Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients

Background: About 40% of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients undergoing anti-EGFR-based therapy have poor outcomes. Treatment failure is not only associated with poorer prognosis but higher healthcare costs. Our aim was to identify novel somatic genetic variants in the primary tumor and assess their effect on anti-EGFR response. Patients and Methods: Tumor (somatic) and blood (germline) DNA samples were obtained from two well-defined cohorts of mCRC patients, those sensitive and those resistant to EGFR blockade. Genetic variant screening of 43 EGFR-related genes was performed using targeted next-generation sequencing (NGS). Relevant clinical data were collected through chart review to assess genetic results. Results: Among 61 patients, 38 were sensitive and 23 were resistant to treatment. We identified eight somatic variants that predicted non-response. Three were located in insulin-related genes (I668N and E1218K in IGF1R, T1156M in IRS2) and three in genes belonging to the LRIG family (T152T in LRIG1, S697L in LRIG2 and V812M in LRIG3). The remaining two variants were found in NRAS (G115Efs*46) and PDGFRA (T301T). We did not identify any somatic variants related to good response. Conclusions: This study provides evidence that novel somatic genetic variants along the EGFR-triggered pathway could modulate the response to anti-EGFR drugs in mCRC patients. It also highlights the influence of insulin-related genes and LRIG genes on anti-EGFR efficacy. Our findings could help characterize patients who are resistant to anti-EGFR blockade despite harboring RAS/BRAF wild-type tumors

Preventing the recurrence of depression with a Mediterranean diet supplemented with extra-virgin olive oil. The PREDI-DEP trial: study protocol

Background: The role of dietary patterns in the prevention of unipolar depression has been analyzed in several epidemiological studies. The primary aims of this study are to determine the effectiveness of an extra-olive oil enriched Mediterranean diet in reducing the recurrence of depression and improving the symptoms of this condition. Methods: Multicenter, two-arm, parallel-group clinical trial. Arm 1, extra-virgin olive oil Mediterranean diet; Arm 2, control group without nutritional intervention. Dieticians are in charge of the nutritional intervention and regular contact with the participants. Contacts are made through our web platform (https://predidep.es/participantes/) or by phone. Recurrence of depression is assessed by psychiatrists and clinical psychologists through clinical evaluations (semi-structured clinical interviews: Spanish SCID-I). Depressive symptoms are assessed with the Beck Depression Inventory. Information on quality of life, level of physical activity, dietary habits, and blood, urine and stool samples are collected after the subject has agreed to participate in the study and once a year. Discussion: To the best of our knowledge, the PREDI-DEP trial is the first ongoing randomized clinical trial designed to assess the role of the Mediterranean diet in the prevention of recurrent depression. It could be a cost-effective approach to avoid recurrence and improve the quality of life of these patients

T-Follicular-Like CD8+ T Cell Responses in Chronic HIV Infection Are Associated With Virus Control and Antibody Isotype Switching to IgG.

T cell responses are considered critical for the in vivo control of HIV, but the contribution of different T cell subsets to this control remains unclear. Using a boosted flow cytometric approach that is able to differentiate CD4+ and CD8+ T cell Th1/Tc1, Th2/Tc2, Th17/Tc17, Treg and Tfh/Tfc-like HIV-specific T cell populations, we identified CD8+ Tfc responses that were related to HIV plasma viral loads and associated with rate of antibody isotype class switching to IgG. This favorable balance towards IgG responses positively correlated with increased virus neutralization, higher avidity of neutralizing antibodies and more potent antibody-dependent cell cytotoxicity (ADCC) in PBMCs from HIV controllers compared to non-controllers. Our results identified the CD8+ Tfc-like T-cell response as a component of effective virus control which could possibly be exploited therapeutically

