Human parvovirus B19 frequency among blood donors after an epidemic outbreak: relevance of the epidemiological scenario for transfusion medicine

A retrospective, cross-sectional study was conducted to determine the frequency of human parvovirus B19 (B19V) infected individuals, viral loads and immunity among blood donors from Argentina, in a post-epidemic outbreak period. B19V DNA and specific IgG were tested in minimum study samples of donors attending a blood bank at Córdoba, Argentina, in 2014. Anti-B19V IgM and viral loads were determined in B19V-positive plasma samples. Seven of 731 samples (0.96%) resulted positive, corresponding to individuals aged 32–53 years, four of them repeat donnors and three first-time donors. Viral loads were <103 IU/mL. None had IgM and 6/7 had IgG, one of them at a high level (in the range of 100–200 IU/ml, and the remaining 5 at low to medium level, 5–50 IU/ml). Thus one case was classified as acute infection (DNA+/IgM-/IgG-) and six as potentially persistent infections (DNA+/IgM-/IgG+). No coinfections with other pathogens of mandatory control in the pre-transfusion screening were detected. Prevalence of IgG was 77.9% (279/358). This study provides the first data of B19V prevalence in blood donors in Argentina, demonstrating high rates of acute and persistent B19V infections and high prevalence of anti-B19V IgG in a post-epidemic period. Further research is needed to elucidate mechanisms/factors for B19V persistence as well as follow-up of recipients in the context of haemo-surveillance programs, contributing to the knowledge of B19V and blood transfusion safety.Fil: Adamo, Maria Pilar. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Blanco, Sebastian. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Fundación Banco Central de Sangre de Córdoba; ArgentinaFil: Viale, Franco Agustín. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Rivadera, Sabrina Ximena. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Rodríguez Lombardi, Gonzalo Ramón. Universidad Nacional de Córdoba. Laboratorio de Hemoderivados; ArgentinaFil: Pedranti, Mauro. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Carrizo, Rubén Horacio. Fundación Banco Central de Sangre de Córdoba; ArgentinaFil: Gallego, Sandra Veronica. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Fundación Banco Central de Sangre de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX

Introduction: The prognostic significance of p53 protein expression in early breast cancer remains uncertain, with some but not all studies finding an association with poorer outcomes. Estrogen receptor (ER) expression is both a positive prognostic marker and predictive of response to endocrine therapies. The relationship between these biomarkers is unknown. Methods: We constructed tissue microarrays (TMAs) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer. Expression of p53 defined as >10% positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections. Results: ER was present (i.e. >1% positive tumor cell nuclei) in 80.1% (880/1092). p53 expression was significantly more frequent when ER was absent, 125/212 (59%) than when ER was present, 171/880 (19%), p <0.0001. A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival (DFS) and overall survival (OS) among patients whose tumors did not express ER, but worse DFS and OS among patients whose tumors expressed ER. The interaction remained significant after allowance for pathologic variables, and treatment. Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared. Conclusions: Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER. The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression. Trial registration Current Controlled Trials ACTRN12607000037404 (Trial VIII) and ACTRN12607000029493 (Trial IX)

Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period

Objectives: People with HIV (PWH) are at an increased risk of atherosclerotic cardiovascular disease. Suboptimal responses to statin therapy in PWH may result from antiretroviral therapies (ARTs). This open-label extension study aimed to evaluate the long-term safety and efficacy of evolocumab up to 52\u200aweeks in PWH. Design: This final analysis of a multinational, placebo-controlled, double-blind, randomized phase 3 trial evaluated the effect of monthly subcutaneous evolocumab 420\u200amg on low-density lipoprotein cholesterol (LDL-C) during the open-label period (OLP) following 24\u200aweeks of double-blind period in PWH with hypercholesterolemia/mixed dyslipidemia. All participants enrolled had elevated LDL-C or nonhigh-density lipoprotein cholesterol (non-HDL-C) and were on stable maximally tolerated statin and stable ART. Methods: Efficacy was assessed by percentage change from baseline in LDL-C, triglycerides, and atherogenic lipoproteins. Treatment-emergent adverse events (TEAEs) were examined. Results: Of the 467 participants randomized in the double-blind period, 451 (96.6%) received at least one dose of evolocumab during the OLP (mean age of 56.4\u200ayears, 82.5% male, mean duration with HIV of 17.4\u200ayears). By the end of the 52-week OLP, the overall mean (SD) percentage change in LDL-C from baseline was -57.8% (22.8%). Evolocumab also reduced triglycerides, atherogenic lipid parameters (non-HDL-C, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, and lipoprotein[a]), and increased HDL-C. TEAEs were similar between placebo and evolocumab during the OLP. Conclusion: Long-term administration of evolocumab lowered LDL-C and non-HDL-C, allowing more PWH to achieve recommended lipid goals with no serious adverse events. Trail registration: NCT02833844. Video abstract: http://links.lww.com/QAD/C441

