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Resumen Introduccion y objetivos La amiloidosis hereditaria por transtirretina (ATTRv) es una enfermedad causada por mutaciones en el gen de la transtirretina que frecuentemente presenta afeccion cardiaca debido al deposito de amiloide en el miocardio. Nuestro objetivo es describir esta afeccion en una cohorte espanola. Metodos Estudio retrospectivo multicentrico de pacientes con ATTRv y afeccion cardiaca provenientes de centros espanoles. Se recogieron datos demograficos, clinicos y geneticos. Resultados En 26 centros se incluyo a 181 pacientes, el 65,2% varones, con una mediana de edad al diagnostico de 62 anos. Las mutaciones mas frecuentes fueron Val50Met (67,7%) y Val142Ile (12,4%). El principal motivo de consulta fue extracardiaco (69%), principalmente neurologico. La media de la fraccion aminoterminal del propeptido natriuretico cerebral (NT-proBNP) fue 2.145 ± 3.586 pg/ml. Lo mas caracteristico del electrocardiograma fueron el patron de seudoinfarto (25,9%) y el bloqueo auriculoventricular (25,3%). El grosor ventricular medio fue 15,4 ± 4,1 mm. El strain longitudinal estaba reducido en segmentos basales en el 29,4%. Se observo realce tardio subendocardico difuso en el 58,8%. En la gammagrafia habia captacion de grados 2-3 en un 75%. En el seguimiento, el 24,9% ingreso por insuficiencia cardiaca, el 34,3% preciso marcapasos y el 31,6%, trasplante hepatico. El 32,5% fallecio, principalmente por insuficiencia cardiaca (28,8%). Las mutaciones diferentes de Val50Met se asociaron en general con un peor pronostico. Conclusiones La ATTRv cardiaca en Espana tiene un espectro genetico y de afeccion heterogeneo. El pronostico es malo principalmente por las complicaciones cardiacas, por lo que son esenciales un diagnostico y un tratamiento precoces.

Introduction and objectives Hereditary transthyretin amyloidosis (hATTR) is a disease caused by mutations in the transthyretin gene that frequently shows cardiac involvement due to amyloid deposition in the myocardium. Our objective was to identify cardiac involvement in a Spanish cohort. Methods Retrospective multicenter study of patients diagnosed with hATTR with cardiac involvement from Spanish centers. We collected demographic, clinical, and genetic data. Results A total of 181 patients from 26 centers were included (65.2% men, with a median age at diagnosis of 62 years). The most frequent mutations were Val50Met (67.7%) and Val142Ile (12.4%). The main reason for consultation was extracardiac symptoms (69%), mainly neurological. The mean N-terminal pro-B-type natriuretic peptide level was 2145±3586 pg/mL. The most characteristic electrocardiogram findings were a pseudoinfarct pattern (25.9%) and atrioventricular block (25.3%). Mean ventricular thickness was 15.4±4.1mm. Longitudinal strain was reduced in basal segments by 29.4%. Late diffuse subendocardial enhancement was observed in 58.8%. Perugini grade 2 or 3 uptake was observed in 75% of scintigraphy scans. During follow-up, 24.9% of the patients were admitted for heart failure, 34.3% required a pacemaker, and 31.6% required a liver transplant. One third (32.5%) died during follow-up, mainly due to heart failure (28.8%). The presence of non-Val50Met mutations was associated with a worse prognosis. Conclusions HATTR cardiac amyloidosis in Spain shows heterogeneous genetic and clinical involvement. The prognosis is poor, mainly due to cardiac complications. Consequently early diagnosis and treatment are vital.

Resumen Introduccion y objetivos La exposicion a radiacion ionizante en los procedimientos de ablacion conlleva riesgos para la salud, sobre todo en pacientes pediatricos. Nuestro objetivo es comparar la seguridad y la eficacia de la ablacion guiada por un sistema de navegacion intracardiaca no fluoroscopica (SNINF) con las de la ablacion guiada exclusivamente por fluoroscopia en pacientes pediatricos. Metodos Se analizaron los resultados de la ablacion con cateter en pacientes pediatricos con vias accesorias de riesgo o taquicardias supraventriculares remitidos a nuestro centro en un periodo de 6 anos. Se compararon los procedimientos guiados solo por fluoroscopia (grupo A) y los guiados por SNINF (grupo B). Resultados Se analizaron 120 procedimientos de ablacion en 110 pacientes (edad, 11 ± 3,2 anos; el 70% varones), 62 procedimientos en el grupo A y 58 en el grupo B. No se encontraron diferencias significativas entre ambos grupos en exito del procedimiento (el 95% del grupo A y el 93,5% del grupo B; p = 0,53), complicaciones (el 1,7 frente al 1,6%; p = 0,23) y recurrencia (el 7,3 frente al 6,9%; p = 0,61). Sin embargo, el tiempo de fluoroscopia (mediana, 1,1 frente a 12 min; p Conclusiones El SNINF para guiar los procedimientos de ablacion en pacientes pediatricos reduce el tiempo de exposicion a la radiacion ionizante. Su empleo generalizado en las ablaciones pediatricas podria reducir el riesgo atribuido a la radiacion.

INTRODUCTION AND OBJECTIVES Ionizing radiation exposure in catheter ablation procedures carries health risks, especially in pediatric patients. Our aim was to compare the safety and efficacy of catheter ablation guided by a nonfluoroscopic intracardiac navigation system (NFINS) with those of an exclusively fluoroscopy-guided approach in pediatric patients. METHODS We analyzed catheter ablation results in pediatric patients with high-risk accessory pathways or supraventricular tachycardia referred to our center during a 6-year period. We compared fluoroscopy-guided procedures (group A) with NFINS guided procedures (group B). RESULTS We analyzed 120 catheter ablation procedures in 110 pediatric patients (11±3.2 years, 70% male); there were 62 procedures in group A and 58 in group B. We found no significant differences between the 2 groups in procedure success (95% group A vs 93.5% group B; P=.53), complications (1.7% vs 1.6%; P=.23), or recurrences (7.3% vs 6.9%; P = .61). However, fluoroscopy time (median 1.1minutes vs 12minutes; P

