Serviços de atenção básica frente à pandemia de covid-19 / Basic care services in front of the covid-19 pandemic

Objetivo: analisar a literatura científica acerca do papel dos serviços de atenção básica frente à pandemia da COVID-19. Método: trata-se de uma revisão integrativa, realizada no período de outubro e novembro de 2020, a partir de fontes secundárias, selecionadas nas bases de dados da MEDLINE, LILACS, BVS, PUBMED e SciELO. Os dados obtidos foram organizados em quadro e fluxograma. Resultados: Dos treze artigos selecionados para este estudo, 100% dos artigos foram publicados em 2020, sendo 69% em periódicos internacionais e 31% em periódicos nacionais. Em relação à base de dados/ biblioteca virtual selecionada, 92% dos artigos podem ser encontrados na BVS, 42% na SciElo e 8% na PubMed. Conclusão: O papel dos serviços de atenção básica frente à pandemia do COVID-19 consiste em monitorar, notificar e fornecer dados sobre a doença. Devendo agir com rapidez na detecção dos sintomas e encaminhamento dos pacientes que ocasionalmente evoluem de uma infecção leve ou moderada para grave, para unidades hospitalares de referência.

Automated Analysis of Proliferating Cells Spatial Organisation Predicts Prognosis in Lung Neuroendocrine Neoplasms

SIMPLE SUMMARY: Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome, particularly for the intermediate domains of adenocarcinomas and large-cell neuroendocrine carcinomas. Moreover, subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. The aim of this study was to design and evaluate an objective and reproducible approach to the grading of lung NENs, potentially extendable to other NENs, by exploring a completely new perspective of interpreting the well-recognised proliferation marker Ki-67. We designed an automated pipeline to harvest quantitative information from the spatial distribution of Ki-67-positive cells, analysing its heterogeneity in the entire extent of tumour tissue—which currently represents the main weakness of Ki-67—and employed machine learning techniques to predict prognosis based on this information. Demonstrating the efficacy of the proposed framework would hint at a possible path for the future of grading and classification of NENs. ABSTRACT: Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome. Subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. Here, we propose a machine learning framework for tumour prognosis assessment based on a quantitative, automated and repeatable evaluation of the spatial distribution of cells immunohistochemically positive for the proliferation marker Ki-67, performed on the entire extent of high-resolution whole slide images. Combining features from the fields of graph theory, fractality analysis, stochastic geometry and information theory, we describe the topology of replicating cells and predict prognosis in a histology-independent way. We demonstrate how our approach outperforms the well-recognised prognostic role of Ki-67 Labelling Index on a multi-centre dataset comprising the most controversial lung NENs. Moreover, we show that our system identifies arrangement patterns in the cells positive for Ki-67 that appear independently of tumour subtyping. Strikingly, the subset of these features whose presence is also independent of the value of the Labelling Index and the density of Ki-67-positive cells prove to be especially relevant in discerning prognostic classes. These findings disclose a possible path for the future of grading and classification of NENs

Neuroendocrine neoplasms of the biliary tree, liver and pancreas: a pathological approach

Neuroendocrine neoplasms of the pancreatobiliary tract and liver are a heterogeneous group that encompass a spectrum of entities with distinct morphological, biological and clinical features. Although in the various anatomical sub-sites of this region they show specific characteristics, these tumors, as a whole, share several etiological and clinical aspects. This review systematically addresses NENs arising in the extrahepatic bile ducts, gallbladder, liver and pancreas, with the principal aim of pinpointing essential diagnostic and classification issues. In addition, the section on hepatic NENs has been expanded to include metastatic disease of unknown primary site

T-Cells Subsets in Castleman Disease: Analysis of 28 Cases Including Unicentric, Multicentric and HHV8-Related Clinical Forms

Castleman disease (CD) is a rare lymphoproliferative disorder that includes various clinico-pathological subtypes. According to clinical course, CD is divided into unicentric CD (UCD) and multicentric CD (MCD). MCD is further distinguished based on the etiological driver in herpes virus-8-related MCD (that can occur in the setting of HIV); in MCD associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes); and idiopathic MCD (iMCD). The latter can also be divided in iMCD-TAFRO (thrombocytopenia, anasarca, fever, myelofibrosis, organomegaly) and iMCD not otherwise specified. To date, CD pathogenesis is still uncertain, but CD may represent the histological and clinical result of heterogeneous pathomechanisms. Transcriptome investigations in CD lymph nodes have documented the expression and up-regulation of different cytokines; furthermore, few recent studies have shown alterations of different T-cell subsets in CD patients, suggesting a possible role of the nodal microenvironment in CD development. On this basis, our study aimed to investigate the distribution of T-cell subsets in the clinico-pathological spectrum of CD. We evaluated the CD4/CD8 ratio and the number of T-regulatory (T-reg) FOXP3+ cells in 28 CD cases. In total, 32% of cases showed a decreased CD4/CD8 ratio due to increased CD8+ T-cells, including both UCD, iMCD, and HHV8+ MCD cases. The T-reg subset analysis revealed a statistically significant (p < 0.0001) lower mean number of FOXP3+ T-reg cells in CD cases when compared with non-specific reactive lymph nodes. We did not find statistically significant differences in T-reg numbers between the different CD subtypes. These findings may suggest that alterations in T-cell subpopulations that can lead to disruption of immune system control may contribute to the numerous changes in different cellular compartments that characterize CD

Coexpression of \u394Np63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations

Introduction: Double occurrence of TTF1 and \u394Np63/p40 (henceforth, p40) within the same individual cells is exceedingly rare in lung cancer. Little is known on their biological and clinical implications. Methods: Two index cases immunoreactive for both p40 and TTF1 and nine tumors selected from The Cancer Genome Atlas (TCGA) according to the mRNA levels of the two relevant genes entered the study. Results: The two index cases were peripherally located, poorly differentiated, and behaviorally unfavorable carcinomas, which shared widespread p40 and TTF1 decoration within the same individual tumor cells. They also retained SMARCA2 and SMARCA4 expression, while variably stained for p53, cytokeratin 5, and programmed death-ligand 1. A subset of basal cells p40+/TTF1+ could be found in normal distal airways. Biphenotypic glandular and squamous differentiation was unveiled by electron microscopy, along with EGFR, RAD51B, CCND3, or NF1 mutations and IGF1R, MYC, CCND1, or CDK2 copy number variations on next-generation sequencing analysis. The nine tumors from TCGA (0.88% of 1018 tumors) shared the same poor prognosis, clinical presentation, and challenging histology and had activated pathways of enhanced angiogenesis and epithelial-mesenchymal transition. Mutation and copy number variation profiles did not differ from the other TCGA tumors. Conclusions: Double p40+/TTF1+ lung carcinomas are aggressive and likely underrecognized non-small cell carcinomas, whose origin could reside in double-positive distal airway stem-like basal cells through either de novo-basal-like or differentiating cell mechanisms according to a model of epithelial renewal

Precision Medicine and Public Health: New Challenges for Effective and Sustainable Health

The development of high-throughput omics technologies represents an unmissable opportunity for evidence-based prevention of adverse effects on human health. However, the applicability and access to multi-omics tests are limited. In Italy, this is due to the rapid increase of knowledge and the high levels of skill and economic investment initially necessary. The fields of human genetics and public health have highlighted the relevance of an implementation strategy at a national level in Italy, including integration in sanitary regulations and governance instruments. In this review, the emerging field of public health genomics is discussed, including the polygenic scores approach, epigenetic modulation, nutrigenomics, and microbiomes implications. Moreover, the Italian state of implementation is presented. The omics sciences have important implications for the prevention of both communicable and noncommunicable diseases, especially because they can be used to assess the health status during the whole course of life. An effective population health gain is possible if omics tools are implemented for each person after a preliminary assessment of effectiveness in the medium to long term

Measurement of the W±ZW^{\pm}Z boson pair-production cross section in pppp collisions at s=13\sqrt{s}=13 TeV with the ATLAS Detector

The production of $W^{\pm}Z$ events in proton--proton collisions at a centre-of-mass energy of 13 TeV is measured with the ATLAS detector at the LHC. The collected data correspond to an integrated luminosity of 3.2 fb$^{-1}$. The $W^{\pm}Z$ candidates are reconstructed using leptonic decays of the gauge bosons into electrons or muons. The measured inclusive cross section in the detector fiducial region for leptonic decay modes is $\sigma_{W^\pm Z \rightarrow \ell^{'} \nu \ell \ell}^{\textrm{fid.}} = 63.2 \pm 3.2$ (stat.) $\pm 2.6$ (sys.) $\pm 1.5$ (lumi.) fb. In comparison, the next-to-leading-order Standard Model prediction is $53.4^{+3.6}_{-2.8}$ fb. The extrapolation of the measurement from the fiducial to the total phase space yields $\sigma_{W^{\pm}Z}^{\textrm{tot.}} = 50.6 \pm 2.6$ (stat.) $\pm 2.0$ (sys.) $\pm 0.9$ (th.) $\pm 1.2$ (lumi.) pb, in agreement with a recent next-to-next-to-leading-order calculation of $48.2^{+1.1}_{-1.0}$ pb. The cross section as a function of jet multiplicity is also measured, together with the charge-dependent $W^+Z$ and $W^-Z$ cross sections and their ratio