Positron emission tomography response and minimal residual disease impact on progression-free survival in patients with follicular lymphoma. A subset analysis from the FOLL05 trial of the Fondazione Italiana Linfomi

The aim of the present study was to analyze the prognostic role of combined PET and BCL2/IGH analysis, performed at the EOT, in a subset study of the phase III trial FOLL05 (NCT00774826), in which patients with FL were randomized to R-CVP (rituximab plus cyclophosphamide, vincristine and prednisone), R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) or R-FM (rituximab plus fludarabine and mitoxantrone).6 This study was conducted in compliance with the Declaration of Helsinki, was approved by the appropriate research ethics committee, and required each patient to provide written informed consent

Genotype/Phenotype Relationship in a Consanguineal Family With Brugada Syndrome Harboring the R1632C Missense Variant in the SCN5A Gene

Brugada syndrome (BrS) is a known cause of sudden cardiac death. The genetic basis of BrS is not well understood, and no one single gene is linked to even a majority of BrS cases. However, mutations in the gene SCN5A are the most common, although the high amount of phenotypic variability prevents a clear correlation between genotype and phenotype. Research techniques are limited, as most BrS cases still remain without a genetic diagnosis, thus impairing the implementation of experimental models representative of a general pathogenetic mechanism. In the present study, we report the largest family to-date with the segregation of the heterozygous variant NM_198056:c.4894C>T (p.Arg1632Cys) in the SCN5A gene. The genotype-phenotype relationship observed suggests a likely pathogenic effect of this variant. Functional studies to better understand the molecular effects of this variant are warranted

COVID-19: impactos na saúde mental e psicossociais na América Latina

The COVID-19 pandemic has not only had health, economic, and political impacts, but also significant psychosocial and mental health consequences worldwide. In this article, different documentation and studies on mental health were analyzed, with the aim of identifying the various problems detected during the pandemic. Methodologically, a narrative and integrative review of the scientific literature was carried out. In Latin America, the most recent studies have documented and made patent effects on the various vulnerized populations such as migrants, women, children, the elderly, people living with significant disabilities, people experiencing marked housing and food insecurity, and temporary workers laboring in what has been referred to as the informal economy. In light of this, it is proposed that addressing these issues should involve the coordination of transnational policies and the definition of an agenda of critical priorities to focus and address. For this to come about, it is important that the empirical evidence generated by regional epidemiological studies contribute to the design of public policies on mental health of the Latin American population, so that they reduce the negative effects as well as prevent the future consequences of a pandemic that is not yet over.La pandemia por el COVID-19 no sólo ha generado diversos impactos en materia de salud, economía y política, sino también importantes consecuencias psicosociales y de salud mental en el mundo. En este trabajo, se analizaron diferentes documentaciones y estudios sobre salud mental, con el objetivo de recuperar las diversas problemáticas detectadas durante la pandemia. Metodológicamente se realizó una revisión narrativa e integrativa de la literatura científica. En América Latina los estudios más recientes comienzan a visualizar diferentes afectaciones sobre las diversas poblaciones vulneralizadas: migrantes, mujeres, niños, los ancianos, personas quienes viven con una discapacidad significativa, personas en situación de calle, trabajadores informales, etc. Frente a este panorama, se plantea que el abordaje de estas cuestiones deberá contar con la coordinación de políticas trasnacionales y la definición de una agenda de prioridades críticas a focalizar y atender. Para esto resulta importante que la evidencia empírica generada por los estudios epidemiológicos regionales contribuya al diseño de las políticas públicas sobre salud mental de la población latinoamericana, de modo que las mismas logren reducir los efectos negativos como también puedan prevenir las consecuencias futuras de una pandemia que todavía no ha finalizado.A pandemia da COVID-19 no mundo tem impactado a área da saúde, os setores da economia e da política e também tem gerado consequências psicossociais, repercutindo de forma significativa no campo da saúde mental. Este estudo de revisão sistemática analisou diversos documentos e pesquisas abordando saúde mental e COVID-19, bem como problematicas geradas durante a pandemia. A metodologia de pesquisa envolveu revisão narrativa e integrativa da literatura científica. Na América Latina, os estudos mais recentes apresentam os inúmeros efeitos da COVID-19 em populações vulneráveis: imigrantes, mulheres, crianças, idosos, pessoas em situação de rua, trabalhadores informais, etc. Diante desse panorama, propõe-se que a abordagem dessas questões inclua a coordenação de políticas transnacionais e a definição de uma agenda de prioridades críticas a serem consideradas. Os resultados empíricos de estudos epidemiológicos realizados em âmbito regional contribuíram para o desenho de políticas públicas em saúde mental da população latino-americana com o objetivo de reduzir os efeitos negativos e prevenir riscos futuros de uma pandemia que ainda não terminou.Fil: Gallegos de San Vicente, Miguel Omar. Pontifícia Universidade Católica de Minas Gerais; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto Rosario de Investigaciones en Ciencias de la Educación. Universidad Nacional de Rosario. Instituto Rosario de Investigaciones en Ciencias de la Educación; ArgentinaFil: Consoli, Andrés J.. University of California; Estados UnidosFil: Ferrari, Ilka Franco. Pontifícia Universidade Católica de Minas Gerais; BrasilFil: Cervigni, Mauricio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto Rosario de Investigaciones en Ciencias de la Educación. Universidad Nacional de Rosario. Instituto Rosario de Investigaciones en Ciencias de la Educación; ArgentinaFil: de Castro Peçanha, Viviane. The Chicago School of Professional Psychology; Estados UnidosFil: Martino, Pablo Luis. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Caycho Rodríguez, Tomás. Universidad Privada del Norte; PerúFil: Razumovskiy, Anastasia. No especifíca

