Caminhos para o Diagnóstico Precoce: Biomarcadores Neurogenéticos na Doença de Alzheimer.

This paper proposes a literature review on neurogenetic biomarkers in Alzheimer's disease (AD), highlighting their fundamental role in early diagnosis and understanding of the disease's pathogenesis. The analysis covers the identification of specific genetic variants, such as those in the TOMM40 gene, and polymorphisms identified through genome-wide association studies (GWAS). Additionally, the differential expression of genes associated with AD in early stages offers a unique opportunity for more effective therapeutic interventions. Despite advances, challenges such as external validation and genetic variability are crucial. The neurogenetic approach represents progress in understanding the genetic heterogeneity in AD, providing a foundation for future research. The abstract highlights the promising implications of neurogenetic biomarkers and emphasizes the importance of ethical and social awareness.Este trabalho propõe uma revisão de literatura sobre biomarcadores neurogenéticos na doença de Alzheimer (DA), destacando seu papel fundamental no diagnóstico precoce e na compreensão da patogênese da doença. A análise abrange a identificação de variantes genéticas específicas, como aquelas no gene TOMM40, e polimorfismos identificados por meio de estudos de associação genômica ampla (GWAS). Além disso, a expressão diferencial de genes associados à DA em estágios iniciais oferece uma oportunidade única para intervenções terapêuticas mais eficazes. Apesar dos avanços, desafios como a validação externa e a variabilidade genética são cruciais. A abordagem neurogenética representa um avanço na compreensão da heterogeneidade genética na DA, fornecendo uma base para pesquisas futuras. O resumo destaca as implicações promissoras dos biomarcadores neurogenéticos e destaca a importância da conscientização ética e social

Abordagens para Prevenção Secundária do Tromboembolismo Pulmonar (TEP): Uma Revisão de Literatura

This literature review aims to investigate contemporary strategies for the secondary prevention of Pulmonary Embolism (PE). The research encompassed recent studies, focusing on anticoagulation, including novel oral anticoagulants, surgical interventions, and advanced diagnostic methods. Emphasizing the importance of personalized treatment considering individual factors, the review underscores the need for additional studies to validate conclusions and inform more robust clinical guidelines. This review contributes to an in-depth understanding of secondary prevention strategies for PE, highlighting the integrated and personalized approach as crucial for optimizing clinical outcomes and reducing PE recurrence.Esta revisão de literatura explora estratégias contemporâneas para a prevenção secundária do Tromboembolismo Pulmonar (TEP). A pesquisa abrangeu estudos recentes, enfocando anticoagulação, incluindo novos anticoagulantes orais, intervenções cirúrgicas, e métodos de diagnóstico avançados. Destaca-se a importância da personalização do tratamento, considerando fatores individuais, enquanto ressalta a necessidade de estudos adicionais para validar conclusões e informar diretrizes clínicas mais sólidas. Esta revisão contribui para uma compreensão aprofundada das estratégias de prevenção secundária do TEP, enfatizando a abordagem integrada e personalizada como crucial para otimizar desfechos clínicos e reduzir recorrências do TEP

Quantificação de lesões agudas e crônicas em ressonância nuclear magnética de sacroilíacas em pacientes com uveíte anterior aguda recorrente: uma prova de conceito