Suelo y planta. Índices. Volumen 2

Effects of the landspreading of pig slurry on the yield and composition of capsi cum annuum. M. P. Bernal, A. Roig, J. Cegarra and R. Madrid.-- Características micromorfológicas de suelos de humedales en zonas semiáridas (Cuenca del Duero). J. Benayas, M. a T. de la Cruz y J. M. a Rey. Benayas.-- Aplicación de la técnica de porosimetría por intrusión de mercurio en el estudio de la porosidad de un conjunto de suelos del NW de España. E. Benito, A. Paz y R. Pini.-- Cambios físicos y químicos durante la maduración de Vitis vinífera, variedad Monastrell, en la D. O. Jumilla. G. Navarro, F. Pardo, P. Jiménez, J. Oliva y S. Navarro.-- Micorrizas vesículo - arbusculares en parcelas que se encuentran en sucesión- regeneración en Jos Andes tropicales. M. Montilla, R. A. Herrera y M. Monasterio.-- Efectos de los incendios forestales sobre el suelo. J. González, M. C. Fernández y G.P. Gimeno.-- Mineralogía de suelos formados sobre calizas en Galicia. M. T. Taboada, M. B. Silva y M. c. Villar.-- Efecto de tratamientos foliares con Ti (IV) sobre nutrición, producción y calidad de fruto en plantas de Capsicum annuum, L. F. Martínez-Sánchez, J. L. Giménez, M. Carvajal, A. Moreno, J. L. Fuentes y C. F. Alcaraz.-- Poder discriminante de las clasificaciones: aplicación a los suelos de la depresión Guadix- Baza (Granada). A. Iriarte, E. Barahona y C. Gil de Carrasco.-- Aspects of elm propagation by soft and hardwood cuttings. L. Mittempergher, G. Bartolini, F. Ferrini and M. Panicucci.-- Metales pesados en las escombreras de la mina Puentes (La Coruña): influencia de las condiciones Eh- pH. F. Macíass, M. T. Barral, C. Monterroso y R. M. Calvo.-- Incidencia del fósforo en la mineralización del nitrógeno orgánico de un lodo de depuradora en dos suelos calizos. Extracción mediante EUF. l. Verdú, l. Gómez, F. Burló y J, Mataix.-- Dinámica del proceso de sorción de fósforo en suelos. Definición de indicadores. T. Crisanto y P. P. Iturbe.-- Estudio de la adsorción de atrazina por polimeros modelos y por un ácido homico mediante la técnica de diálisis. M. Schiavon, J. M. Portal, F. Andreux y G. Bertin.-- Oxidos de hierro sintéticos y agregación en muestras de caolinita y cuarzo. M. Arias, M. T. Barraly F. Díaz-Fierros.-- Fertilization with NPK and humate NPK: Plant yield and nutrient dynamics. A. Benedetti, A. Figliolia, C. Izza, R. lndiati and S. Canali.-- Aplicación de un método de fraccionamiento de especies alumínicas a soluciones de suelos de Galicia. E. Alvarez y R. Calvo.-- Contenido y evolución de 9 elementos químicos en pimiento piquillo a lo largo de su desarrollo. R. Y. Cavero, A. Echeverría, F. Iribarren y M. L. López.-- Distribución del tamaño de poros, porosidad total y su variabilidad con la dedicación en el horizonte orgánico de un cambisol gleico. A. Paz y E. Benito.-- Caracterización de la textura superficial de granos de cuarzo en suelos con horizontes texturalmente contrastados. M. T. Martín Patino, R. J. Ballesta, V. Cala y A. Alvarez .-- Utilización de un lodo aerobio como sustitutivo de fertilizantes fosforados inorgánicos. M. Ayuso, T. Hernández, C. García y F. Costa.-- Movilidad de aldicarb y de carbofurano en columnas de suelo. A. Apaolaza, F. J. Arranz y E. Revilla.-- Degradación de clorofila en cloroplastos incubados en medio isotónico con la fracción celular extracloroplástica. J. Cuello, A. Lahora y B. Stibater.-- Especiación química de zinc y cadmio en suelos de cultivo. V. Cala, A. M. Alvarez, R. Vigil de la Villa y M. Gasea.-- Germination with alternate temperatures of weeds infesting irrigated vegetables. R. González Ponce, A. Herce and M. L. Salas.