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Background: Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed. Methods: This 96-weeks observational study enrolled patients already on treatment with teriflunomide for ≥ 24 weeks. The predictiveness of NEDA-3 and NEDA-3 + at 48 weeks on the change in motor disability at 96 weeks was compared through a two-sided McNemar test. Results: The full analysis set (n = 128; 38% treatment naïve) featured relatively low level of disability (baseline EDSS = 1.97 ± 1.33). NEDA-3 and NEDA-3 + statuses were achieved by 82.8% and 64.8% of patients, respectively at 48 weeks vs. baseline, and by 57.0% and 49.2% of patients, respectively at 96 weeks vs. baseline. All patients except one were free of disability progression at Week 96, and NEDA-3 and NEDA-3 + were equally predictive. Most patients were free of relapse (87.5%), disability progression (94.5%) and new MRI activity (67.2%) comparing 96 weeks with baseline. SDMT scores were stable in patients with baseline score ˃35 and improved significantly in those with baseline score ≤ 35. Treatment persistence was high (81.0% at Week 96). Conclusion: Teriflunomide confirmed its real-world efficacy and was found to have a potentially beneficial effect on cognition. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part.Methods: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models.Results: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy.Discussion: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) accounts for 176 cases per 100,000 inhabitants (female/male ratio = 2:1) in Italy. For most of the patients (67%), the disease course is relapsing-remitting MS (RRMS).Objective: To compare the costs and quality-adjusted life years (QALYs) of teriflunomide in RRMS naïve patients vs. RRMS patients previously treated (experienced) with other disease-modifying therapies in Italy.Methods: A four health states Markov model-supported cost-utility analysis (CUA) covering a 7-year timespan through annual cycles was developed, following the healthcare sector and the societal viewpoints. Part of the parameters that populated the Markov model was obtained from a questionnaire administered to four primary Italian MS centres. Costs of healthcare and non-healthcare resources, expressed in euro (€) 2019, and QALYs were discounted at 3% real social discount rate. One-way, scenario and probabilistic sensitivity analyses tested the uncertainty of the baseline findings.Results: Baseline CUA shows that teriflunomide in RRMS naïve patients is strongly dominant vs. experienced patients (healthcare sector perspective: - €1042.68 and + 0.480 QALYs; societal perspective: - €6782.81 and + 0.480 QALYs). Sensitivity analyses confirmed the robustness of the baseline results.Conclusion: Teriflunomide in RRMS naïve vs. experienced patients is cost-effective and possibly strongly dominant from both the healthcare sector and the society viewpoints in Italy. Our findings need further confirmation from real-world studies. [ABSTRACT FROM AUTHOR]

In particular, all patients with relapsing onset developed clinically definite MS, and all patients with primary-progressive onset had a clinical evolution and MRI findings confirming the diagnosis of MS. At 2018, MS course was: relapsing-remitting in 63 patients, secondary-progressive in 18 patients (within a mean of 9.7 years after disease onset), and primary-progressive in 5 patients. Dear Sirs, Multiple sclerosis (MS) disease course is greatly changed over the last decades. [Extracted from the article]

Background and purpose: Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods: Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results: In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions: Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated. [ABSTRACT FROM AUTHOR]

In people with multiple sclerosis (PwMS), strict follow-up is essential. Telemedicine has the potential to overcome many of the difficulties in routine management. Herein, we present a structured protocol that can be used to remotely manage patients with MS, describing in detail the steps to be taken and exams needed at each stage. A working group was established which developed a tailored protocol that can be adapted to a variety of settings. The overall protocol consisted of 5 phases: enrolment, document sharing phase, pre-evaluation, virtual visit, and post-visit phase, which was divided into 14 individual steps. As of October 2020, 25 virtual visits have been carried out, all via Skype. The patient's caregiver was present during visits and had an active role. The average duration of the virtual visit was 24 min, and that of the pre-visit and post-visit were around 15 min each. Overall satisfaction as rated by physicians was considered high (8.0 ± 0.5). Using the system usability scale (SUS), patients also favorably rated the virtual visit (96.6 ± 6.1). In 20% of cases, the virtual visit was not sufficient to provide adequate information and an in-person clinical visit was recommended. The described protocol has the potential to provide benefits for the healthcare system as well as patients and their caregivers both during and beyond COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background. Anal canal adenocarcinoma (AA) is an uncommon tumor of the gastrointestinal tract. We seek to provide a detailed description of the incidence, demographics, and outcome of this rare tumor in the United States. Methods. The data on anal canal adenocarcinoma from SEER Program, between 1973–2015, were extracted. We analyzed the incidence rates by demographics and tumor characteristics, followed by analysis of its impact on survival. Results. The incidence of AA increased initially by 4.03% yearly from 1973 to 1985 but had a modest decline of 0.32% annually thereafter. The mean age for diagnosis of AA was 68.12 ± 14.02 years. Males outnumbered females by 54.8 to 45.2%. Tumors were mostly localized on presentation (44.4%) and moderately differentiated (41.1%). Age generally correlated with poor overall cancer survival. However, young patients (age <40 years) also showed poor long-term survival. Patients with localized disease and well-differentiated tumors showed better survival outcomes. Surgical intervention improved survival significantly as compared to patients who did not (116.7 months vs 42.7 months, p < 0.01). Conclusions. Anal canal adenocarcinoma demonstrated a poor bimodal cancer-free survival in both younger and older patient groups. Surgery significantly improves odds of survival and should be offered to patients amenable to intervention. [ABSTRACT FROM AUTHOR]

