Effect of siponimod on retinal thickness, a marker of neurodegeneration, in participants with SPMS: Findings from the EXPAND OCT substudy.

Background: People with MS show abnormal thinning of the retinal layers, which is associated with clinical disability and brain atrophy, and is a potential surrogate marker of neurodegeneration and treatment effects.

Objective: To evaluate the utility of retinal thickness as a surrogate marker of neurodegeneration and treatment effect in participants with secondary progressive MS (SPMS) from the optical coherence tomography (OCT) substudy of the EXPAND Phase 3 clinical trial (siponimod versus placebo).

Methods: In the OCT substudy population (n = 159), treatment effects on change in the average thickness of the retinal layer, peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (GCIPL) were analyzed by high-definition spectral domain OCT at months 3, 12, and 24.

Impact of Continuous Ofatumumab Exposure During Pregnancy in Multiple Sclerosis.

Objectives: Anti-CD20 therapies are highly effective treatment options for patients with multiple sclerosis (MS), an inflammatory disorder of the CNS commonly affecting women of childbearing age. Anti-CD20 therapies are however unlicensed for use in pregnancy. Belonging to the IgG1 family, anti-CD20 monoclonal antibodies are likely to cross the placenta, especially after the 20th week of gestation.

Long-term comparison of renal and metabolic outcomes after sodium-glucose co-transporter 2 inhibitor or glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes.

Background: Renal outcomes in patients with type 2 diabetes following treatment with sodium-glucose co-transporter-2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP1RAs) have not been directly compared. This study compared the impact of SGLT2i and GLP1RA therapy on renal function and metabolic parameters.

Methods: Patients with type 2 diabetes who initiated SGLT2i or GLP1RA therapy in a tertiary hospital between January 2009 and August 2023 were included to assess composite renal outcomes, such as a 40% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease, renal death, or new-onset macroalbuminuria.

The Development of Ofatumumab, a Fully Human Anti-CD20 Monoclonal Antibody for Practical Use in Relapsing Multiple Sclerosis Treatment.

The importance of B cells in multiple sclerosis (MS) has been demonstrated through the advent of B-cell-depleting anti-CD20 antibody therapies. Ofatumumab is the first fully human anti-CD20 monoclonal antibody (mAb) developed and tested for subcutaneous (SC) self-administration at monthly doses of 20 mg, and has been approved in the US, UK, EU, and other regions and countries worldwide for the treatment of relapsing MS. The development goal of ofatumumab was to obtain a highly efficacious anti-CD20 therapy, with a safety and tolerability profile that allows for self-administration by MS patients at home and a positive benefit-risk balance for use in the broad relapsing MS population.

Development and usability testing of your MS questionnaire: A patient-based digital tool to monitor symptoms of multiple sclerosis.

Objectives: We describe the development of Your Multiple Sclerosis Questionnaire and present the real-world usability testing results of Your Multiple Sclerosis Questionnaire.

Methods: The Your Multiple Sclerosis Questionnaire tool was developed in four stages to collect feedback from people living with MS (plwMS), patient organizations, and clinicians on content, format, and applicability. To assess its usability, 13 clinicians across 7 countries completed an online survey after using the tool with plwMS in a total of 261 consultations from September, 2020 to July, 2021.

Effects of Initial Combinations of Gemigliptin Plus Metformin Compared with Glimepiride Plus Metformin on Gut Microbiota and Glucose Regulation in Obese Patients with Type 2 Diabetes: The INTESTINE Study.

The efficacy and safety of medications can be affected by alterations in gut microbiota in human beings. Among antidiabetic medications, incretin-based therapy such as dipeptidyl peptidase 4 inhibitors might affect gut microbiomes, which are related to glucose metabolism. This was a randomized, controlled, active-competitor study that aimed to compare the effects of combinations of gemigliptin−metformin vs.

Cardiac mechanisms of the beneficial effects of SGLT2 inhibitors in heart failure: Evidence for potential off-target effects.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) constitute a promising drug treatment for heart failure patients with either preserved or reduced ejection fraction. Whereas SGLT2i were originally developed to target SGLT2 in the kidney to facilitate glucosuria in diabetic patients, it is becoming increasingly clear that these drugs also have important effects outside of the kidney. In this review we summarize the literature on cardiac effects of SGLT2i, focussing on pro-inflammatory and oxidative stress processes, ion transport mechanisms controlling sodium and calcium homeostasis and metabolic/mitochondrial pathways.

Effect of siponimod on magnetic resonance imaging measures of neurodegeneration and myelination in secondary progressive multiple sclerosis: Gray matter atrophy and magnetization transfer ratio analyses from the EXPAND phase 3 trial.

Background: Magnetic resonance imaging (MRI) measurements of gray matter (GM) atrophy and magnetization transfer ratio (MTR; correlate of myelination) may provide better insights than conventional MRI regarding brain tissue integrity/myelination in multiple sclerosis (MS).

Objective: To examine the effect of siponimod in the EXPAND trial on whole-brain and GM atrophy, newly formed normalized magnetization transfer ratio (nMTR) lesions, and nMTR-assessed integrity of normal-appearing brain tissue (NABT), cortical GM (cGM), and normal-appearing white matter (NAWM).

Methods: Patients with secondary progressive multiple sclerosis (SPMS) received siponimod (2 mg/day;  =1037) or placebo ( = 523).

Insulin clearance and incretin hormones following oral and "isoglycemic" intravenous glucose in type 2 diabetes patients under different antidiabetic treatments.

It has not been elucidated whether incretins affect insulin clearance in type 2 diabetes (T2D). We aimed exploring possible associations between insulin clearance and endogenously secreted or exogenously administered incretins in T2D patients. Twenty T2D patients were studied (16 males/4 females, 59 ± 2 years (mean ± standard error), BMI = 31 ± 1 kg/m, HbA1c = 7.

Erucic acid exposure during the first year of life-Scenarios with precise food-based dietary guidelines.

Recently, the European Food Safety Authority (EFSA) issued a tolerable daily intake (TDI) for erucic acid, which is mainly found in rapeseed oil. Infants may be exposed to erucic acid from rapeseed oil indirectly through maternal consumption via breastmilk or the fat component in formula, and directly as a part of complementary feeding (CF). To check the safety of infant nutrition, scenarios for erucic acid exposure were calculated based on the daily food amounts of the German dietary guidelines.

Averting multiple sclerosis long-term societal and healthcare costs: The Value of Treatment (VoT) project.

Background And Purpose: The recent report on Value-of-Treatment (VoT) project highlights the need for early diagnosis-intervention, integrated, seamless care underpinning timely care pathways and access to best treatments. The VoT-multiple-sclerosis (MS) economic case study analysis aimed to estimate the effectiveness/cost-effectiveness of both early treatment and reducing MS risk factors (e.g.

An algorithm using clinical data to predict the optimal individual glucocorticoid dosage to treat multiple sclerosis relapses.

Background: Glucocorticoid (GC) pulse therapy is used for multiple sclerosis (MS) relapse treatment; however, GC resistance is a common problem. Considering that GC dosing is individual with several response-influencing factors, establishing a predictive model, which supports clinicians to estimate the maximum GC dose above which no additional therapeutic value can be expected presents a huge clinical need.

Method: We established two, independent retrospective cohorts of MS patients.

Hyperdense pulmonary artery sign - detection of pulmonary embolism in patients with suspected COVID-19 using non-contrast chest CT.

The request for CT (computed tomography) diagnostic in patients with suspected COVID-19 pneumonia has become part of the daily clinical routine. We reported a case of a 61-year-old patient with flu-like symptoms and a suspected COVID-19 pneumonia. After a negative PCR-test (polymerase chain reaction), a non-contrast enhanced CT was performed which revealed a suspicious hyperdensity in the left pulmonary artery and a pneumonia in the left lower lobe.

Siponimod and Cognition in Secondary Progressive Multiple Sclerosis: EXPAND Secondary Analyses.

Objective: To investigate the effects of siponimod on cognitive processing speed in patients with secondary progressive (SP) multiple sclerosis (MS), by means of a predefined exploratory and post hoc analysis of the Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND) study, a randomized controlled trial comparing siponimod and placebo.

Methods: EXPAND was a double-blind, placebo-controlled phase 3 trial involving 1,651 patients with SPMS randomized (2:1) to either siponimod 2 mg/d or placebo. Cognitive function was assessed with the Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Brief Visuospatial Memory Test-Revised (BVMT-R) administered at baseline, 6-month intervals, and end of treatment.

A Prospective, Randomized Trial Testing Different Regimens of Carbohydrate Administration to Prevent Major Reduction in Plasma Glucose Follwing a Standardized Bout of Moderate Physical Activity in Patients with Type 1 Diabetes.

Aim/hypothesis: It was the aim to prospectively study regimes of "preventive" carbohydrate administration to avoid major reduction in plasma glucose during physical activity.

Methods: 24 patients with type 1 diabetes (age 41±12 years; 11 women, 13 men; BMI 26.5±4.

Long-term safety and efficacy of daclizumab beta in relapsing-remitting multiple sclerosis: 6-year results from the SELECTED open-label extension study.

Objective: SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED.

Methods: Eligible participants who completed 1-2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED.

Risk of hypoglycaemia associated with professional, recreational, and traffic-related activities in patients with type 2 diabetes: a cross-sectional study by questionnaire.

Aims: We aimed to quantify the exposure to physical exercise associated with professional, recreational, or traffic-related activities in patients with type 2 diabetes, which may provoke or aggravate hypoglycaemic episodes, and to assess whether such risks determine the choice of medications minimizing the risk of hypoglycaemia.

Methods: In total, 203 patients with type 2 diabetes (98 women, 105 men, age 65 [56;72; median, inter-quartile range] years, diabetes duration 10 [5;15] years) were recruited from a German diabetes practice. A questionnaire assessed their engagement in professional, recreational, or traffic-related activities.

Dimethyl fumarate vs fingolimod following different pretreatments: A retrospective study.

Objective: Despite frequent use of fingolimod (FTY) and dimethyl fumarate (DMF), studies comparing clinical efficacy and withdrawal rates of DMF and FTY concerning different pretreatment situations are rare. The aim of our study was to compare relapse occurrence and withdrawal rates of DMF and FTY in different pretreatment situations.

Methods: Patients from 4 European centers were retrospectively identified and followed until the 1st relapse after treatment start or if no relapse occurred for a maximum of 2 years.

Incretin-based glucose-lowering medications and the risk of acute pancreatitis and malignancies: a meta-analysis based on cardiovascular outcomes trials.

Some epidemiological data have suggested an elevated risk of acute pancreatitis and pancreatic cancer after exposure to glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors. Recently, such outcomes have been assessed and adjudicated as adverse events of special interest in cardiovascular outcomes studies. We performed a meta-analysis of cases of acute pancreatitis and pancreatic cancer as well as any malignant neoplasm reported in cardiovascular outcomes trials (CVOTs) with GLP-1 receptor agonists and DPP-4 inhibitors.