Impact of statin therapy on mortality and recurrence in female breast cancer: a meta-analysis

BACKGROUND Breast cancer (BC) incidence is estimated to achieve over 3 million new cases and 1 million deaths by 2040. Beyond its physical toll, breast cancer detrimentally affects quality of life, imposing emotional, social, and financial burdens on patients and their families. Statins, commonly prescribed for managing cardiovascular health, have garnered attention for their potential role in breast cancer management. Emerging evidence suggests that statins possess anti-proliferative properties, which could impact breast cancer progression. Understanding the potential benefits of statin therapy in breast cancer patients is crucial for optimizing treatment strategies and improving outcomes. METHODS: WE conducted a comprehensive search of medical databases including PubMed, Cochrane, and Scopus to identify pertinent studies focusing on the impact of Statin therapy in female breast cancer patients. We collected data on All-Cause Mortality, Recurrence Free Survival, Disease-Specific Mortality, and Disease-Free Survival. All statistical analyses were performed using the R statistical software (version 4.3.2). RESULTS: A total of 37 studies and 869.218 patients were included, of whom 136.809 (15,73%) was in the statins group and 745.080 (84%) was in the non-statin users. The majority of the individuals were male 2,278 (84,27%). Statin therapy was associated with a significantly reduced risk of all-cause mortality (HR 0.8635; 95% CI 0.8123­0.8179; P < 0.01; I2 = 93%), disease-specific mortality (HR 0.8462; 95% CI 0.7632­0.9382; P < 0.01; I2 = 97%), and recurrence (HR 0.7638; 95% CI 0.6652­0.8771; P = 0.01; I2 = 51%). Furthermore, statin use was associated with improved disease-free survival (HR 0.8415; 95% CI 0.4220­1.6780; P < 0.01; I2 = 74%). CONCLUSIONS: Our meta-analysis suggests that statin therapy may confer beneficial effects on clinical outcomes in female breast cancer patients, including reduced all-cause mortality, disease-specific mortality, recurrence, and improved disease-free survival. However, further research is warranted to confirm these findings and elucidate the mechanisms underlying these associations.

Floristic diversity and edaphic filters in an urban forest under Cerrado domain, in Cuiabá, Central Western Brazil.

We aimed to characterize the adult and regenerating tree components and their relationships with soil characteristics of a native vegetation remnant in Cuiabá, Mato Grosso, Brazil. The area of the fragment is stratified into "dry area" (lithic neosoil) and "damp area" (gleisoil). We conducted a forest inventory with a random distribution of 25 parcels. We analyzed the physical and chemical components of the soil. We evaluated the vegetation's horizontal structure, diversity, and sample sufficiency using the Bootstrap richness estimator. We classified the species according to dispersal syndrome and ecological group. Overall, we found 93 species in the adult layer and 70 species in the regenerating layer. The similarity dendrograms based on the two evaluated indices demonstrated the existence of the two initially stratified environments in both strata. The IndVal (%) indicated that the set of indicator species differed between the strata. Thereby, the fragment is in an intermediate stage of successional progression. PCA showed that plots in the wet area had higher pH values and Ca, Zn, and Fe levels, while plots in the dry area did not clearly distinguish, varying in terms of K, B, and organic matter content. In CCA, a set of species that occurred exclusively in the damp area showed a strong relationship with the analyzed variables. The area is a diverse ecosystem that efficiently provides ecosystem services to society and should be the subject of long-term conservation and research.

The allelopathic effects of aqueous Talinum triangulare (jacq.) willd extracts on the development of Lactuca sativa L. seedlings.

Plants that produce allelopathic compounds against weeds have emerged as a potential solution for the development of ecologically correct bioherbicides. Talinum triangulare is noteworthy in this regard, as its phytochemical composition encompasses flavonoids, alkaloids and other metabolites that can be used to develop inhibitory weed growth solutions. Lactuca sativa (lettuce) has been widely applied as a bioindicator species for bioherbicides and several chemicals, animal waste, water and soil quality, and atmospheric contamination, among others. In this context, this study aimed to assess the potential allelopathic effect of aqueous T. triangulare extracts on the development of L. sativa seedlings. A completely randomized design employing a 2x4 factorial scheme (shoot and root extracts) x the concentration of each extract (0, 2.5, 5, 7.5%) was applied, comprising four replications. Lactuca sativa seeds were sown on germitest papers soaked with the extracts in a germination chamber at 20°C. Physiological seed evaluations comprising the germination test, where normal and abnormal seedlings are counted on the seventh day after sowing, first normal seedling counts on the fourth day after sowing, and seedling and root length measurements. At the end of the germination test, L. sativa seedlings were separated for morphoanatomical characterizations and chlorophyll a fluorescence analyses. The T. triangulare extracts significantly influenced L. sativa root growth, with shoot extract exposure leading to more abnormal plants and lower root lengths at increasing concentrations and compared to the root extract. Root extract exposure led to evident cellular changes and lower non-photochemical quenching and unregulated dissipation quantum yields at a 5% exposure dose compared to shoot extract exposure. These findings suggest that both aqueous T. triangulare root and shoot extracts from 5% exposure doses exhibit high potential as bioherbicides, acting directly on plant structure, anatomy, quality, size and physiology.

Metabolic Syndrome and Positive Frailty Screening: A Cross-Sectional Study with Community-Dwelling Older Adults.

Background: Metabolic Syndrome is a set of disorders that characterized by the association of three or more risk factors, like the obesity central, dyslipidemia, borderline blood pressure, hyperglycemia, and the increase of triglycerides. However, these factors also can be associated with pathophysiology of frailty. Objectives: verifying whether the metabolic syndrome is associated to the positive frailty screening in the older people. Design: Cross-sectional study. Participants: 443 older people living in Rio Branco, Brazil. Setting: Data collection was carried out in two stages: a personal interview and blood collection. Measurements: The diagnosis of metabolic syndrome was based on the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. The frailty screening was performed using subjective questions validated in a previous study. Descriptive statistics and multinomial logistic regression were used for data analyses. Results: There was a predominance of female older people (69.07%), aged between 60 and 79 years (87.13%), with an income greater than or equal to one minimum wage (72.09%), no cognitive decline (75.94%) and depressive symptoms (63.31%), independent for BADL (86.46%) and dependent for IADL (51.69%). From the total sample, 56.88% of the older people were identified as frail, 34.09% pre-frail and 9.03% non frail. The prevalence of metabolic syndrome was 51.69%. After adjusting by the independent variables, an association between metabolic syndrome and pre-frailty was observed, and older people with metabolic syndrome were more likely to be prefrail (RRR=2.36; 95%CI=1.08-5.18). Conclusion: The metabolic syndrome was associated to the increase chance of screening for prefrailty in the older people evaluated, which reinforces the needy to establish preventive measures in relation to the metabolic syndrome to avoid frailty in the older people.

Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

Quality of life of women from a quilombola community in northeastern Brazil / Qualidade de vida de mulheres de uma comunidade quilombola do nordeste brasileiro

Abstract Quilombola communities are present in many Brazilian states living in precarious health conditions. This is due to geographic isolation, limitations to the access of the area in which they live in, and the lack of quality in the service when it is needed to be provided. Therefore, the aim of this study was to analyze the quality of life of women from a quilombola community in northeastern Brazil. It is an observational, cross-sectional and descriptive study. 160 adult women were first interviewed through a form to collect a profile and then it was applied the WHOQOL Quality of Life questionnaire - bref. It was observed that the women were on average 40.7 years old (±17.25), married, self-declared black, who did not finish elementary school, housewife, had no income, with their own masonry house, with up to 6 rooms, supplied by a box of community treated water. Quality of Life had median scores in the domains: physical (3.18), psychological (3.4), social relationships (3.45) and environment (2.59). With this research, it was possible to characterize the quilombola community of Santa Luzia do Norte-AL regarding the difficulties of access to health and income generation, issues that affect their health condition. The problems described in this study can contribute to health actions being planned and carried out in order to improve socioeconomic and health conditions in this community, considering the social, political and environmental context, valuing their traditional knowledge and practices.

