Disminución de mortalidad en hemopatías malignas con un nuevo método de acondicionamiento para trasplante alogénico mieloablativo

ResumenIntroducciónEl trasplante alogénico de células progenitoras hematopoyéticas (TACPH) es el tratamiento de elección para diversas hemopatías malignas. Sin embargo, la morbimortalidad asociada al procedimiento limita su uso.ObjetivosDescribir la supervivencia de pacientes adultos mexicanos sometidos a un TACPH utilizando BUCY 2 reducido.MétodosEstudio de cohorte retrospectivo de octubre de 1999 a diciembre del 2014. Se evaluaron las características clínicas, la mortalidad asociada a trasplante, la supervivencia libre de enfermedad y la supervivencia global (SG) de 35 pacientes sometidos a TACPH con este nuevo método de acondicionamiento.ResultadosSe incluyó a 35 pacientes sometidos a TACPH, de donador relacionado HLA idéntico, acondicionados con BUCY 2 reducido, con una mediana de edad de 33 años (rango 16-49). El 60% de los pacientes fueron hombres. El diagnóstico más frecuente fue: síndrome mielodisplásico 14 pacientes (40%), leucemia mieloide crónica 9 pacientes (25.7%), leucemias agudas 10 pacientes (23.5%) y hemoglobinuria paroxística 2 pacientes (5.7%). La mediana de células CD34+transfundidas fue de 2.04×106/kg. La mediana de recuperación de neutrófilos y plaquetas fue de 21 y 18 días, respectivamente. La toxicidad más frecuente fue mucositis (91.4%). La mortalidad relacionada al trasplante fue del 5.7% y la SG a 5 años fue del 72.5%.ConclusionesEl método de acondicionamiento BUCY2 reducido conserva un efecto citotóxico que permite erradicar la clona maligna y lograr el injerto con mínima morbimortalidad, representando una mejor alternativa para el TACPH.AbstractIntroductionAllogeneic stem cell transplantation (ASCT) is the ideal treatment for haematological malignancies. However, the morbidity and mortality associated with the procedure limit its use.ObjectivesTo describe clinical characteristics, toxicity, and survival of adult Mexican patients undergoing ASCT using busulfan with a reduced dose of cyclophosphamide (BUCY 2) as a conditioning method.MethodsA prospective cohort study was conducted from October 1999 to December 2014, by performing an analysis of clinical characteristics, complications, and survival of 35 patients using this conditioning regimen.ResultsThe study included 35 patients undergoing ASCT with reduced BUCY 2. All of them had an HLA-matched related donor, with a median age of 33 years (range 16-49), and 60% were male. The patients had the following underlying diseases: myelodysplastic syndrome in 14 patients (40%), chronic myeloid leukaemia in 9 (25.7%), acute leukaemia in 10 (23.5%), and paroxysmal nocturnal haemoglobinuria in 2 (5.7%). The median of transfused CD34+cells was 2.04×106/kg. The median time to neutrophil and platelet recovery was 21 and 18 days, respectively. The most common toxicity was mucositis (91.4%). Transplant related mortality was 5.7%, and 5-year overall survival was 72.5%.ConclusionsThe conditioning method described earlier preserves a cytotoxic effect allowing eradication of the malignant clone, and achieving a graft with acceptable toxicity, and low transplant related mortality, representing a good alternative for ASCT

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Ejercicio de Prospectiva para Contaduría Pública en Colombia en el contexto de la transformación productiva del país en el horizonte al 2025.

Los rasgos indiscutibles del entorno mundial son la incertidumbre, la constante trasformación, la abrumadora cantidad y velocidad de los cambios generados por la globalización, la internalización y las nuevas tecnologías de la información y la comunicación que dificultan, y a su vez generan un reto, en la formación de los profesionales por parte de las instituciones de educación (Kingler, 2007)

