Lipid fingerprint-based histology accurately classifies nevus, primary melanoma, and metastatic melanoma samples

Probably, the most important factor for the survival of a melanoma patient is early detection and precise diagnosis. Although in most cases these tasks are readily carried out by pathologists and dermatologists, there are still difficult cases in which no consensus among experts is achieved. To deal with such cases, new methodologies are required. Following this motivation, we explore here the use of lipid imaging mass spectrometry as a complementary tool for the aid in the diagnosis. Thus, 53 samples (15 nevus, 24 primary melanomas, and 14 metastasis) were explored with the aid of a mass spectrometer, using negative polarity. The rich lipid fingerprint obtained from the samples allowed us to set up an artificial intelligence-based classification model that achieved 100% of specificity and precision both in training and validation data sets. A deeper analysis of the image data shows that the technique reports important information on the tumor microenvironment that may give invaluable insights in the prognosis of the lesion, with the correct interpretation.This project was supported by grants from the Basque Government (KK2017-041 and KK2020-00069 to JAF, BO and MDB and grant IT1491-22 to JAF), the UPV/EHU (GIU17/066 to MDB) and by MINECO (RTC-2015-3693-1)

TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization

While 30%-70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial. Here, we evaluated the interaction between TLR4 and environmental factors in RSV disease and defined the immune mediators associated with severe illness. Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS. RSV-infected infants with severe disease exhibited a high GATA3/T-bet ratio, which manifested as a high IL-4/IFN-γ ratio in respiratory secretions. The IL-4/IFN-γ ratio present in infants with severe RSV is indicative of Th2 polarization. Murine models of RSV infection confirmed that LPS exposure, Tlr4 genotype, and Th2 polarization influence disease phenotypes. Together, the results of this study identify environmental and genetic factors that influence RSV pathogenesis and reveal that a high IL-4/IFN-γ ratio is associated with severe disease. Moreover, these molecules should be explored as potential targets for therapeutic intervention.Fil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Serra, M. Elina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Acosta, Patricio Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Marzec, Jacqui. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Gibbons, Luz. Institute For Clinical Effectiveness And Health Policy, Ciudad Autonoma de Buenos Aires; ArgentinaFil: Salim, Maximiliano. Hospital Evita Pueblo; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rodriguez, Andrea. Hospital Mi Pueblo; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Reynaldi, Andrea. Unidad Asistencial "Dr. César Milstein"; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Garcia, Alejandro. Fundación para la Investigación en Infectología Infantil; Argentina. Unidad Asistencial "Dr. César Milstein"; ArgentinaFil: Bado, Daniela. Unidad Asistencial "Dr. César Milstein"; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Buchholz, Ursula J.. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Hijano, Diego Raúl. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados UnidosFil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Newcomb, Dawn. Vanderbilt University; Estados UnidosFil: Bellabarba, Miguel. Unidad Asistencial "Dr. César Milstein"; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Ferolla, Fausto Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Vanderbilt University; Estados UnidosFil: Berenstein, Ada. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Siniawaski, Susana. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Blumetti, Valeria. Swiss Medical Center; ArgentinaFil: Echavarría, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Pinto, Leonardo. Fundación para la Investigación en Infectología Infantil; Argentina. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Lawrence, Andrea. Vanderbilt University; Estados UnidosFil: Ossorio, Maria Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Grosman, Arnoldo. Hospital Espanol; ArgentinaFil: Mateu, Cecilia Gabriela. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bayle, Carola. Hospital Nacional Professor Dr. Alejandro Posadas; ArgentinaFil: Dericco, Alejandra. Hospital Nacional Professor Dr. Alejandro Posadas; ArgentinaFil: Pellegrini, Mariana. Hospital Nacional Professor Dr. Alejandro Posadas; ArgentinaFil: Igarza, Ignacio. Hospital Nacional Professor Dr. Alejandro Posadas; ArgentinaFil: Repetto, Horacio A.. Hospital Nacional Professor Dr. Alejandro Posadas; ArgentinaFil: Grimaldi, Luciano Alva. Hospital Zonal General de Agudos Lucio Meléndez; ArgentinaFil: Gudapati, Prathyusha. Vanderbilt University; Estados UnidosFil: Polack, Norberto R.. Unidad Asistencial "Dr. César Milstein"; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Shi, Min. National Institute of Environmental Health Sciences ; Estados UnidosFil: Ferrero, Fernando Claudio. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Bergel, Eduardo. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Stein, Renato T.. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Peebles, R. Stokes. Vanderbilt University; Estados UnidosFil: Boothby, Mark. Vanderbilt University; Estados UnidosFil: Kleeberger, Steven R.. National Institute Of Environmental Health Sciences; Estados UnidosFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unido

Risk factors and rate of recurrence after Mohs surgery in basal cell and squamous cell carcinomas: a nationwide prospective cohort (REGESMOHS, Spanish Registry of Mohs Surgery)

Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of long follow-up periods. This study presents the "real-life" results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1-1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3-6.1), being constant over time (0-5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries