bluuebunny/crossref_metadata_2025_split huggingface dataset:
030  Hepatitis C reactivation with fingolimod treatment for relapsing-remitting multiple sclerosis (RRMS)
Authors: Aslanyan Aram , Vilar Javier , Das Joyutpal , Mihalova Tatiana 
Published: May 2022

39-year old female with RRMS switched treatment from Copaxone to Fingolimod due to clinical and radiological disease progression. After 3 years on Fingolimod treatment routine blood moni- toring identified deranged liver function tests (LFT). Additional investigation found positive Hepatitis C virus(HCV) serology, genotype 3, with 270,000 copies. Viral tests for HIV, VZV, HBV, EBV, CMV and autoimmune screening were normal. There were no risk factors for contracting Hepatitis C whilst on MS disease modifying therapy. She had blood transfusion at the age 11 and an intramuscular pain relief when examined in Turkish hospital, 1997. Stable partner of 20 years tested negative for HCV. We describe a case of latent Hepatitis C reactivation secondary to prolonged immunosuppression. Although the increased risks of herpetic viruses’ reactivation with Fingolimod are known, latent HCV reac- tivation is rather unique. Tagawa et al. described Hepatitis C virus reactivation in MS patient with known HCV positivity and undetectable HCV RNA for 4 years prior to Fingolimod exposure. Treatment guidelines do not require viral hepatitis screening prior to Fingolimod therapy. We would like to raise awareness of rare but serious complication of immunosuppressive therapy, hoping to accomplish more extensive viral screening prior to Fingolimod treatment and improve patients’ safety.aram.aslanyan@srft.nhs.uk
032  Systematic review of prediction models in relapsing remitting multiple sclerosis
Authors: Brown Fraser , Kearns Patrick , Glasmacher Stella , Hunt David , Connick Peter , Chandran Siddharthan 
Published: May 2022

BackgroundPrediction of individual disease course in relapsing remitting multiple sclerosis (RRMS) is chal- lenging. This has important implications for informed decision making in clinical practice.ObjectivesTo conduct a systematic review in order to establish methodological quality of published prediction models in RRMS.MethodsWe searched Medline, Embase and Web of Science. Reviewers screened abstracts and full text for eligibility and assessed risk of bias. Studies reporting development or validation of prediction models for adults with RRMS were included. Data collection was guided by checklist for critical appraisal and data extraction for systematic reviews and applicability and methodological quality assessment by prediction model risk of bias assessment tool.Results30 studies were included. Applicability was assessed as high risk of concern in 29 studies. Risk of bias was assessed as high for all studies. The single most frequently included predictor was baseline EDSS (n=11). T2 Lesion volume or number and brain atrophy were each retained in seven studies. Five studies included external validation. None included impact analysis.ConclusionsAlthough a number of prediction models for RRMS have been reported, most are at high risk of bias and lack external validation and impact analysis, restricting their application in clinical practice.fraser@tonnard.co.uk
033  Ocrelizumab: serum Ig levels and serious infections
Authors: Schmierer Klaus , Bar-Or Amit , Bermel Robert , Weber Martin S , Hughes Richard , Lin Chien-Ju , Wang Jian- mei , Craviero Licinio , Hauser Stephen L , Derfuss Tobias 
Published: May 2022

BackgroundAn apparent association between decreased Ig levels and serious infections (SIs) was pre- viously reported. Here, we characterised the temporal evolution of Ig levels and risk of SIs by baseline Ig quartile over 6 years in OPERA I/II (NCT01247324/NCT01412333), ORATORIO (NCT01194570), and their open-label extensions.MethodsSerum Ig levels were measured ≥24 weeks. Baseline IgG/IgM/IgA quartiles (g/L) were determined; Q1 represents the lowest quartile. Changes in Ig levels and SI rates by baseline quartiles were assessed.ResultsOver 6 years, mean change in IgG levels, g/L (% change) per year by quartile were: Q1, -0.24 (-2.9%); Q2, -0.32 (-3.2%); Q3, -0.40 (-3.6%); Q4, -0.40 (-3.0%) in OPERA, and Q1, -0.23 (-2.9%); Q2, -0.28 (-2.9%);Q3 -0.35 (-3.1%); Q4, -0.51 (-3.8%) in ORATORIO. SI rates/100PY (95% CI) were: Q1, 1.63 (0.95–2.61); Q2, 1.55(0.90–2.48); Q3, 1.51 (0.86–2.45); Q4, 1.11 (0.57–1.94) in OPERA, and Q1, 4.04 (2.66–5.87); Q2, 3.81 (2.46–5.62); Q3, 5.39 (3.76–7.50); Q4, 2.17 (1.22–3.59) in ORATORIO. Changes in IgM/IgA will also be presented.ConclusionsPatients with lower baseline IgG demonstrated less absolute IgG decline, but similar per- centage decline, versus patients with higher baseline IgG. SI rates were low, and similar across quartiles.k.schmierer@qmul.ac.uk
036  Ocrelizumab real-world effectiveness in patients with relapsing and primary progressive multiple sclerosis: MuSicalE baseline data
Authors: Hobart Jeremy , Pesch Vincent van , Rovira Alex , Alroughani Raed , Cutter Gary , Craveiro Licinio , Dzhenkova Dima , Kuenzel Thomas , Kantaria Rakesh , Trojano Maria 
Published: May 2022

BackgroundMuSicalE (NCT03593590) is an ongoing, observational study assessing ocrelizumab effec- tiveness/safety in patients with relapsing or primary progressive multiple sclerosis (MS) treated with ocre- lizumab in routine care.MethodsPatients with relapsing-remitting MS (RRMS), relapsing secondary progressive MS (rSPMS) or primary progressive MS (PPMS) initiating ocrelizumab per local label/guidelines are included. The primary endpoint is change in SymptoMScreen score (measures 12 common MS symptoms [range, 0–6]; higher scores indicate greater impairment).ResultsAs of 5 August 2019, 324 patients were eligible for analyses. Overall, patients with rSPMS (n=25) had a longer mean disease duration (16.7 years) versus patients with RRMS (8.6 years; n=243) or PPMS (9.2 years; n=54). Mean [SD] baseline Expanded Disability Status Scale score was higher in patients with rSPMS (5.2 [1.7]) or PPMS (5.0 [1.5]), versus RRMS (3.3 [1.7]). Baseline mean (SD) total SymptoMScreen scores in patients with RRMS, rSPMS and PPMS were 23.0 (13.3), 26.8 (11.9) and 28.7 (11.2), respectively. UK-specific baseline data, including other patient-reported outcomes from secondary end points, will also be presented.ConclusionsBaseline demographics and disease characteristics show expected differences in relapsing and progressive patients. MuSicalE will inform the real-world effectiveness/safety of ocrelizumab in a broad MS population. Recruitment is ongoing.jeremy.hobart@plymouth.ac.uk
039  Disease modifying treatments and cancer monitoring in MS; the need for a nation-wide disease registry
Authors: Das Joyutpal , Warrens Hilary , Aslanyan Aram , Mihalova Tatiana 
Published: May 2022

The immune system is inextricably linked to both cancer and Multiple Sclerosis (MS). National population- based cohort studies in Denmark and Norway have attempted to elucidate the relationship between cancer and MS, but results are conflicting. The advent of highly-efficacious disease modifying treatments (DMTs) in recent years revolutionised MS treatment, but the effect of their immunomodulating mechanism on cancer risk is unclear. Studies thus far have been limited by lack of cancer risk factor data and statistical power. In this pilot study, we identified the relevant data, including patient and cancer characteristics, DMT use, and important risk factors that may confound treatment effects. These data was collected for MS patients with cancer under the care of Salford Royal Foundation Trust. This highlighted the incomplete- ness of records, and the need for a framework for data collection. Moreover, data collection relied on multiple sources. Integration of the resultant question proforma into patient records will be a simple tool to enable reliable, homogeneous data collection. Deepening understanding of the effect of DMTs on cancer risk will improve risk-benefit treatment analysis in MS, thus improving care. Indeed, the institution of a nation-wide patient registry for such data in the UK will facilitate necessary future research.j.das@doctors.org.uk
Unique inflammatory transcriptional profiles distinguish between sALS cases of long and short disease duration
Authors: Elliott Elizabeth , Gregory Jenna M , Dando Owen , McDade Karina , Smith Colin , Chandran Siddharthan 
Published: May 2022

Amyotrophic Lateral Sclerosis (ALS) is incurable, progressively fatal and a highly heterogeneous neuro- degenerative disease. Significant variation exists across the phenotypic presentation and genetic back- ground of the condition. The identification of TDP-43 protein aggregates as a pathological hallmark of ALS has established the condition as a proteinopathy. As TDP-43 is ubiquitously expressed and regulates transcription and splicing, understanding the transcriptional profiles associated with distinct ALS clinical phenotypes, particularly those associated with neuro-resilience, is a critical yet understudied area. We carried out transcriptional profiling on motor cortex samples from a cohort of sporadic ALS cases to determine the transcriptional signatures associated with long and short disease duration. Bioinformatic gene ontology analyses identified unique inflammatory transcriptional profiles associated with these extreme disease phenotypes. Our data demonstrate that inflammatory pathway dysregulation can dis- tinguish between phenotypic extremes in ALS. Characterising the molecular profile of clinically heteroge- neous cases provides vital insight in to the underlying pathophysiology of the condition. Understanding the molecular basis of factors which confer neuro-resilience will facilitate the development of targeted disease therapies. The ability to distinguish between molecular subtypes of ALS will enable the stratifica- tion of future trials to test these therapies and also to advance disease prognostication. 17e.elliott@ed.ac.uk
042  Determinants of baseline disability in relapsing remitting multiple sclerosis
Authors: Brown Fraser , Kearns Patrick , Martin Sarah-Jane , Connick Peter , Hunt David , Chandran Siddharthan 
Published: May 2022

BackgroundDeterminants of multiple sclerosis aetiology and natural history remain unknown.ObjectivesTo determine factors associated with level of disability measured by Expanded Disability Severity Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS).MethodsWe collected demographic, clinical, smoking and alcohol history in an incidence cohort of patients with RRMS recruited within six months of diagnosis. Ordinal logistic regression was used to examine association of EDSS with clinical and demographic features. Linear regression was used to examine asso- ciation between the same variables and MSFC.ResultsWe recruited 440 patients. Mean age at onset was 33.61 and 75.9% were female. Age at onset was shown to be associated with higher disability as measured by EDSS and MSFC. Sex was not signifi- cantly associated with outcome. After adjustment for age and sex, time to diagnosis, current smoking, having ever smoked and obesity were associated with higher EDSS whereas having ever smoked were associated with worse MSFC scores.ConclusionsDisability in relapsing-remitting multiple sclerosis is partly determined by demographic features and modifiable risk factors even early in disease course. Much of the variation remains to be elucidated and individualised risk prediction is an unmet need.fraser@tonnard.co.uk
043  Efficacy of siponimod in secondary progressive multiple sclerosis with active disease: EXPAND study subgroup analysis
Authors: Gold Ralf , Kappos Ludwig , Bar-Or Amit , Vermersch Patrick , Giovannoni Gavin , Fox Robert J , Rouyrre Nicolas , Karlsson Goril , Cree Bruce AC 
Published: May 2022

BackgroundSiponimod, a selective sphingosine 1-phosphate receptor modulator, demonstrated clini- cally relevant effects in a typical secondary progressive multiple sclerosis (SPMS) population in the Phase 3 EXPAND study, with 21% and 26% reductions in 3- and 6-month confirmed disability progression (CDP) versus placebo.MethodsPost hoc subgroup analysis was performed in patients with active disease (defined as the presence of relapses in 2 years before screening and/or ≥1 T1 gadolinium-enhancing [Gd ] lesion at baseline) to assess the efficacy of siponimod 2mg versus placebo in this population.ResultsThis analysis included 779 SPMS patients with active disease (siponimod [n=516], placebo [n=263]). The proportion of patients with relapse in the 2 years prior to study was 76% and with Gd lesions at baseline 45%. Siponimod significantly reduced 3-month CDP risk by 31% (HR [95% CI]: 0.69 [0.53, 0.91]; p=0.0094) and 6-month CDP risk by 37% (HR [95% CI]: 0.63 [0.47, 0.86], p=0.0040) versus placebo. Reductions in risk of 6 month SDMT worsening, ARR, and MRI endpoints were also seen.ConclusionsIn this subgroup of active SPMS patients from EXPAND, benefits on disability progression were more pronounced with clinically relevant effects across disability progression, cognitive processing speed, and MRI inflammatory disease activity.g.giovannoni@qmul.ac.uk
047  Multiple sclerosis patient perspectives: disease education and communication needs
Authors: O’Neill Jessica , Ayer Mavis , Colhoun Samantha , Daykin Nicola , Hamill Brenda , Gabriele Simone , Florio Jordanne , Pulcini Serena , Thomson Alison 
Published: May 2022