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857). Copyright © 2022 Llera, Abdelhay, Artagaveytia, Daneri-Navarro, Müller, Velazquez, Alcoba, Alonso, Alves da Quinta, Binato, Bravo, Camejo, Carraro, Castro, Castro-Cervantes, Cataldi, Cayota, Cerda, Colombo, Crocamo, Del Toro-Arreola, Delgadillo-Cisterna, Delgado, Dreyer-Breitenbach, Fejerman, Fernández, Fernández, Fernández, Franco-Topete, Gabay, Gaete, Garibay-Escobar, Gómez, Greif, Gross, Guerrero, Henderson, Lopez-Muñoz, Lopez-Vazquez, Maldonado, Morán-Mendoza, Nagai, Oceguera-Villanueva, Ortiz-Martínez, Quintero, Quintero-Ramos, Reis, Retamales, Rivera-Claisse, Rocha, Rodríguez, Rosales, Salas-González, Sanchotena, Segovia, Sendoya, Silva-García, Trinchero, Valenzuela, Vedham, Zagame, United States-Latin American Cancer Research Network (US-LACRN) and Podhajcer.Fil: Llera, Andrea Sabina. Fundación Instituto Leloir-CONICET. Molecular and Cellular Therapy Laboratory; ArgentinaFil: Abdelhay, Eliana Saul Furquim Werneck. Instituto Nacional de Câncer. Bone Marrow Transplantation Unit; BrasilFil: Artagaveytia, Nora. Universidad de la República. Hospital de Clínicas Manuel Quintela; UruguayFil: Daneri-Navarro, Adrián. Universidad de Guadalajara; MéxicoFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: Velazquez, Carlos. Universidad de Sonora; MéxicoFil: Alcoba, Elsa B. Hospital Municipal de Oncología María Curie; ArgentinaFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; UruguayFil: Alves da Quinta, Daniela B. Fundación Instituto Leloir-CONICET. Molecular and Cellular Therapy Laboratory; ArgentinaFil: Alves da Quinta, Daniela B. Universidad Argentina de la Empresa (UADE). Instituto de Tecnología (INTEC); ArgentinaFil: Binato, Renata. Instituto Nacional de Câncer. Bone Marrow Transplantation Unit; BrasilFil: Bravo, Alicia Inés. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Camejo, Natalia. Universidad de la República. Hospital de Clínicas Manuel Quintela; UruguayFil: Carraro, Dirce Maria. AC Camargo Cancer Center. Centro Internacional de Pesquisa (CIPE). Laboratory of Genomics and Molecular Biology; BrasilFil: Castro, Mónica. Instituto de Oncología Angel Roffo; ArgentinaFil: Castro-Cervantes, Juan M. Hospital de Especialidades CMNO-IMSS; MéxicoFil: Cataldi, Sandra. Instituto Nacional del Cáncer; UruguayFil: Cayota, Alfonso. Institut Pasteur de Montevideo; UruguayFil: Cerda, Mauricio. Universidad de Chile. Instituto de Neurociencias Biomédicas. Facultad de Medicina. Centro de Informática Médica y Telemedicina. Instituto de Ciencias Biomédicas (ICBM). Integrative Biology Program; ChileFil: Colombo, Alicia. Universidad de Chile. Facultad de Medicina y Hospital Clínico. Department of Pathology; ChileFil: Crocamo, Susanne. Instituto Nacional de Câncer. Oncology Department; BrasilFil: Del Toro-Arreola, Alicia. Universidad de Guadalajara; MéxicoFil: Delgadillo-Cisterna, Raúl. Hospital de Especialidades CMNO-IMSS; MéxicoFil: Delgado, Lucía. Universidad de la República. Hospital de Clínicas Manuel Quintela; UruguayFil: Dreyer-Breitenbach, Marisa. Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcantara Gomes; BrasilFil: Fejerman, Laura. University of California Davis. Department of Public Health Sciences and Comprehensive Cancer Center; Estados UnidosFil: Fernández, Elmer A. Universidad Católica de Córdoba. CONICET. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas [Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE); ArgentinaFil: Fernández, Elmer A. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Fernández, Wanda. Hospital San Borja Arriarán; ChileFil: Franco-Topete, Ramón A. Universidad de Guadalajara. Hospital Civil de Guadalajara. Organismo Público Descentralizado (OPD); MéxicoFil: Gabay, Carolina. Instituto de Oncología Angel Roffo; ArgentinaFil: Gaete, Fancy. Hospital Luis Tisne; ChileFil: Garibay-Escobar, Adriana. Universidad de Sonora; MéxicoFil: Gómez, Jorge. Texas A&M University; Estados UnidosFil: Greif, Gonzalo. Institut Pasteur de Montevideo; UruguayFil: Gross, Thomas G. Center for Global Health, National Cancer Institute; Estados UnidosFil: Guerrero, Marisol. Hospital San José; ChileFil: Henderson, Marianne K. Center for Global Health, National Cancer Institute; Estados UnidosFil: Lopez-Muñoz, Miguel E. Universidad de Sonora; MéxicoFil: Lopez-Vazquez, Alejandra. Universidad de Sonora; MéxicoFil: Maldonado, Silvina. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Morán-Mendoza, Andrés J. Hospital de Gineco-Obstetricia CMNO-IMSS; MéxicoFil: Nagai, Maria Aparecida. Sao Paulo University Medical School. Cancer Institute of São Paulo (ICESP). Center for Translational Research in Oncology; BrasilFil: Oceguera-Villanueva, Antonio. Instituto Jalisciense de Cancerologia; MéxicoFil: Ortiz-Martínez, Miguel A. Hospital General Regional No. 1. IMSS; MéxicoFil: Quintero, Jael. Universidad de Sonora; MéxicoFil: Quintero-Ramos, Antonio. Universidad de Guadalajara; MéxicoFil: Reis, Rui M. Hospital de Câncer de Barretos. Molecular Oncology Research Center; BrasilFil: Retamales, Javier. Grupo Oncológico Cooperativo Chileno de Investigación; ChileFil: Rivera-Claisse, Ernesto. Centro Estatal de Oncologia; MéxicoFil: Rocha, Darío. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Rodríguez, Robinson. Hospital Central de las Fuerzas Armadas; UruguayFil: Rosales, Cristina. Hospital Municipal de Oncología María Curie; ArgentinaFil: Salas-González, Efrain. Hospital de Gineco-Obstetricia CMNO-IMSS; MéxicoFil: Sanchotena, Verónica. Hospital Municipal de Oncología María Curie; ArgentinaFil: Segovia, Laura. Hospital Barros Luco Trudeau; ChileFil: Sendoya, Juan Martín. Fundación Instituto Leloir-CONICET. Molecular and Cellular Therapy Laboratory; ArgentinaFil: Silva-García, Aida A. Universidad de Guadalajara. Hospital Civil de Guadalajara. Organismo Público Descentralizado (OPD); MéxicoFil: Trinchero, Alejandra. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Valenzuela, Olivia. Universidad de Sonora; MéxicoFil: Vedham, Vidya. National Cancer Institute. Center for Global Health; Estados Unido

