Spielberg, Austria

Effect of Using an Object Handling Serious Game on Upper Limb Rehabilitation for Children with Neurological Disorders

Efficacy Investigation of the Medical Device Apneal® on Smartphone for Sleep Apnea-Hypopnea Syndrome Diagnosis

68Ga-FAPI-46 PET/CT for Predicting Histological Response in Triple-negative Breast Cancer (FAP-IT)

Prospective multicenter study evaluating the prediction of histological response of pembrolizumab in combination with neoadjuvant chemotherapy by pre-treatment 68Ga-FAPI-46 PET/CT imaging in patients with early-stage high-risk TNBC. Patients will receive the newly established standard of care of neoadjuvant pembrolizumab 200 mg Q3W given with 4 cycles of paclitaxel + carboplatin, then with 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, patients will receive adjuvant pembrolizumab for 9 cycles or until recurrence or unacceptable toxicity. The 68Ga-FAPI-46 PET/CT scan will be performed for each patient pre-therapy and on the same machine as the 18F-FDG PET/CT scan and within 14 days before the start of treatment.

Study to Evaluate the Efficacy and Safety of Subcutaneous Sonelokimab Compared with Placebo in Adult Participants with Moderate to Severe Hidradenitis Suppurativa

Patient's Perspective on the Evolution of Hidradenitis Suppurativa Burden After Secukinumab Initiation

This study is a prospective (primary data), national, descriptive, non-interventional, multicentre study conducted by medical practice and hospital-based dermatologists across different geographical regions in France. This real-world study does not change the physician-patient relationship or patient management or follow-up. Physicians remain free with their prescriptions and patient follow-up procedures. In fact, secukinumab initiation and all treatment decisions will be made according to routine medical care and independently of study participation. Recruited patients will be longitudinally followed-up for the duration of the study, up to 24 months (± 3 months) after secukinumab initiation or secukinumab treatment discontinuation before the end of the 24 months of follow-up (early discontinuation).

DESTINY Breast Respond HER2-low Europe

This non-interventional study will investigate the effectiveness withT-DXd, the demographic and clinical characteristics of the patients, treatment patterns, tolerability, management of adverse drug reactions (ADRs), and patient experience of T-DXd in patients with HER2-low unresectable and/or metastatic breast cancer. Patients will be treated according to the proposed indication statement in the Summary of Product Characteristics (SmPC). No drug product will be administered as part of this study. Data on conventional chemotherapy (i.e., including but not limited to capecitabine, eribulin, gemcitabine, paclitaxel and nab-paclitaxel) will also be collected in a disease registry part of the study.

Evaluation of Targeted Prostate Biopsies Under MRI: Tolerance and Contribution in the Therapeutic Decision - Exploratory Study

Prostate cancer is the most common cancer in France and is the third most common cancer death in men. Early detection is based on family and ethnic history, digital rectal examination and total PSA testing. It is done at age 50 for the general population but is restricted to men with an estimated survival of more than 10 years. In case of clinical suspicion of prostate cancer, the diagnosis is based on the realization of prostate biopsies. Until recently, 12 so-called "systematic" (BS) biopsies were performed under ultrasound control, according to a standardized protocol, which allowed sampling of the entire prostate. Since the latest recommendations of the French Association of Urology in 2020, an MRI is systematically indicated before performing biopsies. Indeed, MRI is a sensitive technique that will increase the suspicion of significant prostate cancer. An MRI is considered "positive" if at least one suspicious area with a PI-RADS score ≥ 3 is detected. In this case, the French Association of Urology recommends performing so-called targeted biopsies (BC) on these suspicious areas associated with the 12 SBs. From a technical point of view, ultrasound is the reference examination for performing targeted biopsies on suspicious lesions detected on MRI, either by visual guidance (cognitive identification) or by image fusion techniques, MRI and ultrasound. It is now technically possible to perform biopsies directly under MRI in clinical practice, but the development of this approach remains limited in France. This technique makes it possible to biopsy the suspect area without resorting to image fusion, thus limiting targeting errors. As only MRI can detect cancerous lesions, this study is based on the hypothesis that targeted biopsies alone taken under MRI could make it possible to make a therapeutic decision within the framework of a multidisciplinary consultation meeting (RCP) without resorting to systematic biopsies under ultrasound.

Crosstalk Between Mucosal-Associated Invariant T (MAIT) Cells and the Gut Microbiota and Mucosa in the Development of Type 1 Diabetes in Children

