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Background: Multiple sclerosis (MS) is frequently accompanied by comorbid conditions. Objectives: This study aimed to determine the prevalence of key comorbid conditions in people with multiple sclerosis (pwMS) and assess their impact on quality of life and work-related activities. Methods: A cross-sectional study involving 755 pwMS from two third-level Italian MS centers was conducted. Comorbidities were identified from medical records, and quality of life was assessed using the EQ-5D-3L questionnaire. Work-related challenges were evaluated using the Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job). Results: 53.8% of pwMS had at least one comorbidity. Hypertension, depression, and anxiety were the most prevalent. Comorbidity presence was associated with reduced quality of life scores in almost all EQ-5D-3L domains and greater job difficulties in all but one MSQ-Job domain. Conclusion: Comorbidities in pwMS are prevalent and have a profound influence on quality of life and work-related activities. This comprehensive study offers new insights into the role of comorbidities in MS within the Italian context, emphasizing the need for a multidisciplinary approach in MS management. Further research is crucial to deepen our understanding of these findings in the broader Italian MS community. [ABSTRACT FROM AUTHOR]

Background: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients. Objective: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis. Methods: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death). Results: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course. Conclusion: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. Objectives: To compare diagnostic performances of two different data-driven SPMS definitions. Methods: Data-driven SPMS definitions based on a version of Lorscheider's algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist's definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). Results: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%). Conclusion: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist's definition and the global accuracy of DDA seems to be higher than the EXPAND definition. [ABSTRACT FROM AUTHOR]

Background: The etiology of pediatric-onset multiple sclerosis is unknown although putative genetic and environmental factors appear to be involved. Among children multiple sclerosis onset occurs closer to the susceptibility window thank in adults and the exposure to etiological environmental factors is more informative. An Italian multicentre case-control study (the PEDiatric Italian Genetic and enviRonment ExposurE, PEDIGREE study) was designed to investigate environmental exposures in pediatric-onset multiple sclerosis and their interaction with genetics. Objectives: To collect evidence on exposures to environmental risk factors in pediatric-onset multiple sclerosis, a questionnaire was developed for the Italian population (PEDIGREE Questionnaire) and is presented. Methods: PEDIGREE Questionnaire develops from an existing tool used in case-control studies on pediatric-onset multiple sclerosis in US Americans, and was translated, adapted and tested for the contents perceived relevance, acceptability, feasibility and reliability in a population of Italian pediatric subjects and their parents recruited from clinics and general population. Results: PEDIGREE Questionnaire contents were overall deemed relevant by the study population, acceptable for 100% participants and feasible for at least 98%. PEDIGREE Questionnaire degree of reliability ranged 56% to 72%. Conclusion: PEDIGREE Questionnaire proves to be an efficient tool to assess environmental exposures in the Italian pediatric population. We encourage the dissemination of population-specific questionnaires and shared methodology to optimize efforts in MS etiological research. [ABSTRACT FROM AUTHOR]

Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p < 0.001) and EDSS (β = 0.16, p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p = 0.01) and EDSS (β = −0.06, p < 0.001). Neither presentation was associated with changes in relapse risk. Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach. [ABSTRACT FROM AUTHOR]

Background: No uniform criteria for a sensitive identification of the transition from relapsing–remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). Methods: Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. Results: SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p < 0.0001), than those identified by the ND (n = 3868, 20.0%). In both groups, the most consistent risk factors (p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. Conclusion: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition. [ABSTRACT FROM AUTHOR]

