Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Guidelines For The Diagnosis, Classification, Prophylaxis And Treatment Of Chronic Graft-versus-host Disease [diretrizes Para O Diagnóstico, Classificação, Profilaxia E Tratamento Da Doença Enxerto Contra Hospedeiro Crônica]

The lack of widely-used standardized diagnostic criteria may impair both the true evaluation of chronic graft-versus-host disease and the correlation of its severity with transplant-related mortality. At the I Consensus of the Brazilian Society of Bone Marrow Transplantation - SBTMO that took place in June 2009, the Group of GVHD Studies Brazil-Seattle (GEDECH), presented the guidelines for diagnosis, classification, prophylaxis and treatment of chronic GVHD as proposed by the National Institutes of Health and based on the reality in Brazilian Centers. These proposals, including standardization of features used in diagnosis and tools to score involved organs and to assess the overall severity, should be used in clinical studies of chronic graft-versus-host disease. These criteria are useful to better analyze the incidence of this disease, in addition to evaluate the extension of the involvement of organs or the site affected and its influence on late transplantation mortality. Prophylaxis and treatment proposed for this important complication of hematopoietic stem cell transplantations were discussed and graded according to the levels of evidence established by the National Institutes of Health.32SUPPL. 12239Shulman, H.M., Sullivan, K.M., Weiden, P.L., Chronic graft-versus-host syndrome in man. 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Diagnosis and staging working group report (2005) Biol Blood Marrow Transplant, 11 (12), pp. 945-956Martin, P.J., Weisdorf, D., Przepiorka, D., Hirschfeld, S., Farrell, A., Rizzo, J.D., Design of Clinical Trials Working Group National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. Design of Clinical Trials Working Group report (2006) Biol Blood Marrow Transplant, 12 (5), pp. 491-505Pavletic, S.Z., Martin, P., Lee, S.J., Mitchell, S., Jacobsohn, D., Cowen, E.W., Response criteria working group. 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(6), pp. 459-465Foss, F.M., Divenuti, G.M., Chin, K., Prospective study of extracorporeal photopheresis in steroid-refractory or steroid-resistant extensive chronic graft-versus-host disease: Analysis of response and survival incorporating prognostic factors (2005) Bone Marrow Transplant, 35 (12), pp. 1187-1193Carnevale-Schianca, F., Martin, P., Sullivan, K., Flowers, M., Gooley, T., Anasetti, C., Changing from cyclosporine to tacrolimus as salvage therapy for chronic graft-versus-host disease (2000) Biol Blood Marrow Transplant, 6 (6), pp. 613-620Tzakis, A.G., Abu-Elmagd, K., Fung, J.J., Bloom, E.J., Nour, B., Greif, F., FK 506 rescue in chronic graft-versus-host-disease after bone marrow transplantation (1991) Transplant Proc, 23 (6), pp. 3225-3227Couriel, D.R., Saliba, R., Escalon, M.P., Hsu, Y., Ghosh, S., Ippoliti, C., Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease (2005) Br J Haematol, 130 (3), pp. 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Desempenho de um motor de trator agrícola em bancada dinamométrica com biodiesel de óleo de frango e misturas binárias com óleo diesel Performance of an agricultural tractor engine in dynamometer with chicken oil biodiesel and binary mixtures with diesel oil

O Brasil, terceiro maior produtor de biodiesel do mundo e terceiro maior produtor mundial de frango, pode incrementar, na sua matriz energética, o uso de óleo oriundo de aves como alternativa aos combustíveis fósseis e à redução da dependência do óleo de soja para esse fim. O país dispõe de mais de 350 milhões de litros de óleo de frango por ano. Considerando a aplicação dos combustíveis alternativos para os motores a diesel, em máquinas agrícolas, o trabalho teve por objetivo avaliar o desempenho do motor de um trator agrícola de 53kW acoplado pela TDP em bancada dinamométrica, operando com biodiesel metílico de óleo de frango e misturas com óleo diesel, sendo: B5 (testemunha), B20, B40, B60, B80 e B100. Avaliaram-se a potência, o torque, a reserva de torque, o consumo de combustível, o consumo de energia e a eficiência térmica do motor. O ensaio foi instalado com delineamento inteiramente casualizado (DIC) em esquema fatorial com seis tratamentos. Os resultados foram submetidos à análise de variância e as médias ajustadas por equações de regressão. Foram observadas perdas na geração de potência e torque, aumento no consumo de combustível, redução do consumo energético e melhoria na eficiência térmica do motor, de acordo com o aumento da proporção de biodiesel na mistura.<br>Brazil, the world third largest producer of biodiesel, and also the third largest producer of chicken, may increase the energy matrix, using oil derived from chicken, as an alternative to fossil fuels and reduce dependence on soybean oil for this purpose. The country can produce over 350 million liters of chicken oil per year. Considering the application of alternative fuels on diesel engines in agricultural machinery. The study aimed to evaluate the performance of a engine agricultural tractor with 53kW coupled by PTO in dynamometer bench operating with methyl biodiesel oil chicken and mix with diesel oil. Fuels B5 (reference), B20, B40, B60, B80 and B100 mixtures were used. The power, torque, torque reserve, fuel consumption, energy consumption and thermal efficiency of the engine were evaluated. The trial was conducted with a completely random design (CRD) in a factorial design with six treatment, which was held after the analysis of variance and adjusted means for the regression equations. Losses were observed in the generation of power and torque, increase in fuel consumption, reduction of energy consumption and improvement in engine thermal efficiency, according to the increasing proportion of biodiesel in the blend