Background: The increasing multiple sclerosis (MS) prevalence is varying across the macroscopic regional areas. Only few studies have explored the microscopic geographic variation of MS prevalence, which could highlight MS spatial clusters.Objective: In this ecological study, we aimed to estimate 2016 MS prevalence in the province of Pavia (Northern Italy) and to describe MS risk geographical variation across small area units, compared to the year 2000.Methods: Bayesian models were fit to estimate area-specific MS relative risks. The mean of the posterior marginal distribution of relative risks differences for each area were used to describe the risk variation.Results: The 2016 overall prevalence was 169.4 per 100,000 inhabitants (95% CI 158.8-180.6). The Bayesian mapping of MS showed some clusters of higher and lower disease prevalence. Furthermore, several municipalities located in the north part of the province were more at risk with respect to the year 2000.Conclusions: The current MS prevalence sets the province of Pavia among high-risk areas and, compared with the previous prevalence estimate (86 per 100,000 in year 2000), indicates an increased MS risk. The Bayesian mapping highlighted area with a significantly higher/lower MS risk where to investigate etiologic hypotheses based on environmental and genetic exposures. [ABSTRACT FROM AUTHOR]

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups. [ABSTRACT FROM AUTHOR]

Interferon-beta (IFNβ) is effective treatments for relapsing multiple sclerosis (MS). IFNβ treatment includes subcutaneous (SC) IFNβ-1b, intramuscular (IM) and SC IFNβ-1a, and SC pegylated IFNβ-1a (PEG-IFNβ-1a). PEG-IFNβ-1a offers the advantage of a prolonged duration of action with a less frequent administration (every 2 weeks) and a higher patient adherence. However, the use of SC interferons could be characterized by potential skin toxicity. Injection site reactions (ISRs), featured by erythema, edema, pain, and pruritus, are the most common adverse reactions. ISRs are mild or moderate in the vast majority of cases, but they can be severe enough to induce drug discontinuation. Therefore, it is very important to adopt strategies to minimize ISRs by proper patient education and counseling. These include rotation of injection sites, use of autoinjectors, use of medication at room temperature, cold compress, or local anesthetic cream before injection, early application of medium to high potency topical corticosteroids with gauze medication, and nonsteroidal anti-inflammatory drugs taken before and for 24 h after the injection. [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]

The article presents the statement from the European association of endoscopic surgeons on the use of robotics in general surgery. The statement includes robotic surgery having a potential in sophisticated electromechanical systems to perform complex surgical tasks. Conclusions drawn include little or no advantage of robotic systems in general surgery, severe lack of high quality data on robotic surgery and the need of a specific set of skills and training for surgeons.

Multiple sclerosis (MS) is the main cause of chronic disability in young people during their most productive years of life and therefore carries a high social and economic burden. The present study aimed to: (1) verify the capacity of an administrative data source to furnish data for constructing a model able to detect the occurrence of clinical relapses in MS patients and (2) validate the constructed theoretical model on a set of real-world data. Two MS experts identified some administrative variables as proxies of clinical relapses. Thereafter, the two MS experts analysed 889 events in 100 MS patients, considering only the administrative data relating to these patients, while a third neurologist independently analysed the real-world data (documented medical history) of the same patients in the same period. Absolute concordance between the theoretical model and the real-world data was found in 86 % of the events. The model we propose is easily and rapidly applicable, requiring the collection of just a few variables that are already present in local health authority administrative databases in Italy. It can be used to estimate, with a good level of reliability, the occurrence of relapses in various settings. Moreover, the model is also exportable to different and larger MS cohorts and could be useful for healthcare planning and for evaluating the efficacy of drugs in the real-world, thus favouring better resource allocation and management. [ABSTRACT FROM AUTHOR]