Background: Transverse myelitis (TM) is an inflammatory disorder that can be idiopathic or associated with central nervous system autoimmune/dysimmune inflammatory diseases, connective tissue autoimmune diseases, or post-infectious neurological syndromes. Prognosis of initial TM presentations is uncertain. Objective: To identify outcome predictors in TM. Methods: Retrospective study on isolated TM at onset. Scores ⩾3 on the modified Rankin scale (mRS) marked high disability. Results: A total of 159 patients were identified. TM was classified as follows: idiopathic (I-TM, n = 53), post-infectious (PI-TM, n = 48), associated with multiple sclerosis (MS-TM, n = 51), or neuromyelitis optica spectrum disorders/connective tissue autoimmune diseases/neurosarcoidosis (n = 7). At follow-up (median, 55 months; interquartile range, 32–80), 42 patients were severely disabled, and patients with I-TM or PI-TM showed the worst outcomes. Predictors of disability were infectious antecedents, sphincter and pyramidal symptoms, high mRS scores, blood–cerebrospinal fluid barrier damage, lumbar magnetic resonance imaging (MRI) lesions on univariate analysis, and older age (odds ratio (OR), 1.1; 95% confidence interval (CI), 1.0–1.1), overt/subclinical involvement of the peripheral nervous system (PNS) (OR, 9.4; 95% CI, 2.2–41.0), complete TM (OR, 10.8; 95% CI, 3.4–34.5) on multivariate analysis. Conclusion: Our findings help define prognosis and therapies in TM at onset. Infectious antecedents and PNS involvement associate with severe prognosis. Nerve conduction studies and lumbar MRI could improve the prognostic assessment of this condition. [ABSTRACT FROM AUTHOR]

Background: Some environmental factors have been already associated to increased risk of multiple sclerosis (MS), but it is plausible that additional factors might play a role. Objective: To investigate in MS patients the relationship between inflammatory activity, detected by brain magnetic resonance imaging (MRI) with gadolinium (Gd), and air pollution, namely, particulate matters with diameter less than 10 μm (PM10). Methods: We analyzed from 52 remitting MS patients 226 brain MRIs, 34% with (Gd+MRI) and 66% without (Gd-MRI) T1-Gd-enhancing lesions. Daily recording of PM10 in the 30 days before MRI examination was obtained by monitors depending on the residence of subjects. Results: PM10 levels in the 5, 10, 15, 20, and 25 days before brain MRIs were higher (plus 16%, 21%, 24%, 25%, and 21%, respectively) with reference to Gd+MRI versus Gd-MRI. There was a significant association between Gd+MRI and PM10 levels (p = 0.013), independent of immune therapies, smoker status, and season. In patients who had two repeated MRIs with opposite outcomes (Gd-MRI and Gd+MRI), PM10 levels were strongly higher in concurrence with Gd+MRI (p < 0.0001). Conclusion: Our findings suggest that air pollution may be a risk factor for MS favoring inflammatory exacerbations. [ABSTRACT FROM AUTHOR]

Background: Few studies have analysed long-term effects of immunomodulatory disease modifying drugs (DMDs). Objective: Assessment of the efficacy of DMDs on long-term evolution of multiple sclerosis, using a Bayesian approach to overcome methodological problems related to open-label studies. Methods: MS patients from three different Italian multiple sclerosis centres were divided into subgroups according to the presence of treatment in their disease history before the endpoint, which was represented by secondary progression. Patients were stratified on the basis of the risk score BREMS (Bayesian risk estimate for multiple sclerosis), which is able to predict the unfavourable long-term evolution of MS at an early stage. Results: We analysed data from 1178 patients with a relapsing form of multiple sclerosis at onset and at least 10 years of disease duration, treated (59%) or untreated with DMDs. The risk of secondary progression was significantly lower in patients treated with DMDs, regardless of the initial prognosis predicted by BREMS. Conclusions: DMDs significantly reduce the risk of multiple sclerosis progression both in patients with initial high-risk and patients with initial low-risk. These findings reinforce the role of DMDs in modifying the natural course of the disease, suggesting that they have a positive effect not only on the inflammatory but also on the neurodegenerative process. The study also confirms the capability of the BREMS score to predict MS evolution. [ABSTRACT FROM AUTHOR]

Air pollution is a risk factor for multiple sclerosis - Yes Multiple sclerosis (MS) is a multifactorial disease in which certain environmental factors can act as triggers of an abnormal immune response in genetically susceptible individuals. Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI. [Extracted from the article]

Background: The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed. Objective: We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators. Methods: Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted. Results: Of the 3326 included patients, 345–1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b (p≤0.001). No differences in 12-month confirmed progression of disability were observed. Conclusion: Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely. [ABSTRACT FROM AUTHOR]

The article presents a study which analyzes risk of relapse phenotype recurrence in patients with multiple sclerosis (MS). MSBase, an international observational registry, was used and the association between relapse phenotypes and history of similar relapses were tested through multivariable logistic regression models. The study found that relapse phenotype was associated with demographic and clinical characteristics and phenotypic recurrence significantly more common.