Introduction: Acute anterior uveitis is an inflammation of the middle layer of the eye and is related to human leukocyte antigen B27 (HLA-B27) and the concept of spondyloarthritis (SpA). Objectives: To assess the prevalence of definite SpA by combined T1W/STIR MRI (global MRI), to quantify acute and chronic lesions in SIJ using MRI in patients with rAAU with and without back symptoms, and to assess which MRI lesion-based criteria optimally reflect the global MRI designation of definite SpA. Methods: A total of 50 consecutive patients with rAAU without prior rheumatologic diagnosis were included in this cross-sectional study and were compared to 21 healthy volunteers. They were evaluated for the presence of inflammatory back pain and classified according to modified New York criteria (Nym), ASAS (Assessment on SpondyloArthritis International Society) for axial SpA (ax-SpA) and peripheral (p-SpA), as well as fibromyalgia. Patients underwent radiography (XR) and MRI of the SI according to ASAS recommendations. Both MRI and XR were evaluated independently by two rheumatologists, and the discrepant cases read by a radiologist. The identification and quantification of acute and chronic lesions were performed according to MORPHO/SPARCC (The Spondyloarthritis Research Consortium of Canada) group protocol. The following laboratory tests were also performed: antinuclear antibody (ANA), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C- reactive protein (CRP) and HLA-B27. Results: rAAU patients were classified as ax-SpA (Group 1, n=20) according to ASAS criteria (2009); non-specific back pain (Group 2, n=6) and asymptomatic (Group 3, n=24). The groups were similar regarding age, sex, ethnicity, age at onset of uveitis, current uveitis activity and duration of eye disease. HLA-B27 was positive in 48% of those with rAAU. Considering only group 3, nine (37.5%) patients had SIJ MRI and/or X-ray positive for axial SpA (5 MRI and x-ray, 1 MRI, 3 x-ray). MRI scans compatible with SpA in groups 1(n=12) and 3 (n=6) were similar regarding acute and chronic lesions analysed according to MORPHO. The best sensitivity/specificity criterion to define a positive global MRI assessment was bone marrow edema (BME) ? 3 (92%/94%). Conclusions: This is the first study evaluating SIJ MRI in patients with rAUU without back symptoms showing positive findings for sacroiliitis, confirming a uvea-axial spine link, and BME ? 3 as optimal for a positive MRI.Introdução: A uveíte anterior é a inflamação da camada intermediária do globo ocular e está relacionada ao human leukocyte antigen B27 (HLA-B27) e ao conceito das espondiloartrites (EpA). Objetivos: Avaliar a prevalência de lesões agudas e crônicas em articulações sacroilíacas (SI) em pacientes com uveíte anterior aguda recorrente (UAAr) e quantificá-las por meio da ressonância nuclear magnética (RNM). Adicionalmente, verificar a frequência de lombalgia inflamatória e do HLA-B27, bem como estabelecer qual o critério, baseado em combinações de lesões na RNM SI, apresenta o melhor desempenho para a definição de avaliação global de RNM positiva para EpA. Métodos: Nesse estudo transversal com grupo controle, foram incluídos 50 pacientes, de ambos os sexos e maiores de 18 anos de idade, que tivessem apresentado pelo menos dois episódios de UAA, sem diagnóstico prévio de qualquer doença reumatológica, sendo comparados a 21 controles saudáveis. Foram avaliados quanto à presença de lombalgia inflamatória, critérios classificatórios Nova Iorque modificado (NYm), ASAS (Assessment on SpondyloArthritis International Society) para EpA axial (EpA-ax) e periférica (EpA-p), bem como para fibromialgia. Os pacientes realizaram radiografia (Rx) e RNM das SI, conforme recomendações do ASAS. Tanto as imagens de RNM quanto as radiografias foram avaliadas por dois reumatologistas de modo independente, segundo protocolo MORPHO do grupo SPARCC (The Spondyloarthritis Research Consortium of Canada), sendo os casos discrepantes lidos por um radiologista. Foram realizados, ainda, os seguintes exames laboratoriais: fator antinúcleo (FAN), fator reumatóide (FR), velocidade de hemossedimentação (VHS), proteina C reativa (PCR) e HLA-B27. Resultados: Os pacientes com UAAr foram classificados em EpA-ax (Grupo 1, n=20), lombalgia mecânica inespecífica (Grupo 2, n= 6) e assintomáticos (Grupo 3, n=24). Os grupos eram similares quanto à idade, sexo, cor da pele, idade de início, tempo de doença e atividade da uveíte. O HLA-B27 foi positivo em 48% daqueles com UAAr. Considerando apenas o grupo 3, nove (37,5%) pacientes apresentavam RNM e/ou Rx de SI compatível com EpA (5 RNM e RX, 1 RNM, 3 Rx). O critério com melhor sensibilidade e especificidade para definir avaliação global da RNM positiva foi edema da medula óssea (EMO) ? 3 (92%/94%). Conclusão: Esse é o primeiro estudo que avaliou os achados da RNM de SI em pacientes com UAAr e assintomáticos do ponto de vista axial e periférico, demonstrando sacroiliíte ativa, uma prova de conceito da ligação entre o envolvimento uveal e axial. Além disso, aponta EMO ? 3 como ideal para definição global de RNM positiva.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016

Pelvic, global postural and sagittal balance parameters and bone neoformation in spine of ankylosing spondylitis patients.

Objetivos: Comparar os parâmetros pélvicos (Incidência pélvica – IP, versão pélvica – VP e inclinação sacral – IS) de pacientes com espondilite anquilosante (EA) com diferentes intensidades de neoformação óssea na coluna vertebral (CV) e correlacioná-la com parâmetros de equilíbrio sagital e postura global. Além disso, desenvolver um escore global ASPeCTS (Axial SPondyloarthritis Computerized Tomography Score) para avaliar a neoformação óssea da CV total. Métodos: Um total de 117 pacientes com EA foram incluídos nesse estudo transversal. Realizaram a tomografia computadorizada de baixa dose de radiação (TC-bd) para quantificação da neoformação óssea da CV, bem como o EOS para obtenção do eixo vertical sagital – EVS, ângulo espinossacral – AES, dos parâmetros pélvicos e das medidas das curvaturas cervical, torácica e lombar. A categorização da intensidade da neoformação óssea foi usada para classificar os pacientes em três grupos principais: 1- Até 24,9%, 2- 25 a 50,9% e 3- 51% ou mais, independente da topografia de cada compartimento e segmento da CV total. Resultados: As médias de idade e tempo de doença foram 50,9±11,1 e 21,1±9,68 anos, respectivamente. A maior parte dos pacientes estavam nos grupos 1 (n=55, 47%) e 3 (n=46, 39,3%). Não houve correlação significativa entre os valores de IP e a intensidade da neoformação óssea. Em contrapartida, houve correlação entre a magnitude da neoformação óssea total, independentemente da topografia anterior ou posterior, com a VP (r=0,507 a 0,541; p<0,001) e com o incremento da cifose torácica (r=0,607 a 0,625; p<0,001), perda de lordose lombar (r=-0,536 a -0,577; p<0,001) e aumento do EVS (r=0,547 a 0,570, p<0,001), bem como redução do AES (r=-0,421 a -0,687; p<0,001). Observou-se, ainda, diferença significativa entre as médias de ganho de cifose torácica entre os grupos 1, 2 e 3 (11,0±12,76°; 22,13±14,15° e 35,12±15,15°, respectivamente) enquanto a diferença entre as médias de perda de lordose lombar foi significativa apenas entre os grupos 1 e 2 quando comparados ao grupo 3 (-1,09±9,83°, -4,94±17,12°, -18,48±15,31°, respectivamente). Em análise multivariada, verificou-se que o aumento de um grau na IS acarreta o aumento médio de 2,39mm no EVS, enquanto o aumento de um grau na VP acarreta uma redução média de 0,86 mm no EVS. Já o aumento de um grau de cifose T1-T12 e de lordose L1-S1, além do que seria a esperada pela IP, acarreta um aumento médio de 0,92 mm e a uma redução média de 2,79mm de EVS, respectivamente. Conclusões: Esse é o primeiro estudo a detalhar os parâmetros pélvicos, de postural global e equilíbrio sagital em pacientes com EA por meio do EOS, evidenciando correlação entre o incremento da neoformação óssea e o desequilíbrio sagital. Foi observado ganho de cifose torácica em grupo de intensidade intermediária de neoformação, mesmo antes de perda significativa de lordose lombar, quando comparado ao grupo com maior intensidade de neoformação óssea. O escore ASPeCTS é o primeiro a avaliar globalmente a neoformação óssea da CV total de pacientes EA, com excelente reprodutibilidade entre os leitores e em todos os segmentos e compartimentos da CV.Objectives: To compare the pelvic parameters (Pelvic Incidence – PI, Pelvic Tilt – PT and Sacral Slope – SS) of patients with ankylosing spondylitis (AS) classified according to the intensity of structural damage in spine and to correlate it with the sagittal balance and global posture parameters. To develop the ASPeCTS score (Axial SPondyloarthritis Computerized Tomography Score), which assesses total spine structural damage, including the anterior and posterior compartments. Methods: A total of 117 AS patients were included in this cross-sectional study. All of them underwent low-radiation-dose computed tomography (ld-CT) to assess structural damage of the anterior and posterior segments of the total spine, as well as EOS imaging to obtain measurements of sagittal vertical axis (SVA), spino-sacral angle, pelvic parameters and spinal curvatures. Patients were categorized into three main groups according to the intensity of structural damage quantified using ASPeCTS methodology: 1- up to 24.9%, 2- 25 to 50.9% and 3- 51% or more. Results: Mean age and disease duration were 50.9±11.1 years-old and 21.1±9.68 years, respectively. Most patients were in groups 1 (n=55, 47%) and 3 (n=46, 39.3%). There was no significant correlation between PI values and the intensity of structural damage. On the other hand, there was a correlation between the magnitude of total structural damage, regardless of anterior or posterior topography, with PT (r=0.507 to 0.541; p<0.001) and with the increase in thoracic kyphosis (r=0.607 to 0.625; p< 0.001), loss of lumbar lordosis (r=-0.536 to -0.577; p<0.001) and increase in SVA (r=0.547 to 0.570, p<0.001), as well as reduction of spino-sacral angle (r=-0.421 to -0.687; p<0.001). There was also a significant difference between the means of increment in thoracic kyphosis between groups 1, 2 and 3 (11.0±12.76°; 22.13±14.15° and 35.12±15.15°, respectively) while the difference between the means of loss of lumbar lordosis was significant only between groups 1 and 2 when compared to group 3 (-1.09±9.83°, -4.94±17.12°, -18.48±15.31°, respectively). In a multivariate analysis, it was found that the increase of one degree in the SS leads to an average increase of 2.39mm in SVA, while the increase of one degree in the PT causes an average reduction of 0.86mm in SVA. On the other hand, increasing one degree of T1-T12 kyphosis and L1-S1 lordosis, in relation to the values expected for the patient from his PI, leads to an average increase of 0.92mm and an average reduction of 2.79mm of SVA, respectively. Conclusions: This is the first study to detail the pelvic, global posture and sagittal balance parameters in patients with AS using EOS, showing a correlation between the intensity of structural damage and sagittal imbalance. An increment in thoracic kyphosis without a significant loss of lumbar lordosis was observed in the group with an intermediate intensity when compared to the group with the highest intensity of structural damage. The ASPeCTS score is the first one to globally assess total spine structural damage in AS patients, with excellent reproducibility among readers and in all spinal segments and compartments

