9 research outputs found
Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival
Get PDF© 2021 by the authors.Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.This study was funded by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013–
2016): ISCIII (PI09/02221, PI12/01635, PI15/02101, and PI18/0135) and co-financed by the European
Development Regional Fund “A way to achieve Europe” (ERDF), the Biomedical Research Network
in Cancer: CIBERONC (CB16/12/00446), Red Temática de investigación cooperativa en cáncer:
RTICC (RD12/0036/0073), La Asociación Española contra el Cáncer: AECC (Grupos Coordinados
Estables 2016), Fundación Mutua Madrileña (FMM) / XVI Convocatoria de Ayudas a la Investigación
en Salud 2019 and Asociación Cáncer de Páncreas (ACanPan); Asociación Española de Pancreatología
(AESPANC) / IV Becas de Investigación Carmen Delgado/Miguel Pérez-Mateo 2019. The European
Union’s Horizon 2020 research and innovation program under grant agreement No 857381, project
VISION (Strategies to strengthen scientific excellence and innovation capacity for early diagnosis of
gastrointestinal cancers).Peer reviewe
Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA
Get PDFThe screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E-4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E-4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease
Establishment of Pancreatic Cancer-Derived Tumor Organoids and Fibroblasts From Fresh Tissue.
No full textTumor organoids are three-dimensional (3D) ex vivo tumor models that recapitulate the biological key features of the original primary tumor tissues. Patient-derived tumor organoids have been used in translational cancer research and can be applied to assess treatment sensitivity and resistance, cell-cell interactions, and tumor cell interactions with the tumor microenvironment. Tumor organoids are complex culture systems that require advanced cell culture techniques and culture media with specific growth factor cocktails and a biological basement membrane that mimics the extracellular environment. The ability to establish primary tumor cultures highly depends on the tissue of origin, the cellularity, and the clinical features of the tumor, such as the tumor grade. Furthermore, tissue sample collection, material quality and quantity, as well as correct biobanking and storage are crucial elements of this procedure. The technical capabilities of the laboratory are also crucial factors to consider. Here, we report a validated SOP/protocol that is technically and economically feasible for the culture of ex vivo tumor organoids from fresh tissue samples of pancreatic adenocarcinoma origin, either from fresh primary resected patient donor tissue or patient-derived xenografts (PDX). The technique described herein can be performed in laboratories with basic tissue culture and mouse facilities and is tailored for wide application in the translational oncology field
MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis
Get PDFModel for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH
Interaction of different molecules with the hydrogenation and desulfurization sites of NiMoS supported particles with different morphology
No full textClinical characteristics and outcome of SARS-CoV-2 infection in admitted patients with chronic lymphocytic leukemia from a single European country
Get PDFSpain has been one the most affected countries by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) pandemic [1, 2]. Patients with chronic lymphocytic leukemia (CLL) could be at risk of more severe COVID-19 clinical forms [3] since they often carry immune perturbations aggravated by treatments used for the disease itself [4]. Two major series on patients with COVID-19 and CLL encompassing different countries and health systems reported heterogeneous factors related to the outcome [5, 6]. Herein, we are presenting the largest series of CLL patients with proved COVID-19 from a single country and Health system.Peer reviewe
Métodos y mediciones
No full textActitud y conducta hacia la salud oral en estudiantes de la comuna de AraucoAnálisis de instrumentos de registro odontológicos en la red de APS de la Región MetropolitanaAnálisis de la eficiencia relativa del Hospital de Cabildo mediante la aplicación del análisis de fronteraAnálisis de letalidad intrahospitalaria y acumulada a 30 días de eventos IAM, 2003-2007Análisis del programa de cáncer cervicouterino en Chile con metodología de marco lógicoAños de vida perdidos por muerte prematura: efecto de diferentes criterios de corrección de subregistrosCalidad global de la alimentación de mujeres asistidas por el sistema de salud público chilenoCarga de mortalidad para el estado de Río de Janeiro, BrasilCausas de extracciones permanentes en adultos atendidos en la Posta Central, ChileComparación del consumo de drogas en escolares hombres utilizando metodología de pares y cuestionario autoregistradoCuidado hospitalario de pacientes con accidente cerebrovascular isquémico atendidos bajo régimen GESDescripción de dimensiones del constructo de calidad de vida en niños de 2-5 añosDistribución de benzodiacepinas en establecimientos del SNSS, período 2006-2008Evaluación de