Turncoat antibodies unmasked in a model of autoimmune demyelination: from biology to therapy.

Autoantibodies contribute to many autoimmune diseases, yet there is no approved therapy to neutralize them selectively. A popular mouse model, experimental autoimmune encephalomyelitis (EAE), could serve to develop such a therapy, provided we can better understand the nature and importance of the autoantibodies involved. Here we report the discovery of autoantibody-secreting extrafollicular plasmablasts in EAE induced with specific myelin oligodendrocyte glycoprotein (MOG) antigens.

Real-world efficacy of the dabrafenib-trametinib (D-T) combination in BRAF V600E-mutated metastatic non-small cell lung cancer (NSCLC): Results from the IFCT-2004 BLaDE cohort.

Background: BRAF V600E mutations occur in 2-5 % of advanced non-small cell lung cancer (NSCLC) patients. The dabrafenib-trametinib (D-T) combination was associated with improved and durable OS in patients in phase II. This study (IFCT-2004 BLaDE study) reported the efficacy of D-T combination in a large retrospective French real-world multicenter cohort of patients with advanced BRAF V600E-mutated NSCLC.

Lurbinectedin in extensive-stage small-cell lung cancer: a brief report of the IFCT-2105 LURBICLIN study.

Background: Small-cell lung cancer (SCLC) is a highly aggressive type of lung cancer. Lurbinectedin is recommended as second-/third-line treatment for advanced, previously treated SCLC.

Materials And Methods: LURBICLIN is a nationwide, non-interventional, retrospective chart review study, based on the cohort of consecutive patients enrolled in the named patient use for lurbinectedin in France.

The urotensin II receptor triggers an early meningeal response and a delayed macrophage-dependent vasospasm after subarachnoid hemorrhage in male mice.

Subarachnoid hemorrhage (SAH) can be associated with neurological deficits and has profound consequences for mortality and morbidity. Cerebral vasospasm (CVS) and delayed cerebral ischemia affect neurological outcomes in SAH patients, but their mechanisms are not fully understood, and effective treatments are limited. Here, we report that urotensin II receptor UT plays a pivotal role in both early events and delayed mechanisms following SAH in male mice.

Capmatinib efficacy for METex14 non-small cell lung cancer patients: Results of the IFCT-2104 CAPMATU study.

Background: Capmatinib is a selective MET inhibitor with demonstrated efficacy in a phase II study of non-small cell lung cancer (NSCLC) patients harboring METex14 mutations. However, the real-world outcomes of capmatinib are largely unknown. From June 2019, the French Early Access Program (EAP) provided capmatinib to METex14 NSCLC patients who were ineligible for or for whom first-line standard therapies had failed.

Study design and rationale for IFCT- 2203 TAXIO: A study that aims to evaluate the effectiveness of a first-line chemotherapy regimen without etoposide, combined with durvalumab, for patients with extensive disease small cell lung cancer.

Background: Studies have shown improvement in overall survival with anti-PD1/PD-L1 molecules in combination with cisplatin/carboplatin and etoposide as a first-line treatment for Small Cell Lung Cancer (SCLC). However, first-line efficacy remains limited and well below that observed in Non-Small Cell Lung Cancer (NSCLC). Etoposide may have a detrimental effect on lymphocyte activation, which could explain the limited benefit of immunotherapy in the first line and the lack of benefit in the second line for patients previously exposed to high levels of etoposide.

A new physiological manikin to test and compare ventilation devices during cardiopulmonary resuscitation.

Background: There is a lack of bench systems permitting to evaluate ventilation devices in the specific context of cardiac arrest.

Objectives: The objective of the study is to assess if a new physiological manikin may permit to evaluate the performances of medical devices dedicated to ventilation during cardiopulmonary resuscitation (CPR).

Methods: Specific CPR-related features required to reproduce realistic ventilation were implemented into the SAM (Sarthe Anjou Mayenne) manikin.

Age-dependent impact of streptozotocin on metabolic endpoints and Alzheimer's disease pathologies in 3xTg-AD mice.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease with a complex origin, thought to involve a combination of genetic, biological and environmental factors. Insulin dysfunction has emerged as a potential factor contributing to AD pathogenesis, particularly in individuals with diabetes, and among those with insulin deficiency or undergoing insulin therapy. The intraperitoneal administration of streptozotocin (STZ) is widely used in rodent models to explore the impact of insulin deficiency on AD pathology, although prior research predominantly focused on young animals, with no comparative analysis across different age groups.

Overcrowding in the Dispatching Centre During the COVID-19 Crisis: Are Medical Students a Resource?

Introduction: In February, the emergence of COronaVIrus Disease 2019 (COVID - 19) in France made it necessary to rapidly adapt emergency and SAMU services in order to take care of many infected patients. To respond to the increase in the number of calls in the dispatch centers, reinforcements were necessary on the fronts of the Medical Regulation Assistants (ARM). The aim of this study was to assess the relevance of medical students' responses to first calls exclusively concerning COVID-19.