-- Evaluación de la fertilidad de los vertisoles de la provincia de Badajoz (España) mediante cultivos experimentales. Producción en materia seca y nutrientes del cultivo. A. García y A. López.-- Isozymes peroxidase in cytokinin treated seedlings of Corylus avellana L. C. Colinas, C. Díaz-Sala and R. Rodríguez.-- Respuestas de las plantas a la contaminación por metales pesados. J. Barceló y Ch. Poschenrieder.-- N, P and K balance in winter wheat in the pampean semiarid region of Argentina. R. A. Rosell, M. R. Landriscini and J. A. Galantini.-- Utilización de residuos urbanos como fertilizantes orgánicos. T. Hernández, C. García, F. Costa, J. A. Valero y M. Ayuso.-- Inducción de organogénesis en cotiledones de Pinus canariensis. C. Martínez Pulido.-- Hidróxidos de aluminio sintéticos y agregación en muestras de caolinita y cuarzo . . M. Arias, M. T. Barral y F. Díaz-Fierros.-- Producción de endoglucanasas por Glomus mosseae y su posible implicación en la colonización de raf<::es de cebolla. J. M. García-Garrido, l. García-Romera y J. A. Ocampo.-- Estudio comparado de la fracción mineral del suelo de cultivo· y de las heces' de Allolobophora molleri (Lumbricidae) Rosa, 1889.D. Trigo y D. J. Díaz Cosín.-- Determinación de la homogeneidad múltiple utilizando diferentes niveles de taxones en perfiles de suelos de la cuenca media y alta del río Motatán. Estados Mérida y Trujillo. Venezuela. J. Jaimes, J. Oballos y G. Ochoa.-- Adsorción - desorción de picloram por arcillas y óxidos. E. A. Ferreiro, S. G. de Bussetti.-- Influencia de la carga y el potencial hídrico durante la compactación sobre la resistencia a la tracción de unidades estructurales de suelo en estado seco. A. Paz y J. Guérif.-- Residuos orgánicos: Incidencia de su aplicación sobre la composición mineral del fruto del tomate, I. Gómez, J. Navarro-Pedreño y J. Mataix.-- Growth, cell wall elasticity and plasticity in Zea mays L. coleoptiles exposed to cadmium. B. Gunsé, M. Llugany, Ch. Poschenrieder and J. Barceló.-- Effects of high zinc and cadmium concentrations on the metallophyte Thlaspi caerulescens J. et C. Presl. (Brassicaceae). J. Módico, Ch. Poschenrieder, M. D. Vázquez and J. Barceló.--Determinación del grado ·de contaminación de los rlos mediante el estudio conjunto de la composición de sus aguas y sedimentos. A. Bustos, C. Ortega y I. Sastre.-- Influencia del grado de madurez de un residuo urbano sobre la germinación y disponibilidad de nitrógeno. M. Ayuso, T. Hernández, F. Costa, C. García y J. A. Pascual.-- Influencia del nitrógeno sobre el desarrollo in vitro del portainjerto de vid.--A. Villegas, C. Mozuelos, M. Cantos y A. Troncoso.-- Efecto del alpechín sobre la solubilización de metales pesados. M. Bejarano y L. Madrid.-- Aporte foliar de titanio a plantas de pimiento pimentonero. Influencia sobre el balance de nutrición en pericarpio de fruto. M. Carvajal, M. J. Frutos, J. L. Giménez, C. F. Alcaraz y F. Martínez-Sánchez.-- Effects of phosphate, sulfate and molibdate on the uptake and distribution of technetium-99 in bush bean plants. A. Bennássar, C. Cabot, J. Barceló y Ch. Poschenrieder.-- Uptake, translocation and efficiency of nutrients in Phaseolus vulgaris L. cv. contender exposed to aluminum. N. Massot, Ch. Poschenrieder and J. Barceló.-- Efecto del cadmio sobre Ü1. absorción y distribución de manganeso en distintas variedades de Lactuca. A. Gárate, I. Ramos y J. J. Lucena.-- Efecto residual de diferentes residuos orgánicos sobre un cultivo de cebada. F. Costa, T. Hernández, C. García, M. Ayuso, J. A. Pascual y A. Polo.