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Terapias inmunomoduladoras e inmunosupresoras en polineuropatía desmielinizante inflamatoria crónica refractaria. Revisión de la literatura
No full textIntroducción
La polineuropatía desmielinizante inflamatoria crónica (CIDP) se define como una neuropatía inmunomediada con recaídas y remisiones o un curso progresivo en el tiempo superior a 2 meses. En la mayoría de los casos el tratamiento con glucocorticoides, inmunoglobulina intravenosa (IgIV) o plasmaféresis (PE) permite la estabilización del cuadro clínico o logra la remisión completa.
Un grupo de pacientes, sin embargo, bien es refractario a dichos tratamientos o dependiente de los mismos, convirtiéndose en verdaderos desafíos, por lo cual hay necesidad de opciones terapéuticas eficaces y seguras como segunda o tercera línea de tratamiento.
Objetivo
El objetivo de la siguiente revisión es analizar la eficacia y la seguridad del rituximab y otros inmunomoduladores propuestos para el tratamiento de la CIDP refractaria.
Desarrollo
Se realizó una revisión de la literatura científica sobre los distintos tratamientos en la CIDP. Para la búsqueda bibliográfica se utilizaron las bases de datos PubMed y Cochrane, utilizando como palabras claves: azatioprina, ciclofosfamida, micofenolato, CIDP y rituximab. Se incluyeron artículos en inglés, francés y español. Finalmente se seleccionaron 33 artículos.
Conclusiones
El rituximab es una buena opción terapéutica en aquellos pacientes con CIDP refractaria que requieren tratamientos de segunda línea, siendo particularmente efectivo en las nodo-paranodopatías seropositivas. Aunque no existen trabajos comparativos entre los inmunosupresores de segunda línea randomizados doble ciego, el rituximab demostró una considerable efectividad, escasos efectos adversos y potencialmente menor tiempo de respuesta, en comparación con otros agentes inmunomoduladores utilizados.Fil: Zambrano, Darío. Hospital Francisco Santojanni. Servicio de Neurología; Argentina.Fil: Alessandro, Lucas. Fleni. Departamento de Neurología. Sección de Enfermedades Neuromusculares; Argentina.Fil: Barroso, Fabio Adrián. Fleni. Departamento de Neurología. Sección de Enfermedades Neuromusculares; Argentina
COVID-19 Lockdown Effects on Acute Stroke Care in Latin America
No full textObjectives
COVID-19 pandemic has forced important changes in health care worldwide. Stroke care networks have been affected, especially during peak periods. We assessed the impact of the pandemic and lockdowns in stroke admissions and care in Latin America.
Materials and Methods
A multinational study (7 countries, 18 centers) of patients admitted during the pandemic outbreak (March-June 2020). Comparisons were made with the same period in 2019. Numbers of cases, stroke etiology and severity, acute care and hospitalization outcomes were assessed.
Results
Most countries reported mild decreases in stroke admissions compared to the same period of 2019 (1187 vs. 1166, p = 0.03). Among stroke subtypes, there was a reduction in ischemic strokes (IS) admissions (78.3% vs. 73.9%, p = 0.01) compared with 2019, especially in IS with NIHSS 0–5 (50.1% vs. 44.9%, p = 0.03). A substantial increase in the proportion of stroke admissions beyond 48 h from symptoms onset was observed (13.8% vs. 20.5%, p < 0.001). Nevertheless, no differences in total reperfusion treatment rates were observed, with similar door-to-needle, door-to-CT, and door-to-groin times in both periods. Other stroke outcomes, as all-type mortality during hospitalization (4.9% vs. 9.7%, p < 0.001), length of stay (IQR 1–5 days vs. 0–9 days, p < 0.001), and likelihood to be discharged home (91.6% vs. 83.0%, p < 0.001), were compromised during COVID-19 lockdown period.