calidad, implementación del control odontológico del niño sano en CAP'S, Región del MauleEvaluación de la satisfacción del usuario interno de la Unidad de Cuidados Básicos del Hospital MetropolitanoEvaluación del protocolo de referencia de cefalea tensional y migraña en consultorio Llay-LlayEvaluación económica del Programa de Fluoración del Agua en ChileFactores de riesgo de enfermedad hipertensiva del embarazo en la UCI del H.G EcatepecImpacto de reforma sanitaria en autorizaciones sanitarias y de desempeño en instalaciones de radiodiagnóstico dentalInstitucionalidad de la investigación en salud pública en ChileLetalidad intrahospitalaria y a 30 días de los eventos de accidente cerebrovascular isquémico en ChileLimitaciones y desafíos de la investigación en salud pública en ChileMejora de agudeza visual y utilización cirugía de segundo ojo en pacientes con cataratas GESMortalidad infantil en la Región Metropolitana II del Estado de Río de Janeiro, 1981-2008Mortalidad por cáncer de tiroides en Chile en el período 1985-2007Mortalidad por tumores cerebrales en población infantil y adolescente, ciudad Río de Janeiro, 1980-2007Mortalidad por tumores del sistema nervioso central en adultos, Río de Janeiro, 1980 a 2007Prevalencia de anemia ferropriva en una muestra representativa de beneficiarios del PNACPrevalencia de caries y fluorosis previo a la fluoruración del agua potable en TemucoPrevalencia de traumatismos dentoalveolares en niños del Hospital Dr. Sótero del Río, enero-junio 2010Propuesta de un indicador de la calidad para los centros de salud familiarSalud pública y la emergencia del dispositivo clínico en la modernidad nacionalSatisfacción de funcionalidad familiar en adolescentes entre 12 y 18 años consumidores de drogasValidación cualitativa del cuestionario ASAQ para la determinación de la conducta sedentaria en escolare
Métodos y mediciones
Get PDFActitud y conducta hacia la salud oral en estudiantes de la comuna de AraucoAnálisis de instrumentos de registro odontológicos en la red de APS de la Región MetropolitanaAnálisis de la eficiencia relativa del Hospital de Cabildo mediante la aplicación del análisis de fronteraAnálisis de letalidad intrahospitalaria y acumulada a 30 días de eventos IAM, 2003-2007Análisis del programa de cáncer cervicouterino en Chile con metodología de marco lógicoAños de vida perdidos por muerte prematura: efecto de diferentes criterios de corrección de subregistrosCalidad global de la alimentación de mujeres asistidas por el sistema de salud público chilenoCarga de mortalidad para el estado de Río de Janeiro, BrasilCausas de extracciones permanentes en adultos atendidos en la Posta Central, ChileComparación del consumo de drogas en escolares hombres utilizando metodología de pares y cuestionario autoregistradoCuidado hospitalario de pacientes con accidente cerebrovascular isquémico atendidos bajo régimen GESDescripción de dimensiones del constructo de calidad de vida en niños de 2-5 añosDistribución de benzodiacepinas en establecimientos del SNSS, período 2006-2008Evaluación de calidad, implementación del control odontológico del niño sano en CAP'S, Región del MauleEvaluación de la satisfacción del usuario interno de la Unidad de Cuidados Básicos del Hospital MetropolitanoEvaluación del protocolo de referencia de cefalea tensional y migraña en consultorio Llay-LlayEvaluación económica del Programa de Fluoración del Agua en ChileFactores de riesgo de enfermedad hipertensiva del embarazo en la UCI del H.G EcatepecImpacto de reforma sanitaria en autorizaciones sanitarias y de desempeño en instalaciones de radiodiagnóstico dentalInstitucionalidad de la investigación en salud pública en ChileLetalidad intrahospitalaria y a 30 días de los eventos de accidente cerebrovascular isquémico en ChileLimitaciones y desafíos de la investigación en salud pública en ChileMejora de agudeza visual y utilización cirugía de segundo ojo en pacientes con cataratas GESMortalidad infantil en la Región Metropolitana II del Estado de Río de Janeiro, 1981-2008Mortalidad por cáncer de tiroides en Chile en el período 1985-2007Mortalidad por tumores cerebrales en población infantil y adolescente, ciudad Río de Janeiro, 1980-2007Mortalidad por tumores del sistema nervioso central en adultos, Río de Janeiro, 1980 a 2007Prevalencia de anemia ferropriva en una muestra representativa de beneficiarios del PNACPrevalencia de caries y fluorosis previo a la fluoruración del agua potable en TemucoPrevalencia de traumatismos dentoalveolares en niños del Hospital Dr. Sótero del Río, enero-junio 2010Propuesta de un indicador de la calidad para los centros de salud familiarSalud pública y la emergencia del dispositivo clínico en la modernidad nacionalSatisfacción de funcionalidad familiar en adolescentes entre 12 y 18 años consumidores de drogasValidación cualitativa del cuestionario ASAQ para la determinación de la conducta sedentaria en escolare
Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort.
No full textLongitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19.
We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both.
Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53).
In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes
