Longitudinal trajectories of digital upper limb biomarkers for multiple sclerosis.

Background: Upper limb dysfunction is a common debilitating feature of relapsing-remitting multiple sclerosis (RRMS). We aimed to examine the longitudinal trajectory of the iPad®-based Manual Dexterity Test (MDT) and predictors of change over time.

Methods: We prospectively enrolled RRMS patients (limited to Expanded Disability Status Scale (EDSS) < 4).

The impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study.

Background: The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort.

Objective: To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort.

The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability.

The key DNA repair enzyme DNA-PKcs has several and important cellular functions. Loss of DNA-PKcs activity in mice has revealed essential roles in immune and nervous systems. In humans, DNA-PKcs is a critical factor for brain development and function since mutation of the prkdc gene causes severe neurological deficits such as microcephaly and seizures, predicting yet unknown roles of DNA-PKcs in neurons.

Ethylene Oxide Hemoglobin Adducts in Cord Blood and Offspring's Size at Birth: The NewGeneris European Cohort Study.

Background: Prenatal ethylene oxide exposure may have adverse effects on fetal development. We examined the relationships between ethylene oxide hemoglobin (Hb) adduct levels and offspring's size at birth in a prospective European mother-child study.

Methods: This study included 1106 singletons from the NewGeneris project (2006-2010) with ethylene oxide Hb adducts measured in cord blood.

Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60.

Background: Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

Background: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers.

Methods: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018.

Managing cognitive impairment and its impact in multiple sclerosis: An Australian multidisciplinary perspective.

Cognitive impairment in multiple sclerosis (MS) affects approximately 40-70% of patients and can have varying degrees of severity. Even mild cognitive impairment can impact on quality of life and productivity. Despite this, patients are not routinely screened or monitored for cognitive impairment in Australia due to a range of issues, with time and space being the main limiting factors.

The Patient-Determined Disease Steps scale is not interchangeable with the Expanded Disease Status Scale in mild to moderate multiple sclerosis.

Background And Purpose: The validity, reliability, and longitudinal performance of the Patient-Determined Disease Steps (PDDS) scale is unknown in people with multiple sclerosis (MS) with mild to moderate disability. We aimed to examine the psychometric properties and longitudinal performance of the PDDS.

Methods: We included relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score of less than 4.

Smartphone monitoring of cognition in people with multiple sclerosis: A systematic review.

Background: Current cognitive monitoring of people with multiple sclerosis (pwMS) is sporadic, resource intensive and insensitive for detection of real-world cognitive performance and decline. Smartphone applications may provide us with a more sensitive biomarker for cognitive decline that reflects real-world performance. The goal of this study was to perform a systematic review and qualitative synthesis of all current smartphone apps monitoring cognition in pwMS.

Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosis.

Background: To compare the effectiveness and treatment persistence of ocrelizumab, cladribine and natalizumab in patients with relapsing-remitting multiple sclerosis switching from fingolimod.

Methods: Using data from MSBase registry, this multicentre cohort study included subjects who had used fingolimod for ≥6 months and then switched to ocrelizumab, cladribine or natalizumab within 3 months after fingolimod discontinuation. We analysed relapse and disability outcomes after balancing covariates using an inverse-probability-treatment-weighting method.

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial.

Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus disease 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia.

Methods: In this multicentre, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with COVID-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for three consecutive days or placebo in addition to standard dexamethasone.

Subjective versus objective performance in people with multiple sclerosis using the MSReactor computerised cognitive tests.

Background: Perceived cognitive impairment in MS is associated with adverse changes in employment capacity, sexual function, and aspects of daily living. Studies have shown relationships between perceived cognitive impairment and objective neuropsychological functioning and mood. Subjective cognitive performance in people with MS has not previously been compared to their objective performance on a computerised cognitive battery.

Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons.

Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are clinically diagnosed using neuropsychological and cognitive tests, expensive neuroimaging-based approaches (MRI and PET) and invasive and time-consuming lumbar puncture for cerebrospinal fluid (CSF) sample collection to detect biomarkers. Thus, a rapid, simple and cost-effective approach to more easily access fluids and tissues is in great need. Here, we exploit the chemical direct reprogramming of patient skin fibroblasts into neurons (chemically induced neurons, ciNs) as a novel strategy for the rapid detection of different pathological markers of neurodegenerative diseases.

