Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina / Core data set for real world data in multiple sclerosis: customization for latin america from a global task force recommendation

Introducción: Los objetivos primarios del core data set son reducir la heterogeneidad y promover la armonización entre las fuentes de datos en la esclerosis múltiple (EM), reduciendo así el tiempo necesario para ejecutar esfuerzos en la recolección de datos de vida real. Recientemente, un grupo liderado por la Multiple Sclerosis Data Alliance ha desarrollado un core data set para la recolección de datos del mundo real en EM a nivel global. Nuestro objetivo ha sido adaptar y consensuar este conjunto de datos globales a las necesidades de América Latina para que pueda ser implementado por los registros ya desarrollados y en proceso de desarrollo en la región. Material y métodos. Se conformó un grupo de trabajo regionalmente y se adaptó el core data set creado globalmente (proceso de traducción al español, incorporación de variables regionales y consenso sobre variables que se iban a utilizar). El consenso se obtuvo a través de la metodología Delphi remoto de ronda de cuestionarios y discusión a distancia de las variables del core data set. Resultados: Veinticinco profesionales de América Latina llevaron adelante el proceso de adaptación entre noviembre de 2022 y julio de 2023. Se estableció un acuerdo sobre un core data set de nueve categorías y 45 variables, versión 2023, con la sugerencia de implementarlo en registros desarrollados o en vías de desarrollo y cohortes de EM en la región. Conclusión: El core data set busca armonizar las variables recolectadas por los registros y las cohortes de EM en América Latina con el fin de facilitar dicha recolección y permitir una colaboración entre fuentes. Su implementación facilitará la recolección de datos de vida real y la colaboración en la región.(AU)

Introduction: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region. Material and methods: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables. Results: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region. Conclusion: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.(AU)

[Core data set for real world data in multiple sclerosis: customization for latin america from a global task force recommendation]. / Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.

INTRODUCTION: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region. MATERIAL AND METHODS: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables. RESULTS: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region. CONCLUSION: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.

TITLE: Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.Introducción. Los objetivos primarios del core data set son reducir la heterogeneidad y promover la armonización entre las fuentes de datos en la esclerosis múltiple (EM), reduciendo así el tiempo necesario para ejecutar esfuerzos en la recolección de datos de vida real. Recientemente, un grupo liderado por la Multiple Sclerosis Data Alliance ha desarrollado un core data set para la recolección de datos del mundo real en EM a nivel global. Nuestro objetivo ha sido adaptar y consensuar este conjunto de datos globales a las necesidades de América Latina para que pueda ser implementado por los registros ya desarrollados y en proceso de desarrollo en la región. Material y métodos. Se conformó un grupo de trabajo regionalmente y se adaptó el core data set creado globalmente (proceso de traducción al español, incorporación de variables regionales y consenso sobre variables que se iban a utilizar). El consenso se obtuvo a través de la metodología Delphi remoto de ronda de cuestionarios y discusión a distancia de las variables del core data set. Resultados. Veinticinco profesionales de América Latina llevaron adelante el proceso de adaptación entre noviembre de 2022 y julio de 2023. Se estableció un acuerdo sobre un core data set de nueve categorías y 45 variables, versión 2023, con la sugerencia de implementarlo en registros desarrollados o en vías de desarrollo y cohortes de EM en la región. Conclusión. El core data set busca armonizar las variables recolectadas por los registros y las cohortes de EM en América Latina con el fin de facilitar dicha recolección y permitir una colaboración entre fuentes. Su implementación facilitará la recolección de datos de vida real y la colaboración en la región.

Identification of regulatory T cell molecules associated with severity of multiple sclerosis.

BACKGROUND: Regulatory CD4+ T cells (Tregs) exhibit functional alterations in patients with multiple sclerosis (MS). Transforming growth factor (TGF)-ß is a key regulator of Treg development and function. OBJECTIVE: The objective of this study is to determine whether the expression of functionally relevant TGF-ß-regulated molecules is altered in Tregs from patients with MS. METHODS: Expression of nine Treg markers was analyzed by multi-color flow cytometry in CD4+ T cells and Treg subpopulations of 31 untreated MS patients and age- and sex-matched healthy donors (HDs). Correlations between Treg marker expression and clinical variables were sought. RESULTS: Expression of the transcription factor Helios, which defines thymic-derived Tregs, was decreased in this Treg subpopulation. The frequency of peripherally generated Tregs was increased in patients with MS, particularly in patients with progressive MS. Low frequencies of thymic-derived Tregs were associated with magnetic resonance imaging (MRI) lesion-burden and a high relapse rate. Four surface markers associated with TGF-ß signaling (ABCA1, BTLA, DNAM-1, and GARP) were differentially expressed on Tregs from patients with MS and HDs. Expression levels of CD73, CD103, ABCA1, and PAR2 showed strong correlations with disease severity. CONCLUSION: We have identified novel markers abnormally expressed on Tregs from patients with MS that could detect patients with severe disease.

Opsoclonus-myoclonus-ataxia syndrome associated with central nervous system HIV-1 escape phenomenon. / Síndrome opsoclono-mioclono-ataxia asociado a fenómeno de escape viral por virus de la inmunodeficiencia humana en el sistema nervioso central.