MS is a progressive disease that significantly impacts quality-of-life (QoL).This study aimed to identify unmet disease education and communication needs in people with MS (pwMS) to empower informed decisions, enable self-management and to maintain independence for as long as possible. A Steering Group of MS nurses and patient representatives formed and two studies for pwMS were co-developed: a qualitative Online Patient Community activity (using Ipsos’ Syndicated MS Online Patient Community) and a quantitative online survey (via the MS Trust). Data were analyzed from 28 and 117 respondents with relapsing remitting MS (RRMS), from the Ipsos’ Syndicated MS Online Patient Community and quantitative survey, respectively. Data from the quantitative survey revealed: 50% reported knowing a ‘great deal’ or a ‘fair amount’ about disability progression. Maintaining independence was a key goal for pwMS, however only 33% reported they felt that they could ‘plan for the long term’, and 21% said they set goals for managing their MS. Data from this study will explore the relationship between perceived knowledge, planning for the future, and impact on QoL. This study highlights the importance of understanding unmet needs in education, linking disease progression and impact on future QoL in pwMS.Acknowledgements: This project was sponsored by Roche Products Ltd. Ipsos MORI UK Ltd provided support in developing and conducting the surveys and performing data analysis, which was funded by Roche Products Ltd.jessica.oneill.jo1@roche.com
048  Postprandial somnolence in people with multiple sclerosis
Authors: Christmas Tatiana , Singh Neena , Reyes Saul , Allen-Philbey Kimberley , Giovannoni Gavin 
Published: May 2022

ObjectivesTo identify whether people with MS (pwMS) suffer from postprandial somnolence (PPS) more than people without MS (controls), to examine whether the severity of MS is correlated to the severity of PPS and to describe strategies pwMS are using to reduce their symptoms of PPS.BackgroundpwMS might be more sensitive to PPS, but no studies confirming this association have been published.MethodsA cross-sectional study was conducted among pwMS at The Royal London Hospital, London. Patients and controls completed an online survey including demographics, comorbidities and Stanford Sleepiness Score (SSS) one hour after lunch.ResultsSurvey responses of 77 pwMS (mean age 45.3 ± 11.5 years; 62.3% female) and 37 controls (mean age 47.02 ± 13.9 years; 63.8% female) were obtained. The mean SSS for pwMS was 3.46 ± 1.67, whilst the mean SSS for controls was 2.52 ± 1.18 (p=0.001). No linear correlation was observed between EDSS and SSS (R2=0.011). 63% of pwMS reported making self-administered changes to their diet to help their symptoms.ConclusionsPwMS were affected by PPS more than controls. EDSS was not predictive of PPS severity in pwMS. pwMS are adopting self-management strategies to reduce their symptoms of PPS.tatiana.christmas@nhs.net
050  Late onset recurrent neutropenia following ocrelizumab therapy in multiple sclerosis
Authors: Talaei Maryam , Ingram Gillian , Petheram Kate , Pearson Owen R 
Published: May 2022

Ocrelizumab, an anti-CD20 monoclonal antibody similar to rituximab, has demonstrated efficacy in relapsing(RR) and primary progressive MS. Late onset neutropenia (LON) is a rare side-effect of rituximab and there only 2 cases reported related to ocrelizumab. We discuss 2 treatment naive patients with active RRMS who developed LON after ocrelizumab treatment.A 31y female presented with neutropenic sepsis 115 days after third ocrelizumab infusion, requiring treatment with intravenous antibiotics and granulocyte colony stimulating factor (G-CSF). Subsequent multiple episodes of recurrent grade 4 neutropenia occurred over the next 6 months, often requiring G-CSF treatment. Bone marrow aspiration demonstrated normocellular granulopoiesis.A 35y male developed neutropenic sepsis 119 days after first ocrelizumab infusion which recovered rapidly with G-CSF. He received the second dose of ocrelizumab 3 months later, and at 5 months follow up after his third infusion had no recurrent neutropenia.The two cases demonstrate the spectrum of late onset neutropeniaof LON with oOcrelizumab. The aetiology of LON is poorly understood but hypothesised to be autoimmune in nature. The cases are important to raise the clinical suspicion of this life threatening complication of disease modifying therapy. Further experience is required to understand risk of recurrence and when to re-challenge with ocrelizumab.maryam.talaei@wales.nhs.uk
053  Multiple Sclerosis Prevalence: Cardiff and Vale population-based cohort
Authors: Hawken Jonathan , Robertson Neil , Tallantyre Emma , Wynford-Thomas Ray , Anderson Valerie , Loveless Sam 
Published: May 2022