Background Catheter ablation of premature ventricular complexes from aortic sinus cusps (ASC‐PVC) is a complex procedure that conventionally requires coronary catheterization (CC) to localize coronary artery ostium (CAO). Little published information is available on the mapping and ablation with zero‐fluoroscopy (ZF) of ASC‐PVC. The aim of the study was to determine the efficacy and safety of ASC‐PVC ablation with a ZF approach guided by 3D intracardiac echocardiography integration in the electroanatomical mapping system (ICE 3D‐EAM). Methods This observational study included one patient cohort treated conventionally and another treated with ICE 3D‐EAM‐guided ZF ablation. Clinical, efficacy, and safety outcomes were evaluated acutely and at 3 months follow‐up. Results The study included 21 patients with ASC‐PVC: 10 in the ZF group (age 49 ± 16 years, 60% males) and 11 in the control group (age 47 ± 15 years, 27% males). Fluoroscopy was not required for any patient in the ZF group. Acute success was obtained in 80% of the ZF group vs 55% of the control group (P = .36). The recurrence rate was 30% in the ZF group vs 27% in the control group (P = 1). One nonsevere complication was observed in the ZF group (P = .48). Conclusions ZF catheter ablation of ASC‐PVC guided by ICE 3D‐EAM is feasible, effective, and safe., The graphical abstract shows the workflow for ZF ablation approach of ASC‐PVC using ICE 3D‐EAM. The key point is the ICE 3D‐EAM reconstruction which allows to assess the distance of the ablation catheter tip to CAO. Note that if the distance is at least >5 mm from earliest LVAT to CAO, the ablation is started. On the other hand, with a distance

Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis. This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up. This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality. A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up. LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management. The project was partially funded by a grant from the Catalan Society of Cardiology (Barcelona, Spain). Hospital Universitario Virgen de la Arrixaca (Murcia, Spain) was supported by a grant from the Foundation Marató TV3 (218/C/2015) (Barcelona, Spain). Hospital Universitario y Politécnico La Fe (Valencia, Spain) was partially supported by Fondo Europeo de Desarrollo Regional (“Unión Europea, Una forma de hacer Europa”) (Madrid, Spain) and the Instituto de Salud Carlos III (La Fe Biobank PT17/0015/ 0043) (Madrid, Spain). Dr Guala was supported by funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I) (Madrid, Spain). Dr La Mura was supported by a research grant from the Cardiopath PhD program (Naples, Italy). Prof de la Pompa was supported by grants PID2019-104776RB-I00 and CB16/11/00399 (CIBER CV) from the Spanish Ministry of Science, Innovation and Universities. Dr Bayes-Genis was supported by grants from CIBER Cardiovascular (CB16/11/00403 and 16/11/00420) (Madrid, Spain) and AdvanceCat 2014-2020 (Barcelona, Spain); and has received advisory board and lecture fees from Novartis, Boehringer Ingelheim, Vifor, Roche Diagnostics, and Critical Diagnostics. Dr Pontone has received speaker honorarium and/or institutional research grants from GE Healthcare, Bracco, Boehringer Ingelheim, and HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

Aims: Dilated cardiomyopathy (DCM) associated with dystrophin gene (DMD) mutations in individuals with mild or absent skeletal myopathy is often indistinguishable from other DCM forms. We sought to describe the phenotype and prognosis of DMD associated DCM in DMD mutation carriers without severe skeletal myopathy. Methods and results: At 26 European centres, we retrospectively collected clinical characteristics and outcomes of 223 DMD mutation carriers (83% male, 33 ± 15 years). A total of 112 individuals (52%) had DCM at first evaluation [n = 85; left ventricular ejection fraction (LVEF) 34 ± 11.2%] or developed DCM (n = 27; LVEF 41.3 ± 7.5%) after a median follow-up of 96 months (interquartile range 5–311 months). DCM penetrance was 45% in carriers older than 40 years. DCM appeared earlier in males and was independent of the type of mutation, presence of skeletal myopathy, or elevated serum creatine kinase levels. Major adverse cardiac events (MACE) occurred in 22% individuals with DCM, 18% developed end-stage heart failure and 9% sudden cardiac death or equivalent. Skeletal myopathy was not associated with survival free of MACE in patients with DCM. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Individuals without DCM had favourable prognosis without MACE or death during follow-up. Conclusions: DMD-associated DCM without severe skeletal myopathy is characterized by incomplete penetrance but high risk of MACE, including progression to end-stage heart failure and ventricular arrhythmias. DCM onset is the major determinant of prognosis with similar survival regardless of the presence of skeletal myopathy.

Supplementary data associated with this article can befound, in the online version, at https://doi.org/10.1016/j.medcli.2021.06.015, Introduction and purpose: Atrial fibrillation (AF) is common in patients admitted with severe COVID- 19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. Methods: We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleed- ing, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. Results: 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p = 0.003; 52 (34.4%) vs 35 (23.2%), p = 0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. Conclusions: AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk., Antecedentes y objetivos: La fibrilación auricular (FA) es frecuente en pacientes ingresados por COVID-19 grave. Sin embargo, los datos sobre el manejo de la anticoagulación crónica en estos pacientes son escasos. Analizamos la anticoagulación y la incidencia de episodios cardiovasculares mayores en pacientes con FA ingresados por la COVID-19. Métodos: Retrospectivamente, se identificaron todos los pacientes con FA ingresados por la COVID-19 entre marzo y mayo de 2020, en 9 hospitales espa ̃noles. Se seleccionó un grupo control de pacientes ingresados consecutivamente por la COVID-19 sin FA. Se compararon las características basales, inci- dencia de hemorragias mayores, episodios trombóticos y mortalidad. Para reducir potenciales factores de confusión se realizó un emparejamiento por puntuación de propensión, así como un análisis multivariante para predecir hemorragia mayor y mortalidad. Resultados: Se incluyeron 305 pacientes con FA ingresados por la COVID-19. Tras el emparejamiento por puntuación de propensión, 151 pacientes con FA fueron emparejados con 151 controles. Durante el ingreso, la heparina de bajo peso molecular fue el principal anticoagulante y la incidencia de hemorragia mayor y mortalidad fue mayor en el grupo de FA (16[10,6%] vs. 3[2%], p = 0,003; 52[34,4%] vs. 35[23,2%], p = 0,03, respectivamente). El análisis multivariante demostró la presencia de FA como predictor indepen- diente de sangrados y mortalidad intrahospitalaria en los pacientes con la COVID-19. En el grupo de FA, un segundo análisis multivariante identificó valores elevados de dímero-D como predictor independiente de hemorragia mayor intrahospitalaria. Conclusiones: Los pacientes con FA ingresados por la COVID-19 representan una población de alto riesgo de sangrado y mortalidad durante el ingreso. Parece recomendable individualizar la anticoagulación durante el ingreso, considerando el riesgo específico de sangrado y trombosis.

