Pub Date : 2026-01-02DOI: 10.1016/j.msard.2026.106968
Aimee Banks , Autumn Zuckerman , Josh DeClercq , Leena Choi , Katie R. Cruchelow , Megan Schneider
Background
When treating multiple sclerosis, lymphopenia is an established side effect of fumaric acids. Research demonstrating the impact of switching fumarates on lymphocyte counts is scarce. The objective of this study is to characterize the incidence and severity of lymphopenia in patients transitioning from dimethyl fumarate (DMF) to monomethyl fumarate (MMF) or diroximel fumarate (DRF).
Methods
A single center, retrospective review of adult medical records at the Vanderbilt Multiple Sclerosis Clinic who filled prescriptions for DMF then either DRF or MMF between January 1st, 2019 and February 28th, 2023.
Results
Patients who switched to DRF experienced a greater median percent change in absolute lymphocyte count (ALC) [45% decrease (IQR -95 to -14)] compared to those who switched to MMF [6% increase (IQR -4 to 17)]. Patients who switched to MMF, on average, had an ALC at follow-up 1.8 times higher than those switched to DRF (95% CI 1.4 to 2.3; p < 0.001). Additionally, patients switched to DRF were more likely to experience grade 2 or 3 lymphopenia compared to patients switched to MMF.
Conclusion
Our study demonstrated that patients switched to DRF had a significantly lower ALC at follow-up and were more likely to have lymphopenia compared to patients switched to MMF.
背景：在治疗多发性硬化症时，富马酸的副作用是淋巴细胞减少。研究表明切换富马酸盐对淋巴细胞计数的影响是稀缺的。本研究的目的是表征从富马酸二甲酯（DMF）过渡到富马酸单甲基（MMF）或富马酸双洛西梅尔（DRF）的患者淋巴细胞减少的发生率和严重程度。方法对范德比尔特多发性硬化症诊所在2019年1月1日至2023年2月28日期间开具DMF或DRF或MMF处方的成人医疗记录进行单中心回顾性分析。结果与改用MMF的患者相比，改用DRF的患者绝对淋巴细胞计数（ALC）的中位百分比变化更大[减少45% (IQR -95至-14)][增加6% (IQR -4至17)]。转换为MMF的患者，随访时ALC平均比转换为DRF的患者高1.8倍（95% CI 1.4至2.3;p < 0.001）。此外，与转向MMF的患者相比，转向DRF的患者更有可能出现2级或3级淋巴细胞减少。结论：我们的研究表明，与改用MMF的患者相比，改用DRF的患者在随访时ALC显著降低，并且更有可能出现淋巴细胞减少。
{"title":"Retrospective review of lymphocyte changes when switching between fumarates in patients with multiple sclerosis","authors":"Aimee Banks , Autumn Zuckerman , Josh DeClercq , Leena Choi , Katie R. Cruchelow , Megan Schneider","doi":"10.1016/j.msard.2026.106968","DOIUrl":"10.1016/j.msard.2026.106968","url":null,"abstract":"<div><h3>Background</h3><div>When treating multiple sclerosis, lymphopenia is an established side effect of fumaric acids. Research demonstrating the impact of switching fumarates on lymphocyte counts is scarce. The objective of this study is to characterize the incidence and severity of lymphopenia in patients transitioning from dimethyl fumarate (DMF) to monomethyl fumarate (MMF) or diroximel fumarate (DRF).</div></div><div><h3>Methods</h3><div>A single center, retrospective review of adult medical records at the Vanderbilt Multiple Sclerosis Clinic who filled prescriptions for DMF then either DRF or MMF between January 1st, 2019 and February 28th, 2023.</div></div><div><h3>Results</h3><div>Patients who switched to DRF experienced a greater median percent change in absolute lymphocyte count (ALC) [45% decrease (IQR -95 to -14)] compared to those who switched to MMF [6% increase (IQR -4 to 17)]. Patients who switched to MMF, on average, had an ALC at follow-up 1.8 times higher than those switched to DRF (95% CI 1.4 to 2.3; <em>p</em> < 0.001). Additionally, patients switched to DRF were more likely to experience grade 2 or 3 lymphopenia compared to patients switched to MMF.</div></div><div><h3>Conclusion</h3><div>Our study demonstrated that patients switched to DRF had a significantly lower ALC at follow-up and were more likely to have lymphopenia compared to patients switched to MMF.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106968"},"PeriodicalIF":2.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.msard.2025.106945
E. Ann Yeh , Michael Levy , Chris Hawkes , Jeannette Lechner-Scott , Gavin Giovannoni
{"title":"Large language models in academic writing","authors":"E. Ann Yeh , Michael Levy , Chris Hawkes , Jeannette Lechner-Scott , Gavin Giovannoni","doi":"10.1016/j.msard.2025.106945","DOIUrl":"10.1016/j.msard.2025.106945","url":null,"abstract":"","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"105 ","pages":"Article 106945"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-31DOI: 10.1016/j.msard.2025.106962
Roger Santana de Araujo , Guilherme Diogo Silva , Thiago Trajano , Edgar Carnero Contentti , Juan Ignacio Rojas , Carolin Schwake , Ilya Ayzenberg , Douglas Kazutoshi Sato , Mateus Boaventura de Oliveira , Tarso Adoni , Dagoberto Callegaro , Samira Luisa Apóstolos-Pereira
Introduction
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) attacks are usually treated with corticosteroids, but therapeutic plasma exchange (TPE) may provide additional benefits.
Objective
To assess the response to TPE in MOGAD attacks.
Methods
We performed a systematic review and meta-analysis of observational studies reporting outcomes of MOGAD attacks treated with TPE, searching PubMed, Embase, and Scopus from inception to November 24, 2024. The primary outcome was recovery at last follow-up, classified as complete, partial, or none. Secondary analysis explored predictors of response through meta-regression on aggregated data.
Results
Forty-nine studies comprising 475 attacks were included. Most patients were female (56 %), presenting mainly with optic neuritis (60 %) or myelitis (37.7 %). TPE was combined with intravenous methylprednisolone in 93 % and with intravenous immunoglobulin in 11.8 %. The pooled complete recovery rate was 30 % (95 % CI 22–40, I² = 74 %), and the overall response rate (complete or partial) was 90 % (95 % CI 82–94, I² = 59.9 %). Meta-regression indicated a slightly better response in brainstem syndrome (p=0.023) and a poorer response in cerebral syndrome (p=0.044), with no significant correlation between complete recovery and age, sex, other clinical syndromes, or use as first-line therapy.
Conclusion
TPE is associated with high overall response rates in MOGAD attacks. Randomized trials are needed to confirm efficacy and define prognostic factors.
髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOGAD）发作通常用皮质类固醇治疗，但治疗性血浆交换（TPE）可能提供额外的益处。目的评价TPE治疗MOGAD发作的疗效。方法：我们对报道TPE治疗MOGAD发作结果的观察性研究进行了系统回顾和荟萃分析，检索PubMed、Embase和Scopus，时间从开始到2024年11月24日。主要结局为最后随访时的恢复，分为完全、部分或无恢复。二级分析通过汇总数据的元回归探讨了反应的预测因素。结果纳入49项研究，共475例。大多数患者为女性（56%），主要表现为视神经炎（60%）或脊髓炎（37.7%）。TPE联合静脉注射甲基强的松龙的占93%，联合静脉注射免疫球蛋白的占11.8%。合并完全恢复率为30% (95% CI 22-40, I²= 74%)，总有效率（完全或部分）为90% （95% CI 82-94, I²= 59.9%）。meta回归显示，脑干综合征的疗效稍好（p=0.023），而脑综合征的疗效较差（p=0.044），完全恢复与年龄、性别、其他临床综合征或作为一线治疗无显著相关性。结论tpe与MOGAD发作总有效率高相关。需要随机试验来确认疗效和确定预后因素。
{"title":"Therapeutic plasma exchange for MOG antibody-associated disease attacks: a systematic review and meta-analysis","authors":"Roger Santana de Araujo , Guilherme Diogo Silva , Thiago Trajano , Edgar Carnero Contentti , Juan Ignacio Rojas , Carolin Schwake , Ilya Ayzenberg , Douglas Kazutoshi Sato , Mateus Boaventura de Oliveira , Tarso Adoni , Dagoberto Callegaro , Samira Luisa Apóstolos-Pereira","doi":"10.1016/j.msard.2025.106962","DOIUrl":"10.1016/j.msard.2025.106962","url":null,"abstract":"<div><h3>Introduction</h3><div>Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) attacks are usually treated with corticosteroids, but therapeutic plasma exchange (TPE) may provide additional benefits.</div></div><div><h3>Objective</h3><div>To assess the response to TPE in MOGAD attacks.</div></div><div><h3>Methods</h3><div>We performed a systematic review and meta-analysis of observational studies reporting outcomes of MOGAD attacks treated with TPE, searching PubMed, Embase, and Scopus from inception to November 24, 2024. The primary outcome was recovery at last follow-up, classified as complete, partial, or none. Secondary analysis explored predictors of response through meta-regression on aggregated data.</div></div><div><h3>Results</h3><div>Forty-nine studies comprising 475 attacks were included. Most patients were female (56 %), presenting mainly with optic neuritis (60 %) or myelitis (37.7 %). TPE was combined with intravenous methylprednisolone in 93 % and with intravenous immunoglobulin in 11.8 %. The pooled complete recovery rate was 30 % (95 % CI 22–40, I² = 74 %), and the overall response rate (complete or partial) was 90 % (95 % CI 82–94, I² = 59.9 %). Meta-regression indicated a slightly better response in brainstem syndrome (p=0.023) and a poorer response in cerebral syndrome (p=0.044), with no significant correlation between complete recovery and age, sex, other clinical syndromes, or use as first-line therapy.</div></div><div><h3>Conclusion</h3><div>TPE is associated with high overall response rates in MOGAD attacks. Randomized trials are needed to confirm efficacy and define prognostic factors.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106962"},"PeriodicalIF":2.9,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.msard.2025.106952
Kathryn Mizzi , Ruben J. Cauchi
Multiple Sclerosis (MS) is a chronic, disabling autoimmune disease of the central nervous system (CNS). While its aetiology is multifactorial, compelling evidence now implicates Epstein-Barr virus (EBV) as a primary aetiological agent. This review summarises the extensive epidemiological and mechanistic data supporting a causal link between EBV infection and MS. Epidemiological studies demonstrate that EBV infection confers >30-fold increased risk for MS, with seroconversion preceding the onset of neuroaxonal damage. The leading proposed mechanism is molecular mimicry, where antibodies and T cells targeting the EBV nuclear antigen 1 (EBNA1) cross-react with CNS proteins, such as GlialCAM, initiating autoimmune-mediated demyelination. This process is modulated by synergistic interactions with genetic risk factors, and environmental factors like smoking and adolescent obesity. A critical evaluation of the experimental models used to investigate this connection is presented. In vitro systems using patient-derived cells have confirmed dysregulated immune responses to EBV antigens, while in vivo models – ranging from murine experimental autoimmune encephalomyelitis (EAE) and humanised mice to non-human primate models with homologous γ-herpesviruses – have been instrumental in demonstrating the role of EBV in breaking immune tolerance and driving neuroinflammation. Despite their utility, each model possesses limitations, underscoring the need for next-generation model systems that more accurately recapitulate the complex interplay between the virus, host genetics, and the CNS environment. Future research focused on refining these models is crucial for developing targeted EBV-based therapeutics, such as vaccines or antiviral agents, to prevent or treat MS.