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.Peer reviewe

El futuro después del COVID-19

El libro reúne ensayos de 27 autoras y autores en el contexto del inicio de la pandemia del Covid-19. Plantea diagnósticos, analiza dimensiones sociales, políticas y culturales. Y ofrece un panorama plural del debate en un momento de emergencia.Fil: Follari, Roberto Agustin. Universidad Nacional de Cuyo; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Canelo, Paula Vera. Universidad Nacional de San Martín. Instituto de Altos Estudios Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro de Innovación de los Trabajadores. Universidad Metropolitana para la Educación y el Trabajo. Centro de Innovación de los Trabajadores; ArgentinaFil: Sztulwark, Diego. Universidad de Buenos Aires; ArgentinaFil: Palermo, Vicente Antonio. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González, Horacio. Universidad de Buenos Aires; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Tokatlian, Juan Gabriel. Universidad de San Andrés; Argentina. Universidad Nacional de Colombia; Colombia. Universidad de los Andes; ColombiaFil: Forster, Ricardo. Universidad Nacional de Córdoba; ArgentinaFil: Fidanza, Eduardo. Academia Nacional de Periodismo; ArgentinaFil: Boron, Atilio Alberto. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Estudios de América Latina y el Caribe; Argentina. Universidad Nacional de Avellaneda; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: Segato, Rita Laura. Unesco; Argentina. Universidad de Brasilia; BrasilFil: Rebón, Julián. Universidad de Buenos Aires. Centro de Estudios Avanzados; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentina. Consejo Latinoamericano de Ciencias Sociales; ArgentinaFil: Svampa, Maristella Noemi. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Viale, Enrique. Asociación Argentina de Abogados Ambientalistas; ArgentinaFil: Carreiras, Helena. Instituto Universitario de Lisboa; Portugal. Instituto de Defensa Nacional de Portugal; PortugalFil: Malamud, Andrés. University of Maryland; Estados Unidos. Max-planck-institut Für Europäische Rechtsgeschichte.; AlemaniaFil: Sarlo Sabajanes, Beatriz Ercilia. Columbia University; Estados Unidos. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barrancos, Dora Beatriz. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto Interdisciplinario de Estudios de Género; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Waisbord, Silvio Ricardo. The George Washington University; Estados Unidos. University of Pennsylvania; Estados UnidosFil: Casullo, María Esperanza. Universidad Nacional de Río Negro; Argentina. University of Richmond; Estados Unidos. University Brown; Estados UnidosFil: Mignolo, Walter. University of Duke; Estados UnidosFil: Valdettaro, Sandra Catalina. Universidad Nacional de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Humanidades y Artes. Centro de Estudios Culturales Urbanos; ArgentinaFil: Alarcon, Cristian Francisco. Universidad Nacional de San Martín; ArgentinaFil: López, María Pia Luján. No especifíca;Fil: Moreno, María. No especifíca;Fil: Maffía, Diana. Universidad de Buenos Aires. Facultad de Filosofía y Letras; ArgentinaFil: Giunta, Andrea Graciela. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Teoría e Historia del Arte "Julio E. Payró"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabezón Cámara, Gabriela. University of California at Berkeley; Estados Unidos. Universidad Nacional de las Artes; ArgentinaFil: Grimson, Alejandro. Universidad Nacional de San Martín. Instituto de Altos Estudios Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

The tale of TILs in breast cancer : a report from the International Immuno-Oncology Biomarker Working Group

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed deathligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.The National Health and Medical Research Council of Australia; the Cure; the Royal Australasian College of Physicians; the NIH/NCI ; the National Breast Cancer Foundation of Australia Endowed Chair; the Breast Cancer Research Foundation, New York and the Breast Cancer Research Foundation (BCRF).www.nature.com/npjbcanceram2022Immunolog