INTRODUCTION: Opsoclonus-myoclonus-ataxia (OMA) syndrome is a rare neurological disorder characterized by involuntary conjugate saccadic eye movements, myoclonus, and ataxia. Few reports exist on patients with HIV and OMA. CASE REPORT: A 41-year-old man diagnosed with HIV-1 infection in 1997 coursed with multiple anti-retroviral schemes as a consequence of poor adherence. In 2008 he presented an HIV-1 viral load of 100,000 copies/mL and a CD4+ T cell count of 10 cells/mm3. In 2013 our patient arrived with an 11-month history of progressive opsoclonus and ataxia. He had undetectable plasma HIV-1 RNA load and CD4+ of 606 cells/mm3. No opportunistic infections were found. Cerebrospinal fluid analysis showed mildly elevated protein concentration and HIV-1 viral load of 534 copies/mL. Cerebrospinal fluid co-receptor tropism test showed selective CCR5 usage. A brain magnetic resonance imaging showed hippocampal atrophy and T2-weighted hyperintensities. Our patient exhibited a dramatic recovery and cerebrospinal fluid HIV clearance after adjustment of anti-retroviral treatment based on genotyping resistance and tropism analyses. CONCLUSIONS: In patients with HIV presenting cengral nervous system dysfunction without opportunistic infections, cerebro-spinal fluid and plasma HIV-1 viral load, resistance and tropism tests should be performed to assess a potential viral escape and to design the appropriate anti-retroviral therapy in an individual patient basis.

TITLE: Síndrome opsoclono-mioclono-ataxia asociado a fenómeno de escape viral por virus de la inmunodeficiencia humana en el sistema nervioso central.Introducción. El síndrome opsoclono-mioclono-ataxia (OMA) es un trastorno neurológico infrecuente caracterizado por movimientos oculares conjugados sacádicos involuntarios, mioclonías y ataxia. Existen pocos casos en la bibliografía de pacientes con virus de la inmunodeficiencia humana (VIH) y OMA. Caso clínico. Varón de 41 años y diagnóstico de infección por el VIH-1 desde 1997, que cursó con múltiples esquemas antirretrovirales debido a una pobre adhesión al tratamiento. En 2008 presentó una carga viral de 100.000 copias/mL y una cuenta linfocitaria CD4+ de 10 células/mm3. En 2013 sufrió un cuadro progresivo de 11 meses de evolución caracterizado por opsoclonía y ataxia. En ese momento, su carga viral era indetectable, y la cuenta de CD4+, de 606 células/mm3. Se descartaron infecciones oportunistas. El examen del líquido cefalorraquídeo demostró hiperproteinorraquia leve y una carga viral de 534 copias/mL. El examen del tropismo de correceptor en el líquido cefalorraquídeo demostró un uso selectivo de CCR5. La resonancia magnética cerebral objetivó atrofia hipocámpica e hiperintensidades en las secuencias ponderadas en T2. El paciente mostró una recuperación clínica franca y un aclaramiento de la carga viral en el líquido cefalorraquídeo tras el ajuste de antirretrovirales basado en la resistencia de genotipo y el análisis de tropismo. Conclusiones. En pacientes con infección por el VIH y disfunción del sistema nervioso central sin infecciones oportunistas, debería llevarse a cabo una determinación de la carga viral en el plasma y el líquido cefalorraquídeo para descartar un potencial fenómeno de escape viral, así como exámenes de resistencia y tropismo para diseñar el tratamiento antirretroviral adecuado.

Natural history of longitudinally extensive transverse myelitis in 35 Hispanic patients with systemic lupus erythematosus: good short-term functional outcome and paradoxical increase in long-term mortality.

Background and objective Acute transverse myelitis (TM) is an infrequent neurological complication of systemic lupus erythematosus (SLE). Short-term outcome varies widely between cohorts. Little is known about the epidemiology and long-term functional outcome of TM associated to SLE. Methods Patients with SLE and acute TM were identified during hospital admission, visits to the Emergency Room or the Neurology Outpatient Clinic. We evaluated ambispectively those patients with SLE presenting with clinical myelopathy and corroborated with spinal MRI. Cases were divided as partial (non-paralyzing) or complete (paralyzing). We determined long-term functional outcome as well as mortality in those patients with follow-up periods of at least five years. Results We identified 35 patients (partial, n = 15; complete, n = 20) in which complete clinical and imaging data were available (26 with follow-up ≥ 5 years). Patients with complete TM were significantly older than those with partial forms. Positive antiphospholipid antibodies were observed in 80% of patients, suggesting a possible mechanistical role. Surprisingly, functional recovery at one year was in general good; however, we observed a five-year mortality of 31% because of sepsis (in 10 cases) or pulmonary embolism (in one case). Conclusions Short-term outcome of SLE-related TM is generally good, and recurrence rate is low. However, we observed a long-term fatality rate of 31% for reasons unrelated to TM, suggesting that TM is a manifestation of severe immune dysregulation and a predictor of severity and mortality in patients with SLE.