Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II.

Background: In the phase III ASCLEPIOS I and II trials, participants with relapsing multiple sclerosis receiving ofatumumab had significantly better clinical and magnetic resonance imaging (MRI) outcomes than those receiving teriflunomide.

Objectives: To assess the efficacy and safety of ofatumumab versus teriflunomide in recently diagnosed, treatment-naive (RDTN) participants from ASCLEPIOS.

Methods: Participants were randomized to receive ofatumumab (20 mg subcutaneously every 4 weeks) or teriflunomide (14 mg orally once daily) for up to 30 months.

An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion.

Huntington's Disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the huntingtin (HTT) gene. The mutant HTT (mHTT) protein causes neuronal dysfunction, causing progressive motor, cognitive and behavioral abnormalities. Current treatments for HD only alleviate symptoms, but cerebral spinal fluid (CSF) or central nervous system (CNS) delivery of antisense oligonucleotides (ASOs) or virus vectors expressing RNA-induced silencing (RNAi) moieties designed to induce mHTT mRNA lowering have progressed to clinical trials.

Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting.

Background: Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure.

Methods: Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months.

Evaluation of a Novel Zonular Tension Restoring Accommodating Silicone IOL Design: Pilocarpine and Cyclopentolate-Induced Effect 20 Months after Implantation.

Purpose: To investigate a novel zonular-stress restoring accommodating 1-piece silicone IOL. . Angeles City, Philippines.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC.

Quantification of the spatial distribution of primary tumors in the lung to develop new prognostic biomarkers for locally advanced NSCLC.

The anatomical location and extent of primary lung tumors have shown prognostic value for overall survival (OS). However, its manual assessment is prone to interobserver variability. This study aims to use data driven identification of image characteristics for OS in locally advanced non-small cell lung cancer (NSCLC) patients.

A Uniform Description of Perioperative Brain MRI Findings in Infants with Severe Congenital Heart Disease: Results of a European Collaboration.

Background And Purpose: A uniform description of brain MR imaging findings in infants with severe congenital heart disease to assess risk factors, predict outcome, and compare centers is lacking. Our objective was to uniformly describe the spectrum of perioperative brain MR imaging findings in infants with congenital heart disease.

Materials And Methods: Prospective observational studies were performed at 3 European centers between 2009 and 2019.

When SUV Matters: FDG PET/CT at Baseline Correlates with Survival in Soft Tissue and Ewing Sarcoma.

Introduction: The role of positron-emission tomography/computed-tomography (PET/CT) in the management of sarcomas and as a prognostic tool has been studied. However, it remains unclear which metric is the most useful. We aimed to investigate if volume-based PET metrics (Tumor volume (TV) and total lesions glycolysis (TLG)) are superior to maximal standardized uptake value (SUVmax) and other metrics in predicting survival of patients with soft tissue and bone sarcomas.

Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium.

Background: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use.

Methods: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV.

Anti-ADAMTS13 autoantibody profiling in patients with immune-mediated thrombotic thrombocytopenic purpura.

Anti-A Disintegrin and Metalloproteinase with a ThromboSpondin type 1 motif, member 13 (ADAMTS13) autoantibodies cause a severe ADAMTS13 deficiency in immune-mediated thrombotic thrombocytopenic purpura (iTTP). ADAMTS13 consists of a metalloprotease (M), a disintegrin-like (D) domain, 8 thrombospondin type 1 repeats (T1-T8), a cysteine-rich (C), a spacer (S), and 2 CUB domains (CUB1-2). We recently developed a high-throughput epitope mapping assay based on small, nonoverlapping ADAMTS13 fragments (M, DT, CS, T2-T5, T6-T8, CUB1-2).

Point-of-care ultrasound (POCUS) practices in the helicopter emergency medical services in Europe: results of an online survey.

Background: The extent to which Point-of-care of ultrasound (POCUS) is used in different European helicopter EMS (HEMS) is unknown. We aimed to study the availability, perception, and future aspects of POCUS in the European HEMS using an online survey.

Method: A survey about the use of POCUS in HEMS was conducted by a multinational steering expert committee and was carried out from November 30, 2020 to December 30, 2020 via an online web portal.

Visceral Leishmaniasis in pregnancy and vertical transmission: A systematic literature review on the therapeutic orphans.