Resumen Introduccion y objetivos Segun las guias de muerte subita, se debe considerar un desfibrilador automatico implantable (DAI) para los pacientes con miocardiopatia dilatada debida a variantes en el gen de la lamina (LMNA) con al menos 2 factores: varones, fraccion de eyeccion del ventriculo izquierdo (FEVI) Metodos Se evaluo la relacion entre factores de riesgo y eventos cardiovasculares en una cohorte de 140 portadores de variantes en LMNA (54 probandos, 86 familiares, edad ≥ 16 anos). Se considero: a) evento arritmico mayor (EAM) si hubo descarga apropiada del DAI o muerte subita, y b) muerte por insuficiencia cardiaca, incluidos los trasplantes. Resultados Se identificaron 11 variantes nuevas y 21 previamente publicadas. La FEVI Conclusiones En el registro REDLAMINA, los unicos 2 predictores asociados con EAM fueron la TVNS y la FEVI

Background: Coffee contains many bioactive substances that can play a role on colorectal cancer. Epidemiological evidence of coffee intake and colorectal cancer is, however, inconsistent. Aim: To provide further information on the risk of colorectal cancer in relation to coffee consumption. Methods: Data derive from two companion case-control studies conducted in Italy and Spain within the European Union Project on Health Impacts of long-term exposure to disinfection by-products in Drinking Water and the Spanish Multi-Case Control study on Cancer. These included a total of 2289 incident cases with colorectal cancer and 3995 controls with information on coffee intake. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were derived from unconditional logistic regression models, adjusted for study centre, sex, age, education, smoking, and other covariates. Results: Compared with never coffee drinkers, the OR was 0.99 (95% CI 0.95-1.02) for total coffee consumption. There was no significant trend in risk with dose or duration, the ORs being 0.95 (95% CI 0.72-1.25) for an amount of five or more cups per day of coffee and 0.95 (95% CI 0.75-1.19) for a duration of consumption of 50 years or longer. The OR was 1.04 (95% CI 0.87-1.25) for two or more cups per day of decaffeinated coffee. There were no heterogeneity across strata of various covariates, as well as no apparent differences between various anatomical subsites. Conclusion: This large pooled analysis of two studies shows no association of coffee and decaffeinated coffee with colorectal cancer risk.

Introduction and objectives Atrioventricular block (AVB) in the presence of bradycardic drugs (BD) can be reversible, and pacemaker implantation is controversial. Our objective was to analyze the pacemaker implantation rate in the mid-term, after BD suspension, and to identify predictive factors. Methods We performed a cohort study that included patients attending the emergency department with high-grade AVB in the context of BD. We studied the persistence of AVB after BD discontinuation, recurrence in patients with AVB resolution, and the predictive variables associated with pacemaker requirement at 3 years. Results Of 127 patients included (age, 79 [71-83] years), BAV resolved in 60 (47.2%); among these patients, recurrence occurred during the 24-month median follow-up in 40 (66.6%). Pacemaker implantation was required in 107 patients (84.3%), despite BD discontinuation. On multivariable analysis, the variables associated with pacemaker need at 3 years were heart rate C I, 1.82-36.17), symptoms other than syncope (OR, 4.09; 95%CI, 1.18-14.13), and wide QRS (OR, 5.65; 95%CI, 1.77-18.04). Concomitant antiarrhythmic treatment was associated with AVB resolution (OR, 0.12; 95%CI, 0.02-0.66). Conclusions More than 80% of patients with AVB secondary to BD require pacemaker implantation despite drug discontinuation. Predictive variables were wide QRS, heart rate

Resumen Introduccion y objetivos El bloqueo auriculoventricular (BAV) en presencia de farmacos bradicardizantes (FBZ) puede ser reversible, y esta en controversia el implante de marcapasos. El objetivo es analizar la necesidad de tratamiento con marcapasos a medio plazo, tras la suspension de los FBZ, e identificar factores predictores. Metodos Se estudio a una cohorte de pacientes que acudieron a urgencias con BAV de alto grado mientras tomaban FBZ. Se estudio la persistencia de BAV tras la interrupcion del farmaco, la recurrencia en los pacientes con resolucion del BAV y las variables predictoras asociadas con la necesidad de marcapasos a los 3 anos de seguimiento. Resultados De 127 pacientes (edad, 79 [71-83] anos), en 60 (47,2%) se resolvio el BAV; de estos, en 40 (66,6%) el BAV recurrio en los 24 meses de seguimiento medio; 107 pacientes (84,3%) tuvieron indicacion de implante de marcapasos pese a suspenderse los FBZ. Las variables asociadas con la necesidad de marcapasos a los 3 anos en el multivariable fueron: frecuencia cardiaca Conclusiones Mas del 80% de los pacientes con BAV secundario a FBZ precisan implante de marcapasos a pesar de suspenderlos; los predictores son el QRS ancho, la frecuencia cardiaca

Introduction and objectives Several studies have linked the presence of atrial fibrillation (AF) with reduced estimated glomerular filtration rate (eGFR). Our objective was to compare changes in eGFR in patients with AF after pulmonary vein (PV) ablation depending on the success of the technique, as well as to examine the relationship between eGFR and several biomarkers. Methods Prospective cohort of patients with AF referred to our center for PV ablation with a 1-year follow-up. We estimated eGFR using the Chronic Kidney Disease Epidemiology Collaboration formula at baseline and at 3 and 12 months. Biomarkers (B-type natriuretic peptide, corin, and galectin-3) were measured before ablation and at 12 months. Results We studied 124 patients (age 55 ± 10 years, 69.4% men). Seventy-five had paroxysmal AF (60.5%). The mean baseline eGFR was 90.8 [77.8-100.0] mL/min/1.73 m2. The eGFR increased at the end of follow-up, with a statistically significant difference between patients with recurrence at 12 months and those without (−1.1 [-6.0 to 8.8] mL/min/1.73 m2 vs 7.1 [−0.6 to 14.2] mL/min/1.73 m2, P = .017). The improvement in eGFR at 12 months was inversely proportional to baseline eGFR. B-type natriuretic peptide and corin levels improved at 12 months, while galectin-3 levels worsened, which was unrelated to eGFR. Conclusions In patients with AF treated with PV ablation, an overall improvement in eGFR was observed, which was more marked in the subgroup without recurrences, although without significant differences on multivariate analysis.