Background: The short-term results of the Sigma trial show that laparoscopic sigmoid resection (LSR) used electively for diverticular disease offers advantages over open sigmoid resection (OSR). This study aimed to compare the overall mortality and morbidity rates after evaluation of the clinical outcomes at the 6-month follow-up evaluation. Methods: In a prospective, multicenter, double-blind, parallel-arm, randomized control trial, eligible patients were randomized to either LSR or OSR. The short-term results and methodologic details have been published previously. Follow-up evaluation was performed at the outpatient clinic 6 weeks and 6 months after surgery. Results: In this trial, 104 patients were randomized for either LSR or OSR, and the conversion rate was 19.2%. The LSR approach was associated with short-term benefits such as a 15.4% reduction in the major complications rate, less pain, and a shorter hospital stay at the cost of a longer operating time. At the 6-month follow-up evaluation, no significant differences in morbidity or mortality rates were found. Two patients died of cardiac causes (overall mortality, 3%). Late complications (7 LSR vs. 12 OSR; p = 0.205) consisted of three incisional hernias, five small bowel obstructions, four enterocutaneous fistulas, one intraabdominal abscess, one retained gauze, two anastomotic strictures, and three recurrent episodes of diverticulitis. Nine of these patients underwent additional surgical interventions. Consideration of the major morbidity over the total follow-up period (0-6 months) shows that the LSR patients experienced significantly fewer complications than the OSR patients (9 LSR vs. 23 OSR; p = 0.003). The Short Form-36 (SF-36) questionnaire showed significantly better quality of life for LSR at the 6-week follow-up assessment. However, at the 6-month follow-up assessment, these differences were decreased. Conclusions: The late clinical outcomes did not differ between LSR and OSR during the 30-day to 6-month follow-up period. Consideration of total postoperative morbidity shows a 27% reduction in major morbidity for patients undergoing laparoscopic surgery for diverticular disease. [ABSTRACT FROM AUTHOR]

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.

Th1 up-regulation seems to favour autoimmunity, while Th2 up-regulation seems to favour humoral immunity. Accordingly, subjects affected by atopic diseases (such as allergic respiratory diseases, ARDs) should be less prone to autoimmune diseases (such as multiple sclerosis, MS), and vice versa. The recent identification of Th17 cells, which seem to favour the development of both autoimmunity and allergy, led to the revision of the classic Th1/Th2 paradigm. We studied 200 MS patients and 200 controls to analyze the relationships between ARDs and MS. MS patients had less probability to suffer from ARDs (OR = 0.30, p < 0.001) and allergic rhinitis (OR = 0.25, p < 0.001), after adjusting for environmental factors. MS tended to be less severe when associated to ARDs. Our findings add some elements for the comprehension of immune mechanisms involved in MS pathogenesis and suggest to analyze other MS cohorts, in order to evaluate if MS patients affected by allergic diseases show particular clinical findings. [ABSTRACT FROM AUTHOR]

Anastomotic leak is a major complication of colorectal surgery, leading to significant morbidity and mortality. This article focuses on definitions of anastomotic and subclinical leaks, risk factors associated with anastomotic leaks, relevance of surgical rituals, and use of imaging studies in diagnosing leaks. Surgeon skill is one of the most important determinants of clinical anastomotic leakage after colorectal surgery. Other factors known to affect anastomotic healing include: blood supply, steroids, contaminated wound, and nutrition. Although a surgeon makes a decision about technique or a clinical judgment based largely upon personal preference and perception of a particular advantage, surgical rituals such as handsewn vs. stapled anastomois, use of pelvic drains, creation of defunctioning ileostomy are reviewed based on the literature available. Computed tomography (CT) imaging has been reported to be effective in identifying patients with anastomotic leaks and can detect intra-abdominal and perianastomotic abscesses, which can mimic the signs and symptoms of an anastomotic leak. However, watersoluble contrast enema seems superior to CT for diagnosis of anastomotic leak. [ABSTRACT FROM AUTHOR]

