Münnerstadt, Germany

Phase II Trial of ART + Dual bNAbs vs. ART + Placebo During Primary HIV-1 Infection-impact on Post-ART Control

The study proposes to test an intervention consisting of dual long-acting HIV-specific broadly neutralizing antibodies (3BNC117-LS & 10-1074-LS ) + ART, at primary HIV-1 infection, and to compare it to ART only regarding HIV-1 replication. The study aims to enrol 69 participants in French (Ile-de-France) clinical centres. Participants will have been diagnosed with primary HIV-1 infection, will start ART during early phase of Primary HIV infection, and will interrupt ART 52 weeks later. Study duration will vary by participant, depending on the time of ART interruption and the time to viral rebound.

Analysis of Biological Characteristics of Advanced ALK-rearranged NSCLC

BioEXALK is a prospective study evaluating the biological characteristics of advanced ALK-rearranged NSCLC treated with new generation TKIs in first line, included in the national EXPLORE ALK cohort (GFPC 03-2019). Explore ALK GFPC 03-2019 is a non-interventional, national, multi-center cohort of ALK-rearranged NSCLC patients, whose RCB reference is 2020-A00771-38 and which obtained an approval from the IDF II Ethic Committee on 25/05/2020. Biological analysis will be performed on tissue at diagnosis and at the time of disease progression when available and on circulating tumor DNA (ctDNA) on three timepoints (diagnosis, at first tumor evaluation and at the time of disease progression). - Tissue : RNAseq will be performed on tumor biopsy (10 slides of 5 microns) to identify the ALK fusion partner and its variant and associated co-mutations.. - ctDNA : NGS panel on DNA including a large panel of fusions and mutations will be performed on blood samples (30mL on EDTA or STRECKs tubes) at diagnosis, at the time of the first evaluation and at the time of progression). For plasma testing, after obtained patient consent, blood samples (35mL on EDTA or STRECKs tubes) at diagnosis, at the first evaluation and at disease progression will be taken. The ALKis include alectinib and brigatinib as first-line therapy or other drugs with marketing authorizations (lorlatinib, entrectinib) or in early access programs (EAPs). Liquid biopsies will be analyzed with a NGS panel allowing the identification of ALK fusion partners and resistance mechanisms (mutations, fusions, copy number variations). Samples will be sent for centralized analysis to the Léon Bérard Center (Lyon). For biological analysis on tissue obtained at diagnosis, the ALK fusion partner and its variant will be identified by RNAseq. Whenever a tissue re-biopsy is performed at the time of disease progression as part of the standard of care management of the patient, the remaining tissue sample will be collected as part of the BioExALK study, so that RNAseq analysis will be performed to look for resistance mechanisms. Tissue samples (10 slides of 5 microns) will be sent for centralized analysis to the Rouen University Hospital.

Severity of the New UK SARS-Cov2 Variant in COVID-19 Infection

SEVASAR is a paired cohort study with retrospective data collection: - Presentation: patients hospitalized for COVID-19 with SARS-CoV-2 variant 20I / 501Y.V1 - Not exposed: patients hospitalized for COVID-19 with SARS-CoV-2 corresponding to wild variants type 20A. EU1 or 20A. EU2 The severity of illness will be compared between pairs. Disease severity will be assessed according to the following definition: defined by a composite criterion including, at 28 days after hospital admission: WHO scale >5 /11 levels, (death OR need for invasive ventilation OR need for high flow ventilation (Optiflex or NIV or CPAP) or high concentration mask. This event will be taken into account regardless of its time of occurrence between the first day of the hospitalization studied and D29 after hospital admission.

Covid-19 Pediatric Observatory

Pilot Study on the Feasibility of Systematic Hepatitis C Screening of Hospitalized Patients

The number of undetected HCV-infected persons has been extrapolated to 75,000 according to the results of a 2014 study. Screening efforts have been set up in groups of people said to be at high viral risk: drug users, prisoners, precarious persons or migrants from highly endemic countries. Nevertheless, the concept of universal screening has not yet been adopted by the guardians and the Ministry. It is in this context that "hepatitis free hospital" projects have been carried out in several French cities such as Nice, Nancy and Marseille. The aim of the HOSPI-VHC study is to evaluate the feasibility and efficiency of systematic HCV screening in all medical and surgical departments of 4 National Association of Hepato-Gastroenterologists of General Hospitals (ANGH) hospitals. This pilot project is part of a public health screening program. It will evaluate the interest and usefulness of implementing universal screening in hospitalized patients without taking into account the existence of viral risk factors. This study will also make it possible to evaluate the implementation of a dedicated care pathway: number of patients screened, number of patients referred for consultation and number of patients accepting the consultation.