Resumen Introduccion y objetivos Varios estudios han relacionado la presencia de fibrilacion auricular (FA) con una tasa de filtrado glomerular estimada (TFGe) reducida. Nuestro objetivo es comparar la evolucion de la TFGe en pacientes con FA tras ablacion de venas pulmonares (VP) en funcion del exito de la tecnica, asi como estudiar la relacion entre TFGe y varios biomarcadores. Metodos Cohorte prospectiva de pacientes con FA remitidos a nuestro centro para ablacion de VP con seguimiento de 1 ano. La TFGe se obtuvo mediante la formula de la Chronic Kidney Disease Epidemiology Collaboration en el momento basal y a los 3 y 12 meses. Se midieron biomarcadores (peptido natriuretico cerebral, corina y galectina-3) antes de la ablacion y a los 12 meses. Resultados Se estudio a 124 pacientes (edad, 55 ± 10 anos; el 69,4% varones); 75 presentaban FA paroxistica (60,5%). La media de la TFGe basal fue de 90,8 [77,8-100,0] ml/min/1,73 m2. La TFGe se incremento al final del seguimiento, con diferencia estadisticamente significativa entre los pacientes que habian sufrido recurrencia a los 12 meses y los que no (–1,1 [–6,0 a 8,8] frente a 7,1 [–0,6 a 14,2] ml/min/1,73 m2; p = 0,017). La mejora de la TFGe a los 12 meses fue inversamente proporcional a la TFGe basal. Las cifras de peptido natriuretico cerebral y corina mejoraron a los 12 meses, mientras que los de galectina-3 empeoraron, sin relacion con la TFGe. Conclusiones En los pacientes con FA tratados con ablacion de VP, se observo una mejora general de la TFGe, mas marcada en el subgrupo que no tuvo recurrencias, aunque sin diferencias significativas en el analisis multivariante.

Gómez Echevarría, José Ramón, cotutor, Fundamentos: La Lepra ha sido y sigue siendo una enfermedad olvidada, infradiagnosticada y cargada de gran estigma social, que influye en muchos aspectos de la vida de las personas afectadas, aisladas ante el rechazo, especialmente si padecen deformidades visibles. Métodos: Estudio cualitativo fenomenológico basado en entrevistas semiestructuradas a pacientes diagnosticados de Lepra, familiares de enfermos fallecidos y personal sanitario del Sanatorio de Fontilles, junto con 2 grupos de discusión. El trabajo de campo se realizó entre los meses de abril y agosto del 2021. Resultados: Se han entrevistado a 7 pacientes diagnosticados de Lepra y familiares, 4 mujeres y 3 varones de entre 75-88 años residentes de Fontilles y 1 profesional de dicho centro. Además, se llevó a cabo una discusión con personal sanitario y otra, con personas no relacionadas con el ambiente sanitario, detectándose la gran carga física y psicológica de esta enfermedad. Mientras la sociedad desconoce aspectos básicos de la enfermedad, fundamentales para eliminar la estigmatización, los propios afectados que la han “superado”, evitan nombrarla y siguen aislándose, entre los muros del leprosorio. Conclusión: La reducción del estigma ayudaría a eliminar las barreras encontradas en la prevención, tratamiento y soporte, facilitando el acceso a un diagnóstico precoz. De esta forma se evitaría la progresión de la enfermedad y las graves consecuencias e impacto en la vida social, económica y psicosocial de los enfermos, promoviendo su inclusión y evitando la discriminación., Background: Leprosy has been and still is an illness in oblivion, underdiagnosed and highly stigmatised in society whilst impacting the lives of people, -hence, being isolated by the rejection of society, especially when one suffers visible deformities. Design: Qualitative phenomenological study was based on 2 discussion groups and semi-structured interviews of patients diagnosed with Leprosy, relatives of the cited patients, as well as health worker working in the Sanatorium of Fontilles. Field work was carried out between April and August 2021. Results: A study has been conducted via an interview to both 5 diagnosed patients with Leprosy and 2 family members, amongst them 3 males and 4 females, ranging 75-88 years, living in Fontilles and a health worker of the referred sanatorium. In addition, two discussions took place, one of which was held between health workers and the other one with non-health workers- highlighting a tremendous physical and mental stress on patients. Whilst society doesn´t reckon the basics of Leprosy, those who have overcome the illness are still isolating themselves within the walls of the leper colony. Discussion: Decrease of Leprosy stigma entails helping to destroy barriers based on prevention, treatment and support, which in turn enables access to early diagnosis. Such course of action would avoid the development of the disease and the social, economic and psychosocial impact in the lives of Leprosy patients and further foster their inclusion in society., Máster Universitario en Acción Humanitaria Sanitaria (M161)

Background: Arrhythmogenic cardiomyopathy (AC) is a life-threatening disease which predispose to malignant arrhythmias and sudden cardiac death (SCD) in the early stages of the disease. Risk stratification relies on the electrical, genetic, and imaging data. Our study aimed to investigate how myocardial deformation parameters may identify the subjects at risk of known predictors of major ventricular arrhythmias.Methods: A cohort of 45 subjects with definite or borderline diagnosis of AC was characterized using the advanced transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) and divided into the groups according to the potential arrhythmic risk markers, such as non-sustained ventricular tachycardia (NSVT), late gadolinium enhancement (LGE), and genetic status. Layer-specific global longitudinal strain (GLS) by TTE 2D speckle tracking was compared in patients with and without these arrhythmic risk markers.Results: In this study, 23 (51.1%) patients were men with mean age of 43 ± 16 years. Next-generation sequencing identified a potential pathogenic mutation in 39 (86.7%) patients. Thirty-nine patients presented LGE (73.3%), mostly located at the subepicardial-to-mesocardial layers. A layer-specific-GLS analysis showed worse GLS values at the epicardial and mesocardial layers in the subjects with NSVT and LGE. The epicardial GLS values of −15.4 and −16.1% were the best cut-off values for identifying the individuals with NSVT and LGE, respectively, regardless of left ventricular ejection fraction (LVEF).Conclusions: The layer-specific GLS assessment identified the subjects with high-risk arrhythmic features in AC, such as NSVT and LGE. An epicardial GLS may emerge as a potential instrument for detecting the subjects at risk of SCD in AC.