Extra-musculoskeletal manifestations driving the therapeutic decision-making in patients with Spondyloarthritis: a 12-month follow-up prospective cohort study

Abstract Background The extra-musculoskeletal manifestations (EMMs) such as recurrent acute anterior uveitis (rAAU), psoriasis (Ps), and inflammatory bowel disease (IBD), are related to the Spondyloarthritis (SpA), as well as they are associated with disease activity and poor prognosis. However, there are no data addressing its relevance regarding therapeutic decision-making in clinical practice. Objective To evaluate the impact of EMMs to drive the treatment decision-making in patients with SpA in a 12-month follow-up. Patients and methods SpA patients, according to the axial and peripheral ASAS classification criteria, as well as CASPAR criteria, with any active EMM, defined as main entry criteria, were included in this longitudinal cohort study. Individuals with a history of any disease or condition that could be associated with some of the studied endpoints, including neoplasms and infectious diseases, were excluded. Specific tools related to each EMM, including Psoriasis Area Severity Index (PASI), ophthalmologic evaluation, according to the Standardization of Uveitis Nomenclature (SUN) criteria, and gut complaints were used at baseline and during the 3-, 6- and 12-month of follow-up as outcomes measures over time. Descriptive and inferential analyses were used appropriately, including Pearson’s correlation test, chi-squared test, and ANOVA. P value less than 0.05 was considered as significant. Results A total of 560 patients were enrolled, of whom 472 meet the eligibility criteria. The majority (N = 274; 59.6%) had one or more EMM related to SpA umbrella concept. Among the EMM, the one that most influenced therapeutic decision-making was psoriasis (28.5%), followed by uveitis (17.5%) and IBD (5.5%), regardless of musculoskeletal manifestations. Clinical improvement of EMMs outcomes was observed in most patients over 12-month follow-up, especially in those with rAAU and IBD (P < 0.001). Conclusion Our results showed that EMMs guided the therapeutic decision-making in half of SpA patients, regardless of musculoskeletal condition, suggesting the inter-disciplinarity among the rheumatologist, ophthalmologist, dermatologist, and gastroenterologist plays a crucial role to manage them

To be or not to B27 positive: implications for the phenotypes of axial spondyloarthritis outcomes. Data from a large multiracial cohort from the Brazilian Registry of Spondyloarthritis

Abstract Background There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). Methods The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. Results A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. Conclusions Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population