De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

Retinal thinning differentiates treatment effects in relapsing multiple sclerosis below the clinical threshold.

Objective: To investigate retinal layer thinning as a biomarker of disease-modifying treatment (DMT) effects in relapsing multiple sclerosis (RMS).

Methods: From an ongoing prospective observational study, we included patients with RMS, who (i) had an optical coherence tomography (OCT) scan within 6 to 12 months after DMT start (rebaseline) and ≥1 follow-up OCT ≥12 months after rebaseline and (ii) adhered to DMT during follow-up. Differences between DMT in thinning of peripapillary-retinal-nerve-fiber-layer (pRNFL) and macular ganglion cell-plus-inner plexiform-layer (GCIPL) were analyzed using mixed-effects linear regression.

Switching from natalizumab to antiCD20 monoclonal antibodies: Short transition interval is associated with improved outcome.

Objective: To investigate the impact of transition interval length when switching from natalizumab (NTZ) to anti-CD20 monoclonal antibodies (antiCD20) on recurrent disease activity and safety in relapsing multiple sclerosis (RMS).

Methods: Aggregating data from 8 MS centres in Austria, Switzerland, and Germany, we included RMS patients who (i) continuously received NTZ for ≥3 months, (ii) were switched to antiCD20, and (iii) had ≥12 months follow-up after switch. The primary endpoint was occurrence of relapse after switch, secondary endpoints included severe infections (CTCAE grade ≥3).

Disability progression is a question of definition-A methodological reappraisal by example of primary progressive multiple sclerosis.

Background: Different definitions of disability progression by Expanded Disability Status Scale (EDSS) may influence frequency and/or time to event.

Methods: In this multicenter cohort study, we included PPMS patients with follow-up ≥24 months and ≥3 available EDSS scores overall (≥1 per year). We applied 672 definitions of disability progression including different minimal EDSS increase, required confirmation and fixed/roving-baseline score.

Neurofilament Light Chain Is Associated With Acute Mountain Sickness.

Background: Neurological symptoms are common in acute mountain sickness (AMS); however, the extent of neuroaxonal damage remains unclear. Neurofilament light chain (NfL) is an established blood biomarker for neuroaxonal damage.

Objective: To investigate whether plasma (p) NfL levels increase after simulated altitude exposure, correlate with the occurrence of AMS, and might be mitigated by preacclimatization.

Cerebrospinal fluid red blood cells and total protein are associated with clinical outcome in spontaneous subarachnoid hemorrhage.

Background And Purpose: Prognostication in patients with spontaneous subarachnoid hemorrhage (SAH) can be challenging. The aim of this study was to assess whether cerebrospinal fluid (CSF) red blood cell (RBC) count and total protein (TP) concentration are associated with SAH prognosis.

Methods: Patients with SAH treated at the neurological intensive care unit (ICU) in Innsbruck were included in this real-world, observational study.

Association of Disease-Modifying Treatment With Outcome in Patients With Relapsing Multiple Sclerosis and Isolated MRI Activity.

Background And Objectives: Isolated value of MRI metrics in relapsing multiple sclerosis (RMS) as a surrogate marker of response to disease-modifying treatment (DMT) and, thus, as decision criteria for DMT escalation in the absence of clinical signs of disease activity is still a matter of debate. The aim of this study was to investigate whether DMT escalation based on isolated MRI activity affects clinical outcome.

Methods: Combining data from 5 MS centers in Austria and Switzerland, we included patients with RMS aged at least 18 years who (1) had initiated first-line, low-to-moderate-efficacy DMT (interferon β, glatiramer acetate, teriflunomide, or dimethyl fumarate) continued for ≥12 months, (2) were clinically stable (no relapses or disability progression) on DMT for 12 months, (3) had MRI at baseline and after 12 months on DMT, and (4) had available clinical follow-up for ≥2 years after the second MRI.

Alemtuzumab treatment for multiple sclerosis in Austria: An observational long-term outcome study.

Background/objective: Observational real-world study to analyze the clinical effects of alemtuzumab (ALEM) and subsequent disease-modifying therapy (DMT) usage in multiple sclerosis (MS).

Methods: Data retrieved from the Austrian MS treatment registry (AMSTR) included baseline (BL) characteristics (at ALEM start), annualized relapse rate (ARR), 6-month confirmed progression independent of relapse activity (PIRA; ≥ 0.5-point Expanded Disability Status Scale (EDSS) score increase), 6-month confirmed disability improvement (CDI; ≥ 0.

Antiproliferative Activity of -Acylhydrazone Derivative on Hepatocellular Carcinoma Cells Involves Transcriptional Regulation of Genes Required for G2/M Transition.

Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage.

Olfactory threshold as a biomarker of long-term relapse activity in multiple sclerosis.

Background: Olfactory threshold (OT) is a marker of short-term inflammatory activity in multiple sclerosis (MS).

Objective: To investigate whether OT predicts long-term MS clinical disease course.

Methods: This was a 6-year prospective longitudinal study on MS patients at the MS clinic Innsbruck.

Sex impacts treatment decisions in multiple sclerosis.

Background: Individual disease-modifying treatment (DMT) decisions might differ between female and male people with MS (pwMS).

Objective: To identify sex-related differences in DMT strategies over the past decades in a real-world setting.

Methods: In this cohort study, data from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), a nationwide prospectively collected registry mandatory for reimbursement, were retrospectively analyzed.

Early intensive versus escalation treatment in patients with relapsing-remitting multiple sclerosis in Austria.

Objectives: To compare the effectiveness of early intensive treatment (EIT) versus escalation treatment (ESC) in a nationwide observational cohort of almost 1000 people with relapsing-remitting multiple sclerosis (RRMS).

Materials And Methods: The EIT cohort started with alemtuzumab (AZM), cladribine (CLAD), fingolimod (FTY), natalizumab (NTZ), ocrelizumab (OCR), or ozanimod (OZA); whereas, the ESC cohort was escalated from dimethylfumarate (DMF) or teriflunomide (TERI) to AZM, CLAD, FTY, NTZ, OCR, or OZA within the Austrian MS Treatment Registry. Patients had to stay on therapy for at least 3 months and up to 16 years.

Antimicrobial and wound healing potential of naphthoquinones encapsulated in nanochitosan.

The use of chitosan in pharmaceutical formulations is an advantageous approach due to this compound intrinsic biodegradability and biocompatibility, as well as ready availability and low polymer cost. Herein, the naphthoquinones 3- chloromethylene-menadione (NQ1) and 2,3-dichloro-1,4-naphthoquinone (NQ2) were nanoencapsulated into chitosan (CNP) by the ionotropic gelatinization technique and characterized by DLS, FTIR, SEM, TGA and DSC, and their release profiles evaluated. The antimicrobial and wound healing activities were investigated.

Subarachnoid haemorrhage or traumatic lumbar puncture. Differentiation by cerebrospinal fluid parameters in a multivariable approach.

Lumbar puncture (LP) is recommended in patients with thunderclap headache and negative computed tomography to rule out spontaneous subarachnoid haemorrhage (SAH). Blood contamination of cerebrospinal fluid (CSF) due to traumatic LP poses a diagnostic dilemma. Therefore, routine CSF parameters were investigated to distinguish between SAH and a traumatic LP.

Multiple sclerosis in the elderly: a retrospective cohort study.

Background: There is a lack of knowledge of disease course, prognosis, comorbidities and potential treatments of elderly MS patients.

Objective: To characterize the disease course including disability progression and relapses, to quantify the use of DMTs and to identify comorbidities and risk factors for progression in elderly multiple sclerosis (MS) patients.

Methods: This is a retrospective study of 1200 Austrian MS patients older than 55 years as of May 1st, 2017 representing roughly one-third of all the MS patients of this age in Austria.

Odour discrimination and identification as a biomarker of long-term disability worsening in multiple sclerosis.

Background: Odour discrimination and identification (DI) are markers associated with disability worsening and neuroaxonal damage in multiple sclerosis (MS).

Objective: The main objective of this research is to investigate whether longitudinal change of DI predicts long-term MS disease course.

Methods: This is a 6-year prospective longitudinal study on MS patients at the MS Clinic Innsbruck.

Long-term outcome of natalizumab-associated progressive multifocal leukoencephalopathy in Austria: a nationwide retrospective study.

Background/objective: The use of natalizumab (NAT) in multiple sclerosis (MS) may be complicated by progressive multifocal leukoencephalopathy (PML), a rare and life-threatening opportunistic brain infection. We aimed to analyze the course of MS after PML recovery together with the long-term outcome of NAT-associated PML (NAT-PML) in Austria.

Methods: Retrospective study based on identification of cases in the nationwide Austrian MS treatment registry (AMSTR) and MS centers with review of patient records.

Induction of a different immune response in non-titanized compared to titanized polypropylene meshes.

It is well known that pelvic organ prolapse (POP) significantly reduces the quality of life of affected women and in many cases requires corrective surgery. Aim of the study was to compare the immune response against titanized versus non-titanized meshes, especially macrophage polarization and immune checkpoint association. For this, we analyzed 644 POP surgeries, which were performed between 2017 and 2022, in our department.

Diagnostic Performance of Adding the Optic Nerve Region Assessed by Optical Coherence Tomography to the Diagnostic Criteria for Multiple Sclerosis.

Background And Objectives: The optic nerve has been recommended as an additional region for demonstrating dissemination in space (DIS) in diagnostic criteria for multiple sclerosis (MS). The aim of this study was to investigate whether adding the optic nerve region as determined by optical coherence tomography (OCT) as part of the DIS criteria improves the 2017 diagnostic criteria.

Methods: From a prospective observational study, we included patients with a first demyelinating event who had complete information to assess DIS and a spectral domain OCT scan obtained within 180 days.

Immune profiling in multiple sclerosis: a single-center study of 65 cytokines, chemokines, and related molecules in cerebrospinal fluid and serum.

Introduction: The understanding of the pathophysiology of multiple sclerosis (MS) has evolved alongside the characterization of cytokines and chemokines in cerebrospinal fluid (CSF) and serum. However, the complex interplay of pro- and anti-inflammatory cytokines and chemokines in different body fluids in people with MS (pwMS) and their association with disease progression is still not well understood and needs further investigation. Therefore, the aim of this study was to profile a total of 65 cytokines, chemokines, and related molecules in paired serum and CSF samples of pwMS at disease onset.

Lower initial red blood cell count in cerebrospinal fluid predicts good functional outcome in patients with spontaneous subarachnoid haemorrhage.

Background And Purpose: Red blood cell (RBC) degradation after subarachnoid haemorrhage (SAH) negatively affects functional outcome. Although the detection of RBCs in the cerebrospinal fluid (CSF) is a widely available part of neurological routine diagnostics, the prognostic value as a biomarker remains unclear. This study was undertaken to investigate whether CSF RBC count correlates with established radiological markers of SAH volume and whether the CSF RBC count can predict functional outcome in SAH patients.