DNA repair protein DNA-PK protects PC12 cells from oxidative stress-induced apoptosis involving AKT phosphorylation.

Background: Emerging evidence suggest that DNA-PK complex plays a role in the cellular response to oxidative stress, in addition to its function of double strand break (DSB) repair. In this study we evaluated whether DNA-PK participates in oxidative stress response and whether this role is independent of its function in DNA repair.

Methods And Results: We used a model of HO-induced DNA damage in PC12 cells (rat pheochromocytoma), a well-known neuronal tumor cell line.

Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: A Sarculator-based risk stratification analysis of the ISG-STS 1001 randomized trial.

Background: The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS.

Methods: This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS.

Association Between Cognitive Trajectories and Disability Progression in Patients With Relapsing-Remitting Multiple Sclerosis.

Background And Objectives: Longitudinal cognitive trajectories in multiple sclerosis are heterogeneous and difficult to measure. We aimed to identify discrete longitudinal reaction time trajectories in relapsing-remitting multiple sclerosis using a computerized cognitive battery and to assess the association between trajectories of reaction time and disability progression.

Methods: All participants serially completed computerized reaction time tasks measuring psychomotor speed, visual attention, and working memory.

Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trial.

MRP-1 is implicated in multidrug resistance and was described as prognostic in high-risk patients with soft-tissue sarcoma (STS) in a previous study. The current research aimed to validate MRP-1 prognostic/predictive value in localized sarcomas treated with anthracyclines plus ifosfamide within the ISG-1001 phase III study. In addition, the inhibitory activity on MRP-1 was investigated in preclinical studies to identify new combinations able to increase the efficacy of standard chemotherapy in STS.

Rehabilitation for lung cancer patients undergoing surgery: results of the PUREAIR randomized trial.

Background: Surgery for non-small cell lung cancer is proven to be the most effective treatment in early stages, although concerns exist on its negative impact on patients' overall fitness.

Aim: To establish whether intensive pulmonary rehabilitation, preoperative and postoperative, improves exercise capacity in patients undergoing lung resection.

Design: Single center, unblinded, designed for superiority, 1:1 randomized controlled trial with two parallel arms.

Prognostic Impact of Muscle Quantity and Quality and Fat Distribution in Diffuse Large B-Cell Lymphoma Patients.

Baseline CT scans of 116 patients (48% female, median 64 years) with diffuse large B-cell lymphoma (DLBCL) were retrospectively reviewed to investigate the prognostic role of sarcopenia and fat compartment distributions on overall survival (OS), progression-free survival (PFS), and early therapy termination. Skeletal muscle index (SMI), skeletal muscle density (SMD), and intermuscular adipose tissue (IMAT) were quantified at the level of the third lumbar vertebra (L3) and proximal thigh (PT). Low L3-SMD, but not low L3-SMI, was associated with early therapy termination ( = 0.

Direct Reprogramming of Somatic Cells to Neurons: Pros and Cons of Chemical Approach.

Translating successful preclinical research in neurodegenerative diseases into clinical practice has been difficult. The preclinical disease models used for testing new drugs not always appear predictive of the effects of the agents in the human disease state. Human induced pluripotent stem cells, obtained by reprogramming of adult somatic cells, represent a powerful system to study the molecular mechanisms of the disease onset and pathogenesis.

Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV-2 Infection Severity.

(1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective was to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1 h, 48 h or continuously with 10 M nicotine, a concentration mimicking human exposure to a cigarette.

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile.

Objective: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia.

Planned Yellow Fever Primary Vaccination Is Safe and Immunogenic in Patients With Autoimmune Diseases: A Prospective Non-interventional Study.

Yellow Fever (YF) vaccination is suggested to induce a large number of adverse events (AE) and suboptimal responses in patients with autoimmune diseases (AID); however, there have been no studies on 17DD-YF primary vaccination performance in patients with AID. This prospective non-interventional study conducted between March and July, 2017 assessed the safety and immunogenicity of planned 17DD-YF primary vaccination in patients with AID. Adult patients with AID (both sexes) were enrolled, along with healthy controls, at a single hospital (Vitória, Brazil).