Despite the significant benefits of laparoscopic surgery, limitations still exist. One of these limitations is the loss of several degrees of freedom. Robotic surgery has allowed surgeons to regain the two lost degrees of freedom by introducing wristed laparoscopic instruments. At the first Pelvic Surgery Meeting held in Brescia in June 2007, the participants focused on the role of robotic surgery in pelvic operations surgery for malignancy including prostate, rectal, uterine, and cervical carcinoma. All members of the interdisciplinary panel were asked to define the role of robotic surgery in prostate, rectal, and uterine carcinoma. All key statements were reformulated until a consensus within the group was achieved (Murphy et al., Health Technol Assess 2(i–v):1–88, 1998). For the systematic review, a comprehensive literature search was performed in Medline and the Cochrane Library from January 1997 to June 2007. The keywords used were Da Vinci®, telemonitoring, laparoscopy, neoplasms for urology, colorectal, gynecology, visceral surgery, and minimally invasive surgery. The pelvic surgery meeting was supported by Olympus Medical Systems Europa. As of December 31, 2007, there were 795 unit shipments worldwide of the Da Vinci®: 595 in North America, 136 in Europe, and 64 in the rest of the world (). It was estimated that, during 2007, approximately 50,000 radical prostatectomies were performed with the Da Vinci® robot system in the USA, reflecting market penetration of 60% of radical prostatectomies in the USA. This utilization represents 50% growth as in 2006 only 42% of all radical prostatectomies performed in the USA employed robotics. While robotic prostatectomy has become the most widely accepted method of prostatectomy, robotic hysterectomy and proctectomy remain far less widely accepted. The theoretical benefits of the increased degrees of freedom and three-dimensional visualization may be outweighed in these areas by the loss of haptic feedback, increased operative times, and increased cost. [ABSTRACT FROM AUTHOR]

Abnormalities of swallowing are commonly encountered in Multiple Sclerosis (MS), especially in the most disabled patients. The disturbances usually involve oral and pharyngeal phases of swallowing, although upper oesophageal sphincter dysfunction has also been detected. MS patients need to be effectively evaluated and managed in order to recognize dysphagia before any medical complications such as aspiration pneumonia appear. An integrated approach is proposed to define the severity of dysphagia and to devise the most appropriate therapeutic/rehabilitative methodology. [ABSTRACT FROM AUTHOR]

This paper represents a current opinion on the impact surgeons may have on the variability of the quality of care of rectal cancer surgery. No systematic review of the evidence available in the literature is provided. The objective is to present a concise insight on selected outcomes of care studies, to review the limitations of such studies and to discuss the value of process of care studies. Outcomes of care studies measure what happens to patients, and process of care studies measure what is done to patients. Three variables are reviewed: training, volume and individual skill. It is concluded that the quality of the selected outcomes of care studies is not sufficient to draw definitive conclusions on whether surgeons are a variable. Further efforts should prompt process of care studies on rectal cancer surgery. This implies that outcomes should be measured, processes of care modified and outcomes measured again. This cycle should be continuously repeated in order to achieve the best quality of care. [ABSTRACT FROM AUTHOR]

Sixty relapsing-remitting multiple sclerosis (MS) patients were selected on the basis of their score on the Fatigue Severity Scale (FSS) and formed two groups: 40 patients (fatigued MS; MSf) scored above the 75th percentile of a previously assessed representative MS sample (100 patients), and 20 age- and sex-matched patients (nonfatigued MS patients; MSnf) scored below the 25th percentile. The patients underwent clinical evaluation (Expanded Disability Status Scale (EDSS)), further assessment of fatigue (Fatigue Impact Scale), scales evaluating depression (Hamilton Depression Rating Scale (HDRS) and Beck's Depression Inventory (BDI)) and neuropsychological tests. All patients were evaluated for muscle fatigability and central activation by means of a biomechanical test of sustained contraction; they also underwent somatosensory evoked potentials (SSEPs) and transcranial magnetic stimulation (TMS). The patients of the MSf subgroup were then randomized to one of the following two treatments: 4-aminopyridine (4-AP) 24 mg/day and fluoxetine (FLX) 20 mg/day. After a one-week titration this treatment proceeded for 8 weeks. At the end of the treatment, EDSS, fatigue and depression scores were further evaluated. At baseline, fatigue test scores consistently correlated with depression and cognitive test scores, but not with the fatigability test. Fatigue scores decreased in both treatment groups in a similar way. Due to the design of the study, this cannot be disjoined from a placebo effect. The changes of fatigue scores could not be predicted in the FLX group, whereas in the 4-AP group higher basal fatigability test scores were associated with greater reduction in fatigue scores. [ABSTRACT FROM AUTHOR]