Conclusions
In this Latin America survey, there was a mild decrease in admissions of IS during the COVID-19 lockdown period, with a significant delay in time to consultations and worse hospitalization outcomes.Fil: Pujol Lereis, Virginia Andrea. Fleni. Departamento de Neurología. Centro Integral de Neurología Vascular; Argentina.Fil: Flores, Alan. Hospital Universitari Joan XXIII; España.Fil: Barboza, Miguel A. Hospital Dr. Rafael Calderón Guardia; Costa Rica.Fil: Abanto-Argomedo, Carlos. Instituto Nacional de Ciencias Neurológicas; Perú.Fil: Amaya, Pablo. Fundación Valle del Lili; Colombia.Fil: Bayona, Hernán. Hospital Universitario Fundación Santa Fe de Bogotá; Colombia.Fil: Bonardo, Pablo. Hospital Británico de Buenos Aires; Argentina.Fil: Diaz-Escobar, Luis. Hospital de Clínicas; Paraguay.Fil: Gómez-Schneider, Maia. Sanatorio de Los Arcos; Argentina.Fil: Góngora-Rivera, Fernando. Universidad Autónoma de Nuevo León; México.Fil: Lavados, Pablo M. Clínica Alemana Universidad del Desarrollo; Chile.Fil: León, Carolina. Hospital Regional del ISSSTE "Dr. Valentín Gómez Farías"; México.Fil: Luraschi, Adriana. Hospital "Dr. Ignacio Pirovano"; Argentina.Fil: Márquez-Romero, Juan Manuel. Instituto Mexicano del Seguro Social; México.Fil: Ouriques-Martins, Sheila C. Hospital Moinhos de Vento; Brasil.Fil: Navia, Víctor Hugo. Clínica Alemana Universidad del Desarrollo; Chile.Fil: Ruiz-Franco, Angélica. Hospital Juárez; México.Fil: Vences, Miguel Ángel. Hospital Nacional Edgardo Rebagliati Martins; Perú.Fil: Ameriso, Sebastián Francisco. Fleni. Departamento de Neurología. Centro Integral de Neurología Vascular; Argentina
Impact of Social Isolation on People with Dementia and Their Family Caregivers
No full textBackground: People with dementia and their family caregivers may face a great burden through social isolation due to the COVID-19 pandemic, which can be manifested as various behavioral and clinical symptoms.
Objective: To investigate the impacts of social isolation due to the COVID-19 pandemic on individuals with dementia and their family caregivers.
Methods: Two semi-structured questionnaires were applied via telephone to family caregivers of people diagnosed with dementia in three cities in Argentina, Brazil, and Chile, in order to assess clinical and behavioral changes in people with dementia and in their caregivers.
Results: In general, 321 interviews were conducted. A significant decline in memory function has been reported among 53.0%of people with dementia. In addition, 31.2%of individuals with dementia felt sadder and 37.4%had increased anxiety symptoms. These symptoms of anxiety were greater in individuals with mild to moderate dementia, while symptoms of agitation were greater in individuals with severe dementia. Moreover, compulsive-obsessive behavior, hallucinations, increased forgetfulness, altered appetite, and increased difficulty in activities of daily living were reported more frequently among individuals with moderate to severe dementia. Caregivers reported feeling more tired and overwhelmed during this period and these symptoms were also influenced by the severity of dementia.
Conclusion: Social isolation during the COVID-19 pandemic triggered a series of negative behavioral repercussions, both for people with dementia and for their family caregivers in these three South American countries.Fil: Dos Santos Azevedo, Lílian Viana. Universidade Federal de Minas Gerais; Brasi.Fil: Calandri, Ismael Luis. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Slachevsky, Andrea. Geroscience Center for Brain Health and Metabolism; Chile.Fil: Graviotto, Héctor Gastón. Hospital César Milstein; Argentina.Fil: Santos Vieira, María Carolina. aculdade Ciências Médicas de Minas Gerais; Brasil.Fil: Bezerra de Andrade, Caíssa. Universidade Federal de Minas Gerais; Brasil.Fil: Peredo Rossetti, Adriana. Faculdade Ciências Médicas de Minas Gerais; Brasil.Fil: Barroso Generoso, Alana. Rede Mater Dei de Saúde e AURUS Ensino e Pesquisa do Envelhecimento; Brasil.Fil: Carvalho Carmona, Karoline. Universidade Federal de Minas Gerais; Brasil.Fil: Aparecida Cardoso Pinto, Ludmilla. Universidade Federal de Minas Gerais; Brasil.Fil: Sorbara, Marcos. Hospital César Milstein; Argentina.Fil: Pinto, Alejandra. Universidade Federal de Minas Gerais; Brasil.Fil: Guajardo, Tania. Universidad de Chile; Chile.Fil: Olavarria, Loreto. Universidad de Chile; Chile.Fil: Thumala, Daniela. Geroscience Center for Brain Health and Metabolism; Chile.Fil: Crivelli, Lucía. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Vivas, Ludmila. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Tonidandel Barbosa, Maira. Universidade Federal de Minas Gerais; Brasil.Fil: Serrano, Cecilia M. Hospital César Milstein; Argentina
Predicting Outcome in Guillain-Barré Syndrome: International Validation of the Modified Erasmus GBS Outcome Score
No full textBackground and objectives: The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity.
Methods: We used prospective data from the first 1,500 patients included in IGOS, aged ≥6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors.
Results: For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort.
Discussion: mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, also in countries outside the Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America.
Classification of evidence: This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS.
Trial registration information: NCT01582763.Fil: Doets, Alex Y. University Medical Centre Rotterdam; Países Bajos.Fil: Lingsma, Hester F. University Medical Centre Rotterdam; Países Bajos.Fil: Walgaard, Christa. University Medical Centre Rotterdam; Países Bajos.Fil: Islam, Badrul. Icddr; BangladeshFil: Papri, Nowshin. Icddr; BangladeshFil: Davidson, Amy. University of Glasgow; Reino Unido.Fil: Yamagishi, Yuko. Kindai University Faculty of Medicine; Japón.Fil: Kusunoki, Susumu. Kindai University Faculty of Medicine; Japón.Fil: Dimachkie, Mazen M. University of Kansas Medical Center; Estados Unidos.Fil: Waheed, Waqar. University of Vermont Medical Centre; Estados Unidos.Fil: Kolb, Noah. University of Vermont Medical Centre; Estados Unidos.Fil: Islam, Zhahirul. Icddrb; BangladeshFil: Deen Mohammad, Quazi. National Institute of Neurosciences and Hospital; Bangladesh.Fil: Harbo, Thomas. Aarhus University Hospital; Dinamarca.Fil: Sindrup, Soren H.. Odense University Hospital; Dinamarca.Fil: Chavada, Govindsinh. University of Glasgow; Reino Unido.Fil: Willison, Hugh J. University of Glasgow; Reino Unido.Fil: Casasnovas, Carlos. Bellvitge University Hospital; España.Fil: Barroso, Fabio Adrián. Fleni. Departamento de Neurología. Sección de Enfermedades Neuromusculares; Argentina
Empagliflozin in Heart Failure with a Preserved Ejection Fraction
No full textBackground: Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.
Methods: In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure.
Results: Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin.
Conclusions: Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).Fil: Anker, Stefan D.. Charité Universitätsmedizin Berlin; Alemania.Fil: Butler, Javed. University of Mississippi Medical Center; Estados Unidos.Fil: Gerasimos, Filippatos. National and Kapodistrian University of Athens School of Medicine; Grecia.Fil: Ferreira, João Pedro. Université de Lorraine; Francia.Fil: Bocchi, Edimar. Universidade de São Paulo; Brasil.Fil: Böhm, Michael. Semmelweiss University; Hungría.Fil: Brunner-La Rocca, Hans Pieter. Maastricht University Medical Center; Holanda.Fil: Choi, Dong-Ju. Seoul National University Bundang Hospital; Corea.Fil: Chopra, Vijay. Max Superspeciality Hospital; India.Fil: Chuquiure-Valenzuela, Eduardo. National Institute of Cardiology; México.Fil: Giannetti, Nadia. McGill University Health Centre; Canadá.Fil: Juan Esteban, Gomez-Mesa. Universidad Icesi; Colombia.Fil: Janssens, Stefan. University Hospitals Leuven; Bélgica.Fil: Januzzi, James L. Massachusetts General Hospital; Estados Unidos.Fil: Gonzalez-Juanatey, Jose R. University Hospital; España.Fil: Merkely, Bela. Semmelweiss University; Hungría.Fil: Nicholls, Stephen J. Monash University; Australia.Fil: Perrone, Sergio Víctor. Fleni. Servicio de Cardiología; Argentina.Fil: Piña, Ileana L. Central Michigan University; Estados Unidos
Arrhythmias and Electrocardiographic findings in Coronavirus disease 2019: a systematic review and meta-analysis
No full textBackground: Coronavirus disease 2019 (COVID-19) primarily causes lung infection, but recent studies have shown that cardiac involvement is associated with a worse prognosis.