Very Large Sizes in Adolescents : Tibial and Femoral EPIphysiodesis

By "very large size" we mean a size greater than +3 SD (standard deviation) on the updated French reference curves. Most of the very large sizes are constitutional. The first step in the management of the paediatrician endocrinologist with very large body height is to collect the auxological parameters (family height, not just parental height, birth height, weight, height, head circumference, body mass index, height, sitting height) and plot the corresponding adolescent growth curves. The clinical stage (interview, clinical examination) will attempt to rule out a diagnosis other than a very large constitutional size: a recent statural acceleration related to a hormonal cause with specific medical treatment (hyperthyroidism or hyper androgeny or early puberty or acromegaly or more rarely estrogen deficiency by mutation of the CYP19A1 aromatase gene or by mutation of the ERα receptor) and will seek a syndrome in which the very large size is a sign among others. Among the main syndromes are Klinefelter's syndrome (prevalence 1 person/1,200 or 1/600 boy births), Marfan's syndrome (about 1/6,000 births, prevalence 1 to 5 persons/ 10000), triple X syndrome (1 to 5 persons/10,000). Additional examinations will be guided by diagnostic hypotheses; the very large constitutional diagnosis remains a diagnosis of elimination. The very large constitutional size is defined as family, i.e. related to the size of at least 1 of the 2 parents or close family members of the parents. The target size can be calculated as an indication: - Target size =[father size (cm) + mother size (cm) +13] /2 for boys - Target size =[father size (cm) + mother size (cm) -13] /2 for girls However, experience shows that the target size is a poor prognostic tool in very large constitutional sizes: growth is always above it. Very large constitutional size remains the most frequent diagnosis among etiological diagnoses of very large sizes. The therapeutic question follows the diagnostic stage. Only very large sizes secondary to a hormonal cause can benefit from specific medical treatment. Outside these situations, a therapeutic discussion will be proposed based on the size prognosis estimated by the pediatrician endocrinologist. In the event of a predicted very large size and if this represents an inconvenience for the adolescent, the paediatrician endocrinologist may propose a growth-blocking treatment. Very large sizes can be disabling and cause a difficult psychological experience, so some families are in need of growth-restricting treatment, especially girls who consult more often and earlier than boys. The estimation of adult prognosis by the pediatrician endocrinologist, formerly based on Bayley and Pinneau's tables, has been replaced by more modern software integrating Greulich and Pyle's tables, Tanner Whitehouse 2 and 3, and taking into account parental sizes and ethnic origin. This automated reading of bone maturation makes it possible to be more accurate in predicting final size, an essential step before any therapeutic discussion. In the international literature (mainly the United States, Northern Europe and Australia) it is relatively consensual to consider a growth-blocking treatment for a prognosis ≥185 cm for girls and ≥ 200 cm for boys. For our study, we will use a prognosis ≥ 184 cm for girls and ≥ 198 cm for boys, which corresponds to a size of +3 SD on the updated French curves. Currently in France, the therapeutic possibilities to slow down growth and thus reduce the final adult size are: - Either medical treatments: excluding MA and causing many side effects; - Or surgical treatments: performed anecdotally in France and based on publications from Northern Europe.

Research of the Consequences on the Digestive Tract Following the Proposed Treatments for a Urinary Infection in Children

Survey on Epidemiology of Hypoparathyroidism in France

Very few data has been published on the epidemiology of hypoparathyroidism worldwide. None exists specifically in France. Hypoparathyroidism could led to complications: e.g. symptomatic hypocalcemia, calcifications (brain, eye and other soft tissues), nephrolithiasis/nephrocalcinosis, renal insufficiency. Here,the investigators plan to collect data about both epidemiology, medication and complication of hypoparathyroidism in France.

Randomised Study Evaluating Adjuvant Chemotherapy After Resection of Stage III Colonic Adenocarcinoma in Patients of 70 and Over

Colorectal cancer occurs mainly in elderly patients. Recent estimation showed that in France more than 50% of the patients diagnosed with a colorectal cancer are 70 years old or more. Adjuvant chemotherapy has demonstrated a benefit on disease-free survival and overall survival after a stage III colon cancer resection. Nevertheless adjuvant chemotherapy is poorly used in elderly patients. Prognostic improvement with chemotherapy based on 5FU is suggested by a post-hoc analysis of randomized prospective clinical trial. But elderly patients in this study were highly selected and patients older than 80 represented only 0.7% of the total population. Thus, there is still a concern about the benefit of adjuvant 5FU-based chemotherapy in very elderly unselected patients. The recommended treatment for stage III adjuvant chemotherapy is a combination of fuoropyrimidine and oxaliplatin. Nevertheless oxaliplatin did not demonstrated survival advantage in elderly patients. Altogether there are still two matters of debate: - First, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for unfit elderly patients? - Second, is there a benefit of oxaliplatin-based adjuvant chemotherapy for fit elderly patients? The aim of this randomized phase III study is to evaluate the benefit for disease-free survival of adjuvant chemotherapy in elderly patient and which chemotherapy. The elderly patient population will be dichotomized into two groups according to physician's choice after a multidisciplinary evaluation involving a geriatrician, with two different randomization assignments. The patients with an expected life-expectancy below 4 years according Lee score are excluded of this study. Some biological tumour abnormalities are more frequently observed in elderly (i.e. mismatch repair deficiency), therefore an evaluation of specific biological prognostic factors is needed in elderly population.

Rapid Sequence Intubation and Hemodynamic Disorders in the Operating Room: a Prospective Multicenter Observational Study