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

PurposesMost molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.Patients and methodsWe collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes.ResultsPAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors.ConclusionsThis is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America.Clinical trial registrationClinicalTrials.gov (Identifier: NCT02326857)

Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial

PURPOSEBreast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC).PATIENTS AND METHODSThe MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery.RESULTSOverall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor–negative-human epidermal growth factor receptor 2–positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%).CONCLUSIONIn LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA

Biodiversidad 2016. Estado y Tendencias de la Biodiversidad Continental de Colombia

Esta tercera entrega del reporte anual de la biodiversidad en Colombia profundiza en la línea editorial iniciada el año 2014 mediante nuevas propuestas analíticas y gráficas, con la intención de garantizar que la información llegue a todos los públicos y pueda ser discutida de manera amena sin sacrificio de calidad. La apuesta comunicativa sigue siendo central en el proyecto institucional y los nuevos lenguajes con los que estamos aprendiendo a conversar con la sociedad y las instituciones son un experimento que esperamos sea cada vez más satisfactorio: ya estamos construyendo la versión 2017 con el apoyo de las nuevas tecnologías digitales de manera que la potencia de la conexión vital colombiana se exprese en toda su capacidad. Por los contenidos es evidente que aún distamos mucho de tener una capacidad de seguimiento sistemático para la mayoría de temas relativos a la gestión de la biodiversidad y los servicios ecosistémicos, la única manera de evaluar si las medidas de política y las inversiones que realiza la sociedad están teniendo los efectos deseados. De hecho, parte de las limitaciones reconocidas por robustamente los cambios positivos o negativos que afectan los diferentes niveles de organización de la vida planetaria, por lo cual las mismas metas de Aichi, nuestra carta de navegación global, están pendientes de verificación. Un propósito adicional de este proceso es la invitación a todos los colombianos para contribuir con la construcción y alimentación de los indicadores básicos de seguimiento a la gestión, ya que es imposible identificar las tendencias de largo plazo en que están inmersas la flora y fauna colombianas sin el apoyo de las instituciones, los investigadores y los ciudadanos: en el país de la megadiversidad, el reto es inmenso. Por este motivo, este reporte irá abriendo sus páginas a expertos, incluso indígenas o de comunidades locales, para que presenten de manera sistemática y documentada sus perspectivas del cambio ambiental y sus efectos en la biodiversidad, con el ánimo de promover el compromiso de todos en su gestión. La única manera de superar el riesgo de extinción es mediante un activo proceso de aprendizajes sociales que haga que todos los sectores asuman una parte de la compleja responsabilidad que significa proteger todas las formas de vida del país, una décima parte mal contada de las planetarias. Agradezco a las decenas de personas que contribuyeron con este reporte, a quienes nos han apoyado en todas las etapas de producción y a sus lectores y usuarios, quienes son en último término los jueces de su utilidad.Bogotá, D. C