As treatment options expand for all disease phases of MS, accurate epidemiological data reflecting contemporary patterns of disease by direct clinical assessment remain key to planning and delivering services. This study describes disease frequency and phenotype in a South Wales population on 01/01/2019 according to McDonald 2017 diagnostic criteria.831 MS cases were identified in a population of 496,413. Prevalence 167/100,000 (95% CI 156–179); females 236/100,000, males 97/100,000, sex ratio 2.5:1 (F:M), mean age 52.6 (range 17–91). Age specific preva- lence was highest in females aged 50–54 (403/100,000). European population standardised prevalence 189/10,000. Disease course: 55.3% relapsing, 34.8% secondary progressive, and 9.9% primary progressive disease. 76.1% had a disability assessment and 36% an interval MR brain within 12 months of prevalence day. EDSS: <4.0 (45.3%), 4.0–5.5 (11.2%), 6.0–7.5 (31.2%), 8–9.5 (12.3%). MR brain: 73% stable; 22% active(new T2 ± Gd+); the remainder had features of MS but no relevant comparison scan. 39.6% of patients had prior DMT use of which highly effective treatments 17.3%.These data sets establish a trend of increasing prevalence but remain less than recent estimates from the MS Society (179/100,000) for Wales, and offer baseline estimates of disease course classification and activity to plan services.drhawken@outlook.com
058  Serum neurofilament-light concentration and real-world outcome in MS
Authors: Anderson Valerie , Bentley Emily , Loveless Sam , Bianchi Lucia , Harding Katharine E , Thomas Ray Wynford- , Giovannoni Gavin , Robertson Neil P , Marta Monica , Tallantyre Emma C 
Published: May 2022

Predicting clinical outcome in multiple sclerosis (MS) remains challenging, and biomarkers capable of providing prognostic information would be valuable in shaping therapeutic decisions. Neurofilament light (NfL) measurements have shown promise in predicting clinical outcomes in MS. We evaluated the relationship between serum NfL (sNfL), measured at diagnosis in 164 people with MS, with contemporary disability, short-term (1-year) and medium-term (5-year) clinical outcomes. Analyses were adjusted for relevant confounders. sNfL concentration at diagnosis was modestly but significantly associated with baseline EDSS score (B=0.264, 95% CI 0.043 to 0.485, p=0.020). However, no significant associations were found between baseline sNfL and the incidence of relapse at 12-months, time to sustained accumulation of disability or 5-year change in EDSS. Dichotomising baseline sNfL according to previously cited cut-offs (</> 14.2pg/ml and </> 90th percentile for age) did not change these results. sNfL appears to be of limited clinical utility in predicting future irreversible neurological disability, in a largely treated population, and remains insufficiently validated to shape treatment decisions at the time of diagnosis. Further studies exploring the value of sequential sNfL measurement and developing valid, universally accepted cut-offs are needed before sNfL can be incorporated as a prognostic marker in the clinic.tallantyreec@cardiff.ac.uk
060  Profiling cases of impaired immunity in neurology using a novel screening test
Authors: Handley Amy , Jolles Stephen , Tallantyre Emma 
Published: May 2022

Previous research has indicated that calculated globulin (CG) derived from routine liver function testing can be used as a screening test for low immunoglobulin (Ig) levels. Disease modifying drugs (DMD) are increasingly used in neurology, with the need for a better understanding of their immunosuppressive impact and an ability to screen for complications. In this retrospective audit we identified 32 cases with low CG levels (<23g/L) in 18 neurology patients, occurring between January 2017 and January 2018. Only 4 out of 18 (22%) had their Ig levels checked within 2 months of the abnormal screening (CG) result, but serum Ig data was available at any subsequent time point in 13 out of 18 patients. Of the 13 patients with low CG, 7 (54%) had low serum Igs and 6 (33%) had low lymphocyte levels. Some cases of low Ig were observed in people receiving DMDs that are not specifically targeted at B-cell depletion. Documented infections were present in 83% of the patients with low Ig levels, most commonly urinary tract and chest infections. Calculated globulin is an inexpensive screening tool that has the potential to provide value in neuroinflammatory clinics by detecting secondary antibody deficiency in people receiving DMDs.HandleyAD1@cardiff.ac.uk
Parity from gauge symmetry
Authors: Maiezza Alessio , Nesti Fabrizio 
Published: May 2022

AbstractWe argue that Left-Right parity symmetry $${\mathcal {P}}$$
P
can arise as a discrete remnant of a unified gauge symmetry. The high-energy unification necessarily includes the gauging of the Lorentz symmetry, bringing into the game gravitational interactions, and leading to a gravi-GUT scheme. Parity emerges unbroken below the Planck scale, and can be broken spontaneously at lower energies making contact with the Standard Model. This framework motivates the spontaneous origin of parity violation as in Left-Right symmetric theories with $${\mathcal {P}}$$
P
. The possible unifying gauge groups are identified as $$\mathrm{SO}(1,7)$$

SO
(
1
,
7
)

for gravitational and weak interactions, or $$\mathrm{SO}(7,7)$$

SO
(
7
,
7
)

for a complete unification.