Evaluating multiple sclerosis severity loci 30 years after a clinically isolated syndrome.

The first genome-wide significant multiple sclerosis severity locus, rs10191329, has been pathologically linked to cortical lesion load and brain atrophy. However, observational cohorts such as MSBase have not replicated associations with disability outcomes, instead finding other loci. We evaluated rs10191329 and MSBase loci in a unique cohort of 53 people followed for 30 years after a clinically isolated syndrome, with deep clinical phenotyping and MRI measures of inflammation and neurodegeneration.

CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series.

Background: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. B cells have a central role in the pathogenesis of systemic sclerosis.

Big data and artificial intelligence applied to blood and CSF fluid biomarkers in multiple sclerosis.

Artificial intelligence (AI) has meant a turning point in data analysis, allowing predictions of unseen outcomes with precedented levels of accuracy. In multiple sclerosis (MS), a chronic inflammatory-demyelinating condition of the central nervous system with a complex pathogenesis and potentially devastating consequences, AI-based models have shown promising preliminary results, especially when using neuroimaging data as model input or predictor variables. The application of AI-based methodologies to serum/blood and CSF biomarkers has been less explored, according to the literature, despite its great potential.

Multiple sclerosis: emerging epidemiological trends and redefining the clinical course.

Multiple sclerosis is a chronic, inflammatory, and neurodegenerative disease of the central nervous system and a major cause of neurological disability in young adults. Its prevalence and incidence are increasing, and it has been estimated at over 2.8 million cases worldwide, in addition to recent trends towards a shift in MS prevalence to older ages, with peak prevalence estimates in the sixth decade of life.

CD19-CAR T-cell therapy induces deep tissue depletion of B cells.

Objectives: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo.

Methods: Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs.

The evolving contribution of MRI measures towards the prediction of secondary progressive multiple sclerosis.

Background: In multiple sclerosis (MS), both lesion accrual and brain atrophy predict clinical outcomes. However, it is unclear whether these prognostic features are equally relevant throughout the course of MS. Among 103 participants recruited following a clinically isolated syndrome (CIS) and followed up over 30 years, we explored (1) whether white matter lesions were prognostically more relevant earlier and brain atrophy later in the disease course towards development of secondary progressive (SP) disease; (2) if so, when the balance in prognostic contribution shifts and (3) whether optimised prognostic models predicting SP disease should include different features dependent on disease duration.

Using the Progression Independent of Relapse Activity Framework to Unveil the Pathobiological Foundations of Multiple Sclerosis.

Progression independent of relapse activity (PIRA), a recent concept to formalize disability accrual in multiple sclerosis (MS) independent of relapses, has gained popularity as a potential clinical trial outcome. We discuss its shortcomings and appraise the challenges of implementing it in clinical settings, experimental trials, and research. The current definition of PIRA assumes that acute inflammation, which can manifest as a relapse, and neurodegeneration, manifesting as progressive disability accrual, can be disentangled by introducing specific time windows between the onset of relapses and the observed increase in disability.

A Self-Applied Psychological Treatment for Gambling-Related Problems via The Internet: A Pilot, Feasibility Study.

The main purpose of this study was to evaluate the feasibility of an online psychological intervention for individuals with gambling-related problems, supported by ecological momentary assessments and interventions (EMAs and EMIs), along with weekly phone-calls, before conducting a randomized controlled trial. Participants were required to complete 3 of the 8 modules of the program based on cognitive-behavioral therapy (CBT) and extensions and innovations of CBT. The study measured the outcomes of feasibility (i.

Artificial intelligence applied to MRI data to tackle key challenges in multiple sclerosis.

Artificial intelligence (AI) is the branch of science aiming at creating algorithms able to carry out tasks that typically require human intelligence. In medicine, there has been a tremendous increase in AI applications thanks to increasingly powerful computers and the emergence of big data repositories. Multiple sclerosis (MS) is a chronic autoimmune condition affecting the central nervous system with a complex pathogenesis, a challenging diagnostic process strongly relying on magnetic resonance imaging (MRI) and a high and largely unexplained variability across patients.

Bispecific T cell engager therapy for refractory rheumatoid arthritis.

Bispecific T cell engagers (BiTEs) kill B cells by engaging T cells. BiTEs are highly effective in acute lymphoblastic leukemia. Here we treated six patients with multidrug-resistant rheumatoid arthritis (RA) with the CD19xCD3 BiTE blinatumomab under compassionate use.

Optic chiasm involvement in multiple sclerosis, aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein-associated disease.

Background: Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated.

Aims: To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON-) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers.

Vaccine Safety and Immunogenicity in Patients With Multiple Sclerosis Treated With Natalizumab.

Importance: Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay.

Objective: To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment.

Design, Setting, And Participants: This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022.

Prediction of disease activity and treatment failure in relapsing-remitting MS patients initiating daily oral DMTs.

Background: Limited data exist regarding treatment response prediction to oral disease-modifying therapies (DMTs) in multiple sclerosis (MS).

Objectives: We assessed the capacity of available scoring systems to anticipate disease activity parameters in naïve relapsing-remitting MS (RRMS) patients initiating daily oral DMTs, hypothesizing that they exhibit different predictive potentials.

Methods: We conducted a retrospective study and applied the Rio Score (RS), modified Rio Score (mRS), and MAGNIMS Score 12 months after DMT initiation.

Trans-Synaptic Degeneration in the Visual Pathway in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Background And Objectives: We aimed to assess the presence of retinal neurodegeneration independent of optic neuritis (ON) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the development of trans-synaptic anterograde degeneration in these patients after ON.

Methods: Cross-sectional, retrospective study of 34 adult patients with MOGAD and 23 healthy controls (HC). Clinical, optical coherence tomography (OCT), and MRI data were collected.

CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.

Background: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission.

Methods: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide.

What contributes to disability in progressive MS? A brain and cervical cord-matched quantitative MRI study.

Background: We assessed the ability of a brain-and-cord-matched quantitative magnetic resonance imaging (qMRI) protocol to differentiate patients with progressive multiple sclerosis (PMS) from controls, in terms of normal-appearing (NA) tissue abnormalities, and explain disability.

Methods: A total of 27 patients and 16 controls were assessed on the Expanded Disability Status Scale (EDSS), 25-foot timed walk (TWT), 9-hole peg (9HPT) and symbol digit modalities (SDMT) tests. All underwent 3T brain and (C2-C3) cord structural imaging and qMRI (relaxometry, quantitative magnetisation transfer, multi-shell diffusion-weighted imaging), using a fast brain-and-cord-matched protocol with brain-and-cord-unified imaging readouts.

Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial.

Background: Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease.

Methods: The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain.

Progression Independent of Relapse Activity in Multiple Sclerosis: Closer to Solving the Pathologic Puzzle.

Progression independent of relapse activity (PIRA) is one of the main mechanisms of disability accrual in multiple sclerosis (MS) even in people with relapsing-remitting MS (RRMS). PIRA can occur at any stage of the disease and is associated with unfavorable long-term outcomes, especially if PIRA occurs early in the disease course. The pathologic substrates of PIRA are not yet well understood, although there is growing evidence suggesting that PIRA may occur mainly in a predominant neurodegenerative context, sometimes in combination with an acute inflammatory activity.