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Background: Enhanced characterization of the atrial electrical substrate may lead to better comprehension of atrial fibrillation (AF) pathophysiology., Objective: With the use of high-density substrate mapping, we sought to investigate the occurrence of functional electrophysiological phenomena in the left atrium and to assess potential association with arrhythmia recurrences after catheter ablation., Methods: Sixty-three consecutive patients with AF referred for ablation were enrolled. Analysis of conduction abnormalities relied on two acquired left atrial electroanatomic maps (sinus and atrial paced rhythm). We classified conduction abnormalities as fixed (if these were present in both rhythms) or functional rhythm dependent (if unmasked in one of the two rhythms). Esophagus and aorta locations were recorded to check the correspondence with abnormal conduction sites., Results: There were 234 conduction abnormalities detected, of which 125 (53.4%) were functional rhythm dependent. The most frequent anatomic site of functional phenomena was the anterior wall, followed by the posterior wall, in sinus rhythm and the pulmonary venous antra in paced rhythm. Sites of functional phenomena in 82.6% of cases corresponded with extracardiac structures, such as sinus of Valsalva of ascending aorta anteriorly and the esophagus posteriorly. Most (88%) areas with functional phenomena had normal bipolar voltage. After pulmonary vein ablation, the number of residual functional phenomena is an independent predictor of AF recurrence (hazard ratio, 2.539 [1.458-4.420]; P = .001) with a risk of recurrences at multivariable Cox analysis., Conclusion: Dual high-density mapping (during sinus and paced rhythms) is able to unmask functional, rhythm-dependent phenomena that are predictive of AF recurrences during follow-up., Competing Interests: Disclosures Dr Frontera has received speaker fees from Biosense Webster. Francesca Comi was an employee at Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this manuscript to disclose., (Copyright © 2024 Heart Rhythm Society. All rights reserved.)

We aimed to assess the treatment strategies utilized in patients with neuromyelitis optica spectrum disorder (NMOSD) experiencing relapses, including their frequency, types, and response after 6 months based on the Expanded Disability Status Scale (EDSS) score., Methods: We conducted a retrospective study involving NMOSD patients from the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177). Treatment response at 6 months was categorized as "good" if the EDSS score decreased by ≥1 point after a nadir EDSS score ≤ 3, or by ≥2 points after a nadir EDSS score > 3, "poor" if the EDSS score decrease was slighter, and as "absent" if the EDSS score remained unchanged or worsened., Results: We included 120 NMOSD patients (seropositive N = 75), who experienced 250 NMOSD-related relapses and received 248 treatments. At 6 months, complete recovery was achieved in 70/98 (71.4%) and 15/19 (79%) patients, respectively. Predictors of a "good" response in our regression model were a younger age at disease onset (OR:3.54, CI95% 2.45-5.01, p < 0.0001) and a short delay from onset of relapse to treatment initiation (OR:1.56, CI95% 1.22-2.13, p = 0.004)., Conclusions: Approximately two-thirds of patients experienced complete recovery, and younger age and a short delay to start treatment were independent predictors of a "good" response., Competing Interests: Declaration of Competing Interest The authors declared no potential conflict of interest with respect to this research, authorship, and/or publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Knowledge of the safety and efficacy of disease-modifying therapies (DMTs) in older patients with Multiple Sclerosis (pwMS) is limited due to their exclusion from clinical trials. Our purpose is to evaluate the choice of DMTs in pwMS older than 50 years old in a real-world setting., Methods: Cross-sectional study of pwMS from the Argentine MS and NMOSD Registry. We included patients under 35 and above 50 years old prescribed DMTs. Disease activity was categorized as highly active (HA) or not highly active (NHA), and DMTs were classified as low efficacy therapies (LET) or high efficacy therapies (HET)., Results: 1460 patients (65% females) were enrolled. The HA group comprised 241 patients, 198 young (82.2%) and 43 older (17.8%). The NHA group included 1219 patients, 893 young (73%) and 326 older (27%). In the NHA group, older patients received LET more frequently than younger patients (66% versus 44%; p < 0.01). In the HA group, older patients received LET in 61% of cases, whereas younger patients received HET in 71% (p = 0.01)., Conclusion: The study shows the preference of LET in older patients regardless of disease activity. However it does not demonstrate a difference in disability in older patients based on low vs high efficacy DMTs used, probably due to the design of the study. Further longitudinal studies are warranted to address this issue., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study aimed to collect and analyze the literature data regarding Chiari network (CN) and other right atrium (RA) remnants comprising the Eustachian and Thebesian valves (EV, ThV) as a potential entrapment site during different percutaneous cardiac procedures (PCP)., Methods and Results: A systematic search was conducted using Pubmed and Embase databases following the PRISMA guidelines to obtain available data concerning PCP associated with entrapment of inserted materials within CN-EV-ThV. The final analysis included 41 patients who underwent PCP with reported material entrapment within these RA remnants. The PCP was atrial septal defect (ASD)/patent foramen ovale (PFO) closure, catheter ablation, and pacemaker/defibrillator implantation in 44%, 22%, and 17% of patients, respectively. The entrapped materials were ASD/PFO devices, multipolar electrophysiology catheters, passive-fixation pacing leads, and J-guidewires in about 30%, 20%, 15%, and 10% of patients, respectively. Intraprocedural transthoracic, transoesophageal and intracardiac echocardiography showed sensitivity to reveal these structures of 20%, ∼95%, and 100%, respectively. A percutaneous approach successfully managed 70% of patients, while cardiovascular surgery was required in 20% and three patients died (7.3%)., Conclusions: CN and other RA remnants may cause entrapment of various devices or catheters during PCP requiring right heart access. The percutaneous approach, guided by intraprocedural imaging, appears safe and effective in managing most patients. Prevention includes recognizing these anatomical structures at baseline cardiac imaging and intraprocedural precautions. Further studies are needed to analyze the actual incidence of this condition, its clinical impact and appropriate management., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Predictors of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) do not include ECG variables. Intrinsicoid deflection (ID) represents the early ventricular depolarization on surface ECG. Delayed ID (DID) has been associated with sudden cardiac arrest (SCA) in the community. In a cohort of consecutive patients with HCM, we assessed whether DID predicts SCA or its surrogates., Methods: We reviewed ECG, clinical and follow-up data of 344 consecutive HCM patients. DID (ID ≥50 ms) was classified as lateral (leads I or aVL), inferior (leads II, III or aVF), and precordial (leads V5 or V6). The endpoint was a combination of SCD, resuscitated SCA or appropriate ICD intervention., Results: The SCA group was composed by 2 secondary prevention ICD recipients and 23 patients that reached the endpoint during follow-up (108 ± 73 months). SCA patients had more frequently massive LV hypertrophy (LVH) or end-stage HCM. ECG indexes of LVH were comparable between SCA and controls. SCA patients were more likely to have DID on ECG lateral leads I/aVL (72% vs 44%; p = 0.008). A non significant trend was observed for inferior and V5/V6 leads. DID I/aVL was associated with SCA in multivariate analysis after correction for massive LVH and end-stage disease (HR: 2.86; 95%CI: 1.14-7.13; p = 0.02)., Conclusions: In HCM patients DID is associated with increased risk of SCA. Its prognostic value extends beyond that of LVH. If confirmed in prospective studies, the prognostic power of this ECG marker could be used to refine risk prediction., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: The objective of this study was to determine by a conjoint analysis the preferences for a range of disease-modifying treatment attributes in patients with multiple sclerosis (MS) and treating neurologists., Methods: This was a cross-sectional study throughout Argentina between August 2020 and February 2021. Participating patients were adults with relapsing-remitting MS, who had received a long-term specific disease-modifying treatment for at least the past 3 months and their treating neurologist. Patients and neurologist were sampled from the Argentinean MS patient registry (RelevarEM). We applied the methodology of conjoint analysis. Patient preferences for hypothetical treatment were collected from the overall sample and from stratified subgroups according to the expanded disability status scale (EDSS) score. An ordinary least squares regression model was used to estimate parameters., Results: A total of 275 patients from 25 centers (31 principal investigators) were included, mean age was 43.2 ± 10.9 years, 59.6% were female, and mean EDSS was 3.1 ± 2. For the entire sample, we observed that patients had higher preferences for treatments with lower side effect risks (28.7 relative preference [RP]), lower frequency of administration (21.4 RP), and higher impact on relapses (19.6 RP). Patients with a higher EDSS give significantly greater importance to a less frequent administration regime and the oral route than patients with a lower EDSS (23.5 RP vs 20.1 [P =.02] and 17.1 vs 15.3 [P =.03], respectively). For neurologists, the most important attribute was to prevent disease progression (RP 29.3)., Conclusion: Our study contributes to the understanding of treatment selection preferences from the perspectives of both patient and neurologists., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Myelin-associated glycoprotein (MAG) is a key molecule involved in the nurturing effect of myelin on ensheathed axons. MAG also inhibits axon outgrowth after injury. In preclinical stroke models, administration of a function-blocking anti-MAG monoclonal antibody (mAb) aimed to improve axon regeneration demonstrated reduced lesion volumes and a rapid clinical improvement, suggesting a mechanism of immediate neuroprotection rather than enhanced axon regeneration. In addition, it has been reported that antibody-mediated crosslinking of MAG can protect oligodendrocytes (OLs) against glutamate (Glu) overload by unknown mechanisms., Purpose: To unravel the molecular mechanisms underlying the protective effect of anti-MAG therapy with a focus on neuroprotection against Glu toxicity., Results: MAG activation (via antibody crosslinking) triggered the clearance of extracellular Glu by its uptake into OLs via high affinity excitatory amino acid transporters. This resulted not only in protection of OLs but also nearby neurons. MAG activation led to a PKC-dependent activation of factor Nrf2 (nuclear-erythroid related factor-2) leading to antioxidant responses including increased mRNA expression of metabolic enzymes from the glutathione biosynthetic pathway and the regulatory chain of cystine/Glu antiporter system xc - increasing reduced glutathione (GSH), the main antioxidant in cells. The efficacy of early anti-MAG mAb administration was demonstrated in a preclinical model of excitotoxicity induced by intrastriatal Glu administration and extended to a model of Experimental Autoimmune Encephalitis showing axonal damage secondary to demyelination., Conclusions: MAG activation triggers Glu uptake into OLs under conditions of Glu overload and induces a robust protective antioxidant response., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Currently, there are several reasons to promote worldwide the concept of multiple sclerosis care units (MSCU) for a better management of affected patients. Ideally, the MSCU should have some human and technical resources that distinguish and improve the care of affected patients; however, local, and regional aspects should be considered when recommending how these units should operate. The objective of these consensus recommendations was to review how MSCU should work in Latin America to improve long-term outcomes in MS patients., Methods: A panel of neurology experts from Latin America dedicated to the diagnosis and care of MS patients gathered virtually during 2019 and 2020 to carry out a consensus recommendation about objectives and functioning implementation of MSCU in Latin America. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used., Results: Recommendations focused on the objectives, human and technical resources, and the general functioning that MSCU should have in Latin America., Conclusions: The recommendations of these consensus guidelines attempt to optimize the health care and management of MS patients by setting how MSCU should work in our region., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Green roofs are strategic tools that can play a significant role in the creation of sustainable and resilient cities. They have been largely investigated thanks to their high retention capacity, which can be a valid support to mitigate the pluvial flood risk and to increase the building thermal insulation, ensuring energy saving. Moreover, green roofs contribute to restoring vegetation in the urban environment, increasing the biodiversity and adding aesthetic value to the city. The new generation of multilayer green roofs present an additional layer with respect to traditional ones, which allows rainwater to be stored, which, if properly treated, can be reused for different purposes. This paper offers a review of benefits and limitations of green roofs, with a focus on multilayer ones, within a Water-Energy-Food-Ecosystem nexus context. This approach enables the potential impact of green roofs on the different sectors to be highlighted, investigating also the interactions and interconnections among the fields. Moreover, the Water-Energy-Food-Ecosystem nexus approach highlights how the installation of traditional and multilayer green roofs in urban areas contributes to the Development Goals defined by the 2030 Sustainable