Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

Objective: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis.

Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study.

Background: Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis.

Evaluating severity of white matter lesions from computed tomography images with convolutional neural network.

Purpose: Severity of white matter lesion (WML) is typically evaluated on magnetic resonance images (MRI), yet the more accessible, faster, and less expensive method is computed tomography (CT). Our objective was to study whether WML can be automatically segmented from CT images using a convolutional neural network (CNN). The second aim was to compare CT segmentation with MRI segmentation.

Effect of Intravenous Interferon β-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

Importance: Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage.

Objective: To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS.

Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease.

Extreme obesity (EO) (BMI >50 kg/m) is frequently associated with neuropsychiatric disease (NPD). As both EO and NPD are heritable central nervous system disorders, we assessed the prevalence of protein-truncating variants (PTVs) and copy number variants (CNVs) in genes/regions previously implicated in NPD in adults with EO ( = 149) referred for weight loss/bariatric surgery. We also assessed the prevalence of CNVs in patients referred to University College London Hospital (UCLH) with EO ( = 218) and obesity (O) (BMI 35-50 kg/m; = 374) and a Swedish cohort of participants from the community with predominantly O ( = 161).

Thrombopoetin receptor agonist therapy in thrombocytopenia: ITP and beyond.

Eltrombopag is well established in treatment of severe immune thrombocytopenia (ITP) and is increasingly commonplace in second-line management. A role is also suggested for both bridging therapy for surgery, as well as treating thrombocytopenia due to non-immune aetiologies. We present the largest single-centre experience with eltrombopag, with our cohort of 62 patients.

Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura.

Background: Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high.

Recent advances in antibody-based therapies for Hodgkin Lymphoma.

Although a poster child for the development and refinement of multi-modal multi-agent therapeutic strategies, Hodgkin Lymphoma has, until recently, lagged behind other lymphomas in terms of the use of therapeutic monoclonal antibodies. This situation has now changed dramatically, with the rapid emergence both of a toxin-conjugated tumour-selective anti-CD30 antibody, and of antibodies targeting immunological checkpoints, most notably PD-1 (also termed PDCD1). The former provides an efficient targeting vehicle for delivery of a potent synthetic anti-mitotic drug, with ultimate efficacy independent of immunological activity.

Trial of the route of early nutritional support in critically ill adults.

Background: Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route.

Methods: We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units.

14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends.

Antiphospholipid Syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity occurring in patients with persistent antiphospholipid antibodies (aPL). The primary objective of the APS Treatment Trends Task Force, created as part of the 14th International Congress on aPL, was to systematically review the potential future treatment strategies for aPL-positive patients. The task force chose as future clinical research directions: a) determining the necessity for controlled clinical trials in venous thromboembolism with the new oral direct thrombin or anti-factor Xa inhibitors pending the results of the ongoing rivaroxaban in APS (RAPS) trial, and designing controlled clinical trials in other forms of thrombotic APS; b) systematically analyzing the literature as well as aPL/APS registries, and creating specific registries for non-warfarin/heparin anticoagulants; c) increasing recruitment for an ongoing primary thrombosis prevention trial, and designing secondary thrombosis and pregnancy morbidity prevention trials with hydroxychloroquine; d) determining surrogate markers to select patients for statin trials; e) designing controlled studies with rituximab and other anti-B-cell agents; f) designing mechanistic and clinical studies with eculizumab and other complement inhibitors; and g) chemically modifying peptide therapy to improve the half-life and minimize immunogenicity.