Objectives: We conducted a systematic review and meta-analysis to examine the prevalence of cardiac arrhythmias detected by the electrocardiogram and their relationships with adverse outcomes in patients with COVID-19.
Methods: PubMed and Google were searched for studies that reported on cardiac arrhythmias and/or examined the relationship between arrhythmias and adverse outcomes.
Results: Thirty studies with 12,713 participants were included in the systematic review, and 28 studies (n = 12,499) in the meta-analysis. The mean age was 61.3 ±16.8 years; 39.3% were female. In 25 studies with 7,578 patients, the overall prevalence of cardiac arrhythmias was 10.3% (95% confidence interval [CI]: 8.4% to 12.3%). The most common arrhythmias documented during hospitalization were supraventricular arrhythmias (6.2%, 95% CI: 4.4% to 8.1%) followed by ventricular arrhythmias (2.5%, 95% CI: 1.8% to 3.1%). The incidence of cardiac arrhythmias was higher among critically ill patients (relative risk [RR]: 12.1, 95% CI: 8.5 to 17.3) and among non-survivors (RR: 3.8, 95%, CI: 1.7 to 8.7). Eight studies reported changes in the QT interval. The prevalence of QTc >500 ms was 12.3% (95% CI: 6.9% to 17.8%). ST-segment deviation was reported in eight studies, with a pooled estimate of 8.7% (95% CI: 7.3% to 10.0%).
Conclusion: Our meta-analysis showed that QTc prolongation, ST-segment deviation, and various other cardiac arrhythmias were observed in patients hospitalized with COVID-19. The presence of cardiac arrhythmias was associated with a worse prognosis. This article is protected by copyright. All rights reserved.Fil: García-Zamora, Sebastián. Fleni. Departamento de Cardiología; Argentina.Fil: Lee, Sharen. The Chinese University of Hong Kong; China.Fil: Haseeb, Sohaib. James Cook University; Australia.Fil: Bazoukis, George. General Hospital of Athens "Evangelismos"; Grecia.Fil: Tse, Gary. Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease; China.Fil: Alvarez-Garcia, Jesus. Mount Sinai Hospital; Estados Unidos.Fil: Gul, Enes Elvin. Madinah Cardiac Centre; Arabia Saudita.Fil: Çinier, Göksel. Dr.SiyamiErsek Hospital Thoracic and Cardiovascular Surgery Training and Research Hospital; Turquía.Fil: Bryce, Alexander. Queen's University; Canadá.Fil: Martins Pinto-Filho, Marcelo. Universidade Federal de Minas Gerais; Brasil.Fil: Liu, Tong. Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease; China.Fil: Baranchuk, Adrian. Queen's University; Canadá
Resiliencia de docentes en distanciamiento social preventivo obligatorio durante la pandemia de COVID-19
No full texta situación de pandemia por COVID-19 motivó en todos los países la adopción de medidas extremas para evitar la propagación del virus. El cierre de escuelas, colegios y universidades cambió sorpresiva y radicalmente las actividad de docentes, estudiantes y familias; en pocas semanas los sistemas educativos debieron cambiar y adaptarse. La resiliencia docente fue la clave del éxito de esta transformación. Se estudió a 2.272 docentes de diversos países de Iberoamérica a través de un cuestionario online diseñado para conocer los aspectos principales de su resiliencia, el impacto del COVID-19 en su condición de distanciamiento social, su soporte emocional, sus habilidades para la educación online, las emociones experimentadas y cambios en su estilo de vida, entre otros. Se utilizó la Escala de Resiliencia de Connor-Davinson (CD-RISC 10) como medida de resiliencia. A través de la RISC-10 se dividió la muestra en dos grupos, grupo de alta resiliencia (AR) y grupo de baja resiliencia (BR) y se obtuvieron medias y desvíos de cada ítem para cada grupo, además de la magnitud de efecto para observar el impacto de la diferencia en cada uno de ellos. Los resultados del estudio evidencian una asociación positiva entre los docentes con alta resiliencia y la percepción del evento disruptivo de la pandemia como una oportunidad, la percepción del soporte emocional brindado, la actividad física, la necesidad de formación en neuroeducación, el manejo de herramientas de educación online, las habilidades socioemocionales para enfrentar los cambios, la experiencia de emociones de valencia positiva y la instrumentación de cambios en el estilo de vida durante la pandemia. La resiliencia no solo es importante como recurso previo y de desarrollo personal del docente, sino también lo es como “acto pedagógico” al generar modelos de docentes capaces de enfrentar la adversidad desde una perspectiva de oportunidad de crecimiento.Fil: Román, Fabián. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Forés Miravalles, Anna. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Calandri, Ismael Luis. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina. Red Iberoamericana de Neurociencia Cognitiva; España. Universidad Maimónides; Argentina.Fil: Gautreaux, Rosalba. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Antúnez, Alejandro. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Ordhei, Dalul. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Calle, Lenin. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Poenitz, Victoria. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Correa Pérez, Kethy Luz. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Torresi, Sandra. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Barceló-Martínez, Ernesto. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Conejo, Mauricio. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Ponnet, Veerle. Red Iberoamericana de Neurociencia Cognitiva; España.Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina. Red Iberoamericana de Neurociencia Cognitiva; España. Universidad de la Costa; Colombia
An fMRI study of cognitive reappraisal in major depressive disorder and borderline personality disorder
No full textBackground: One common denominator to the clinical phenotypes of borderline personality disorder (BPD) and major depressive disorder (MDD) is emotion regulation impairment. Although these two conditions have been extensively studied separately, it remains unclear whether their emotion regulation impairments are underpinned by shared or distinct neurobiological alterations.
Methods: We contrasted the neural correlates of negative emotion regulation across an adult sample of BPD patients (n = 19), MDD patients (n = 20), and healthy controls (HCs; n = 19). Emotion regulation was assessed using an established functional magnetic resonance imaging cognitive reappraisal paradigm. We assessed both task-related activations and modulations of interregional connectivity.
Results: When compared to HCs, patients with BPD and MDD displayed homologous decreased activation in the right ventrolateral prefrontal cortex (vlPFC) during cognitive reappraisal. In addition, the MDD group presented decreased activations in other prefrontal areas (i.e., left dorsolateral and bilateral orbitofrontal cortices), while the BPD group was characterized by a more extended pattern of alteration in the connectivity between the vlPFC and cortices of the visual ventral stream during reappraisal.
Conclusions: This study identified, for the first time, a shared neurobiological contributor to emotion regulation deficits in MDD and BPD characterized by decreased vlPFC activity, although we also observed disorder-specific alterations. In MDD, results suggest a primary deficit in the strength of prefrontal activations, while BPD is better defined by connectivity disruptions between the vlPFC and temporal emotion processing regions. These findings substantiate, in neurobiological terms, the different profiles of emotion regulation alterations observed in these disorders.Fil: De la Peña-Arteaga, Víctor. L'Hospitalet de Llobregat; España.Fil: Berruga-Sánchez, Mercedes. L'Hospitalet de Llobregat; España.Fil: Steward, Trevor. University of Melbourne; Australia.Fil: Martínez-Zalacaín, Ignacio. L'Hospitalet de Llobregat; España.Fil: Goldberg, Ximena. Institut d'Investigació i Innovació Sanitària Parc Taulí; España.Fil: Wainsztein, Agustina Edith. Consejo Nacional de Investigación Científica y Tecnológica; Argentina. Fleni. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina.Universidad de Buenos Aires. Facultad de Medicina. Departamento de Salud Mental; Argentina. Universidad Católica Argentina; Argentina.Fil: Abulafia, Carolina. Consejo Nacional de Investigación Científica y Tecnológica; Argentina. Fleni. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina.Fil: Cardoner, Narcís. Institut d'Investigació i Innovació Sanitària Parc Taulí; España.Fil: Castro, Mariana Nair. Consejo Nacional de Investigación Científica y Tecnológica; Argentina. Fleni. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Salud Mental; Argentina.Fil: Guinjoan, Salvador M. Laureate Institute for Brain Research; Estados Unidos.Fil: Soriano-Mas, Carles. L'Hospitalet de Llobregat; España
Characteristics of Patients with Late- vs. Early-Onset Val30Met Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS)
No full textIntroduction: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a clinically heterogeneous disease caused by mutations in the transthyretin (TTR) gene. The most common mutation, Val30Met, can manifest as an early- or late-onset disease.
Methods: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease and asymptomatic patients with TTR mutations. This is a descriptive analysis of symptomatic patients with ATTRv Val30Met amyloidosis with late- (age at least 50 years) vs. early-onset (age less than 50 years) disease in THAOS (data cutoff August 1, 2019).
Results: Of 1389 patients with ATTRv Val30Met amyloidosis, 491 (35.3%) had late-onset disease. Compared with early-onset, patients with late-onset were more likely to be male (66.2% vs. 53.6%) and have a longer mean (standard deviation [SD]) time from onset to diagnosis (3.8 [3.4] vs. 2.7 [4.1] years). Late-onset disease was associated with more severe neurological impairment at enrollment (median [10th, 90th percentile] derived Neuropathy Impairment Score in the Lower Limbs, 25.0 [4.0, 69.3] vs. 8.0 [0, 54.8]; Neurologic Composite Score, 42.0 [2.0, 155.0] vs. 21.0 [0, 102.0]). Cardiac findings were more prominent in late-onset disease. An overall interpretation of electrocardiogram as abnormal was reported in 72.1% of late-onset patients (vs. 44.3% early-onset). A left-ventricular septal thickness of at least 12 mm was reported in 69.7% of late-onset patients (vs. 14.6% early-onset). All differences were statistically significant (p < 0.001).
Conclusion: In THAOS, late-onset ATTRv Val30Met amyloidosis is common, presenting with more severe neurologic and cardiac findings at enrollment. Heterogeneity of disease may make it more difficult to diagnose. Increased recognition of late-onset ATTRv Val30Met amyloidosis could lead to more timely diagnosis and improve patient outcomes.Fil: Waddington Cruz, Marcia. Federal University of Rio de Janeiro; Brasil.Fil: Wixner, Jonas. Umeå University; Suecia.Fil: Amass, Leslie. Pfizer Inc; Estados Unidos.Fil: Kiszko, Jan. Pfizer Inc; Estados Unidos.Fil: Chapman, Doug. Pfizer Inc; Estados Unidos.Fil: Ando, Yukio. Kumamoto University; Japón.Fil: Barroso, Fabio Adrián. Fleni. Departamento de Neurología. Sección de Enfermedades Neuromusculares; Argentina
Automatic and unbiased segmentation and quantification of myofibers in skeletal muscle
Full text linkSkeletal muscle has the remarkable ability to regenerate. However, with age and disease muscle strength and function decline.
Myofiber size, which is affected by injury and disease, is a critical measurement to assess muscle health. Here, we test and
apply Cellpose, a recently developed deep learning algorithm, to automatically segment myofibers within murine skeletal muscle.
We first show that tissue fixation is necessary to preserve cellular structures such as primary cilia, small cellular antennae,
and adipocyte lipid droplets. However, fixation generates heterogeneous myofiber labeling, which impedes intensity-based
segmentation. We demonstrate that Cellpose efficiently delineates thousands of individual myofibers outlined by a variety
of markers, even within fixed tissue with highly uneven myofiber staining. We created a novel ImageJ plugin (LabelsToRois)
that allows processing multiple Cellpose segmentation images in batch. The plugin also contains a semi-automatic erosion
function to correct for the area bias introduced by the different stainings, identifying myofibers as accurately as human experts.
We successfully applied our segmentation pipeline to uncover myofiber size differences between two different muscle injury
models, cardiotoxin and glycerol. Thus, Cellpose combined with LabelsToRois allows for fast, unbiased, and reproducible
myofiber quantification for a variety of staining and fixation conditions.Fil: Waisman, Ariel. Fleni. Laboratorio de Investigación Aplicada a Neurociencias; Argentina.Fil: Norris, Alessandra. University of Florida College of Medicine. Department of Pharmacology and Therapeutics; Estados Unidos.Fil: Costa, Martín Elías. Universidad de Buenos Aires; Argentina.Fil: Kopinke, Daniel. University of Florida College of Medicine. Department of Pharmacology and Therapeutics; Estados Unidos