Objectives:. To evaluate the clinical characteristics, course and prognosis of Devic’s neuromyelitis optica (DNO), to evaluate the prognostic role of demographic and clinical features, to evaluate the current DNO diagnostic criteria. Methods:. Demographic, clinical, CSF and MRI data of patients affected by DNO were collected from fifteen Italian MS centres. Inclusion criteria were: 1) two or more acute episodes of neurological dysfunction indicating involvement of the optic nerve and spinal cord, in a simultaneous or subsequent temporal relationship; 2) no evidence of lesions beyond the optic nerve or the spinal cord; 3) brain MRI at onset negative or non-specific for multiple sclerosis (MS) (white matter lesions ≤ 2). Disability was scored by means of Kurtzke’s Expanded Disability Status Scale (EDSS). Results:. 46 patients with relapsing DNO were included, 37 females and 9 males, with mean age at onset of 40.1 ± 16.3 years (range 12–77 years). The follow up duration was 8.8 ± 3.5 years, the mean annualised relapse rate was 1.3 ± 1.2. After 5, 10 and 15 years EDSS 3.0 was reached respectively by 65%, 82 % and 86% of cases, EDSS 6.0 respectively by 42%, 53 % and 69% of cases, EDSS 10 respectively by 8%, 12% and 23% of cases. The probability of reaching EDSS 3 was statistically correlated with age at onset, interval between the first and 2nd attack, and relapse rate. The probability of reaching EDSS 6.0 was correlated with the residual EDSS at onset and to relapse rate.During the follow up, brain white matter lesions appeared in 8 subjects. Spinal cord MRI showed lesions extending across 3 or more segments in 39 subjects, only 1 lesion involving 1 segment in 4 subjects, and was normal in 3 subjects. One or more CSF abnormalities were found at least once in 29/44 patients (65.9 %), the most frequent findings being pleocytosis (38.6 %), oligoclonal bands (34.1 %), high protein level (25 %), and high albumin ratio (20.5 %). Conclusions:. DNO has a poor prognosis in most cases. Compared with MS, DNO patients have a higher age at onset, females are more frequently affected, the course is more severe. Brain and spinal cord MRI permit the differentiation of DNO from MS. CSF supports the probability of DNO if it shows increased cells and proteins. [ABSTRACT FROM AUTHOR]

Background: To compare Expanded Disability Status Scale (EDSS) trajectories over time between Multiple Sclerosis (MS) groups with pediatric (POMS), adult (AOMS) and late (LOMS) onset, and between patients with and without progression independent of relapse activity (PIRA). Methods: Patients with a first visit within 1 year from onset, ≥ 5-year follow-up and ≥ 1 visit every 6 months were selected from the Italian MS Register. Adjusted disability trajectories were assessed by longitudinal models for repeated measures. Comparisons between groups and between patients with and without PIRA in subgroups were performed by evaluating the yearly differences of mean EDSS score changes versus baseline (delta-EDSS). A first CDA event was defined as a 6-months confirmed disability increase from study baseline, measured by EDSS (increase ≥ 1.5 points with baseline EDSS = 0; ≥ 1.0 with baseline EDSS score ≤ 5.0 and ≥ 0.5 point with baseline EDSS > 5.5). PIRA was defined as a CDA event occurring more than 90 days after and more than 30 days before the onset of a relapse. Results: 3777 MS patients (268 POMS, 3282 AOMS, 227 LOMS) were included. The slope of disability trajectories significantly diverged in AOMS vs POMS starting from the second year of follow-up (Year 2: delta2-EDSS 0.18 (0.05; 0.31), p = 0.0054) and then mean delta2-EDSS gradually increased up to 0.23 (0.07; 0.39, p = 0.004) at year 5. Patients with PIRA had significant (p < 0.0001) steeper increase in EDSS scores than those without PIRA in all groups, although in POMS, the disability trajectories began to diverge later and at a lesser extent with delta-EDSS score of 0.48 vs 0.83 in AOMS and 1.57 in LOMS, at 3 years after the first PIRA. Conclusions: Age is relevant in determining disability progression in MS. POMS shows a less steep increase in EDSS scores over time than older patients. The effect of PIRA in accelerating EDSS progression is less pronounced in POMS than in AOMS and LOMS. [ABSTRACT FROM AUTHOR]

[Display omitted] Multiple sclerosis (MS) is a neurological disorder characterized by immune dysregulation. It begins with a first clinical manifestation, a clinically isolated syndrome (CIS), which evolves to definite MS in case of further clinical and/or neuroradiological episodes. Here we evaluated the diagnostic value of transcriptional alterations in MS and CIS blood by machine learning (ML). Deep sequencing of more than 200 blood RNA samples comprising CIS, MS and healthy subjects, generated transcriptomes that were analyzed by the binary classification workflow to distinguish MS from healthy subjects and the Time-To-Event pipeline to predict CIS conversion to MS along time. To identify optimal classifiers, we performed algorithm benchmarking by nested cross-validation with the train set in both pipelines and then tested models generated with the train set on an independent dataset for final validation. The binary classification model identified a blood transcriptional signature classifying definite MS from healthy subjects with 97% accuracy, indicating that MS is associated with a clear predictive transcriptional signature in blood cells. When analyzing CIS data with ML survival models, prediction power of CIS conversion to MS was about 72% when using paraclinical data and 74.3% when using blood transcriptomes, indicating that blood-based classifiers obtained at the first clinical event can efficiently predict risk of developing MS. Coupling blood transcriptomics with ML approaches enables retrieval of predictive signatures of CIS conversion and MS state, thus introducing early non-invasive approaches to MS diagnosis. [ABSTRACT FROM AUTHOR]

The author reflects on randomized trials in clinical reserach. It states that colorectal clinicians must perform randomized trials only if they have no clue about the value of two available methods of treatment. It focuses on the importance of blinding in randomized trials, along with random operation design.

Aim: To propose a simple tool for early prediction of unfavourable long term evolution of multiple sclerosis (MS). Methods: A Bayesian model allowed us to calculate, within the first year of disease and for each patient, the Bayesian Risk Estimate for MS (BREMS) score that represents the risk of reaching secondary progression (SP). Results: The median BREMS scores were higher in 158 patients who reached SP within 10 years compared with 1087 progression free patients (0.69 vs 0.30; p<0.0001). The BREMS value was related to SP risk in the whole cohort (p<0.0001) and in the subgroup of 535 patients who had never been treated with immune therapies, thus reasonably representing the natural history of the disease (p<0.000001). Conclusions: The BREMS score may be useful both to identify patients who are candidates for early or for more aggressive therapies and to improve the design and analysis of clinical therapeutic trials and of observational studies. [ABSTRACT FROM AUTHOR]

Cerebral venous thrombosis (CVT) has been described in several cases of clinically definite multiple sclerosis (MS). In the majority of these, lumbar puncture followed by intravenous corticosteroid treatment was suspected as the cause. We report what is, to our knowledge, the first case of a patient with a multifocal clinically isolated syndrome suggestive of MS onset, who developed multiple CVT after lumbar puncture and during high-dose i.v. corticosteroid treatment. We conclude that the sequence 'lumbar puncture followed by corticosteroid treatment' may be a contributory risk factor for the development of CVT when associated with other risk factors. [ABSTRACT FROM AUTHOR]

Discusses the evidence in support of a laparoscopic approach to the treatment of uncomplicated diverticulitis of the sigmoid colon. Risk factors of open surgery, including more adhesions to the abdominal wall; Lower morbidity rates for older patients undergoing laparoscopic surgery; Shorter recovery time and hospital stay.

The authors provide insight into the current status of enhanced recovery pathways (ERPs) in elective colorectal surgery. Topics include the analogy of ERPs with a package deal marketing promotion, the elements of ERP and its potential in improving the value of colorectal care, and the importance of teamwork in the implementation of ERP.

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for both Relapsing and Primary Progressive forms of Multiple Sclerosis (MS) treatment. OCR is postulated to act via rapid B cell depletion; however, by analogy with other anti-CD20 agents, additional effects can be envisaged, such as on Protein Kinase C (PKC). Hence, this work aims to explore novel potential mechanisms of action of OCR in peripheral blood mononuclear cells from MS patients before and after 12 months of OCR treatment. We first assessed, up-stream, PKCβII and subsequently explored two down-stream pathways: hypoxia-inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF), and human antigen R (HuR)/manganese-dependent superoxide dismutase (MnSOD) and heat shock proteins 70 (HSP70). At baseline, higher levels of PKCβII, HIF-1α, and VEGF were found in MS patients compared to healthy controls (HC); interestingly, the overexpression of this inflammatory cascade was counteracted by OCR treatment. Conversely, at baseline, the content of HuR, MnSOD, and HSP70 was significantly lower in MS patients compared to HC, while OCR administration induced the up-regulation of these neuroprotective pathways. These results enable us to disclose the dual positive action of OCR: anti-inflammatory and neuroprotective. Therefore, in addition to B cell depletion, the effect of OCR on these molecular cascades can contribute to counteracting disease progression. [ABSTRACT FROM AUTHOR]

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: Predicting disease progression in patients with the first clinical episode suggestive of multiple sclerosis (MS) is crucial for personalized therapeutic approaches. This study aimed to develop the EUMUS score for accurately estimating the risk of early evidence of disease activity and progression (EDA). Methods: Retrospective analysis was conducted on data from 221 patients with a first clinical MS episode collected from four Italian MS centers. Various variables including socio-demographics, clinical features, cerebrospinal fluid analysis, evoked potentials, and brain MRI were considered. A prognostic multivariate regression model was identified to develop the EUMUS score. The optimal cutoff for predicting the transition from no evidence of disease activity (NEDA3) to EDA was determined. The accuracy of the prognostic model and score were tested in a separate UK MS cohort. Results: After 12 months, 61.54% of patients experienced relapses and/or new MRI lesions. Younger age (OR 0.96, CI 0.93–0.99; p = 0.005), MRI infratentorial lesion(s) at baseline (OR 2.21, CI 1.27–3.87; p = 0.005), positive oligoclonal bands (OR 2.89, CI 1.47–5.69; p = 0.002), and abnormal lower limb somatosensory-evoked potentials (OR 2.77, CI 1.41–5.42; p = 0.003) were significantly associated with increased risk of EDA. The EUMUS score demonstrated good specificity (72%) and correctly classified 80% of patients with EDA in the independent UK cohort. Conclusions: The EUMUS score is a simple and useful tool for predicting MS evolution within 12 months of the first clinical episode. It has the potential to guide personalized therapeutic approaches and aid in clinical decision-making. [ABSTRACT FROM AUTHOR]