We analyzed the association between salivary melatonin rhythm and prostate cancer (PCa).A total of 40 PCa cases and 41 controls from the CAPLIFE study were analyzed to determine the salivary melatonin rhythm through 6 saliva samples. Amplitude (maximum melatonin peak) was categorized as low or high using the cutoff point median of the controls. Acrophase (time of maximum melatonin peak) was classified as early or late using the same criteria. In addition, the following data were collected: characteristics related to sleep habits, and clinical and sociodemographic information. Melatonin rhythms were represented for cases and controls and analyzed according to urinary symptoms, tumor aggressiveness and tumor extension. Variations in melatonin levels were estimated using generalized estimating equations on the ln-transformed values. To estimate the association between amplitude, acrophase and PCa, adjusted odds ratio (aOR) and 95% CI were calculated using logistic regression models.The mean age was 67.0 years (SD 7.3) for cases and 67.5 (SD 5.5) for controls. Melatonin levels were always lower in PCa cases than in controls. On average, melatonin levels in cases were -64.0% (95% CI -73.4, -51.4) than controls. PCa cases had lower amplitude, 26.0 pg/ml (SD 27.8) vs 46.3 pg/ml (SD 28.2; p0.001). A high amplitude was associated with a decreased risk of PCa, aOR=0.31 (95% CI 0.11, 0.86), while a late acrophase could be increased risk of PCa, aOR=2.36 (95% CI 0.88, 6.27).Patients with PCa always had lower melatonin levels than men without PCa, independent of urinary symptomatology or extension and aggressiveness of the tumor.

Introduction Arrhythmogenic Cardiomyopathy (ACM) is a life-threatening entity which predispose to malignant arrhythmias and sudden cardiac death even in early stages of the disease. Deformation techniques obtained by echocardiography are promising tools which can identify subtle pathologic changes in the myocardial wall. Our aim is to investigate how myocardial deformation parameters may be affected throughout ACM spectrum. Methods A cohort of ACM 45 subjects, was characterized using advanced transthoracic echocardiography and divided into groups according to left ventricle ejection fraction (LVEF). Twenty-three healthy volunteers were also included as control group (CG). We analyzed regional wall motion abnormalities and left ventricular myocardial deformation parameters by 2D Speckle Tracking, such as global longitudinal strain (GLS), mechanical dispersion (MD) [standard deviation (SD) and range (delta)]. Results 23 (51,1%) of the ACM cohort were men, with a mean age of 43,13±16,55 years. Next-generation sequencing identified a potential pathogenic mutation in 37 (82,2%) of the patients. Those ACM subjects with low LVEF (ACM-L) presented lower GLS values when compared to those with normal LVEF (ACM-N) (−16,17±2,68% vs. ACM-N −19,39±2,97%; p Conclusions MD may be an additive tool for identifying ACM patients in early stages of the disease when LVEF is still preserved. Funding Acknowledgement Type of funding sources: None.

Khalid Saeed Khan is a Distinguished Investigator funded by the Beatriz Galindo (senior modality) Program grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government., Simple Summary Results from individual studies on the association between obesity and prostate cancer mortality remain inconclusive; additionally, several large cohort studies have recently been conducted. We aimed to systematically review all available evidence and synthetize it using meta-analytic techniques. The results of our study showed that obesity was associated with prostate cancer specific mortality and all-cause mortality. The temporal association was consistent with a dose-response relationship. Our results demonstrated that obesity, a potentially modifiable prognostic factor, was associated with higher prostate cancer mortality. This study improved the evidence regarding the potential impact of lifestyle on improving prostate cancer prognosis. Strategies aimed at maintaining normal, or reducing abnormal, body mass index in diagnosed prostate cancer patients might improve survival. These results should guide urologists, oncologists, patients, policy-makers and primary care providers with respect to evidence-based practice and counselling concerning lifestyle changes after prostate cancer diagnosis., The aim of this study was to systematically review all evidence evaluating obesity as a prognostic factor for PC mortality. Cohort and case-control studies reporting mortality among PC patients stratified by body mass index (BMI) were included. The risk of mortality among obese patients (BMI >= 30) was compared with the risk for normal weight (BMI < 25) patients, pooling individual hazard ratios (HR) in random-effects meta-analyses. Reasons for heterogeneity were assessed in subgroup analyses. Dose-response associations for BMI per 5 kg/m(2) change were assessed. Among 7278 citations, 59 studies (280,199 patients) met inclusion criteria. Obesity was associated with increased PC-specific mortality (HR: 1.19, 95% CI: 1.10-1.28, I-2: 44.4%) and all-cause mortality (HR: 1.09, 95% CI: 1.00-1.18, I-2: 43.9%). There was a 9% increase (95% CI: 5-12%, I-2: 39.4%) in PC-specific mortality and 3% increase (95% CI: 1-5%, I-2: 24.3%) in all-cause mortality per 5 kg/m(2) increase in BMI. In analyses restricted to the higher quality subgroup (NOS >= 8), obesity was associated with increased PC-specific mortality (HR: 1.24, 95% CI: 1.14-1.35, I-2: 0.0%) and maintained the dose-response relationship (HR: 1.11 per 5 kg/m(2) increase in BMI, 95% CI: 1.07-1.15, I-2: 26.6%). Obesity had a moderate, consistent, temporal, and dose-response association with PC mortality. Weight control programs may have a role in improving PC survival., Ministry of Science, Innovation, and Universities of the Spanish Government

This study was supported by research grants from CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Spain (PI16/01858, PI18/01573, PI20/01568), co-funded by European Union (ERDF), "A way to make Europe"., Supplementary data to this article can be found online at https://doi. org/10.1016/j.envint.2021.106734, Background Despite restrictions on their production and use, most of the population is still exposed to Persistent Organic Pollutants (POPs), including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). These chemicals are thought to contribute to the aetiology of highly prevalent chronic conditions, such as cardiovascular diseases (CVDs), although current evidences are still controversial. Objectives To explore the potential contribution of historical POP exposure to 15-year pharmaceutical consumption in relation to CVD. Methods This study is framed within GraMo adult cohort. Participants (n = 387) were recruited in two hospitals in Granada province, Southern Spain (2003–2004). Historical exposure to 5 OCPs and 3 non-dioxine-like PCBs was estimated by analysing adipose tissue concentrations at recruitment. Pharmaceutical consumption from recruitment until year 2017 was quantified by reviewing dispensation databases. Average consumption increase (ACI) in CVD medication was calculated by subtracting average consumption in 2002 to the average yearly consumption during follow-up. ACI was expressed as Defined Daily Dose (DDD)/year units. Data analyses were carried out using a multivariable multinomial logistic regression and weighted quantile sum regression (WQS), with ACI categorized in quartiles (Q) as the dependent variable. Results Concentrations of most pollutants showed a positive trend with the quartiles of ACI. Particularly, PCB-153 showed increasing and statistically significant odds ratios (ORs) for Q2 (OR: 1.27, 95% confidence interval (CI): 1.07–1.52), Q3 (OR: 1.49, 95 %CI: 1.17–1.88) and Q4 (OR: 1.42, 95 %CI: 1.13–1.78) vs Q1. Similarly, beta-hexachlorocyclohexane (β-HCH) also showed increasing ORs, that reached statistical significance in Q4 (OR: 1.36, 95 %CI: 1.06–1.74) vs Q1. These findings were corroborated by WQS analyses, that revealed a significant mixture effect, predominantly accounted for by PCB-153 and β-HCH. Discussion Our results suggest that long-term POP exposure might represent a modifiable risk factor for CVD. These findings are relevant for public health campaigns and management, since pharmaceutical consumption is considered an indicator of both morbidity and health expenditure., CIBER de Epidemiología y Salud Pública, Santa Ana and San Cecilio Hospitals RYC-2016-20155, European Commission, Instituto de Salud Carlos III PI16/01858, PI18/01573, PI20/01568 ISCIII Ministerio de Economía, Industria y Competitividad, Gobierno de España, European Regional Development Fund, Ministerio de Economía, Industria y Competitividad, Gobierno de España

Many adult cancer patients present one or more physical comorbidities. Besides interfering with treatment and prognosis, physical comorbidities could also increase the already heightened psychological risk of cancer patients. To test this possibility, we investigated the relationship between physical comorbidities with depression symptoms in a sample of 2073 adult cancer survivors drawn from the nationally representative National Health and Nutrition Examination Survey (NHANES) (2007–2018) in the U.S. Based on information regarding 16 chronic conditions, the number of comorbidities diagnosed before and after the cancer diagnosis was calculated. The number of comorbidities present at the moment of cancer diagnosis was significantly related to depression risk in recent but not in long-term survivors. Recent survivors who suffered multimorbidity had 3.48 (95% CI 1.26–9.55) times the odds of reporting significant depressive symptoms up to 5 years after the cancer diagnosis. The effect of comorbidities was strongest among survivors of breast cancer. The comorbidities with strongest influence on depression risk were stroke, kidney disease, hypertension, obesity, asthma, and arthritis. Information about comorbidities is usually readily available and could be useful in streamlining depression screening or targeting prevention efforts in cancer patients and survivors. A multidimensional model of the interaction between cancer and other physical comorbidities on mental health is proposed., Sara Borrell - the Health Institute Carlos III (Expde: CD19/00203)

(1) Background: Over the last decade, genetic counseling clinics have moved from single-gene sequencing to multigene panel sequencing. Multiple genes related to a moderate risk of breast cancer (BC) have emerged, although many questions remain regarding the risks and clinical features associated with these genes. (2) Methods: Ninety-six BC index cases (ICs) with high-risk features for hereditary breast and ovarian cancer (HBOC) and with a previous uninformative result for BRCA1/2 were tested with a panel of 41 genes associated with BC risk. The frequency of pathogenic variants (PVs) was related to the clinical characteristics of BC. (3) Results: We detected a PV rate of 13.5% (excluding two cases each of BRCA1 and MUTYH). Among the 95 assessed cases, 17 PVs were identified in 16 ICs, as follows: BRCA1 (n = 2), CHEK2 (n = 3), ATM (n = 5), MUTYH (n = 2), TP53 (n = 2), BRIP1 (n = 1), CASP8 (n = 1), and MSH2 (n = 1). We also identified a novel loss-of-function variant in CASP8, a candidate gene for increased BC risk. There was no evidence that the clinical characteristics of BC might be related to a higher chance of identifying a PV. (4) Conclusions: In our cohort, which was enriched with families with a high number of BC cases, a high proportion of mutations in ATM and CHEK2 were identified. The clinical characteristics of BC associated with moderate-risk genes were different from those related to BRCA1/2 genes.

Background: Gastric cancer is the fifth most frequent tumor worldwide. In Spain, it presents a large geographic variability in incidence, suggesting a possible role of environmental factors in its etiology. Therefore, epidemiologic research focused on environmental exposures is necessary. Objectives: To assess the association between risk of gastric cancer (by histological type and tumor site) and residential proximity to industrial installations, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer conducted in Spain (MCC-Spain). Methods: In this study, 2664 controls and 137 gastric cancer cases from 9 provinces, frequency matched by province of residence, age, and sex were included. Distances from the individuals' residences to the 106 industries located in the study areas were computed. 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 industries, adjusting for matching variables and potential confounders. Results: Overall, no excess risk of gastric cancer was observed in people living close to the industrial installations, with ORs ranging from 0.73 (at ≤2.5 km) to 0.93 (at ≤1.5 km). However, by industrial sector, excess risks (OR; 95%CI) were found near organic chemical industry (3.51; 1.42-8.69 at ≤2 km), inorganic chemical industry (3.33; 1.12-9.85 at ≤2 km), food/beverage sector (2.48; 1.12-5.50 at ≤2 km), and surface treatment using organic solvents (3.59; 1.40-9.22 at ≤3 km). By specific pollutant, a statistically significant excess risk (OR; 95%CI) was found near (≤3 km) industries releasing nonylphenol (6.43; 2.30-17.97) and antimony (4.82; 1.94-12.01). Conclusions: The results suggest no association between risk of gastric cancer and living in the proximity to the industrial facilities as a whole. However, a few associations were detected near some industrial sectors and installations releasing specific pollutants. The authors thank all those who took part in this study by providing questionnaire data. This study was funded by: Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) e grants EVP-1178/14 and GCTRA18022MORE); “Acción Transversal del Cáncer”, approved on the Spanish Ministry Council on October 11, 2007; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP); Spain’s Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416); Carlos III Institute of Health (ISCIII) grants, co-funded by ERDF fundsea way to build Europee (grants PI08/0533, PI08/1359, PI08/1770, PS09/00773, PS09/01286, PS09/01662, PS09/01903, PS09/02078, PI11/00226, PI11/01403, PI11/01810, PI11/01889, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/00613, PI14/01219, PI15/00069, PI15/00914, PI15/01032, PI17-00092, PI17CIII/00034); the Fundación Marqués de Valdecilla (API 10/09); the Junta de Castilla y León (LE22A10-2); the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra); the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10); the Recercaixa (2010ACUP 00310); the European Commission grants FOOD-CT-2006-036224-HIWATE; the Catalan Government-Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850; the Catalan Government DURSI grant 2014SGR647; the Fundación Caja de Ahorros de Asturias; and the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. No

Funding Acknowledgements Type of funding sources: None. Background Left ventricular noncompaction (LVNC) is a heterogeneous entity with a wide phenotypic expression. Risk factors have not been well established and prognostic stratification remains challenging. Purpose Describe prognostic role of CMR on long term outcomes of LVNC patients. Methods Retrospective multicentric longitudinal cohort study of consecutive patients fulfilling imaging diagnostic criteria for LVNC (Jenni echo criteria and Petersen and Jacquier CMR criteria). Demographic, ECG, genetic, family and treatment variables were recorded. Baseline CMR was used for the analysis. LV ejection fraction (LVEF) was categorized according to heart failure (HF) guidelines and late gadolinium enhancement (LGE) was visually assessed in a binary way. End points were HF, ventricular arrhythmias (VA), systemic embolisms (SE) and all-cause death. Major adverse cardiovascular events (MACE) were the combination of the four previous end points. In patients with initially preserved LVEF (≥ 50%), LV adverse remodelling (LVAR) was defined as an LVEF < 50% and/or absolute decrease of ≥10% in LVEF at last follow-up. Results 585 patients from 12 referral centres were included from 2000 to 2018. Age at diagnosis was 45 ± 20 years, 334 (57%) were male, baseline LVEF was 48 ± 17% and 18% presented LGE. During a median follow-up of 5.1 years (IQR 2.3-8.1), 110 (19%) patients presented HF, 87 (15%) VA, 18 (3%) SE and 34 (6%) died. MACE occurred in 223 (38%) patients. LVEF was independently associated with HF, VA, SE and MACE: HR were 1.08, 1.02, 1.04 and 1.02 respectively (all p < 0.05). LGE was more frequent in patients with reduced LVEF (39 Vs 53%, p < 0.001) and was associated with higher HF and VA risk in patients with an LVEF > 35% (HR 2.69 and 2.48 respectively, p < 0.05) (Figure 1). No MACE (0%) occurred during long-term follow-up in patients with preserved LVEF, no LGE as well as no ECG abnormalities and no family aggregation. 305 (52%) patients presented with initially preserved LVEF, and 230 (75%) of those had LVEF available at last follow-up. LVAR occurred in 50 (22%) patients: 22 (10%) had an LVEF < 50% and 41 (18%) an absolute ≥ 10% decrease in LVEF. LGE was independently associated with LVAR (HR 3.51, p = 0.045) (Figure 2). Conclusions Cardiac magnetic resonance has an important prognostic role in LVNC. LVEF is the most powerful predictor of events. Myocardial fibrosis is associated with worse outcomes in patients without severe systolic dysfunction, as well as with left ventricular adverse remodelling in those with initially preserved LVEF. Besides, CMR may identify a low-risk subgroup of LVNC patients. Therefore, CMR should be used in risk stratification in LVNC.

Ablation of macroreentrant atrial tachycardia in patients with mechanical prosthetic valves represents a challenge for electrophysiologists, because of the complexity of the procedure and the potential complications. Moreover, the need for fluoroscopy in this type of procedure is greater, due to the risk of interference between the prosthetic valve and the ablation or mapping catheter. We present two cases of patients with mechanical prosthetic valves and atrial flutter who underwent successful ablation with no complications using the CartoUnivu™ tool, which integrates the electroanatomical map and the fluoroscopy image.

We present a case of sarcomeric hypertrophy cardiomyopathy diagnosed in a child who had hypertrophy degree regression during adolescence, with no left ventricular dysfunction and no increase of the ventricular diameters. (Level of Difficulty: Intermediate.), Graphical abstract, We present a case of sarcomeric hypertrophy cardiomyopathy diagnosed in a child who had hypertrophy degree regression during adolescence, with no left ventricular…

Resumen Introduccion y objetivos En 4 miembros de una familia espanola se identifico una mutacion en los canales cardiacos Nav1.5 (p.R1644H) descrita ya y relacionada con el sindrome de QT largo con anterioridad. Sin embargo, solo 1 de los portadores presentaba el intervalo QT prolongado. En los otros 3 individuos se identifico una nueva mutacion con cambio de sentido en los canales cardiacos Cav1.2 (p.S1961N). En este trabajo se analizaron las caracteristicas funcionales de los canales p.S1961N Cav1.2 para averiguar si dicha mutacion regula la expresividad del sindrome de QT largo en esta familia. Metodos La corriente de calcio tipo L (ICaL) se registro mediante la tecnica de patch-clamp en celulas de ovario de hamster chino transfectadas transitoriamente con los canales cardiacos humanos en su forma nativa o mutada. Resultados La expresion de canales p.S1961N disminuye significativamente la densidad de la ICaL. Al sustituir el ion calcio por bario para suprimir la inactivacion dependiente del calcio de los canales Cav1.2, se demostro que la mutacion acelera significativamente la inactivacion dependiente del voltaje de los canales Cav1.2 y disminuye la constante de tiempo de inactivacion. Como consecuencia, la carga total que atraviesa los canales p.S1961N Cav1.2 disminuye significativamente. Los efectos que las mutaciones p.S1961N Cav1.2 y p.R1644H Nav1.5, por separado o en combinacion, producen sobre las caracteristicas de los potenciales de accion (PA) se simularon mediante un modelo matematico de PA ventriculares humanos. Los resultados demuestran que la mutacion p.S1961N Cav1.2 abrevia la duracion del PA y suprime la prolongacion inducida por la mutacion p.R1644H de los canales Nav1.5. Conclusiones La mutacion p.S1961N en los canales Cav1.2 disminuye la ICaL, un efecto que podria abreviar la duracion de los PA ventriculares humanos. La presencia de esta mutacion que disminuye la funcion de los canales Cav1.2 compensa funcionalmente los efectos producidos por la mutacion de los canales Nav1.5 que aumenta su funcion y prolonga la duracion de los PA.

Three models using partial least squares regression of near infrared reflectance spectroscopy were developed for the first time to evaluate the concentration of total alkaloids as nicotine, total nitrogen and total ash in powdered samples of Cuban cigar tobacco. They had lower standard error of cross-validation (SECV) and standard error of prediction (SEP) than those using: (1) principal components regression; (2) multiple linear regression and (3) other partial least squares models previously published for this and other tobacco types. SECV values in mass fraction units were: 0.0010, 0.0011 and 0.0048, respectively. The coefficients of determination (R2) in calibration were: 0.99, 0.94 and 0.96, respectively. Standard error of prediction values were: 0.0011, 0.0012 and 0.0049, respectively. The r2 obtained when comparing the predicted values using the validation set with the reference data was nearly the same as in calibration. The equation for total alkaloids as nicotine was good for quantification, and for process control, development and applied research according to the quotients range/standard error of prediction and standard deviation/standard error of prediction, respectively. Equations for the other analytes were as good as the one for alkaloids, but suitable only for screening purposes. Joint F-tests on the regression coefficients from ordinary least squares and iterative reweighted least squares fittings among predicted and reference data indicated slopes and intercepts enclosing 1 and 0, respectively. The relative systematic errors between the near infrared spectroscopy predicted values and the reference methods are close to the same figures reported previously for traditional analytical procedures under intermediate precision and reproducibility conditions; hence, the models are suitable for this industrial context.

BACKGROUND The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. OBJECTIVES The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. METHODS Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR) RESULTS After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.092.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction #35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene. CONCLUSIONS In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene. (J Am Coll Cardiol 2021;78:1682-1699) (c) 2021 by the American College of Cardiology Foundation.

Continuous exposure to low doses of persistent organic pollutant (POPs), such as those occurring in the general population, might contribute to the burden of type 2 diabetes mellitus (T2DM). However, evidences from longitudinal studies are scarce. We aimed to explore the associations of accumulated POP exposure with the development of T2DM by means of 1) longitudinal associations with the 16-year incidence of the disease, and 2) complementary cross-sectional analyses with markers of glucose homeostasis at recruitment. Organochlorine pesticide and polychlorinated biphenyl (PCB) concentrations were analyzed in adipose tissue samples and incident T2DM cases were retrieved from clinical records. Homeostatic model assessment values of insulin sensitivity/resistance and β-cell function at recruitment were calculated. Linear and Cox-regression models were performed. In individuals with normal weight/overweight (n = 293), we observed positive dose–response relationships between the studied POPs and T2DM risk, particularly for hexachlorobenzene (HCB) [hazard ratio (HR): 3.96 for 4th quartile versus 1st quartile (Q1); confidence interval (CI) 95%: 0.79, 19.71]. PCB-180 showed a positive but seemingly non-linear association with T2DM risk [HR of 3er quartile (Q3) versus Q1: 6.48; CI 95%: 0.82, 51.29]. Unadjustment for body mass index considerably increased the magnitude of the associations. In the cross-sectional study (n = 180), HCB and PCB-180 were inversely associated with insulin sensitivity and positively associated with insulin resistance parameters. Our results suggest that a higher burden of specific POPs in adipose tissue may disrupt glucose homeostasis, possibly contributing to increase T2DM risk, especially in nonobese adults., Ramon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain) RYC-2016-20155, Instituto de Salud Carlos III, European Commission PI16/01858 PI18/01573 PI20/01568

Background: Some studies have reported an inverse association between type 2 diabetes mellitus (T2DM) and prostate cancer (PCa), but results on this issue are still inconsistent. In this study, we evaluate whether this heterogeneity might be related to differences in this relationship by tumour or by individual genetic susceptibility to PCa. Methods: We studied 1047 incident PCa cases and 1379 randomly selected controls, recruited in 7 Spanish provinces for the population-based MCC-Spain case-control. Tumour were classified by aggressiveness according to the International Society of Urological Pathology (ISUP), and we constructed a PCa polygenic risk score (PRS) as proxy for genetic susceptibility. The epidemiological questionnaire collected detailed self-reported data on T2DM diagnosis and treatment. The association between T2DM status and PCa was studied by fitting mixed logistic regression models, and, for its association by aggressiveness of PCa, with multinomial logistic regression models. To evaluate the possible modulator role of PRS in this relationship, we included the corresponding interaction term in the model, and repeated the analysis stratified by PRS tertiles. Results: Globally, our results showed an inverse association between T2DM and overall PCa limited to grade 1 tumours (ORISUP = 1: 0.72; 95% CI: 0.53-0.98), which could be compatible with a detection bias. However, PCa risk also varied with duration of diabetes treatment -inversely to metformin and positively with insulin-, without differences by aggressiveness. When we considered genetic susceptibility, T2DM was more strongly associated with lower PCa risk in those with lower PRS (ORtertile 1: 0.31; 95% CI: 0.11-0.87), independently of ISUP grade. Conclusions: Our findings reinforce the need to include aggressiveness and susceptibility of PCa, and T2DM treatments in the study of the relationship between both diseases.