Natalizumab extended-interval dosing in a real-life context: efficacy study

Introduction: Natalizumab (NTZ) is a widely used second-line treatment for multiple sclerosis (MS), administered with a fourweeks infusion interval. Extending the interval between two infusions could reduce the economic costs of this therapy, the incidence of rare side effects such as progressive multifocal leukoencephalopathy and improve the patients' quality of life with less frequent day-hospitalizations. Aim(s): At the Fondation Rothschild Hospital in Paris, for sanitary reasons during COVID-19 lockdown, patients were systematically switched to a 6-weeks NTZ extended-interval dosing (EID) from April 2020 to the present day. In this monocentric retrospective study, we aimed at evaluating the clinical and radiological efficacy of NTZ EID compared to the 4 weeks standard-interval dosing (SID) in adult patients with active MS. Method(s): We screened the local pharmacy database for NTZ administration and included all adult patients diagnosed with MS and treated with NTZ for at least 6 months with a SID, before being treated with an EID for at least 12 months. Data about disease activity, treatments received, MRI and clinical data were retrospectively collected from the local French MS observatory (OFSEP) database. The primary outcomes were the incidence of MS attacks, new MRI lesions or the presence of gadoliniumenhancing lesions during NTZ SID or EID. Result(s): A total of 49 patients were included for final analysis. 21 (42.9%) were male, with a median MS duration from the first symptom to NTZ introduction of 60 [30, 110] months. Patients were treated for a median time of 34.6 [15.1, 72.4] months by a SID, followed by a median time of 18.6 [14.7, 20.6] months by an EID. The mean EDSS before EID was 2.0 [1.5, 3.0] and 1.5 [0.0, 2.8] during EID. During natalizumab SID, one patient (2%) presented a new MS attack, 5/45 patients (11%) had new MRI lesions, with gadolinium enhanced lesions in 1/45 (2%) patient. This did not differ significantly during natalizumab EID where no MS attack were observed (p = 1), new MRI lesions were present in 1/41 (2%) patient and no gadolinium-enhancing lesion was found. Patients were followed for a median time of 130 [78, 205] months in total. Conclusion(s): We did not observe more clinical attacks or MRI activity signs when extending the interval between NTZ infusions from 4 to 6 weeks. Data from randomized controlled trials are needed to allow better consideration of side-effects and safety.

Dietary obesity in mice is associated with lipid deposition and metabolic shifts in the lungs sharing features with the liver.

Obesity is associated with both chronic and acute respiratory illnesses, such as asthma, chronic obstructive pulmonary disease (COPD) or increased susceptibility to infectious diseases. Anatomical but also systemic and local metabolic alterations are proposed contributors to the pathophysiology of lung diseases in the context of obesity. To bring perspective to this discussion, we used NMR to compare the obesity-associated metabolomic profiles of the lung with those of the liver, heart, skeletal muscles, kidneys, brain and serum from male C57Bl/6J mice fed with a high-fat and high-sucrose (HFHSD) diet vs. standard (SD) chow for 14 weeks. Our results showed that the lung was the second most affected organ after the liver, and that the two organs shared reduced one-carbon (1C) metabolism and increased lipid accumulation. Altered 1C metabolism was found in all organs and in the serum, but serine levels were increased only in the lung of HFHSD compared to SD. Lastly, tricarboxylic acid (TCA)-derived metabolites were specifically and oppositely regulated in the serum and kidneys but not in other organs. Collectively, our data highlighted that HFHSD induced specific metabolic changes in all organs, the lung being the second most affected organ, the main alterations affecting metabolite concentrations of the 1C pathway and, to a minor extend, TCA. The absolute metabolite quantification performed in this study reveals some metabolic specificities affecting both the liver and the lung, that may reveal common metabolic determinants to the ongoing pathological process.

Design for the automation of an Ambu Spur II manual respirator

This article shows the design of a device to automatize an Ambu Spur II manual respirator. The aim of this compassionate medicine device is to provide an emergency alternative to conventional electric respirators—which are in much shortage—during the present COVID-19 pandemic. To develop the device, the classical method of product design based on concurrent engineering has been employed. First, the specifications of the machine have been determined, including the func-tion determining the air volume provided at every moment of the breathing cycle;second, an ade-quate compression mechanism has been designed;third, the control circuit of the motor has been determined, which can be operated via a touchscreen and which includes sensor feedback;fourth, the device has been materialized with readily available materials and market components, mostly of low cost;and fifth, the machine has been successfully tested, complying with sanitary regulations and operating within desirable ranges. The device has been already manufactured to supply respirators to several hospitals around the Catalan Autonomous Community in Spain, but can also be replicated in developing countries such as Ecuador. © 2021 by the author. Licensee MDPI, Basel, Switzerland.