XPERT® breast cancer STRAT4 as an alternative method of identifying breast cancer phenotype in Cape Verde (preliminary results)

INTRODUCTION: Breast cancer (BC) is a public health problem in developing countries, including Cape Verde. Immunohistochemistry (IHC) is the gold standard technique used for BC phenotypic characterisation to support efficient therapeutic decisions. However, IHC is a demanding technique that requires knowledge, trained technicians, expensive antibodies and reagents, controls, and results validation. The low number of cases in Cape Verde increases the risk of expiring the validity of the antibodies, and manual procedures often jeopardise the quality of the results. Thus, IHC is limited in Cape Verde, and an alternative technically easy solution is needed. A point-of-care messenger RNA (mRNA) STRAT4 BC assay to assess estrogen (ER), progesterone (PR), hormone growth factor 2 receptor (HER2), and Ki67, using the GeneXpert platform, has been recently validated on tissues from internationally accredited laboratories, showing excellent concordance with IHC results.To assess whether this technology can be implemented in Cape Verde to guide BC treatment we decided to study the level of agreement between the findings yielded by BC STRAT4 and the results are the same cases obtained by IHC. METHODS: Formalin-fixed and paraffin-embedded (FFPE) tissue samples from 29 Cabo Verdean BC patients diagnosed in Agostinho Neto University Hospital were analysed by applying IHC and BC STRAT4 assay. The time between sample collection and pre-analytic procedures is unknown. All the samples were pre-processed in Cabo Verde (fixed in formalin and embedded in paraffin). IHC studies were performed in referenced laboratories in Portugal. STRAT4 and IHC result concordance was assessed by calculating the percentage of results agreement and Cohen's Kappa (K) statistics. RESULTS: STRAT4 assay failed in 2 out of the 29 analysed samples. Of the 27 successfully analysed samples, STRAT4/IHC results for ER, PR, HER2, and Ki67 were concordant in 25, 24, 25, and 18 cases, respectively. Ki67 was indeterminate in three cases, and PR was indeterminate once.The percentage of agreement between STRAT4 and IHC results for ER, PR, HER2, and Ki67 was 92.59%, 92.31%, 92.59% and 81.82%, respectively. The Cohen's K statistic coefficients for each biomarker were 0.809, 0.845, 0.757 and 0.506, respectively. CONCLUSIONS: According to our preliminary results, a point-of-care mRNA STRAT4 BC assay may be an alternative in laboratories unable to provide quality and/or cost-efficient IHC services. However, more data and improvement on sample pre-analytic processes are required to implement this BC STRAT4 Assay in Cape Verde

Covid-19 Dynamic Monitoring and Real-Time Spatio-Temporal Forecasting

Background: Periodically, humanity is often faced with new and emerging viruses that can be a significant global threat. It has already been over a century post—the Spanish Flu pandemic, and we are witnessing a new type of coronavirus, the SARS-CoV-2, which is responsible for Covid-19. It emerged from the city of Wuhan (China) in December 2019, and within a few months, the virus propagated itself globally now resulting more than 50 million cases with over 1 million deaths. The high infection rates coupled with dynamic population movement demands for tools, especially within a Brazilian context, that will support health managers to develop policies for controlling and combating the new virus. / Methods: In this work, we propose a tool for real-time spatio-temporal analysis using a machine learning approach. The COVID-SGIS system brings together routinely collected health data on Covid-19 distributed across public health systems in Brazil, as well as taking to under consideration the geographic and time-dependent features of Covid-19 so as to make spatio-temporal predictions. The data are sub-divided by federative unit and municipality. In our case study, we made spatio-temporal predictions of the distribution of cases and deaths in Brazil and in each federative unit. Four regression methods were investigated: linear regression, support vector machines (polynomial kernels and RBF), multilayer perceptrons, and random forests. We use the percentage RMSE and the correlation coefficient as quality metrics. / Results: For qualitative evaluation, we made spatio-temporal predictions for the period from 25 to 27 May 2020. Considering qualitatively and quantitatively the case of the State of Pernambuco and Brazil as a whole, linear regression presented the best prediction results (thematic maps with good data distribution, correlation coefficient >0.99 and RMSE (%) <4% for Pernambuco and around 5% for Brazil) with low training time: [0.00; 0.04 ms], CI 95%. / Conclusion: Spatio-temporal analysis provided a broader assessment of those in the regions where the accumulated confirmed cases of Covid-19 were concentrated. It was possible to differentiate in the thematic maps the regions with the highest concentration of cases from the regions with low concentration and regions in the transition range. This approach is fundamental to support health managers and epidemiologists to elaborate policies and plans to control the Covid-19 pandemics

COVID-SGIS: A Smart Tool for Dynamic Monitoring and Temporal Forecasting of Covid-19

Background: The global burden of the new coronavirus SARS-CoV-2 is increasing at an unprecedented rate. The current spread of Covid-19 in Brazil is problematic causing a huge public health burden to its population and national health-care service. To evaluate strategies for alleviating such problems, it is necessary to forecast the number of cases and deaths in order to aid the stakeholders in the process of making decisions against the disease. We propose a novel system for real-time forecast of the cumulative cases of Covid-19 in Brazil. / Methods: We developed the novel COVID-SGIS application for the real-time surveillance, forecast and spatial visualization of Covid-19 for Brazil. This system captures routinely reported Covid-19 information from 27 federative units from the Brazil.io database. It utilizes all Covid-19 confirmed case data that have been notified through the National Notification System, from March to May 2020. Time series ARIMA models were integrated for the forecast of cumulative number of Covid-19 cases and deaths. These include 6-days forecasts as graphical outputs for each federative unit in Brazil, separately, with its corresponding 95% CI for statistical significance. In addition, a worst and best scenarios are presented. / Results: The following federative units (out of 27) were flagged by our ARIMA models showing statistically significant increasing temporal patterns of Covid-19 cases during the specified day-to-day period: Bahia, Maranhão, Piauí, Rio Grande do Norte, Amapá, Rondônia, where their day-to-day forecasts were within the 95% CI limits. Equally, the same findings were observed for Espírito Santo, Minas Gerais, Paraná, and Santa Catarina. The overall percentage error between the forecasted values and the actual values varied between 2.56 and 6.50%. For the days when the forecasts fell outside the forecast interval, the percentage errors in relation to the worst case scenario were below 5%. / Conclusion: The proposed method for dynamic forecasting may be used to guide social policies and plan direct interventions in a cost-effective, concise, and robust manner. This novel tools can play an important role for guiding the course of action against the Covid-19 pandemic for Brazil and country neighbors in South America

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML

Fanconi anemia manifesting as a squamous cell carcinoma of the hard palate: a case report

Fanconi Anemia is a rare autosomal recessive disorder characterized by various congenital malformations, progressive bone marrow failure at a very young age and of solid tumors development. The authors present a rare case of a squamous cell carcinoma of the hard palate in a Fanconi Anaemia patient. The atypical clinical manifestation rendered the diagnosis more difficult. This case, for age of appearance, sex and localization, is unique in international literature. We recommend a quarterly follow up of the oral-rhino-pharynx complex in FA patients and to consider as carcinomas, all oral lesions that last more than two weeks