Unfortunately in the original publication, the affiliation of the author Maria Pia Amato was incorrect. The author inadvertently missed out to include her second affiliation. [ABSTRACT FROM AUTHOR]

Background: Active relapsing–remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) are currently defined as "relapsing MS" (RMS). The aim of this cross-sectional study was to assess drivers of treatment switches due to clinical relapses in a population of RMS patients collected in the Italian MS and Related Disorders Register (I-MS&RD). Methods: RRMS and SPMS patients with at least one relapse in a time window of 2 years before of data extraction were defined as RMS. Factors associated with disease-modifying therapy (DMT) switching due to clinical activity were assessed through multivariable logistic regression models in which treatment exposure was included as the last recorded DMT and the last DMT's class [moderate-efficacy (ME), high-efficacy (HE) DMTs and anti-CD20 drugs]. Results: A cohort of 4739 RMS patients (4161 RRMS, 578 SPMS) was extracted from the I-MS&RD. A total of 2694 patients switching DMTs due to relapses were identified. Switchers were significantly (p < 0.0001) younger, less disabled, more frequently affected by an RR disease course in comparison to non-switcher patients. The multivariable logistic regression models showed that Alemtuzumab (OR 0.08, 95% CI 0.02–0.37), Natalizumab (0.48, 0.30–0.76), Ocrelizumab (0.1, 0.02–0.45) and Rituximab (0.23, 0.06–0.82) exposure was a protective factor against treatment switch due to relapses. Moreover, the use of HE DMTs (0.43, 0.31–0.59), especially anti-CD20 drugs (0.14, 0.05–0.37), resulted to be a protective factor against treatment switch due to relapses in comparison with ME DMTs. Conclusions: More than 50% of RMS switched therapy due to disease activity. HE DMTs, especially anti-CD20 drugs, significantly reduce the risk of treatment switch. [ABSTRACT FROM AUTHOR]

The authors reflect on the transanal total mesorectal excision (TME) quality in obese male patients with low rectal cancer. Topics include the unnecessary abdominoperineal excision (APE), sphincter-sparing resection with an involved circumferential resection margin (CRM), and oncological advantages of transanal TME.

Background: Endothelial progenitor cells (EPCs) have been shown to increase during physiological pregnancy and are believed to play a fundamental role in the process of placentation. Reduced levels of EPCs during pregnancy have been associated with preeclampsia and miscarriage. Women with multiple sclerosis (MS) are not at increased risk of preeclampsia nor of general adverse obstetric outcome, in contrast with some other autoimmune diseases.Objective: The aim of this study was to evaluate circulating EPCs levels in pregnant patients with MS.Methods: CD34+ and CD133+ were longitudinally detected by flow cytometry in the maternal plasma of 29 healthy controls and 9 MS patients and in the cord blood of their newborns.Results: EPCs were affected by pregnancy with the same trend in both groups (CD34+ p = 0.0342; CD133+ p = 0.0347). EPCs during pregnancy were increased in MS (mean ± SD: CD34+ cells 0.038 ± 0.010; CD133+ 0.024 ± 0.009) with respect to healthy controls (mean ± SD: CD34+ cells 0.022 ± 0.006; CD133+ 0.016 ± 0.004), CD34+ p = 0.0004; CD133+ p = 0.0109. EPCs levels of the cord blood of MS patients' newborns mild correlated with maternal EPC levels at delivery (CD34+: spearman's Rho 0.658, p = 0.054; CD133+: spearman's Rho 0.758, p = 0.018).Conclusions: This work identified increased circulating EPC levels during pregnancy, following the same trend both in MS patients and healthy controls. Despite the similar trend, the levels of circulating EPCs were significantly higher in MS patients with respect to the control population. A correlation was also found in MS patients between cord blood EPCs and circulating EPCs at delivery. [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.

The authors discuss issues concerning the controversy on the extent of mesenterectomy in right colectomy. They explain the development of terminology to describe the extent of dissection including D3 extended mesenterectomy, high tie and complete mesenteric excision. They also discuss the importance of preoperative awareness of the vascular anatomy before conducting the procedure and the debate on whether some form of extended lymph node dissection should be implemented in clinical practice.

The article discusses the results of the Colorectal cancer Laparoscopic or Open Resection (COLOR II) randomised trial and the American College of Surgeons Oncology Group (ACOSOG) Z6051 randomised trial on the use of laparoscopic surgery in rectal cancer. Topics discussed include both trials to have found laparoscopic surgery in rectal surgery to be not inferior to open surgery, and COLOR II trial found 84 percent rate of complete total mesorectal excision (TME) in laparoscopic group.

We report a relapsing-remitting multiple sclerosis patient who received monthly intravenous natalizumab. After the fifth dose, the patient had a change in a long-standing mole. Ten months later, the mole became ulcerative and was ablated. Histological examination identified a spreading melanoma reaching the lower dermis (Clark level IV). Considering that at the moment the incidence of melanoma is estimable as about 5 per 100,000 multiple sclerosis person-years treated with natalizumab, and that, in the general population, the incidence of melanoma per 100,000 person-years is more than 10, we may speculate that the occurrence of melanoma during natalizumab treatment in multiple sclerosis is purely a coincidence. [ABSTRACT FROM AUTHOR]

Assesses the frequency and disease association of cerebrospinal fluid (CFS) band patterns. Frequency of CFS band pattern in definite multiple sclerosis (MS) than in all other neurological diseases; Manifestation of identical oligoclonal IgG bands and serum and CSF in patients with central nervous system diseases; Inverse female/ratio and a higher mean age from the group of MS patients with the single CSF band pattern.

Introduction: Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked. This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register. Methods: The Register collects, through a standardized Web-based Application, unique patients. Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated. Results: The Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients. The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000–2015) to 60% (enrolment period 2016–2022). In the cohort of patients registered after 2016, there were ≥ 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2). Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months. Conclusions: Data from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications. [ABSTRACT FROM AUTHOR]

Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments. [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]

The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected by such diseases and on immune-active treatments have been analyzed. The aim is to better understand the relationship between SARS-CoV-2 infection/vaccines with dysimmune CNS diseases by describing 12 cases of multiple sclerosis/myelitis onset or reactivation after exposure to SARS-CoV-2 infection/vaccines and reviewing all published case reports or case series in which MS onset or reactivation was temporally associated with either COVID-19 (8 case reports, 3 case series) or anti-SARS-CoV-2 vaccines (13 case reports, 6 case series). All the cases share a temporal association between viral/vaccine exposure and symptoms onset. This finding, together with direct or immune-based mechanisms described both during COVID-19 and MS, claims in favor of a role for SARS-CoV-2 infection/vaccines in unmasking dysimmune CNS disorders. The most common clinical presentations involve the optic nerve, brainstem and spinal cord. The preferential tropism of the virus together with the presence of some host-related genetic/immune factors might predispose to the involvement of specific CNS districts. [ABSTRACT FROM AUTHOR]

Background: Comorbid conditions are common in people with multiple sclerosis (pwMS). They can delay diagnosis and negatively impact the disease course, progression of disability, therapeutic management, and adherence to treatment. Objective: To quantify the economic impact of comorbidity in multiple sclerosis (MS), based on cost-of-illness estimates made using a bottom-up approach. Methods: A retrospective study was carried out in two northern Italian areas. The socio-demographic and clinical information, including comorbidities data, were collected through ad hoc anonymous self-assessment questionnaire while disease costs (direct and indirect costs of disease and loss of productivity) were estimated using a bottom-up approach. Costs were compared between pwMS with and without comorbidity. Adjusted incremental costs associated with comorbidity were reported using generalized linear models with log-link and gamma distributions or two-part models. Results: 51.0% of pwMS had at least one comorbid condition. Hypertension (21.0%), depression (15.7%), and anxiety (11.7%) were the most prevalent. PwMS with comorbidity were more likely to use healthcare resources, such as hospitalizations (OR = 1.21, p < 0.001), tests (OR = 1.59, p < 0.001), and symptomatic drugs and supplements (OR = 1.89, p = 0.012), and to incur non-healthcare costs related to investment (OR = 1.32, p < 0.001), transportation (OR = 1.33, p < 0.001), services (OR = 1.33, p < 0.001), and informal care (OR = 1.43, p = 0.16). Finally, they experienced greater productivity losses (OR = 1.34, p < 0.001) than pwMS without comorbidity. The adjusted incremental annual cost per patient due to comorbidity was €3,106.9 (13% of the overall costs) with MS disability found to exponentially affect annual costs. Conclusion: Comorbidity has health, social, and economic consequences for pwMS. [ABSTRACT FROM AUTHOR]