Background: Reports on the occurrence and outcome of Visceral Leishmaniasis (VL) in pregnant women is rare in published literature. The occurrence of VL in pregnancy is not systematically captured and cases are rarely followed-up to detect consequences of infection and treatment on the pregnant women and foetus.

Methods: A review of all published literature was undertaken to identify cases of VL infections among pregnant women by searching the following database: Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials; World Health Organization Global Index Medicus: LILACS (Americas); IMSEAR (South-East Asia); IMEMR (Eastern Mediterranean); WPRIM (Western Pacific); ClinicalTrials.

Viral vector-mediated reprogramming of the fibroblastic tumor stroma sustains curative melanoma treatment.

The tumor microenvironment (TME) is a complex amalgam of tumor cells, immune cells, endothelial cells and fibroblastic stromal cells (FSC). Cancer-associated fibroblasts are generally seen as tumor-promoting entity. However, it is conceivable that particular FSC populations within the TME contribute to immune-mediated tumor control.

Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.

Background: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.

Methods: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis.

Fully automated closed-loop glucose control compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis: an open-label, randomized crossover trial.

We evaluated the safety and efficacy of fully closed-loop insulin therapy compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis. In an open-label, multinational, two-center, randomized crossover trial, 26 adults with type 2 diabetes requiring dialysis (17 men, 9 women, average age 68 ± 11 years (mean ± s.d.

Effectiveness and safety of ranibizumab in patients with central retinal vein occlusion: results from the real-world, global, LUMINOUS study.

Objective: To evaluate the effectiveness, treatment patterns and long-term safety of ranibizumab 0.5 mg in treatment-naïve patients with central retinal vein occlusion (CRVO) in a real-world setting.

Methods: LUMINOUS, a 5-year, global, prospective, multicentre, multi-indication, observational, open-label study, recruited treatment naïve or prior treated patients who were treated as per the local ranibizumab label.

Fully automated fast-flow synthesis of antisense phosphorodiamidate morpholino oligomers.

Rapid development of antisense therapies can enable on-demand responses to new viral pathogens and make personalized medicine for genetic diseases practical. Antisense phosphorodiamidate morpholino oligomers (PMOs) are promising candidates to fill such a role, but their challenging synthesis limits their widespread application. To rapidly prototype potential PMO drug candidates, we report a fully automated flow-based oligonucleotide synthesizer.

Adenovirus vector vaccination reprograms pulmonary fibroblastic niches to support protective inflating memory CD8 T cells.

Pathogens and vaccines that produce persisting antigens can generate expanded pools of effector memory CD8 T cells, described as memory inflation. While properties of inflating memory CD8 T cells have been characterized, the specific cell types and tissue factors responsible for their maintenance remain elusive. Here, we show that clinically applied adenovirus vectors preferentially target fibroblastic stromal cells in cultured human tissues.

The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance.

Widespread Plasmodium falciparum resistance to first-line antimalarials underscores the vital need to develop compounds with novel modes of action and identify new druggable targets. Here, we profile five compounds that potently inhibit P. falciparum asexual blood stages.

Economic Burden of Heart Failure in Asian Countries with Different Healthcare Systems.

Background And Objectives: Heart failure (HF) poses substantial economic burden, primarily driven by high hospitalization and mortality rates. This study aimed to understand the economic burden of HF in 4 Asian countries under varying healthcare systems.

Methods: This was a non-interventional, retrospective study conducted in South Korea, Taiwan, Thailand and Malaysia through medical chart review.

A novel blood-based assay for treatment monitoring of tuberculosis.

Objectives: A novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) has been validated for tuberculosis (TB) treatment monitoring using laboratory-based RNA sequencing platforms. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instrument. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment.

Wash-In Leptogenesis.

We present a leptogenesis mechanism based on the standard type-I seesaw model that successfully operates at right-handed-neutrino masses as low as a few hundred TeV. This mechanism, which we dub wash-in leptogenesis, does not require any CP violation in the neutrino sector and can be implemented even in the regime of strong wash-out. The key idea behind wash-in leptogenesis is to generalize standard freeze-out leptogenesis to a nonminimal cosmological background in which the chemical potentials of all particles not in chemical equilibrium at the temperature of leptogenesis are allowed to take arbitrary values.