{"title":"Epstein-Barr virus in multiple sclerosis pathogenesis: The path towards mechanistically faithful models","authors":"Kathryn Mizzi , Ruben J. Cauchi","doi":"10.1016/j.msard.2025.106952","DOIUrl":"10.1016/j.msard.2025.106952","url":null,"abstract":"<div><div>Multiple Sclerosis (MS) is a chronic, disabling autoimmune disease of the central nervous system (CNS). While its aetiology is multifactorial, compelling evidence now implicates Epstein-Barr virus (EBV) as a primary aetiological agent. This review summarises the extensive epidemiological and mechanistic data supporting a causal link between EBV infection and MS. Epidemiological studies demonstrate that EBV infection confers >30-fold increased risk for MS, with seroconversion preceding the onset of neuroaxonal damage. The leading proposed mechanism is molecular mimicry, where antibodies and T cells targeting the EBV nuclear antigen 1 (EBNA1) cross-react with CNS proteins, such as GlialCAM, initiating autoimmune-mediated demyelination. This process is modulated by synergistic interactions with genetic risk factors, and environmental factors like smoking and adolescent obesity. A critical evaluation of the experimental models used to investigate this connection is presented. <em>In vitro</em> systems using patient-derived cells have confirmed dysregulated immune responses to EBV antigens, while <em>in vivo</em> models – ranging from murine experimental autoimmune encephalomyelitis (EAE) and humanised mice to non-human primate models with homologous γ-herpesviruses – have been instrumental in demonstrating the role of EBV in breaking immune tolerance and driving neuroinflammation. Despite their utility, each model possesses limitations, underscoring the need for next-generation model systems that more accurately recapitulate the complex interplay between the virus, host genetics, and the CNS environment. Future research focused on refining these models is crucial for developing targeted EBV-based therapeutics, such as vaccines or antiviral agents, to prevent or treat MS.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106952"},"PeriodicalIF":2.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Individuals diagnosed with multiple sclerosis (MS) are known to face more challenging situations, such as gait initiation (GI), compared to healthy individuals. This provides a deeper insight into the mechanisms that govern dynamic postural control. A search was conducted across several databases, including PubMed, Cochrane, ScienceDirect, Web of Science, Scopus, ProQuest, and Google Scholar. Studies of any design were included if they satisfied the following criteria: the experimental group consisted of individuals with MS or clinically isolated syndrome, the control group included healthy individuals or MS patients, and the studies examined gait patterns across various parameters, such as the center of pressure (COP), center of mass, and anticipatory postural adjustments, while also assessing the gait initiation phase. Utilizing the modified Downs and Black checklist, nine articles were selected for the final analysis. The results indicated deceleration, a reduction in posterior COP displacement, and an increase in COP during anterior GI. Compared with healthy controls, individuals with MS exhibited greater instability during balance recovery and in kinetic parameters of the stance limb. Furthermore, a delay and reduction in muscle activity were noted in individuals with MS who had a history of falls, in contrast to non-falling MS patients and healthy individuals.
与健康个体相比，被诊断患有多发性硬化症（MS）的个体面临着更具有挑战性的情况，例如步态起始（GI）。这为动态姿势控制的机制提供了更深入的见解。在几个数据库中进行了搜索，包括PubMed、Cochrane、ScienceDirect、Web of Science、Scopus、ProQuest和b谷歌Scholar。只要满足以下标准，任何设计的研究都被纳入：实验组由患有多发性硬化症或临床孤立综合征的个体组成，对照组包括健康个体或多发性硬化症患者，研究检查了不同参数的步态模式，如压力中心（COP）、质心和预期姿势调整，同时也评估了步态起始阶段。利用修改后的Downs and Black检查表，选择了9篇文章进行最终分析。结果显示，在前GI过程中，减速，后部COP位移减少，COP增加。与健康对照相比，MS患者在平衡恢复和站立肢体的动力学参数方面表现出更大的不稳定性。此外，与没有跌倒的MS患者和健康个体相比，有跌倒史的MS患者肌肉活动延迟和减少。
{"title":"A comparative study of gait pattern characteristics between individuals with multiple sclerosis and healthy individuals during anticipatory postural adjustment and gait initiation: A scoping review","authors":"Narges Jahantigh Akbari , Fatemeh Ehsani , Marzieh Mortezaejad , Mohammad Yousefi , Khorshid Bijari","doi":"10.1016/j.msard.2025.106949","DOIUrl":"10.1016/j.msard.2025.106949","url":null,"abstract":"<div><div>Individuals diagnosed with multiple sclerosis (MS) are known to face more challenging situations, such as gait initiation (GI), compared to healthy individuals. This provides a deeper insight into the mechanisms that govern dynamic postural control. A search was conducted across several databases, including PubMed, Cochrane, ScienceDirect, Web of Science, Scopus, ProQuest, and Google Scholar. Studies of any design were included if they satisfied the following criteria: the experimental group consisted of individuals with MS or clinically isolated syndrome, the control group included healthy individuals or MS patients, and the studies examined gait patterns across various parameters, such as the center of pressure (COP), center of mass, and anticipatory postural adjustments, while also assessing the gait initiation phase. Utilizing the modified Downs and Black checklist, nine articles were selected for the final analysis. The results indicated deceleration, a reduction in posterior COP displacement, and an increase in COP during anterior GI. Compared with healthy controls, individuals with MS exhibited greater instability during balance recovery and in kinetic parameters of the stance limb. Furthermore, a delay and reduction in muscle activity were noted in individuals with MS who had a history of falls, in contrast to non-falling MS patients and healthy individuals.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106949"},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145940036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1016/j.msard.2025.106950
Tomáš Adamec , Tomáš Hudeček , Dalibor Pastucha , Pavel Hradílek , Adéla Kondé , Anna Šilarová
Background
Cardiorespiratory fitness (CRF) is impaired in patients with multiple sclerosis (MS) regardless of age, but evidence is limited among young and newly diagnosed patients. The aim of the study is to assess CRF using a maximal exercise test on a treadmill and to examine the relationships between CRF, physical activity level, fatigue, depression, and quality of life (QoL) in young patients newly diagnosed with MS.
Methods
This cross-sectional study analyzed baseline data from a sample of 43 patients with MS who completed a maximal exercise test on a treadmill, measurement of body composition, and answered the Beck Depression Inventory second edition, modified Fatigue Impact Scale, and 36-item Short Form Survey QoL.
Results
CRF was significantly lower among patients newly diagnosed with MS (aged 20–45 years) compared to normative values (paired Wilcoxon test, p < 0.001). The median absolute differences between normative values and patients’ maximal oxygen uptake (VO2max) was 8.5 ml/kg/min (interquartile range [IQR]: 2.4–13.4 ml/kg/min), and the median relative differences was 28.3 % (IQR: 7.1–53.9 %). VO2max significantly negatively correlated with fatigue (rS = -0.37, p = 0.013), but not depression (rS = -0.01, p = 0.971). Significant positive correlations were found between VO2max and multiple subscales of QoL, including physical functioning (rS = 0.50, p = 0.001), social functioning (rS = 0.41, p = 0.007), pain (rS = 0.41, p = 0.006), and role limitations due to physical health (rS = 0.31, p = 0.047).
Conclusion
Young patients with newly diagnosed MS already exhibit substantially reduced CRF compared with normative values. Lower VO2max is associated with higher fatigue and poorer physical and social aspects of QoL. These findings highlight the need for interventions aimed at improving CRF as an integral component of rehabilitation programs.
背景：无论年龄大小，多发性硬化症（MS）患者的心肺功能（CRF）都会受损，但在年轻和新诊断的患者中证据有限。本研究的目的是通过在跑步机上进行最大运动测试来评估CRF，并检查新诊断为MS的年轻患者的CRF、身体活动水平、疲劳、抑郁和生活质量（QoL）之间的关系。方法本横断面研究分析了43例MS患者的基线数据，这些患者完成了在跑步机上进行最大运动测试，测量身体成分，并回答了Beck抑郁量表第二版。修正疲劳冲击量表，36项问卷调查问卷。结果与正常值相比，新诊断为MS的患者（20-45岁）的scrf显著降低（配对Wilcoxon检验，p < 0.001）。正常值与患者最大摄氧量（VO2max）的绝对差值中位数为8.5 ml/kg/min（四分位数间距[IQR]: 2.4 ~ 13.4 ml/kg/min），相对差值中位数为28.3% （IQR: 7.1 ~ 53.9%）。VO2max与疲劳呈显著负相关（rS = -0.37, p = 0.013），与抑郁无显著负相关（rS = -0.01, p = 0.971）。VO2max与身体功能（rS = 0.50, p = 0.001）、社会功能（rS = 0.41, p = 0.007）、疼痛（rS = 0.41, p = 0.006）、身体健康导致的角色限制（rS = 0.31, p = 0.047）等多个生活质量分量表存在显著正相关。结论：与正常值相比，新诊断为MS的年轻患者CRF已经明显降低。较低的最大摄氧量与较高的疲劳程度以及较差的身体和社交方面的生活质量有关。这些发现强调了将改善CRF作为康复计划组成部分的干预措施的必要性。
{"title":"Cardiorespiratory fitness in young and newly diagnosed patients with multiple sclerosis: A cross-sectional study","authors":"Tomáš Adamec , Tomáš Hudeček , Dalibor Pastucha , Pavel Hradílek , Adéla Kondé , Anna Šilarová","doi":"10.1016/j.msard.2025.106950","DOIUrl":"10.1016/j.msard.2025.106950","url":null,"abstract":"<div><h3>Background</h3><div>Cardiorespiratory fitness (CRF) is impaired in patients with multiple sclerosis (MS) regardless of age, but evidence is limited among young and newly diagnosed patients. The aim of the study is to assess CRF using a maximal exercise test on a treadmill and to examine the relationships between CRF, physical activity level, fatigue, depression, and quality of life (QoL) in young patients newly diagnosed with MS.</div></div><div><h3>Methods</h3><div>This cross-sectional study analyzed baseline data from a sample of 43 patients with MS who completed a maximal exercise test on a treadmill, measurement of body composition, and answered the Beck Depression Inventory second edition, modified Fatigue Impact Scale, and 36-item Short Form Survey QoL.</div></div><div><h3>Results</h3><div>CRF was significantly lower among patients newly diagnosed with MS (aged 20–45 years) compared to normative values (paired Wilcoxon test, <em>p</em> < 0.001). The median absolute differences between normative values and patients’ maximal oxygen uptake (VO<sub>2</sub>max) was 8.5 ml/kg/min (interquartile range [IQR]: 2.4–13.4 ml/kg/min), and the median relative differences was 28.3 % (IQR: 7.1–53.9 %). VO<sub>2</sub>max significantly negatively correlated with fatigue (r<sub>S</sub> = -0.37, <em>p</em> = 0.013), but not depression (r<sub>S</sub> = -0.01, <em>p</em> = 0.971). Significant positive correlations were found between VO<sub>2</sub>max and multiple subscales of QoL, including physical functioning (r<sub>S</sub> = 0.50, <em>p</em> = 0.001), social functioning (r<sub>S</sub> = 0.41, <em>p</em> = 0.007), pain (r<sub>S</sub> = 0.41, <em>p</em> = 0.006), and role limitations due to physical health (r<sub>S</sub> = 0.31, <em>p</em> = 0.047).</div></div><div><h3>Conclusion</h3><div>Young patients with newly diagnosed MS already exhibit substantially reduced CRF compared with normative values. Lower VO<sub>2</sub>max is associated with higher fatigue and poorer physical and social aspects of QoL. These findings highlight the need for interventions aimed at improving CRF as an integral component of rehabilitation programs.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106950"},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1016/j.msard.2025.106951
Keyvan Hejazi , Gholam Rasul Mohammad Rahimi , Martin Hofmeister
Background
Multiple Sclerosis (MS) is a chronic, progressive autoimmune disorder of the central nervous system, where inflammation plays a pivotal role in its pathophysiology. Exercise training has been proposed as an effective non-pharmacological strategy for managing MS. However, due to inconsistent findings in previous studies, this systematic review and meta-analysis aimed to comprehensively evaluate the effects of long-term exercise interventions on the cytokine profile in patients with MS.
Methods
Six electronic databases (PubMed, EMBASE, SCOPUS, Web of Science, Cochrane Library, and Google Scholar) were searched up to June 27, 2025. Only randomized controlled trials (RCTs) investigating the effects of exercise training on the levels of IL-6, IL-10, IL-17, IL-4, TNF-α, and IFN-γ in adult patients with MS were included. The quality of the articles was assessed using the PEDro scale, selecting studies with a score of 5 or higher. Data were analyzed using a random-effects model, with the effect size calculated as the Standardized Mean Difference (SMD) and a 95 % confidence interval (CI).
Results
A total of 19 RCTs involving 569 participants (329 in the exercise group and 240 in the control group) were included in the meta-analysis. The pooled results showed that exercise training significantly reduced the levels of the pro-inflammatory cytokines TNF-α (SMD: -0.31, p = 0.02), IFN-γ (SMD: -0.73, p < 0.001) and IL-17 (SMD: -0.42, p < 0.001). However, no significant changes were observed in the levels of IL-4 (p = 0.82), IL-6 (p = 0.49), and IL-10 (p = 0.13).
Conclusions
This meta-analysis provides robust evidence that structured exercise training can selectively modulate the inflammatory profile in patients with MS, primarily reducing the key cytokines TNF-α, IFN-γ and IL-17. These findings support the role of exercise as a complementary non-pharmacological therapy for managing inflammation in MS.
多发性硬化症（MS）是一种慢性进行性中枢神经系统自身免疫性疾病，炎症在其病理生理中起着关键作用。运动训练被认为是治疗多发性硬化症的一种有效的非药物策略，然而，由于之前的研究结果不一致，本系统综述和荟萃分析旨在全面评估长期运动干预对多发性硬化症患者细胞因子谱的影响。方法检索6个电子数据库（PubMed， EMBASE， SCOPUS, Web of Science， Cochrane Library和谷歌Scholar），截止到2025年6月27日。仅纳入了调查运动训练对成年MS患者IL-6、IL-10、IL-17、IL-4、TNF-α和IFN-γ水平影响的随机对照试验（RCTs）。采用PEDro量表评估文章的质量，选择得分为5分或更高的研究。采用随机效应模型对数据进行分析，效应大小以标准化平均差（SMD）和95%置信区间（CI）计算。结果共纳入19项随机对照试验，569名受试者（运动组329名，对照组240名）。综合结果显示，运动训练显著降低了促炎细胞因子TNF-α (SMD: -0.31, p = 0.02)、IFN-γ (SMD: -0.73, p < 0.001)和IL-17 （SMD: -0.42, p < 0.001）的水平。然而，IL-4 （p = 0.82）、IL-6 （p = 0.49）和IL-10 （p = 0.13）的水平无显著变化。这项荟萃分析提供了强有力的证据，表明有组织的运动训练可以选择性地调节MS患者的炎症状况，主要是降低关键细胞因子TNF-α、IFN-γ和IL-17。这些发现支持了运动作为一种辅助的非药物治疗来管理MS炎症的作用。
{"title":"Effects of exercise training on some cytokine profiles in patients with multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials","authors":"Keyvan Hejazi , Gholam Rasul Mohammad Rahimi , Martin Hofmeister","doi":"10.1016/j.msard.2025.106951","DOIUrl":"10.1016/j.msard.2025.106951","url":null,"abstract":"<div><h3>Background</h3><div>Multiple Sclerosis (MS) is a chronic, progressive autoimmune disorder of the central nervous system, where inflammation plays a pivotal role in its pathophysiology. Exercise training has been proposed as an effective non-pharmacological strategy for managing MS. However, due to inconsistent findings in previous studies, this systematic review and meta-analysis aimed to comprehensively evaluate the effects of long-term exercise interventions on the cytokine profile in patients with MS.</div></div><div><h3>Methods</h3><div>Six electronic databases (PubMed, EMBASE, SCOPUS, Web of Science, Cochrane Library, and Google Scholar) were searched up to June 27, 2025. Only randomized controlled trials (RCTs) investigating the effects of exercise training on the levels of IL-6, IL-10, IL-17, IL-4, TNF-α, and IFN-γ in adult patients with MS were included. The quality of the articles was assessed using the PEDro scale, selecting studies with a score of 5 or higher. Data were analyzed using a random-effects model, with the effect size calculated as the Standardized Mean Difference (SMD) and a 95 % confidence interval (CI).</div></div><div><h3>Results</h3><div>A total of 19 RCTs involving 569 participants (329 in the exercise group and 240 in the control group) were included in the meta-analysis. The pooled results showed that exercise training significantly reduced the levels of the pro-inflammatory cytokines TNF-α (SMD: -0.31, <em>p</em> = 0.02), IFN-γ (SMD: -0.73, <em>p</em> < 0.001) and IL-17 (SMD: -0.42, <em>p</em> < 0.001). However, no significant changes were observed in the levels of IL-4 (<em>p</em> = 0.82), IL-6 (<em>p</em> = 0.49), and IL-10 (<em>p</em> = 0.13).</div></div><div><h3>Conclusions</h3><div>This meta-analysis provides robust evidence that structured exercise training can selectively modulate the inflammatory profile in patients with MS, primarily reducing the key cytokines TNF-α, IFN-γ and IL-17. These findings support the role of exercise as a complementary non-pharmacological therapy for managing inflammation in MS.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106951"},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1016/j.msard.2025.106948