Agenda., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: During the last 20 years, multiple sclerosis (MS) disease has seen major changes with new diagnostic criteria, a better identification of disease phenotypes, individualization of disease prognosis and the appearance of new therapeutic options in relapsing remitting as well as progressive MS. As a result, the management of MS patients has become more complex and challenging. The objective of these consensus recommendations was to review how the disease should be managed in Argentina to improve long-term outcomes in MS patients., Methods: A panel of 36 experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2018 and 2019 to carry out a consensus recommendation on the management of MS patients in Argentina. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used., Results: Recommendations focused on diagnosis, disease prognosis, tailored treatment, treatment failure identification and pharmacovigilance process., Conclusions: The recommendations of these consensus guidelines attempt to optimize the health care and management of patients with MS in Argentina., Competing Interests: Declaration of competing interest RA, AAP, EAB, MEB, MB, EC, MCC, ND, MIG, OG, DG, MJH, JPH, MJ, EK, RL, JM, PGN, RP, MLS, VS, DS, AT, SAV, AV, CV has nothing to disclose. EC has received reimbursement for developing educational presentations, educational and research grants, consultation fees and travel stipends from Biogen, Genzyme, Merck, Novartis. AGB has received reimbursement for developing educational presentations, educational and research grants, consultation fees and travel stipends from Biogen, Genzyme, Novartis, Teva, Gador, Raffo, Biosidus, Synthon – Bagó and Roche. SB has received reimbursement for research grants and travel stipends from Merck, Biogen and Genzyme. FC received fees for consultancy and Advisory Board membership and fees for travel, academic conferences and research projects from Novartis, Merck-Serono, Teva, Genzyme and Biogen Idec. ECC has received reimbursement for developing educational presentations, educational and research grants, consultation fees and travel stipends from Biogen, Genzyme. NFL has received consulting fees from Biogen, Novartis and Genzyme as a lecturer from Merck Serono, Novartis and Biogen, and collaboration for attendance to national and international congresses from Biogen, Novartis, Merck Serono, Bayer and Gador. GGL has received reimbursement for developing educational presentations, consultations fees, clinical trials fees and travel stipends from Biogen, Genzyme, Merck, Novartis, Teva, Tuteur. ADM has received reimbursement for research grants, and travel stipends from Bagó, Raffo and Biosidus. LP has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis. JIR has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis. RRE has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Schering Argentina, Bayer Schering Pharma, Bayer, Serono Argentina and Merck. VS has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Bayer, Biogen, Genzyme, Merck, Novartis, Roche, Biosidus, Gador and Raffo. MCY has received reimbursement for developing educational presentations and travel/accommodations stipends from Merck-Serono Argentina, Biogen-Idec Argentina, Genzyme Argentina, Bayer Inc., Novartis Argentina and TEVA-Tuteur Argentina. JC has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis, and Roche., (Copyright © 2019. Published by Elsevier B.V.)

Despite the availability of a large amount of information regarding the management and care of relapsing remitting multiple sclerosis (RRMS) patients, there is scant information about recommendations on how to care for primary progressive MS (PPMS) patients. The objective of this study was to review how PPMS patients should be assessed and cared for in Latin America (LATAM)., Methods: A panel of neurology experts from LATAM dedicated to the diagnosis and care of MS patients gathered virtually during 2017 and 2018 to carry out a consensus recommendation on the diagnosis and treatment of PPMS patients in LATAM. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used., Results: Recommendations focused on disease management, and specific and symptomatic disease treatment were determined. The main consensus was that the 2017 McDonald criteria should be used for diagnosis but that the exclusion of regional diseases is strongly recommended; that specific considerations should be taken regarding immunotherapy treatments used in MS due to the scarce evidence available; and that a general approach that considers symptomatic treatment and rehabilitation should be performed in affected patients to improve their status., Conclusions: The recommendations of these consensus guidelines attempt to optimize the health care and management of PPMS patients in LATAM., (Copyright © 2018 Elsevier B.V. All rights reserved.)