Resumo As comunidades quilombolas, estão presentes em diversos estados brasileiros, vivendo em condições de saúde mais precárias. Isto ocorre por conta do isolamento geográfico, das limitações de acesso e da falta de qualidade no serviço quando este é prestado. Nesse sentido, o objetivo do estudo foi analisar a qualidade de vida de mulheres de uma comunidade quilombola do nordeste brasileiro. Estudo observacional, transversal e descritivo. Foram entrevistadas 160 mulheres adultas, através de um formulário para a coleta de perfil e do questionário de Qualidade de Vida WHOQOL - bref. Foi observado que as mulheres tinham em média 40,7 anos (±17,25), casadas, autodeclaradas negras, com fundamental incompleto, do lar, sem renda, com moradia de alvenaria, própria, com até 6 cômodos, abastecidas por caixa de água comunitária, tratada. A Qualidade de Vida, apresentou escores medianos nos domínios: físico (3,18), psicológico (3,4), relações sociais (3,45) e meio ambiente (2,59). Com a realização desta pesquisa foi possível caracterizar a comunidade quilombola de Santa Luzia do Norte-AL quanto as dificuldades de acesso a saúde e geração de renda, fatos que repercutem na sua condição de saúde. Os problemas descritos neste estudo podem contribuir para que ações de saúde sejam planejadas e efetivadas com o intuito de melhorar as condições socioeconômicas e de saúde nessa comunidade, considerando-se o contexto social, político e ambiental, valorizando seus saberes e práticas tradicionais.

Quality of life of women from a quilombola community in northeastern Brazil

Abstract Quilombola communities are present in many Brazilian states living in precarious health conditions. This is due to geographic isolation, limitations to the access of the area in which they live in, and the lack of quality in the service when it is needed to be provided. Therefore, the aim of this study was to analyze the quality of life of women from a quilombola community in northeastern Brazil. It is an observational, cross-sectional and descriptive study. 160 adult women were first interviewed through a form to collect a profile and then it was applied the WHOQOL Quality of Life questionnaire bref. It was observed that the women were on average 40.7 years old (±17.25), married, self-declared black, who did not finish elementary school, housewife, had no income, with their own masonry house, with up to 6 rooms, supplied by a box of community treated water. Quality of Life had median scores in the domains: physical (3.18), psychological (3.4), social relationships (3.45) and environment (2.59). With this research, it was possible to characterize the quilombola community of Santa Luzia do Norte-AL regarding the difficulties of access to health and income generation, issues that affect their health condition. The problems described in this study can contribute to health actions being planned and carried out in order to improve socioeconomic and health conditions in this community, considering the social, political and environmental context, valuing their traditional knowledge and practices.

Resumo As comunidades quilombolas, estão presentes em diversos estados brasileiros, vivendo em condições de saúde mais precárias. Isto ocorre por conta do isolamento geográfico, das limitações de acesso e da falta de qualidade no serviço quando este é prestado. Nesse sentido, o objetivo do estudo foi analisar a qualidade de vida de mulheres de uma comunidade quilombola do nordeste brasileiro. Estudo observacional, transversal e descritivo. Foram entrevistadas 160 mulheres adultas, através de um formulário para a coleta de perfil e do questionário de Qualidade de Vida WHOQOL bref. Foi observado que as mulheres tinham em média 40,7 anos (±17,25), casadas, autodeclaradas negras, com fundamental incompleto, do lar, sem renda, com moradia de alvenaria, própria, com até 6 cômodos, abastecidas por caixa de água comunitária, tratada. A Qualidade de Vida, apresentou escores medianos nos domínios: físico (3,18), psicológico (3,4), relações sociais (3,45) e meio ambiente (2,59). Com a realização desta pesquisa foi possível caracterizar a comunidade quilombola de Santa Luzia do Norte-AL quanto as dificuldades de acesso a saúde e geração de renda, fatos que repercutem na sua condição de saúde. Os problemas descritos neste estudo podem contribuir para que ações de saúde sejam planejadas e efetivadas com o intuito de melhorar as condições socioeconômicas e de saúde nessa comunidade, considerando-se o contexto social, político e ambiental, valorizando seus saberes e práticas tradicionais.