-- Beneficial effects of low chromium III concentrations in iron deficient maize plants. Ch. Poschenrieder, M. D. Vázquez, A. Bonet and J. Barceló.-- Depresión en el rendimiento del maíz causado por altas concentraciones de N residual en el suelo. C. Pozo, C. Cruces, J. M. Ramos, y L. F. García del Moral.-- Selección y caracterización de una línea celular de limonero tolerante a estrés salino. A. Piquera y E. Hellín.-- Efectos del As en el comportamiento vegetal de Lycopersicum esculentum Mili. Relación del As en hojas y frutos con parámetros físicos. F. Burló, A. Carbonell y J. Mataix.--Niveles críticos y equilibrios óptimos de macronutrientes en la fertilización diferenciada de la vid. R. Sarmiento, J. L. García, M. C. Grande, M. C. Vil/alón, A. de Castro y C. Mozuelos.-- Niveles críticos y equilibrios óptimos de micronutrientes en la fertilización diferenciada de la vid. R. Sarmiento, J. L. García, M. C. Grande, M. C. Vil/alón, A. de Castro y C. Mozuelos.-- Efecto de un compost de lodo residual sobre el rendimiento y contenido de Cd y Ni en diversos cultivos. I. Walter, R. Miralles y M. Bigeriego.-- Estudio del eflujo neto de H+ por raíces aeropónicas estériles de plantulas de girasol (Helianthus annuus L.) bajo condiciones de toxicidad de B. F. Espinosa y M. C. Alvarez-Tinaut-- Efecodel riego con aguas residuales urbanas depuradas sobre la disponibilidad de metales pesados para la planta. A. Inglés, M. Gómez y R. Nogales.-- Diferential response of four maize (Zea mays L.) varieties to aluminum toxicity. P. Guevara, Ch. Poschenrieder and Barceló.-- Comparación de los efectos de molibdeno y vanadio en Phaseo/us vulgaris L.: Crecimiento, proteínas y actividades enzimáticas de la nitrato-reducción. D. Saco, M. Alvarez y S. Martín.-- Influencia de la fertirrigación N, P, K sobre diversos nutrientes totales y solubles. Su evolución temporal. J. L. Va/enzuela, A. del Río, A. Sánchez, l. López-Cantarero y L. Romero.-- Valoración de métodos de extracción de mercurio en suelos contaminados. J. J. Lucena, L. E. Hernández, S. Olmos y R. Carpena Ruiz.-- Relaciones entre contenidos totales de Zn, Pb, Cu y Cd en suelos y plantas. A. M. Moreno, L. Pérez y J. González.-- Effect of N-nutrition and irrigation water on Carob-Tree (Ceratonia si/iqua L.). Growth responses. P. Correia y M. A. Martins-LouçaoPeer reviewe

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function.Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system.Results: A total of 3288 patients were included in the analysis, of whom 301 (9.2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P &lt; 0.001). There were no significant differences in rates of readmission between these groups (6.6 versus 8.0 per cent; P = 0.499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0.90, 95 per cent c.i. 0.55 to 1.46; P = 0.659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34.7 versus 39.5 per cent; major 3.3 versus 3.4 per cent; P = 0.110).Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study

Aim: Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery. Method: This was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were divided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30 days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis. Results: A total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7%; routine NGT 5.2%; reactive NGT 10.6%; prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56–1.87, P = 0.932). Conclusion: In patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30 days of surgery compared with reactive insertion