One of the biggest challenges in multiple sclerosis (MS) is the definition of treatment response/failure in order to optimize treatment decisions in affected patients. The objective of this consensus was to review how disease activity should be assessed and to propose recommendations on the identification of treatment failure in RRMS patients in Argentina., Methods: A panel of experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2016 and 2017 to carry out a consensus recommendation on the identification of treatment failure in RRMS patients. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used., Results: Recommendations were established based on published evidence and the expert opinion. Recommendations focused on disease management, disease activity markers and treatment failure identification were determined. Main consensus were: ≥2 relapses during the first year of treatment and/or ≥3 new or enlarged T2 or T1 GAD+ lesions and/or sustained increase of ≥2 points in EDSS or ≥100% in T25FW defines treatment failure in RRMS patients., Conclusions: The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Argentina., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Latin American MS Experts' Forum has developed practical recommendations on the initiation and optimization of disease-modifying therapies in patients with relapsing-remitting multiple sclerosis (RRMS). The recommendations reflect the unique epidemiology of MS and the clinical practice environment in Latin American countries. Treatment response may be evaluated according to changes in relapses; progression, as assessed by the Expanded Disability Status Scale and the Timed 25-foot Walk; and lesion number on magnetic resonance imaging. Follow-up assessments are recommended every six months, or annually for stable patients. Cognitive function should be evaluated in all RRMS patients at baseline and annually thereafter. These recommendations are intended to assist clinicians in Latin America in developing a rational approach to treatment selection and sequencing for their RRMS patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Previous reports have shown that CD24 gene polymorphisms have an important role in the risk of development and progression of multiple sclerosis (MS)., Objective: To investigate the association between P226 polymorphisms (T/C), P1056 (A/G), P1527 (TG/del) and P1626 (A/G) of the CD24 gene and MS, comparing allele and genotype frequencies of patients versus controls., Materials and Methods: We analyzed DNA samples from 102 MS patients and from 205 unrelated healthy individuals. DNA was extracted from peripheral blood and polymorphic regions were amplified by nested PCR. Genotyping was performed by restriction fragments length polymorphisms. Time from disease onset to reach EDSS 6 and time to conversion to secondary progressive phase (SP) were used as variables of survival as well as percentage of patients that reached those endpoints. We used the log Rank test for data comparison (significant p≤0.05)., Results: We found no differences between cases and controls in frequency of polymorphisms at the CD24 gene. 44.6% of patients with the AA genotype (P1626) reached an EDSS 6 vs 16% of patients with other genotypes (p<0.001, HR 3.2, 95% CI 1.4 to 7.4). 45.8% of patients with the AA genotype reached SPMS vs 16.7% without this genotype (p<0.001, HR 3.4, 95% CI 1.5 to 7.8)., Conclusions: This study showed a strong association between the presence of AA genotype in the 1626 polymorphism of the CD24 gene and the risk of disease progression in MS patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The comprehension of the molecular mechanisms leading to Trypanosoma cruzi-elicited heart dysfunction might contribute to design novel therapeutic strategies aiming to ameliorate chronic Chagas disease cardiomyopathy. In C3H/He mice infected with the low virulence T. cruzi Colombian strain, the persistent cardiac inflammation composed mainly of CCR5(+) T lymphocytes parallels the expression of CC-chemokines in a pro-inflammatory IFN-gamma and TNF-alpha milieu. The chronic myocarditis is accompanied by increased frequency of peripheral CCR5(+)LFA-1(+) T lymphocytes. The treatment of chronically T. cruzi-infected mice with Met-RANTES, a selective CCR1/CCR5 antagonist, led to a 20-30% decrease in CD4(+) cell numbers as well as IL-10, IL-13 and TNF-alpha expression. Further, Met-RANTES administration impaired the re-compartmentalization of the activated CD4(+)CCR5(+) lymphocytes. Importantly, Met-RANTES treatment resulted in significant reduction in parasite load and fibronectin deposition in the heart tissue. Moreover, Met-RANTES treatment significantly protected T. cruzi-infected mice against connexin 43 loss in heart tissue and CK-MB level enhancement, markers of heart dysfunction. Thus, our results corroborate that therapeutic strategies based on the modulation of CCR1/CCR5-mediated cell migration and/or effector function may contribute to cardiac tissue damage limitation during chronic Chagas disease.