Jeff Wen Han Thng , Daina L Sturnieks , Phu Hoang , Stephen R Lord , Jasmine C Menant
Objectives
To identify predictors of adherence to a six-month home-based step exergame intervention to prevent falls and determine the effects of adherence on physical, cognitive and psychological function outcomes in people with MS.
Methods
This is a secondary analysis of a multi-site randomised controlled trial of a six-month home-based step exergame intervention versus usual care in 469 people with MS. Intervention participants were asked to undertake step exergame training for 120 min/week. Adherence was captured by the step exergame system. Participants’ baseline characteristics were examined as predictors of adherence. Higher adherers to the intervention were compared to the control group in physical, cognitive and psychological outcome measures.
Results
Older age, lower body mass index, site location and fewer depressive symptoms were independent significant predictors of improved adherence to the step exergame intervention. Compared to control participants (n = 228), high adherers (≥100 min/week) (n = 71) reported fewer symptoms of fatigue following the intervention. In a sub-sample of participants who undertook physical and cognitive tests, 25 high adherers made significantly fewer errors in the Stroop stepping test compared to 104 controls.
Conclusion
People with MS who were older, had a lower body mass index, and reported fewer depressive symptoms were more likely to adhere to a step exergame intervention to prevent falls. Higher adherers demonstrated clinically meaningful benefits, including reduced fatigue and improved performance on a cognitively demanding stepping task, changes that are directly relevant to daily functioning and fall risk. These findings may help identify individuals who require additional support to engage with and fully benefit from home-based exergame programs.
{"title":"Understanding adherence and its impact on function in a six-month step exergame intervention for people with multiple sclerosis","authors":"Jeff Wen Han Thng , Daina L Sturnieks , Phu Hoang , Stephen R Lord , Jasmine C Menant","doi":"10.1016/j.msard.2025.106948","DOIUrl":"10.1016/j.msard.2025.106948","url":null,"abstract":"<div><h3>Objectives</h3><div>To identify predictors of adherence to a six-month home-based step exergame intervention to prevent falls and determine the effects of adherence on physical, cognitive and psychological function outcomes in people with MS.</div></div><div><h3>Methods</h3><div>This is a secondary analysis of a multi-site randomised controlled trial of a six-month home-based step exergame intervention versus usual care in 469 people with MS. Intervention participants were asked to undertake step exergame training for 120 min/week. Adherence was captured by the step exergame system. Participants’ baseline characteristics were examined as predictors of adherence. Higher adherers to the intervention were compared to the control group in physical, cognitive and psychological outcome measures.</div></div><div><h3>Results</h3><div>Older age, lower body mass index, site location and fewer depressive symptoms were independent significant predictors of improved adherence to the step exergame intervention. Compared to control participants (<em>n</em> = 228), high adherers (≥100 min/week) (<em>n</em> = 71) reported fewer symptoms of fatigue following the intervention. In a sub-sample of participants who undertook physical and cognitive tests, 25 high adherers made significantly fewer errors in the Stroop stepping test compared to 104 controls.</div></div><div><h3>Conclusion</h3><div>People with MS who were older, had a lower body mass index, and reported fewer depressive symptoms were more likely to adhere to a step exergame intervention to prevent falls. Higher adherers demonstrated clinically meaningful benefits, including reduced fatigue and improved performance on a cognitively demanding stepping task, changes that are directly relevant to daily functioning and fall risk. These findings may help identify individuals who require additional support to engage with and fully benefit from home-based exergame programs.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106948"},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-24DOI: 10.1016/j.msard.2025.106947
Seema Kalra , David Jenkinson , Sarah Goddard , Krishna Banavathi , Omar Salim , Roby J Abraham , Kelvin P Jordan