The article focuses on a study that estimate and compare the proportion of liability explained by common single nucleotide polymorphisms (SNPs) and the genetic burden of multiple sclerosis (MS)-associated SNPs in progressive onset (PrMS) and bout-onset (BOMS) cases. Study calculated a weighted genetic risk score (wGRS) based on the known MS-associated loci and found that common SNPs explain a greater proportion of phenotypic variance in BOMS.

The article focuses on the study which discusses the effect of pregnancy and postpartum relapses in women with multiple sclerosis (MS) using large international MSBase Registry. It states the observational case-control study performed on pregnancies post-MS. It mentions the favorable effect on relapses as the pregnancy proceeds and peak of early postpartum.

The authors discuss modeling the course and outcomes of multiple sclerosis (MS). Topics addressed include major challenge in MS management, significance of a reliable and personalized model of MS course, and essential point to determine before trying to model the natural history of MS. Also mentioned is MS severity score (MSSS) as a good indicator of clinical disease impact.

Although the literature on laparoscopjc surgery for diverticulitis includes data on more than 1800 patients, the quality of the studies is insufficient to draw definitive evidence-based conclusions. Nonrandomized evidence suggests that laparoscopic resection for uncomplicated diverticulitis of the sigmoid may fare better than its conventional counterpart not only in short-term outcome (preservation of the abdominal wall, shorter disability), but also in the long term (decreased rates of late symptomatic small bowel obstruction). Five-year recurrence rates show that a laparoscopic or conventional access is unlikely to have an impact, provided that the oral bowel end is anastomosed to the proximal rectum rather than to the distal sigmoid. The superiority of laparoscopy should be proven by measuring health-related and patient-centered outcome rather than surrogate endpoints. Areas of concern include replacing a conventional resection with laparoscopic suture, drainage, and colostomy in patients with free perforation and peritonitis. The role of laparoscopic surgery should be limited to resection for uncomplicated diverticulitis of the sigmoid performed by adequately trained surgeons. Benefits can be expected with this procedure, provided that indications for surgery are not influenced by the mode of access and that postoperative complication rates remain within the range of that for traditional colorectal surgery. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Thyroid autoimmunity and dysfunction in multiple sclerosis patients during long-term treatment with interferon beta or glatiramer acetate: An Italian multicenter study" by G. Frisullo and colleagues in the February 10, 2014 issue.

Background: Hartmann's reversal (HR) is associated with significant technical complexity and morbidity. The decision to perform HR is difficult and up to 50% of patients with colostomies do not undergo a reversal. To better guide surgeons and patients with this decision, we sought to assess the surgical risks and outcomes of HR as compared to elective left colectomy (LC). Methods: We conducted a retrospective analysis of a prospective database at a tertiary medical center. Patients undergoing elective Hartmann's reversal and left colectomy between January 2014 and November 2021 were identified. We compared preoperative variables, intraoperative events, and short-term postoperative outcomes. Results: 135 patients were identified: 30 HR and 105 LC. There were no significant differences in demographics or preoperative comorbidities between HR and LC. There were more open and fewer robotic cases in HR (23.3% vs 2.9%, P <.0001; 46.6% vs 76.0%, P <.01). Total operative time was significantly longer in HR than LC (261.8 vs 211.7 minutes, P =.02). There was a significantly higher percentage of intraoperative complications in HR (13.3% vs 1.9%, P <.01). There was a significantly higher rate of minor postoperative complications in HR than LC (46.7% vs 26.7%, P =.04), but not major (6.7% vs 5.8%, P =.85). Time to first flatus/bowel movement was significantly longer in HR than LC (3.6 vs 2.5 days, P <.001). Conclusion: Hartmann's reversal is a more technically challenging operation than elective left colectomy and is associated with significantly higher rates of intraoperative and minor postoperative complications. Future studies should focus on mitigating these risk factors to optimize patient outcomes. [ABSTRACT FROM AUTHOR]