Derivation and validation of a risk-stratification model for patients with probable or proven COVID-19 in EDs: the revised HOME-CoV score.

Background: The HOME-CoV (Hospitalisation or Outpatient ManagEment of patients with SARS-CoV-2 infection) score is a validated list of uniquely clinical criteria indicating which patients with probable or proven COVID-19 can be treated at home. The aim of this study was to optimise the score to improve its ability to discriminate between patients who do and do not need admission.

Methods: A revised HOME-CoV score was derived using data from a previous prospective multicentre study which evaluated the original Home-CoV score.

Lateral flexion of a compliant spine improves motor performance in a bioinspired mouse robot.

A flexible spine is critical to the motion capability of most animals and plays a pivotal role in their agility. Although state-of-the-art legged robots have already achieved very dynamic and agile movement solely relying on their legs, they still exhibit the type of stiff movement that compromises movement efficiency. The integration of a flexible spine thus appears to be a promising approach to improve their agility, especially for small and underactuated quadruped robots that are underpowered because of size limitations.

Embodied bidirectional simulation of a spiking cortico-basal ganglia-cerebellar-thalamic brain model and a mouse musculoskeletal body model distributed across computers including the supercomputer Fugaku.

Embodied simulation with a digital brain model and a realistic musculoskeletal body model provides a means to understand animal behavior and behavioral change. Such simulation can be too large and complex to conduct on a single computer, and so distributed simulation across multiple computers over the Internet is necessary. In this study, we report our joint effort on developing a spiking brain model and a mouse body model, connecting over the Internet, and conducting bidirectional simulation while synchronizing them.

Performances and limits of Bag-Valve-Device for pre-oxygenation and manual ventilation: A comparative bench and cadaver study.

Introduction: Bag-Valve-Device (BVD) is the most frequently used device for pre-oxygenation and ventilation during cardiopulmonary resuscitation (CPR). A minimal expired fraction of oxygen (FeO) above 0.85 is recommended during pre-oxygenation while insufflated volume (VTi) should be reduced during manual ventilation.

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study.

Background: Small cell lung cancer (SCLC) has a tendency towards recurrence and limited survival. Standard-of-care in 1st-line is platinum-etoposide chemotherapy plus atezolizumab or durvalumab,based on landmarkclinical trials.

Methods: IFCT-1905 CLINATEZO is a nationwide, non-interventional, retrospectivestudy of patients with extensive-SCLC receivingatezolizumab plus chemotherapy as part of French Early Access Program.

Comparison of chest compression quality between the overlapping hands and interlocking hands techniques: A randomised cross-over trial.

Background: Performing quality chest compressions is fundamental to the management of cardiopulmonary arrest. The aim of this study was to compare the efficacy of two hand positions: overlapping versus interlocking for performing chest compressions during cardiopulmonary arrest.

Methods: The HP2C (for Hands Position and Chest Compression) was a prospective, randomised, open-label, cross-over, single-centre study.

Pharmacokinetics, biodistribution and toxicology of novel cell-penetrating peptides.

Cell-penetrating peptides (CPPs) have been used in basic and preclinical research in the past 30 years to facilitate drug delivery into target cells. However, translation toward the clinic has not been successful so far. Here, we studied the pharmacokinetic (PK) and biodistribution profiles of Shuttle cell-penetrating peptides (S-CPP) in rodents, combined or not with an immunoglobulin G (IgG) cargo.

A new reservoir-based CPAP with low oxygen consumption: the Bag-CPAP.

Background: Several noninvasive ventilatory supports rely in their design on high oxygen consumption which may precipitate oxygen shortage, as experienced during the COVID-19 pandemic. In this bench-to-bedside study, we assessed the performance of a new continuous positive airway pressure (CPAP) device integrating a large reservoir ("Bag-CPAP") designed to minimize oxygen consumption, and compared it with other CPAP devices.

Methods: First, a bench study compared the performances of Bag-CPAP and four CPAP devices with an intensive care unit ventilator.

Hidden aliens: Application of digital PCR to track an exotic foraminifer across the Skagerrak (North Sea) correlates well with traditional morphospecies analysis.

The problem of invasive species is a well-studied one, but knowledge of free-living unicellular eukaryotic invasive species is lacking. A potentially invasive foraminifer (Rhizaria), Nonionella sp. T1, was recently discovered in the Skagerrak and its fjords.

VEGFR2 and CD34 expression associated with longer survival in patients with pleural mesothelioma in the IFCT-GFPC-0701 MAPS phase 3 trial.

Objectives: VEGF/VEGFR autocrine loop is a hallmark of pleural mesothelioma (PM). We thus assayed the prognostic and predictive values of VEGFR-2 [vascular endothelial growth factor receptor 2 or Flk-1] and CD34, a marker of endothelial cells, in samples from patients accrued in the Mesothelioma Avastin Cisplatin Pemetrexed Study ('MAPS', NCT00651456).

Materials And Methods: VEGFR2 and CD34 expression were assayed using immunohistochemistry in 333 MAPS patients (74.