COVID-19 vaccination in Multiple Sclerosis (MS) has continued clinical relevance. Complex dosing and variability in immunosuppression/ immunomodulation from disease modifying treatments (DMTs) necessitate real-world studies of COVID-19 immunity. We aimed to evaluate if PwMS develop adequate and persistent serological and cellular COVID-19 immunity after vaccination. We conducted a real-world longitudinal study (n = 235) including PwMS (n = 205; Alemtuzumab, Dimethyl fumarate, Fingolimod, Interferon, Natalizumab, Ocrelizumab, no-DMT) and Healthy volunteers (HV) (n = 30). Serological and cellular immunity was tested at ≤18 and ≤24-month after completed COVID-19 vaccine-course. 97 % of both HV and PwMS were immune at ≤18-month, and 96.9 % PwMS and 100 % HV at ≤24-month, (OR 0.33, 95 % CI (0.09, 0.93), p = 0.05)). Both groups showed similar cellular immunity at both timepoints. Vaccine Adverse effects incidence was similar too. PwMS on Ocrelizumab were significantly less likely to have low serological immunity (p < 0.001 at both timepoints). They were more likely to have intact T cell responses than HV (OR 5.4, 95 % CI 1.28-22.60). Despite this, they had higher infections per person year. PwMS on Fingolimod also had low serological immunity (Odd’s ratio 0.33; CI 0.11-0.97) which stayed low despite boosters and only 6 % showed intact cellular immunity, probably due to lymphopenia. Other DMT-treated PwMS (Natalizumab, Dimethyl Fumarate, Interferon, and no no-DMT) showed comparable COVID-19 serological and cellular immunity as HV. We report COVID-19 immunity clearly over time and across various DMT-groups. Ocrelizumab lowered serological but maintained cellular immunity; whilst Fingolimod lowered both. Data support boosters in PwMS, more so on Ocrelizumab and Fingolimod.
在多发性硬化症（MS）中接种COVID-19疫苗具有持续的临床意义。疾病修饰治疗（dmt）免疫抑制/免疫调节的复杂剂量和变异性需要对COVID-19免疫进行现实世界的研究。我们的目的是评估PwMS在接种疫苗后是否产生足够和持续的血清学和细胞COVID-19免疫。我们进行了一项真实世界的纵向研究（n = 235），包括PwMS (n = 205)；阿仑妥珠单抗、富马酸二甲酯、Fingolimod、干扰素、Natalizumab、Ocrelizumab、no-DMT)和健康志愿者（HV） （n = 30）。在完成COVID-19疫苗疗程后≤18个月和≤24个月进行血清学和细胞免疫检测。97%的HV和PwMS患者在≤18个月时免疫，96.9%的PwMS患者和100%的HV患者在≤24个月时免疫，（OR 0.33, 95% CI (0.09, 0.93), p = 0.05）。两组在两个时间点均表现出相似的细胞免疫。疫苗不良反应发生率也相似。使用Ocrelizumab的PwMS患者血清免疫低下的可能性显著降低（两个时间点的p <； 0.001）。他们比HV更有可能有完整的T细胞反应（OR 5.4, 95% CI 1.28-22.60）。尽管如此，他们每年的人均感染率更高。服用Fingolimod的PwMS血清免疫力也较低（Odd’s ratio 0.33; CI 0.11-0.97），尽管有增强剂，但仍保持较低水平，只有6%的PwMS表现出完整的细胞免疫，可能是由于淋巴细胞减少所致。其他dmt治疗的PwMS （Natalizumab、富马酸二甲酯、干扰素和无dmt）显示出与HV相当的COVID-19血清学和细胞免疫。我们清楚地报告了不同时间和不同dmt组的COVID-19免疫情况。Ocrelizumab降低血清学，但维持细胞免疫；而芬戈莫德把两个都放低了。数据支持PwMS的助推器，奥克雷单抗和Fingolimod更是如此。
{"title":"Real-world COVID-19 immunity in multiple sclerosis (CoVaR-MS): A longitudinal follow up study","authors":"Seema Kalra , David Jenkinson , Sarah Goddard , Krishna Banavathi , Omar Salim , Roby J Abraham , Kelvin P Jordan","doi":"10.1016/j.msard.2025.106947","DOIUrl":"10.1016/j.msard.2025.106947","url":null,"abstract":"<div><div>COVID-19 vaccination in Multiple Sclerosis (MS) has continued clinical relevance. Complex dosing and variability in immunosuppression/ immunomodulation from disease modifying treatments (DMTs) necessitate real-world studies of COVID-19 immunity. We aimed to evaluate if PwMS develop adequate and persistent serological and cellular COVID-19 immunity after vaccination. We conducted a real-world longitudinal study (<em>n</em> = 235) including PwMS (<em>n</em> = 205; Alemtuzumab, Dimethyl fumarate, Fingolimod, Interferon, Natalizumab, Ocrelizumab, no-DMT) and Healthy volunteers (HV) (<em>n</em> = 30). Serological and cellular immunity was tested at ≤18 and ≤24-month after completed COVID-19 vaccine-course. 97 % of both HV and PwMS were immune at ≤18-month, and 96.9 % PwMS and 100 % HV at ≤24-month, (OR 0.33, 95 % CI (0.09, 0.93), p = 0.05)). Both groups showed similar cellular immunity at both timepoints. Vaccine Adverse effects incidence was similar too. PwMS on Ocrelizumab were significantly less likely to have low serological immunity (<em>p</em> < 0.001 at both timepoints). They were more likely to have intact T cell responses than HV (OR 5.4, 95 % CI 1.28-22.60). Despite this, they had higher infections per person year. PwMS on Fingolimod also had low serological immunity (Odd’s ratio 0.33; CI 0.11-0.97) which stayed low despite boosters and only 6 % showed intact cellular immunity, probably due to lymphopenia. Other DMT-treated PwMS (Natalizumab, Dimethyl Fumarate, Interferon, and no no-DMT) showed comparable COVID-19 serological and cellular immunity as HV. We report COVID-19 immunity clearly over time and across various DMT-groups. Ocrelizumab lowered serological but maintained cellular immunity; whilst Fingolimod lowered both. Data support boosters in PwMS, more so on Ocrelizumab and Fingolimod.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106947"},"PeriodicalIF":2.9,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-24DOI: 10.1016/j.msard.2025.106946