Gênese e gestão de um processo formativo ao empreendedorismo: desenvolvimento, avaliação e validação

Este artigo apresenta os primeiros passos de um projeto internacional financiado pelo Erasmus plus –Programa que trabalha com quatro países na realização de uma plataforma comum de desenvolvimento de competências empreendedoras. Aqui, nós relatamos as reflexões que estão conduzindo os idealizadores do projeto na construção de um processo não somente educacional mas também de avaliação e validação compartilhada por vários países para assegurar um processo de crescimento real, com normas comuns de formação e de avaliação. Por conseguinte, pretende-se trabalhar com um sumário das atuais orientações da Comunidade Europeia relativas à validação de competências, ao desenvolvimento de competências empreendedoras, ao mapeamento de competências empresariais na Europa e ao estabelecimento de programas de desenvolvimento dessas competências. Por fim, apresenta-se o projeto europeu House of Brain e as atividades que levaram os autores a questionar as ferramentas mais úteis para uma avaliação correta das competências para uma aprendizagem ao longo da vida

The natural history of primary sclerosing cholangitis in 781 children. A multicenter, international collaboration

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes

SCN5A Nonsense Mutation and NF1 Frameshift Mutation in a Family With Brugada Syndrome and Neurofibromatosis

In this case series, we report for the first time a family in which the inherited nonsense mutation [c. 3946C > T (p.Arg1316*)] in the SCN5A gene segregates in association with Brugada syndrome (BrS). Moreover, we also report, for the first time, the frameshift mutation [c.7686delG (p.Ile2563fsX40)] in the NF1 gene, as well as its association with type 1 neurofibromatosis (NF1), characterized by pigmentary lesions (café au lait spots, Lisch nodules, freckling) and cutaneous neurofibromas. Both of these mutations and associated phenotypes were discovered in the same family. This genetic association may identify a subset of patients at higher risk of sudden cardiac death who require the appropriate electrophysiological evaluation. This case series highlights the importance of genetic testing not only to molecularly confirm the pathology but also to identify asymptomatic family members who need clinical examinations and preventive interventions, as well as to advise about the possibility of avoiding recurrence risk with medically assisted reproduction

P3‐209: Impact of Biomarkers On Diagnostic Confidence in Clinical Assessment of Patients with Suspected Alzheimer's Disease and High Diagnostic Uncertainty: An EADC Study

Background: NIA-AA and IWG diagnostic criteria for Alzheimer's Disease (AD) include core structural, functional, and CSF biomarkers. The impact of core biomarkers in clinical settings is still unclear. This study aimed at measuring the impact of core biomarkers on the diagnostic confidence of uncertain AD cases in a routine memory clinic setting. // Methods: 356 patients with mild dementia (MMSE = 20) or Mild Cognitive Impairment possibly due to AD were recruited in 17 European Alzheimer's Disease Consortium (EADC) memory clinics. The following variables were collected: age; sex; MMSE; neuropsychological evaluation including long term memory, executive functions, language and visuospatial abilities. Core biomarkers were collected following local practices: Scheltens’s visual assessment of medial temporal atrophy (MTA) on MR scan; visual assessment of hypometabolism/hypoperfusion on FDG-PET/SPECT brain scan; CSF Aß1-42, tau and phospho-tau levels. At diagnostic workup completion, an estimate of confidence that cognitive complaints were due to AD was elicited from clinicians on a structured scale ranging from 0 to 100. Only cases with uncertain diagnoses (confidence between 15% and 85%) were retained for analysis. Generalized linear models were used to describe the relationship between the collected measures and the diagnostic confidence of AD. // Results: Neuropsychological assessment was carried out in almost all cases (98% of the cases). Medial temporal atrophy ratings were done in 40% of cases, assessment of cortical hypometabolism/hypoperfusion in 34%, and CSF Aß and tau levels in 26%. The markers that better explained the variability of diagnostic confidence were CSF Aß1-42 level (R2=0.46) and hypometabolism/hypoperfusion (R2=0.45), followed by CSF tau level (R2=0.35), MTA assessment (R2=0.32) and. All figures were highly significant, at p<<0.001. The diagnostic confidence variability due to neuropsychological tests for different domains was lower: MMSE (R2=0.29); long term memory (R2=0.23); executive functions (R2=0.05); language (R2=0.02); visuospatial abilities (R2=0.04) even if significant (p<0.01). // Conclusions: The use of core biomarkers in the clinical assessment of subjects with suspected AD and high diagnostic uncertainty is still limited. However, when assessed, these biomarkers show a higher impact on diagnostic confidence of AD than the most widespread clinical measures

Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort.

Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions