St Egreve Cedex, France

French Registry for Monitoring Pregnancies for Multiple Sclerosis

METHODOLOGY Prospective, observational, multicentric and national epidemiological study, within the scope of the OFSEP, including all groups of patients eligible to participate in the Observatoire Français de la Sclérose en Plaque (OFSEP) (definite MS, radiologically isolated syndromes, clinically isolated syndromes, neuromyelitis optica (NMO) and NMO spectrum disorders), with no age limit and an ongoing pregnancy. Women will be followed during pregnancy and in the year after and their children until 6 years of age. STATISTICAL ANALYSIS To be determined for each specific question. EXPECTED RESULTS Interactions between pregnancy and MS course have been well characterized before the therapeutic era. Neurologists and patients are lacking information to weigh benefits and risks of DMDs used immediately before or during pregnancy, including short and long-term risks to the mother and to the child, but also after delivery. This study should help provide better answers to those questions as well as to still controversial questions about locoregional analgesia and breastfeeding. By following these patients within the Observatoire Français de la Sclérose en Plaque (OFSEP) cohort, the investigator will also have access to a comprehensive description of MS before pregnancy but also in the long term.

Dat'Aids Prevention

Serum Neurofilament-light Chain and GFAP Levels in Patients From the OFSEP Cohort at Different Landmarks of Multiple Sclerosis

Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients

Frequency of Pompe Disease in Patients With Myalgia With or Without Hyper Ckemia - Data From the Reference Center (CERCA)

Patients include: clinical examination, enzyme activity assay, muscle testing, cardiological and respiratory workup. Lowered enzyme activity suggests a pathogenic genetic variant to be identified. The secondary objective is to propose genetic counselling and a family investigation in order to identify relatives who are also affected.

Role NLRP3 Inflammasome in Weight Loss Following Sleeve Gastrectomy in Morbidly Obese Patients

Epidemiological studies show a very rapid increase in the epidemic of obesity in the Caribbean population. The latest prevalence data in Martinique show that 6 out of 10 adults are overweight and 1 out of 4 is obese (Body Mass Index, BMI ≥ 30 kg/m2). Obesity with a BMI ≥ 35 kg/m2 is said to be "morbid" because of its association with numerous cardiovascular comorbidities. A balanced diet and physical activity are effective behavioural modalities for weight loss, which, even at low intensity, can reduce cardiovascular complications and the risk of death. However, many patients do not adhere to these constraints over a long period of time and about 50% of them regain weight after the first year. These observations highlight the value of alternative therapies with lasting effects on weight loss and the cardio-metabolic comorbidities of obesity. Bariatric surgery with vertical calibrated vertical gastroplasty with gastric resection (or sleeve gastrectomy) and Roux-en-Y gastric bypass are therapeutic options that are not only effective in the long term for weight loss but also beneficial in terms of insulin resistance and cardiovascular complications. Bariatric surgery is currently indicated for the treatment of morbid obesity with a BMI ≥ 40 kg/m2 or a BMI ≥ 35 kg/m2 in the presence of complications. Some patients nevertheless remain resistant to the beneficial cardio-metabolic effects of bariatric surgery. The reasons for this resistance are attributed to factors such as age > 60 years, female sex, BMI > 45 kg/m2, African-American or Hispanic origin, and history of type 2 diabetes. Regardless of these factors, several studies have pointed out that a chronic low-grade inflammatory state reduces the magnitude of weight loss and thus counters the beneficial cardio-metabolic effects of bariatric surgery. Visceral adipose tissue is largely responsible for the inflammatory syndrome in obese patients, via the activation of nuclear transcription factors (NFkB, in particular) that stimulate the synthesis of numerous mediators and pro-inflammatory cytokines. Obesity can also induce the formation of multi-protein platforms called inflammasomes, including the active assembly of inflammatory caspases (caspase-1, in particular) that cleave the pro-interleukins IL1β and IL18 into mature pro-inflammatory cytokines IL1β and IL18. The role of the inflammasome NLRP3 ("NOD-like receptor family, pyrin domain containing 3") in the inflammatory response has been particularly studied in humans due to its association with multiple chronic inflammatory, infectious and cardio-metabolic pathologies. Among the biomolecules responsible for activation of the NLRP3 inflammasome during obesity are palmitate, sphingolipids and cholesterol crystals. The NLRP3 inflammasome is also activated by mitochondrial production of reactive oxygen species (ROS) and by mitochondrial DNA released from mitochondria damaged by lipo-toxicity phenomena associated with obesity. More generally, the mitochondrial dysfunction of the metabolic syndrome is considered to be the causal intracellular event of the deregulation of the inflammatory response mediated by the inflammasome.

Dual Therapy in HIV Patients in 4 Days a Week Versus 7 Days a Week

Open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48 the non-inferiority of antiretroviral dual therapy taken 4 consecutive days a week versus dual therapy taken 7 days a week, in HIV infected patients with controlled viral load for at least 12 months and stable antiretroviral dual therapy since 4 months. The non-inferiority margin (delta) is 5%. The randomization will be stratified according to the family of the dual therapy at the moment of the inclusion and according to the participation of the substudy or not. The sample size calculation assumes that the true difference in efficacy between the two arms is zero and that the overall response rate is 97% at week 48. A total of 440 patients (220 per arm) is required to provide 80% power to demonstrate non-inferior efficacy for the 4/7 strategy, compared to the daily dual therapy (7/7), with a two-sided significance level of 5% and a non-inferiority margin (delta) of -5%.