Subjects: Multi study. Subjects will be included in the pediatric diabetes and endocrinology unit in Necker Sick children hospital and in the pediatric unit of ANTONY hospital. - Recent-onset (RO) n=40: New onset patients will be included shortly after diagnosis. - At risk (AR) cohort n=70: Routinely screened siblings of T1D patients previously tested positive for HLA DR3 and DR4 will be asked to be a part of the study. - Control (C) cohort (n=50): Control subjects will be patients consulting at Necker Hospital for endocrine testing - Control for Endoscopy (CE) n= 20: patients consulting at Necker Hospital or at Antony hospital for UGI endoscopy Analysis: MAIT cell analysis: For FACS analysis, MAIT cells will be identified as CD3+ CD4- CD161high Vα7.2+ T cells. Surface markers will be analyzed to determine their activation status (CD25, CD69, CD44), their exhaustion (PD1, KLRG1, TIM3), their migration capacity (CCR6), and their proliferation and survival will be analyzed by Ki67 and BCL2 expression. Cytokine production will be assessed after PMA-ionomycin activation, followed by intracytoplasmic staining with antibodies against IL-2, IFN-γ TNF-α, IL-2, IL-4, IL-10, IL-13, IL-17 and granzyme B. To determine the capacity of MAIT cells to response to TCR stimulation (exhaustion), in vitro stimulation will be performed in the presence of specific bacterial ligands. Activation marker expression will be analyzed by FACS and cytokines released in the supernatant by Cytometry based assay. Gut microbiota analysis: Stool samples are collected and directly kept under anaerobic condition. Within an hour the samples are processed: one fraction is aliquoted and frozen at -80°C and another fraction is used to prepared fecal supernatant for the bioassay of MAIT ligands, aliquoted and frozen. Bioassay to measure the presence of MAIT cell ligands by bioassays using WT3 cell line as well as plate bound MR117. 16S sequencing of all samples and according to the results obtained with the bioassay and 16S, 10 samples will be selected for metagenomic analysis. Coxsackie virus B (CVB) infection status: Specific antibodies against coxsackie virus B and CVB specific-qPCR measurement in gut microbiota samples will be performed in all patients of the three cohorts, and analysis of the gut mucosa by q-PCR and immunochemistry will be performed on a subset of patients. Gut integrity: the investigators will assess the permeability of the intestine using the Lactulose-Mannitol test in a sub sample of RO, RD and AR groups (> 5 years of age, n=20). In brief after an overnight fast, the patients will drink 50 ml solution of 5 g lactulose and 2 g mannitol. Urine will be collected during before and 5 hours after ingestion. Gut mucosa analysis: In a subset of patients (without celiac disease as determined by the dosage of antibodies against transglutaminase), duodenal biopsies will be obtained during an IUG endoscopy . Duodenal biopsy will be performed in RD subjects older than 8 years of age and in CE subjects older than 4 years of age. These biopsies will be analyzed by qPCR for the expression of key epithelial molecules such as the fucosyl transferase 2 (fut2), tight junction proteins (occludin, claudin4), antimicrobial peptides (Reg3, LL37) and mucus component (mucin 2). Immune cells function will also be assessed by q-PCR for key cytokines/molecules such as IL-23, IL-17, IL-22, Foxp3, IL-10, TGFb and CVB. Based on previous study, the sample size should allow statistical differences between AR, RO and C groups. The investigators anticipate to observe blood MAIT cell abnormalities in RO patients and some at risk children after seroconversion but before diabetes onset. This new data will strengthen our predictive model (see preliminary data). Since MAIT cells recognize bacterial ligand we hypothesize that MAIT cells alteration could occur in parallel with microbiota changes and/or CVB infection. The investigators anticipate observing gut mucosa abnormalities in RO children and the severity of these abnormalities may correlate with the level of MAIT cells defect and the presence of CVB infection. The investigators expect to demonstrate that MAIT cells represent a new biomarker of progression toward diabetes as well as a functional immune marker of the aggressiveness of the autoimmune disease. As such this study could determine the accurate therapeutic window for preventive strategies based on MAIT cells manipulation.

Post Market Clinical Follow-up Study for Arthroplasty Shoulder System of FX Solutions at the Long Term

Inclusion Criteria - Adult patient (≥ 18 years old) who received one of FX Solutions Shoulder System for indication of hemi or total shoulder replacement. - Patient implanted between 2011 and 2015 with a minimum follow-up of 7 years - Patient has been informed of his participation in a clinical study and did not object to data collection - Patient insured with a social security system Exclusion Criteria - Patient who does not meet the inclusion criteria above - Protected adult - People deprived of their liberty Study Objectives - Primary Objective: To assess functional improvement according to the Constant score evolution compared to its preoperative value - Secondary Objectives, assessment of: To assess against the preoperative value: - the Subjective Shoulder Value score evolution - the American Shoulder and Elbow Surgeons shoulder score evolution To describe in real life - The complications rate - The long-term range of motion - The revision rates and the prosthesis survival curve Endpoints - Primary Endpoint will be the current Constant score (measured during the assessment). The functional improvement will be evaluated according to the evolution of this score compared to its preoperative value. - Secondary Endpoints: Current ASES and SSV scores Current range of Motion Revision rate at a long-term follow-up. Calculation of the survival rates The incidence of complications occurring since implantation Revision rates and survival rates of prostheses Study Groups Group 1: Subjects implanted with HUMELOCK I & II® Anatomic Shoulder System 2011 to 2013 Group 2: Subjects implanted with HUMELOCK II® Reversible System 2011 to 2013 Group 3: Subjects implanted with HUMELOCK Reversed® Shoulder System - 2012 - 2013 Group 4: Subjects implanted with EASYTECH® Anatomic Shoulder System - 2013 - 2014 Group 5: Subjects implanted with EASYTECH® Reversed Shoulder System (For Primary intention only) - 2013- 2014 Group 6: additional group for Subjects who were implanted with EASYTECH® Reversible Shoulder System (Exclusively for Revision of Easytech Anatomic) - 2013 -2014, if applicable Group 7: Subjects implanted with HUMERIS® Anatomic Shoulder System 2014 to 2015 Group 8: Subjects implanted with HUMERIS® Reversible Shoulder System 2014 to 2015

Chemotherapy and Immunotherapy as Treatment for MSS Metastatic Colorectal Cancer With High Immune Infiltrate