Maha Mohammed , Iman EL Agouza , Raghda Zaitoun , Khaled Ahmad , Shaimaa Mohammad , Ola Sallam , Hoda Tomoum
Introduction
Biotinidase deficiency (BD) is a disorder with autosomal recessive inheritance with protean clinical manifestations. Some cases present atypically with a neuroinflammatory phenotype that mimics neuromyelitis optica spectrum disorder. This can occur acutely in children who are otherwise normal leading to misdiagnosis and mismanagement with a potential for residual deficits.
Objective
To investigate biotinidase enzyme activity among children with presentation and radiological findings consistent with myelopathy.
Methods
This prospective observational study included children (≤18 years) admitted to the Pediatric Neurology Department, Ain Shams University Children’s Hospital, with myelopathy and MRI evidence of spinal cord demyelination. Clinical, laboratory, ophthalmological, and neuroimaging data were systematically collected. Serum biotinidase enzyme activity was measured in all participants.
Results
Thirty-nine children with spinal cord demyelination were included (44% male), with a median age at onset of 9 years. BD was identified in four patients. Presenting features included progressive limb weakness and gait disturbance, with optic neuropathy observed in three patients. Neuroimaging consistently demonstrated longitudinally extensive transverse myelitis involving the cervical and/or thoracic spinal cord, frequently accompanied by brainstem signal abnormalities. Prior to diagnosis, patients received immunomodulatory therapies with limited or transient benefit. Following biotin supplementation, all patients demonstrated clinical improvement, with residual deficits observed in those with delayed diagnosis.
Conclusion
BD should be considered in the differential diagnosis of pediatric spinal cord demyelination, particularly in antibody-negative cases or those with suboptimal response to immunotherapy. Further studies incorporating immune biomarkers are needed to determine whether adjunctive management of inflammation, alongside metabolic correction, may improve neurological outcomes.
{"title":"Screening for Biotinidase deficiency in children with spinal cord demyelination","authors":"Maha Mohammed , Iman EL Agouza , Raghda Zaitoun , Khaled Ahmad , Shaimaa Mohammad , Ola Sallam , Hoda Tomoum","doi":"10.1016/j.msard.2025.106946","DOIUrl":"10.1016/j.msard.2025.106946","url":null,"abstract":"<div><h3>Introduction</h3><div>Biotinidase deficiency (BD) is a disorder with autosomal recessive inheritance with protean clinical manifestations. Some cases present atypically with a neuroinflammatory phenotype that mimics neuromyelitis optica spectrum disorder. This can occur acutely in children who are otherwise normal leading to misdiagnosis and mismanagement with a potential for residual deficits.</div></div><div><h3>Objective</h3><div>To investigate biotinidase enzyme activity among children with presentation and radiological findings consistent with myelopathy.</div></div><div><h3>Methods</h3><div>This prospective observational study included children (≤18 years) admitted to the Pediatric Neurology Department, Ain Shams University Children’s Hospital, with myelopathy and MRI evidence of spinal cord demyelination. Clinical, laboratory, ophthalmological, and neuroimaging data were systematically collected. Serum biotinidase enzyme activity was measured in all participants.</div></div><div><h3>Results</h3><div>Thirty-nine children with spinal cord demyelination were included (44% male), with a median age at onset of 9 years. BD was identified in four patients. Presenting features included progressive limb weakness and gait disturbance, with optic neuropathy observed in three patients. Neuroimaging consistently demonstrated longitudinally extensive transverse myelitis involving the cervical and/or thoracic spinal cord, frequently accompanied by brainstem signal abnormalities. Prior to diagnosis, patients received immunomodulatory therapies with limited or transient benefit. Following biotin supplementation, all patients demonstrated clinical improvement, with residual deficits observed in those with delayed diagnosis.</div></div><div><h3>Conclusion</h3><div>BD should be considered in the differential diagnosis of pediatric spinal cord demyelination, particularly in antibody-negative cases or those with suboptimal response to immunotherapy. Further studies incorporating immune biomarkers are needed to determine whether adjunctive management of inflammation, alongside metabolic correction, may improve neurological outcomes<em>.</em></div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106946"},"PeriodicalIF":2.9,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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