Adequacy of Management of Patients With Asthma Exacerbation in Martinique

The rationale for this study is based on the lack of data concerning the characteristics of asthma exacerbations and their emergency management in Martinique, but also the lack of awareness of the adequacy of this management according to the stage of severity, as recommended. Better knowledge of asthma exacerbations, of the stage of clinical severity, of emergency treatments and of post-emergency follow-up, would improve the overall care of asthma patients in Martinique and induce a better control their disease. This prospective clinical research includes all the services of the Martinique University Hospital which take care of asthma patients during or after their exacerbation: Emergency medical assistance service (SAMU), Mobile emergency and resuscitation structure (SMUR), adult and pediatric emergency services, adult and pediatric resuscitation and pulmonology service. In order not to guide or influence the therapeutic decisions of the investigators in charge of the patients in this study, and because the evaluation of the adequacy of the management according to the stage of severity is the main objective of the study, no recommendations or instructions are given to the investigators. Each investigator freely decides on the treatment (diagnosis, assessment of severity, treatment, modalities and prescription for discharge from emergencies, hospitalization or not). This research is the first assessment of asthma exacerbations carried out in our region with the aim of improving their management in order to limit their prognostic impact.

Prevalence of the c.853delT Mutation of the HOXB13 Gene in Prostate Cancer in Martinique

In Martinique, prostate cancer incidence rates are nowadays among the highest worldwide with a high incidence of early-onset and familial forms. Despite the demonstration of a strong familial component, identification of the genetic basis for hereditary prostate cancer is challenging. The screening of the HOXB13 gene is recommended for men who develop an early-onset and/or familial Pca . In fact, the HOXB13 germline variant G84E (rs138213197) was described in men of European descent with prostate cancer risk. Other germline variants were detected in ethnic groups. More recently, we reported a rare HOXB13 mutation, specifically c.853delT (pTer285Lysfs) that appears to be contribute to young Prostate Cancer cases in Martinique. This variant is a stop loss reported only among patients of African ancestry . Regarding the allele frequency of the HOXB13 c.853delT variant observed in the Pca cohort, it will be necessary to assess relative and absolute Pca risks for HOXB13 c.853delT carriers. This information is essential to use this variant in genetic counseling. We propose to sequence the HOXB13 gene of all prostate cancers cases managed in urology consultation in Martinique.

Heart Failure: Don't Forget the Role of Amyloidosis

The heart supplies the organs with oxygen and nutrient-rich blood. During exercise, the heart adapts by increasing the rate of contraction and the rate of blood flow. Heart failure occurs when the heart loses its muscular strength and its normal capacity to contract; it no longer pumps enough blood to allow the organs to receive enough oxygen and nutrients, which are essential for their proper functioning. This syndrome is frequent and serious with a prevalence of 2 to 3% in Europe and a high morbidity and mortality (1st cause of hospitalization with more than 150,000 hospitalizations per year in France, a mortality of 50% at 5 years, i.e. more than most cancers). This mortality is even higher in the West Indies, with an excess of premature mortality related to heart failure of +32.9% in Martinique and +86.9% in Guadeloupe compared with metropolitan France (average annual mortality rate for heart failure in 2008-2010 per 100,000 in habitants under 65 years of age). Some studies have indeed shown a higher prevalence of heart failure in the Afro-Caribbean and Afro-American population with etiologies that differ from the Caucasian population. Among them, transthyretin (TTR) amyloidosis is rare in Europe but very common in African descendants with a prevalence of 3.4% of a transthyretin gene mutation (V122l) in this population (likely to induce hereditary amyloidosis after the fifth decade). It is a serious disease with a median survival of 2 to 6 years depending on the study and is often under-diagnosed with late detection at the time of a major cardiovascular event, such as a stroke or acute heart failure. Screening is done by imaging (cardiac MRI or bone scintigraphy with labelled diphosphonates). According to a study carried out in the Cardiology Department of the Martinique University Hospital (TEAM Amyloidosis study), one out of three left ventricular hypertrophy (LVH) (parietal thickness ≥ 15 mm), diagnosed by echocardiography, is amyloidosis. A study published by Thibaud Damy's team in 2015 already found a 5% prevalence of TTR gene mutation in patients with LVH. It is now accepted that systematic screening for amyloidosis is necessary in cases of LVH > 12 mm associated with at least one risk factor for amyloidosis ("red flags") in order to implement appropriate therapies and thus improve patient survival. The study by Dungu et al. reports that cardiac amyloidosis is an underestimated etiology of acute heart failure in Afro-Caribbean immigrants in London. The study found a high prevalence of cardiac amyloidosis at 11.4% among 211 African-Caribbean immigrants compared to a Caucasian population (1.6%), with a higher mortality of these patients compared to patients with another cause of heart failure (median survival 2.3 years versus 7 years for other etiologies). The study by Arvanitis et al. describes a 5.1% prevalence of the transthyretin gene mutation (V122l) in 101 African Americans with heart failure (compared to 8.5% of mutation carriers among African-Caribbean immigrants in the Dungu study). In these two studies, the prevalences of amyloidosis and the V122I mutation are probably underestimated, given the absence of systematic screening of all heart failure cases and the fact that only patients with left ventricular hypertrophy on transthoracic echography were targeted. In addition, amyloidosis can take different forms from those usually described. Occasional observations in our experience at the University Hospital of Martinique have found cases of heart failure with dilated cardiomyopathy (DCM), associated with transthyretin cardiac amyloidosis. Several similar observations have been found in the literature. The study hypothesise is that cardiac amyloidosis is as common, or more common, in acute heart failure in the French West Indies than elsewhere. A systematic screening for amyloidosis in all patients with acute heart failure would allow early initiation of appropriate treatment and improve their long-term outcome.