Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC

Registro Español de Hemodinámica y Cardiología Intervencionista. XVI Informe Oficial (1990-2006)

Se presentan los resultados del Registro de Actividad de la Sección de Hemodinámica y Cardiología Intervencionista de la Sociedad Española de Cardiología del año 2006. Se recogen los datos de 135 hospitales, de los cuales 125 realizan su actividad predominante en adultos y 10 atienden exclusivamente a pacientes pediátricos. Se realizaron 126.196 estudios diagnósticos, con 113.228 coronariografías, lo que representa un aumento del 7,6% respecto al año 2005 y una tasa de 2.560 coronariografias/millón de habitantes. Se realizaron 57.041 procedimientos intervencionistas coronarios, con un incremento del 7,8% respecto a 2005 y una tasa de 1.293 intervenciones/millón de habitantes. Se implantaron 90.006 stents, de los cuales el 59,3% fueron farmacoactivos. Se llevaron a cabo 10.067 procedimientos de intervencionismo en el infarto agudo de miocardio, lo que supone un incremento del 20,6% respecto al año anterior y representa el 17,6% del total de las intervenciones coronarias percutáneas. El intervencionismo no coronario más frecuente se realiza en las cardiopatías congénitas del adulto, como el cierre de la comunicación interauricular, que es el de mayor número, 334 procedimientos. La valvuloplastia mitral, con 431 casos tratados, apenas presenta cambios respecto al anterior registro, y su éxito está en el 93,6%. La vía de acceso radial se usa cada vez más y mantiene el aumento de años anteriores. Es de destacar el alto grado de participación de los diferentes centros en el actual registro, que hace que sea un referente internacional de la actividad hemodinámica en nuestro país

Trombocitopenia severa, persistente a transfusiones plaquetarias, secundaria a readministración de abciximab en paciente con antecedentes de púrpura trombocitopénica idiopática. Un posible nexo etiopatogénico

La trombocitopenia severa y aguda es una complicación infrecuente después del tratamiento con abciximab, que se soluciona habitualmente con transfusiones de plaquetas. Presentamos el caso de un paciente sometido a intervención coronaria percutánea multivaso que, tras la administración del fármaco durante el procedimiento, desarrolló una trombocitopenia severa persistente a múltiples transfusiones de plaquetas. Este paciente había sido diagnosticado previamente de púrpura trombocitopénica idiopática, aunque no estaba referida en los registros médicos ni era evidente desde el punto de vista analítico. El cuadro se resolvió tras la administración de inmunoglobulina G. Se discuten las implicaciones clínicas y terapéuticas

Justificación y diseño del estudio Concordancia entre RFF e iFR en lesiones del tronco común.: Estudio iLITRO-EPIC-07

Introduction and objectives: Patients with left main coronary artery (LMCA) stenosis have been excluded from the trials that support the non-inferiority of the instantaneous wave-free ratio (iFR) compared to the fractional flow reserve (FFR) in the decision-making process of coronary revascularization. This study proposes to prospectively assess the concordance between the two indices in LMCA lesions and to validate the iFR cut-off value of 0.89 for clinical use. Methods: National, prospective, and observational multicenter registry of 300 consecutive patients with intermediate lesions in the LMCA (angiographic stenosis, 25% to 60%. A pressure gudiewire study and determination of the RFF and the iFR will be performed: in the event of a negative concordant result (FFR > 0.80/iFR > 0.89), no treatment will be performed; in case of a positive concordant result (FFR ≤ 0.80/iFR ≤ 0.89), revascularization will be performed; In the event of a discordant result (FFR> 0.80/iFR ≤ 0.89 or FFR ≤ 0.80/iFR> 0.89), an intravascular echocardiography will be performed and revascularization will be delayed if the minimum lumen area is > 6 mm2. The primary clinical endpoint will be a composite of cardiovascular death, LMCA lesion-related non-fatal infarction or need for revascularization of the LMCA lesion at 12 months. Conclusions: Confirm that an iFR-guided decision-making process in patients with intermediate LMCA stenosis is clinically safe and would have a significant clinical impact. Also, justify its systematic use when prescribing treatment in these potentially high-risk patients. Registered at ClinicalTrials.gov ( Identifier: NCT03767621).Introducción y objetivos: Los pacientes con estenosis en el tronco coronario izquierdo (TCI) han sido excluidos de los ensayos que apoyan la no inferioridad del cociente de presiones en el índice diastólico instantáneo sin ondas (iFR) respecto a la reserva fraccional de flujo (RFF) en la toma de decisiones sobre revascularización coronaria. El presente estudio propone valorar de manera prospectiva la concordancia entre los dos índices en lesiones del TCI y validar el valor de corte del iFR de 0,89 para su uso clínico. Métodos: Registro multicéntrico nacional, prospectivo, observacional, con la inclusión de 300 pacientes consecutivos con lesiones intermedias (estenosis angiográfica 25-60%) en el TCI. Se realizará un estudio con guía de presión y determinación de RFF e iFR. En caso de resultado concordante negativo (RFF > 0,80 / iFR > 0,89), no se realizará tratamiento; en caso de resultado concordante positivo (RFF ≤ 0,80 / iFR ≤ 0,89), se realizará revascularización; en caso de resultado discordante (RFF > 0,80 / iFR ≤ 0,89 o RFF ≤ 0,80 / iFR > 0,89), se realizará estudio con ecocardiografía intravascular y se considerará diferir la revascularización si el área luminal mínima es > 6 mm2. El criterio de valoración clínico primario será la incidencia del combinado de muerte cardiovascular, infarto no mortal relacionado con la lesión del TCI o necesidad de revascularización de la lesión del TCI a los 12 meses. Conclusiones: La demostración de la seguridad clínica en la toma de decisiones del iFR en pacientes con lesiones intermedias en el TCI tendría un impacto clínico importante y justificaría su uso sistemático para la decisión del tratamiento en estos pacientes de potencial alto riesgo. Registrado en ClinicalTrials.gov (identificador: NCT03767621)

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC

Residential proximity to industrial pollution sources and colorectal cancer risk: a multicase-control study (MCC-Spain)

Background: Colorectal cancer is the third most frequent tumor in males and the second in females worldwide. In Spain, it is an important and growing health problem, and epidemiologic research focused on potential risk factors, such as environmental exposures, is necessary. Objectives: To analyze the association between colorectal cancer risk and residential proximity to industries, according to pollution discharge route, industrial groups, categories of carcinogens and other toxic substances, and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). Methods: MCC-Spain included 557 colorectal cancer cases and 2948 controls in 11 provinces, frequency matched by sex, age, and region of residence. Distances were computed from subjects' residences to each of the 134 industries located in the study area. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industrial facilities, adjusting for matching variables and other confounders. Results: Excess risk (OR; 95%CI) of colorectal cancer was detected near industries overall for all distances analyzed, from 1 km (2.03; 1.44-2.87) to 3 km (1.26; 1.00-1.59). In general, industries releasing pollutants to air showed higher excess risks than facilities releasing pollution to water. By industrial sector, excess risk (OR; 95%CI) was found near (≤3 km) production of metals (2.66; 1.77-4.00), surface treatment of metals (1.48; 1.08-2.02), glass and mineral fibers (2.06; 1.39-3.07), organic chemical industry (4.80; 3.20-7.20), inorganic chemical industry (6.74; 4.38-10.36), food/beverage sector (3.34; 2.38-4.68), and surface treatment using organic solvents (6.16; 4.06-9.36). By pollutants, the main excess risks (OR; 95%CI) were found near (≤3 km) industries releasing nonylphenol (9.19; 5.91-14.28), antimony (5.30; 3.45-8.15), naphthalene (3.11; 2.16-4.49), organotin compounds (2.64; 1.76-3.98), manganese (2.53; 1.63-3.93), dichloromethane (2.52; 1.74-3.66), and vanadium (2.49; 1.59-3.91). Conclusions: Our results support the hypothesis that residing in the proximity of industries may be a risk factor for colorectal cancer.This study was funded by: Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) – EVP-1178/14); Spain's Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416); Carlos III Institute of Health (ISCIII) grants, cofunded by ERDF funds–a way to build Europe– (grants PI08/0533, PI08/1359, PI08/1770, PS09/00773-Cantabria, PS09/01286-Leon, PS09/01662-Granada, PS09/01903-Valencia, PS09/02078-Huelva, PI11/00226, PI11/01403, PI11/01810, PI11/01889-FEDER, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/00613, PI14/01219, PI15/00069, PI15/00914, PI15/01032, PI17-00092); the Fundación Marqués de Valdecilla (API 10/09); the Junta de Castilla y León (LE22A10-2); the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10); the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra); the Catalan Government DURSI grant 2014SGR647; the European Commission grants FOOD-CT-2006-036224-HIWATE; the Recercaixa (2010ACUP 00310); Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR72