-Associated Pneumonia Caused by Stenotrophomonas Maltophilia

Abstract Background: The incidence of ventilator-associated pneumonia caused by Stenotrophomonas maltophilia (SM-VAP) is on the rise. This pathology is associated with increased morbidity and mortality in intensive care unit (ICU), notably due to intrinsic resistance and ineffective probabilistic antibiotic therapy. Our study aimed to determine the risk factors for a first episode of SM-VAP in ICU.Methods: This single center retrospective study was conducted from 2010 to 2018 in the polyvalent ICU of Félix Guyon University Hospital in Reunion Island. All patients who developed ventilator-associated pneumonia (VAP) during their ICU stay were consecutively evaluated. Patients with a first episode of SM-VAP were compared to those with a first episode of VAP caused by another microorganism. Results: A total of 89 patients developed a first episode of SM-VAP over the study period. In the group of patients with SM-VAP, infection was polymicrobial in 43.8% of cases and ICU mortality was 49.4%. After multivariate logistic regression analysis, the risk factors for a first episode of SM-VAP were: chronic respiratory failure (Odds Ratio (OR): 4.212; 95% Confidence Interval (CI): 1.776 – 9.989; p = 0.001), chronic renal failure (OR: 2.693; 95% CI: 1.356 – 5.352; p = 0.05), use of third-generation cephalosporins active against Pseudomonas aeruginosa (OR 2.862; 95% CI: 1.505 – 5.442; p = 0.001), and female sex (OR: 2.646; 95% CI: 1.458 – 4.808; p = 0.001). Conclusion: In our study, chronic respiratory failure, chronic renal failure, use of third-generation cephalosporins active against P. aeruginosa, and female sex were identified as risk factors for a first episode of SM-VAP.</jats:p

Prognostic Values of Inflammation and Oxidative Stress Biomarkers on the Risk of Peripheral Arterial Disease in Type 2 Diabetes

International audienceAim: We tested whether inflammation and oxidative stress biomarkers may predict the risk of peripheral arterial disease (PAD) in the SURDIAGENE (SURvie, DIAbete de type 2 et GENEtique) type 2 diabetes cohort.Methods: plasma concentrations of angiopoietin like 2 (ANGPTL2), TNF receptor 1 (TNFR1), fluorescent advanced glycation end products (F-AGE), advanced oxidation protein products (AOPP), protein carbonyl, ischemia-modified albumin (IMA), total reductive capacity of plasma (TRCP) and oxidative hemolysis inhibition assay (OxHLIA) were measured at baseline using ELISA, spectrofluorimetry, spectrophotometry and Folin-Ciocalteu methods. Cox model was fitted to assess the risk of severe PAD, requiring aortic or lower limb revascularization, by increasing tertiles of each biomarker at baseline adjusting for confounding variables. C-statistic was used to test PAD discrimination.Results: Among 1395 participants free for PAD at baseline (men 57%, mean±SD age 65±11 years, diabetes duration 14±10 years), aortic or lower limb revascularization was performed in 66 (4.7%) patients during 5.8±3.2 years of follow-up. The rate of revascularisation was higher in the upper tertiles (T2, T3) compared to the lower one (T1): TNFR1 (HR [95% CI] T2 vs. T1, 1.15 [1.01-1.32]; T3 vs. T1, 1.59 [1.34-1.88], trend pConclusion: Our results suggest that TNFR1, F-AGE, and TRCP can be used to screen severe PAD in type 2 diabetes, and support the role of inflammation and oxidative stress on the pathogenesis of PAD.DisclosureM. Nativel: None. F. Schneider: None. P. Saulnier: None. O. Meilhac: None. P. Rondeau: None. M. Cournot: None. L. Potier: Consultant; Self; Sanofi, Novo Nordisk A/S, Eli Lilly and Company. Board Member; Self; Merck Sharp & Dohme Corp.. G. Velho: None. M. Marre: Board Member; Self; Abbott. Consultant; Self; AstraZeneca. Board Member; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Eli Lilly and Company. Board Member; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. Research Support; Self; Sanofi. Board Member; Self; Servier. R. Roussel: Advisory Panel; Self; AbbVie Inc., Abbott, Eli Lilly and Company, Sanofi, Novo Nordisk A/S, AstraZeneca. Speaker's Bureau; Self; Servier. Consultant; Self; Bayer AG. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Amgen Inc., Sanofi, Novo Nordisk A/S, Danone Research. Stock/Shareholder; Self; Iriade. Advisory Panel; Self; Physiogenex S.A.S.. V. Rigalleau: None. K. Mohammedi: Speaker's Bureau; Self; Novo Nordisk Inc.. Other Relationship; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Sanofi. Other Relationship; Self; Sanofi, Takeda Development Centre Europe Ltd., Boehringer Ingelheim Pharmaceuticals, Inc. S. Hadjadj: Consultant; Self; Abbott, Novo Nordisk A/S, Servier, AstraZeneca, Merck Sharp & Dohme Corp.. Board Member; Self; Valbiotis. Consultant; Self; Sanofi, Eli Lilly and Company

Microencapsulation of mesenchymal stromal cells in covalent alginate hydrogels for cell therapy

International audienceAbstract Osteoarthritis (OA) is the most common inflammatory joint disease and currently lacks an effective curative treatment. Intra-articular injection of mesenchymal stromal cells (MSCs) has gained attention as a relevant therapeutic approach for OA treatment due to the MSC’s ability to secrete anti-inflammatory and immunomodulatory factors. Given their limited viability post-intraarticular injection and the potential leakage of cells out of the injection site, encapsulating MSCs in hydrogels is considered a promising strategy to protect them and provide a suitable 3D microenvironment to support their biological activities. Calcium-cross-linked alginate hydrogels are commonly used for MSC encapsulation, but their long-term in vivo stability remains uncertain. On the other hand, alginate cross-linking by the strain-promoted azide-alkyne cycloaddition (SPAAC) reaction would create a network unaffected by an ionic environment. Hence, this study aimed to develop an alginate-based hydrogel cross-linked via stable and cytocompatible covalent bonds for cell encapsulation. We established for the first time the formation of covalent alginate hydrogels between two SPAAC precursors, namely alginate-BCN and alginate-N 3 . These hydrogels exhibited in vitro stability and enabled the diffusion of molecules of interest. We then generated alginate-based SPAAC microgels of 170 μm in mean diameter, suitable for intra-articular injection. We next encapsulated human adipose MSCs (hASCs) in these alginate-based SPAAC microgels and confirmed their cytocompatibility, with over 90 % of cells remaining viable after 14 days in culture. Finally, the microencapsulated hASCs maintained their biological properties and were able to secrete anti-inflammatory factors (IDO, PGE2, and HGF) when exposed to pro-inflammatory cytokines (TNF-α and IFN-γ). In the end, human activated lymphocytes were cultured in contact with microencapsulated hASCs, and CD3+ T cell proliferation was quantified by flow cytometry. We demonstrated that the encapsulation process did not impair the hASC immunomodulatory activity. Overall, our findings show the potential of alginate-based SPAAC hydrogels for microencapsulating hASCs for cell therapy

Mise en place d'une surveillance spatialisée des malformations congénitales à La Réunion : choix méthodologiques

International audienceIntroduction – The Registry of Congenital Malformations (CM) in Reunion Island (REMACOR) oversees the surveillance of CM for public health and research purposes. This surveillance consists of the exhaustive collec- tion of cases, and temporal analysis of CM. Since 2013, REMACOR has retrospectively geolocalized the data to allow their spatial analysis and the detection of health signals the methodology of which is presented hereunder.Materials and methods – Each case is geolocated according to the mother’s address, using the reference address databases. Birth-related prevalence is then calculated by aggregating cases according to the different administrative scales. The choice of the suitable scale is determined using a Poisson test that estimates the minimum number of births required to perform the analysis in a statistically signi cant manner, and then a compromise between this representativeness of information, data completeness and spatial resolution.Results – 95% of the cases could be geolocalized. Different cluster detection methods are used to identify the most affected areas. Finally, clusters detected at different scales are nally intersected to calculate an index of belonging to 1, 2 or 3 scales.Discussion and conclusion – The spatialized database set up now allows REMACOR to consider the spatial heterogeneity of the distribution of the most frequent CM in order to inform public health stakeholders.Introduction: Le Registre des malformations congénitales de La Réunion (Remacor) assure la surveillance de ces pathologies à des fins de santé publique et de recherche. Cette surveillance consiste en un recueil exhaustif des cas et en l'analyse temporelle de leur survenue. Afin de permettre leur analyse spatiale et la détection de signaux sanitaires, le Remacor a géocodé rétroactivement les données et mis en place une surveillance spatialisée, dont les choix méthodologiques sont présentés ici.Matériel et méthodes: Chaque cas est géolocalisé conformément à l'adresse de la mère. Les prévalences relatives aux naissances sont ensuite calculées par agrégation des cas selon les différentes échelles administratives. Le choix de l'échelle est déterminé à l'aide d'un test de Poisson qui permet d'estimer le nombre de naissances minimum nécessaire pour réaliser l'analyse de manière statistiquement significative, puis d'un compromis entre cette significativité de l'information, la complétude des données et la résolution spatiale.Résultats: Il a été possible de géolocaliser 95% des cas. Différentes méthodes de détection d'agrégats de cas ont été utilisées afin de repérer les zones les plus touchées. Enfin, les agrégats détectés à différentes échelles ont été intersectés pour calculer un indice d'appartenance à 1, 2 ou 3 échelles.Discussion et conclusion: La base de données spatialisée mise en place permet aujourd'hui au Remacor de prendre en compte l'hétérogénéité spatiale de la distribution des malformations congénitales les plus fréquentes pour informer les acteurs de la santé publique