Castilleja De La Cuesta, Spain

Post Market Clinical Follow-Up KeriFuse®

ENDOmetriosis Robotic Assisted Surgery

The ENDO-RAS trial aims to evaluate the safety and effectiveness of robot-assisted laparoscopy compared to conventional laparoscopy for hysterectomy in patients with Deep infiltrating endometriosis and adenomyosis without digestive tract involvement, as verified by magnetic resonance imaging and classified using both the ENZIAN and Deep Pelvic Endometriosis Index classifications. These classifications are used to evaluate Deep infiltrating endometriosis and reproducibly predict the occurrence of postoperative complications. Eligible patients will be recruited from the gynecological surgery department after meeting the inclusion and non-inclusion criteria and signed informed consent forms. Participants will then be randomly assigned to receive either robot-assisted total laparoscopic hysterectomy or total laparoscopic hysterectomy. The ENDO-RAS Trial is a multicenter, randomized, controlled, and open-label study. Eligible patients will be randomized into two parallel groups.

Immunity Markers in Intensive Care Patients and Ventilator-associated Pneumonia

The occurrence of ICU-acquired infections in patients admitted to the intensive care unit (ICU) results in increased morbidity and mortality, increased length of stay in the ICU, and also clearly increased healthcare costs. The incidence of these infections fluctuates between 15% and 40%, depending on the study. A major problem in the ICU is the recurrence and relapse of ventilator-associated pneumonia (VAP), with increased exposure to antibiotics and a probable increase in average length of stay. One of the possible hypothesis that could explain relapses/recurrences of VAP is incorrect conducted antibiotherapy. To prevent this, in the unit, we currently perform antibiotics pharmacological assays and adapt them to the antibiogram. Another possible explanation to treatment failure could be patients' postagressive immunoparalysis. It has clearly been demonstrated that postagressive immunoparalysis is a predisposing state to healthcare related infections. Some markers can be used to monitor this immunoplegia state. Several studies have shown that low HLA-DR expression and reduced CD16 expression (polymorphonuclear neutrophils percentage) is associated with increased susceptibility to develop infections in the ICU. Immunity monitoring could be an interesting tool to identify populations most at risk of developing healthcare-associated infections after a state of shock, and could become an interesting line of thinking for the use of immunomodulatory therapies. To best evaluate these therapies and find a place for them in the current arsenal, it is essential to integrate them into daily practice by linking them to a significant clinical event, such as recurrent healthcare-associated infections, despite properly conducted antibiotic treatment.

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

Evaluation of the Vivo Isar Stent System in Routine Clinical Practice

FIRST-NEC (GFPC 01-2022) - Combination of Durvalumab With Etoposide and Platinum

Large-cell neuroendocrine carcinomas (LCNECs) of the lung are lung tumors (2%) included with small-cell lung cancers (SCLCs) in the subgroup of pulmonary neuroendocrine tumors of high-grade malignancy. Histopathological diagnosis of LCNEC is difficult, with a confirmation rate of only 70-80% after centralized expert-pathologist review. The prognosis of advanced LCNECs is poor, with overall survival (OS) of 8-10 months. The platinum-based regimen is the current recommended first-line treatment for advanced LCNECs in analogy with that given for SCLCs. The previous pivotal GFPC 03-02 trial demonstrated the efficacy of first-line platinum-etoposide in advanced LCNECs with a median Progression-Free Survival (PFS), OS and 1-year PFS of 5 months, 7.7 months and 15% respectively. The GFPC 03-2017 trial has recently reported that 75% of the tumor samples of LCNEC express programmed cell death protein-ligand-1 (PD-L1) in immune infiltrating tumor cells (ICs), and PD-L1 expression on ICs has been previously correlated with clinical efficacy of Immune Checkpoint Inhibitors (ICI) in Non-small Cell Lung Cancer. Numerous retrospective studies have also suggested ICI efficacy against LCNECs with significantly prolonged OS observed in ICI-treated LCNEC patients. Recently, the prospective NIPINEC study results demonstrated second-line nivolumab-ipilimumab efficacy against LCNECs. Moreover, at ESMO 2022, the NICE-NEC prospective phase II study on LCNECs of digestive origin found an impressive efficacy of first-line triplet platinum-etoposide-ICI with a median OS of 13,9 months, and 44 % of long survivor patients (OS>18 months). Finally, the CASPIAN trial demonstrated the superiority of the combination of durvalumab with platinum-etoposide compared to chemotherapy alone in patients with SCLCs, with an acceptable toxicity profile. Therefore, within the network of GFPC centers, the investigators propose a prospective, multicenter, open-label, phase II study with an external control arm (ESME database), that aims at evaluating the efficacy and safety of the combination of durvalumab with platinum-etoposide chemotherapy as first-line treatment in patients with an advanced LCNECs.

First Observatory of Precocious Puberty.

EXOPULSE Mollii Suit & Cerebral Palsy

This work will assess the effects of the EXOPULSE Mollii suit, which is an assistance device applying non-invasive transcutaneous electrostimulation. The EXOPULSE Mollii control unit is a class IIa device, CE marked, and therefore compliant with the Medical Device Directive. Its intended use includes relaxing spastic muscles, maintaining or increasing the range of movement, activating and re-educating muscles, delaying or preventing atrophy due to disuse, increasing local blood flow, and symptomatic relief and management of chronic refractory pain. The available interventions targeting spasticity are faced with some limitations. For instance, botulinum toxin injection does not seem to improve arm and hand capacity, walking, or quality of life. The available oral agents are challenged by their potential side effects, such as sedation, drowsiness, mental confusion, fatigue, ataxia, hallucination, insomnia, nausea, dry mouth, bradycardia, hypotension, and depression, to cite a few. Therefore, developing novel therapies would help to overcome the actual limitations. Transcutaneous Electrical Nerve Stimulation (TENS) has proven some efficacy in spasticity management. However, one should note that practical difficulties could arise when using TENS at home or in clinical practice (i.e., correctly attaching electrodes). To overcome these limitations, the EXOPULSE Mollii suit has been developed by Exoneural Network, a Swedish med-tech company. It represents an innovative approach for non-invasive electro-stimulation to reduce spasticity and improve motor function. EXOPULSE Mollii suits consist of body Garments (Jacket and Pants) and a control unit. The body Garments (Jacket and Pants) is a suit with 58 embedded electrodes that can stimulate 40 groups of muscles, conductive wires, and connectors to a detachable control unit, whose intended purpose is to transmit electric pulses from the control unit to key nerves and corresponding muscle groups throughout the body. The control unit is a battery-powered electrical device that sends low-intensity electric pulses through connectors to the Body Garments which in turn transmits the pulses from the connectors to key nerves and corresponding muscle groups throughout the body. EXOPULSE Mollii suit consists of transcutaneously stimulating the spastic antagonist muscles with an electric current (i.e., low frequency ~20 Hz, low intensity~2 mA), aiming to reduce muscle stiffness. This treatment method's theoretical background primarily refers to the concept of reciprocal inhibition, i.e., that sensory input from a muscle may inhibit the activation of an antagonistic muscle. Thus, the application of the EXOPULSE Mollii suit aims to stimulate a muscle, e.g., the anterior tibialis muscle to reduce reflex-mediated over-activity (i.e., spasticity) of calf muscles by inducing reciprocal inhibition. There is growing evidence now from pilot applications of EXOPULSE Mollii suit indicating beneficial effects of using this suit on activity (i.e., mobility and gross motor function) and participation.

OphtAI Diagnostic Performance Validation for Automated Screening of Eye Diseases

OphtAI-Eval: is a prospective, multicentre, post-marketing clinical follow-up study (SCAC) of diagnostic validation (comparative vs gold standard). It aims to: validate the diagnostic performance of the OphtAI software for the automated screening of diabetic retinopathy, diabetic macular edema, glaucoma, ARM and AMD. Evolucare OphtAI is a medical imaging console for ophthalmology, interfaced with Evolucare Imaging. It allows the detection, by statistical learning algorithms, of the following ocular pathologies using photographs of the retina: - Diabetic retinopathy (DR) (including gradation), - Diabetic macular edema (DME) - Age-related macular degeneration (AMD) - Age-related maculopathy (ARM, early form of AMD), - Glaucoma. Evolucare OphtAI, is available on the French market since March 2019.

Durvalumab Maintenance After Thoracic Chemoradiotherapy in Frail Small Cell Lung Cancer Patients Whose Disease is Limited to the Thorax

Small Cell Lung Cancer (SCLC) is a rare tumor, accounting nowadays for 10-15% of all new lung cancer diagnosis. Approximately one third of patients present with limited disease (LD-SCLC) confined to the chest with a median survival from 18 to 24 months and a 5-year survival rate between 20% and 25%. A platinum-based chemotherapy combined with etoposide and a concurrent thoracic radiotherapy represents the standard of care for LD-SCLC treatment with a median PFS of 12 months. However, sequential radiotherapy may be preferable for patients with poor performance status or having comorbidity predisposing to a worst tolerability. Clinical evidence supports the immunogenicity of SCLC and the involvement of immune activity in SCLC development and prognosis. Several immune checkpoint inhibitors got the approbation in first and further lines for the advanced SCLC in the last decade. The most important results have been achieved in the first-line setting for patients receiving a combination of platinum - etoposide chemotherapy and an anti-PD1/PDL-1 inhibitor compared to chemotherapy alone. However, despite these were the first positive results after a while in this setting, the modest absolute benefit showed (3 months) have to be taking into account. The possibility to enhance the immunotherapy efficacy in SCLC field with the radiotherapy administered as part of the standard treatment for a LD-SCLC seems to be a great opportunity. In the PACIFIC trial, the sequential administration of durvalumab in patients with locally advanced, unresectable, stage III Non-Small-Cell Lung Cancer (NSCLC) whose disease had not progressed following platinum-based concurrent thoracic CRT showed a dramatic overall survival improvement compared to placebo, with manageable toxicities. The ADRIATIC phase III trial, is currently recruiting LD-SCLC patients not progressing after the concomitant CRT (NCT03703297). Patients are randomized to receive durvalumab, durvalumab plus tremelimumab or placebo as maintenance treatment. In this trial, only ECOG PS 0-1 patients able to receive a concomitant CRT are eligible. However, in our clinical practice, LD-SCLC patients may not respect these criteria due to the aggressiveness of cancer and comorbidities. Thus, DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance treatment in frail LD-SCLC patients who have not progressed following platinum-based concomitant or sequential CRT.