Remissão de úlcera de Martorell a partir de intervenção multidimensional de medicina do estilo de vida em portador de hipertensão refratária / Martorell ulcer remission following multidimensional lifestyle medicine intervention in patients with refractory hypertension

INTRODUÇÃO E/OU FUNDAMENTO: Em 1945 Martorell descreveu uma série de casos de úlceras supramaleolares dolorosas secundárias a arteriolosclerose subcutânea em hipertensos mal controlados. Estas úlceras hipertensivas (UH) acometem predominantemente a região laterodorsal do tornozelo, na ausência de doença arterial oclusiva periférica (DAOP), insuficiência venosa crônica ou outras vasculites. Afetam mais comumente mulheres entre 50 e 60 anos, são intensamente dolorosas e estão associadas a hipertensão arterial (HA) mal controlada. MÉTODOS: Relatamos o caso de um paciente de sexo masculino, 56 anos, negro, portador de obesidade grau 2 (peso 115 kg; IMC 37), acompanhado por HA primária refratária, que evoluiu com úlcera maleolar laterodorsal direita crônica e intensamente dolorosa. Apesar da prescrição de 7 classes de anti-hipertensivos (olmesartana, clortalidona, anlodipino, espironolactona, atenolol, hidralazina e clonidina), retornou com Monitorização Residencial da Pressão Arterial (MRPA) fora da meta (média: 146/88mmHg). Na ausência de diabetes, DAOP, insuficiência venosa e outras formas de vasculites, a úlcera foi caracterizada como hipertensiva. O paciente foi então submetido a intervenção comportamental multidimensional como parte de protocolo institucional de medicina do estilo de vida (MEV). O protocolo incluiu telemonitoramento da pressão arterial e da tomada da medicação, além da orientação alimentar e da promoção de atividade física e equilíbrio emocional assistidos via aplicativo gratuito. RESULTADOS: Após duas semanas, obteve-se controle da pressão arterial. Após 6 meses, o paciente apresentou perda de peso de 10 quilos e redução progressiva dos anti-hipertensivos (suspensas hidralazina e clonidina). Cursou com cicatrização completa da UH. Retornou às atividades físicas, manteve adesão ao tratamento e não apresentou recidiva da UH até o momento. CONCLUSÕES: A UH de Martorell é uma condição infrequente e não universalmente reconhecida como entidade clínica independente, não sendo mencionada nos principais textos de referência em HA. No entanto, as características clínicas e histopatológicas dos casos reportados na literatura parecem justificar o diagnóstico, que mais frequentemente é definido por dermatologistas e cirurgiões vasculares. O controle da HA é considerado fundamental para a remissão da úlcera, mas enfrenta o desafio da adesão do paciente ao tratamento. Este é o primeiro relato na literatura a reportar remissão da UH mediante intervenções não farmacológicas fundamentadas na MEV. Independentemente da etiologia, a MEV tem o potencial de atingir a causa primária e de ser benéfica para praticamente todas as formas de úlceras de membros inferiores. Intervenções de MEV deveriam integrar sistematicamente a abordagem terapêutica destes pacientes.

Questionário H-5: um instrumento para o rastreio de crenças limitantes no paciente com hipertensão arterial / H-5 Questionnaire: an instrument for screening limiting beliefs in patients with arterial hypertension

INTRODUÇÃO E/OU FUNDAMENTO: Menos da metade dos pacientes com hipertensão arterial (HA) atinge sua meta terapêutica. A falta de adesão é apontada como a principal causa de resistência ao tratamento. Entre os motivos pelos quais os pacientes não aderem ao plano terapêutico, a falta de letramento em saúde, os mitos e as crenças limitantes (CLs) desempenham papel determinante. Reconhecer e reverter prontamente tais crenças pode ser decisivo para promover a adesão do paciente e o controle pressórico, mas faltam instrumentos que permitam esse rastreio de forma sistemática na prática clínica. MÉTODOS: Elaboramos um Questionário de cinco perguntas (H-5) a partir de análise exploratória das CLs mais frequentemente observadas em ambulatório de referência no tratamento da HA. Cada pergunta do H-5 explora um conjunto de CLs relativas a uma dimensão específica do tratamento anti-hipertensivo. O questionário foi aplicado a 30 pacientes com diagnóstico de HA resistente consecutivamente atendidos em ambulatório público de referência. As perguntas do H-5 são: 1. O que sentimos quando nossa pressão está alta?; 2. Qual o melhor momento para medir a pressão?; 3. Quando podemos parar de tomar o remédio da pressão?; 4. Porque a pressão alta é um problema?; 5. Qual dessas afirmações é verdadeira sobre o estilo de vida? O formato de avaliação foi por respostas fechadas de múltipla escolha, sendo oferecidas 4 opções por pergunta. RESULTADOS: O H-5 foi aplicado na sala de espera antes da consulta, com tempo médio de execução de 6 minutos. A idade média dos pacientes foi 63,9 ± 9,2 anos (sexo feminino: 83%: IMC: 33,1 ± 6,1). N de anti-hipertensivos: 3,9 ± 1,6; PAS media de consultório: 137 ± 17,4 mmHg); escolaridade: 80% apenas ensino fundamental. A Nota Média foi de 3 acertos em 5 (0= 5%; 2= 20%; 3= 50%; 4= 15%; 5=20%) A taxa de acertos por pergunta (P) foi respectivamente: P1= 20%; P2= 20%; P3= 95%; P4= 80%; P5=85%. Apenas 1 a cada 5 pacientes com HA resistente demonstrou saber que a HA é uma condição assintomática ou que a pressão arterial deve ser medida em condições controladas. CONCLUSÕES: A aplicação do Questionário H-5 foi simples e de rápida execução. 80% dos pacientes apresentou algum grau de crenças limitantes em relação ao tratamento da HA.

A jornada ideal do paciente com hiperaldosteronismo primário: proposta de algoritmo a partir da revisão sistemática das diretrizes vigentes / The ideal journey of patients with primary hyperaldosteronism: algorithm proposal based on a systematic review of current guidelines

INTRODUÇÃO E/OU FUNDAMENTO: O Hiperaldosteronismo Primário (HP) é a principal causa de hipertensão arterial (HA) endócrina e estima-se que até 20% dos hipertensos resistentes possa ser portador da condição. Indivíduos com HP apresentam um risco cardiovascular (CV) de 4 a 12 vezes mais elevado que portadores de HA primária. Apesar disso, o HP continua largamente subdiagnosticado, em parte pela falta de padronização de triagem, diagnóstico e tratamento. MÉTODOS: A partir de processo de revisão sistemática das diretrizes nacionais e internacionais de HA e HP, elaboramos um algoritmo ilustrando a Jornada Ideal do Paciente com HP. A busca foi realizada em idioma português e inglês na base MEDLINE/PubMed. Selecionamos as publicações dos últimos 5 anos. O processo foi conduzido simultaneamente por dois pesquisadores e os resultados confrontados. RESULTADOS: Um total de 3.476 artigos foram triados para HA e 1.238 para HP. Após revisão e confrontação foram incluídas 22 diretrizes de HA e 9 diretrizes de HP. A partir da análise dos documentos selecionados a Jornada Ideal do Paciente com HP foi segmentada em 7 etapas: 1-Suspeita (definidas as Red Flags); 2-Rastreio (Concentração Plasmática de Aldosterona e Renina ou Atividade da Renina Plasmática); 3-Diagnóstico Laboratorial (critérios e testes confirmatórios); 4-Diagnóstico Anatômico (exames de imagem); 5-Tratamento Cirúrgico (critérios de encaminhamento); 6-Tratamento Clínico (metas terapêuticas e ajuste posológico); 7-Seguimento (critérios e prazos de reavaliação periódica). Com o intuito de acelerar a jornada do paciente, para cada etapa foram definidos gatilhos e ações esperadas, assim como prazos ideais e prazos razoáveis. CONCLUSÕES: Com base nas melhores evidências atualmente disponíveis e a partir de revisão sistemática das diretrizes vigentes, apresentamos uma proposta de Jornada Ideal do Paciente com HP, como modelo para a implantação de serviços especializados para o rastreio, o diagnóstico, o tratamento e o follow-up do HA.

Role of cyclooxygenases 1 and 2 in the maintenance of colonic mucosal integrity in an experimental colitis model.

The role of cyclooxygenase (COXs) isoforms in maintaining colonic mucosal integrity is not fully understood. This study aimed to evaluate the role of COX-1 and -2 on colonic mucosal integrity in an experimental colitis model. Colitis was induced in Wistar rats by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (20 mg + 50% ethanol). The control group (sham group) received saline only. After 7, 14, or 28 days, colonic samples were removed, and macroscopic lesion scores, wet weight, myeloperoxidase activity, and transepithelial electrical resistance (TER) were determined. In other rat groups, colonic samples from the sham group and a 7th day post-colitis group were mounted in Üssing chambers with the luminal side exposed to a buffer solution (control), acetylsalicylic acid (ASA), SC-560 (COX-1 inhibitor), or celecoxib (COX-2 inhibitor). TER and epithelial permeability to fluorescein were measured. The 7th day colitis group had higher macroscopic damage scores, wet weight, and myeloperoxidase activity and lower basal TER than the sham, 14th day colitis, and 28th day colitis groups. Inhibition of COX-1 but not COX-2 significantly decreased TER and increased permeability to fluorescein in the 7th day post-colitis group compared to the sham group. Additionally, ASA decreased the colonic mucosal integrity on day seven post-colitis compared to the sham group. A decrease in the colonic mucosa integrity in the experimental colitis model can be aggravated only by the inhibition of COX-1, which demonstrated the importance of this enzyme in the maintenance of colonic mucosal integrity.

Opiliofauna (ARACHNIDA: OPILIONES) of the Atlantic Forest in the state of Paraná, Brazil.

Opiliones are arachnids that provide different services in terrestrial ecosystems, especially in tropical forests, which justifies inventory studies to better understand the occurrence and distribution of these arthropods in Brazil, since little is known about the harvestmen fauna in Conservation Units such as in the state of Paraná. In this context, the objective of the present study was to survey the harvestmen fauna at the Iguaçu National Park (PARNA) and in the Bela Vista Biological Refuge (BVBR), from September 2021 to May 2022, using a sampling effort of 40 hours in the BVBR, and 66 hours at the PARNA Iguaçu. Ten species/morphospecies were recorded, highlighting a new occurrence for Brazil, the species Opisthoplatus vegetus. The present study reduces the information gap about Opiliones in the state, which reaffirms the importance of Conservation Units for the protection of the biota in the state of Paraná.

A semi-automated microscopic image analysis method for scoring Ki-67 nuclear immunostaining.

Nuclear proliferation marker MIB-1 (Ki-67) immunohistochemistry (IHC) is used to examine tumor cell proliferation. However, the diagnostic or prognostic value of the Ki-67 nuclear staining intensity and location, defined as nuclear gradient (NG), has not been assessed. This study examined the potential association between Ki-67 NG and cell cycle phases and its effect on the prognosis of pulmonary typical carcinoid (PTC) tumors. We propose a method for classifying the NG of Ki-67 during the cell cycle and compare the results between PTC, pulmonary adenocarcinoma (PAD), and breast ductal carcinoma (BDC). A literature review and objective analysis of IHC-stained paraffin sections were used to determine the Ki-67 labeling index and composed a stratification of the NG into NG1, NG2, and NG3/4 categories. A semi-automated image analysis protocol was established to determine the Ki-67 NG in PTC, PAD, and BDC. High intraobserver consistency and moderate interobserver agreement were achieved in the determination of Ki-67 NG in tumor specimens. NG1 and NG2 were lower in PTC than in PAD and BDC. Cox multivariate analysis of PTC after adjusting for age and number of metastatic lymph nodes showed that Ki-67 NG1 and NG2 significantly predicted clinical outcomes. The semi-automated method for quantification of Ki-67 nuclear immunostaining proposed in this study could become a valuable diagnostic and prognostic tool in PTC.

HLA-B27 did not protect against COVID-19 in patients with axial spondyloarthritis - data from the ReumaCov-Brasil Registry.

BACKGROUND: Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. AIM: To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. METHODS: The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. RESULTS: From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. CONCLUSIONS: No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. TRIAL REGISTRATION: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Cardiovascular mortality in Brazil during the COVID-19 pandemic: a comparison between underlying and multiple causes of death.

OBJECTIVES: The COVID-19 pandemic has differentially impacted cardiovascular disease (CVD) mortality worldwide. Causes of death misclassification may be one of the reasons. We evaluated the impact of the pandemic on CVD mortality in Brazil, comparing underlying causes (UCs) and multiple causes (MCs) of death. STUDY DESIGN: Ecological time-series study. METHODS: An ecological, time-series study was conducted analysing age-standardised death rates for CVD, from epidemiological week (EW) 10/2020 to 39/2021, using data from the Mortality Information System, Brazil. CVD was defined using the International Classification of Diseases (ICD-10) coding, if reported as UC or MC of death. Observed and expected data (mean for the same EW, 2017-2019) were compared. Risk ratios (RiRs) were analysed, and 95% confidence intervals (CIs) were calculated. RESULTS: Age-standardised mortality rate for CVD as UC of death was 165.8 (95%CI: 165.4-166.3) per 100,000 inhabitants, similar to what was expected (165.6/100,000, 95%CI: 165.2-166.1, RiR = 1.00). There was increased out-of-hospital mortality (RiR = 1.18; 95%CI: 1.17-1.19) and deaths of ill-defined causes (RiR = 1.43; 95%CI: 1.42-1.44). The increase in out-of-hospital deaths was more pronounced in the North (RiR = 1.33; 95%CI 1.30-1.36) region, with a less resilient health system. Conversely, as MCs of death, there was a 10% increase in CVD mortality (observed: 243.2 [95%CI: 242.7-243.7], expected: 221.6 [95%CI: 221.1-222.1] per 100,000). An increase also occurred in the North and Central West regions (RiR = 1.16; 95%CI: 1.15-1.18), among men (RiR = 1.11; 95%CI: 1.11-1.12) and individuals aged ≥60 years (RiR = 1.11; 95%CI: 1.10-1.11). CONCLUSIONS: During the pandemic, mortality rates for CVD as MCs of death increased in Brazil, whereas as UC mortality rates did not change. Higher out-of-hospital mortality, misclassification, and competing causes of death may explain this pattern.

Invasive dynamic electrical impedance myography during 100 s of moderate contraction in rats' gastrocnemius muscle.

GOAL: The present study aimed to investigate the behavior of dynamic electrical impedance myography (dEIM) signals during a 100-s period of the dynamic contraction of Wistar rats' gastrocnemius evoked by electrical stimulation and to link the variations in bioimpedance with muscular energy systems. METHODS: Muscle contraction used 30% of the maximum muscular force and persisted for 100 s, along which dynamic bioimpedance signals were acquired. Based on the bioimpedance signals, two parameters, ΔZc and ΔZpc, were calculated to allow the analysis of their changes with the energy systems that supplied adenosine triphosphate (ATP) to the muscle. ΔZc indicated the variation of impedance of a twitch cycle compared to the values observed during the rest period preceding the cycle, and ΔZpc indicated slow bioimpedance variations compared to the values obtained during the rest period. RESULTS: The results indicated that ΔZc followed the force behavior, achieving a change rate of ∼14%. This parameter was associated with instantaneous impedance changes owing to the occurrence of each twitch. CONCLUSION: Although the findings of this study were linked to energy system processes, future studies are required for improving the understanding of the underlying mechanisms involved in dEIM. SIGNIFICANCE: The results contributed to understanding the relation of energy systems that supply ATP to the muscles with dEIM variations that occurred during muscle activity.

A more radical perspective on surgical approach and outcomes in pancreatic cancer-a narrative review.

Background and Objective: Pancreatic adenocarcinoma remains a dismal disease and is expected to become an even greater burden in the near future. This review focuses on the different surgical aspects for pancreaticoduodenectomy (PD), distal and total pancreatectomy (TP), incorporating lessons from both the western and eastern visions in treating pancreatic cancer. Methods: We conducted an extensive literature review through PubMed, prioritizing papers published in the last 5 years, but older emblematic papers were also included. We included articles that explored the treatment of pancreatic adenocarcinoma, with focus on the surgical aspect and strategies to improve outcomes. References of selected articles were also reviewed to identify any missed studies. Only papers in English were included. Key Content and Findings: As evidence continues to build, it is clear that both systemic and surgical therapies have a fundamental and complementary role. State of art surgical treatment encompasses complete mesopancreas excision for radical lymphadenectomy. Preoperative planning of dissection planes, extensive knowledge of vascular anatomic variations, oncological principles and expertise for vascular resections are mandatory to perform a more radical operation, in pursuit of improved outcomes. Conclusions: Based on current data, patient selection remains key and a more radical surgical approach brings more accomplishing results bringing as to believe that more is better.