Variant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis.

BACKGROUND: Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in EVC or EVC2. Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum. METHODS: We conducted molecular studies in 46 individuals from 43 unrelated families with a preliminary clinical diagnosis of EvC and 3 affected individuals from a family with WAD and retrospectively analysed clinical data. The deleterious effect of selected variants of uncertain significance was evaluated by cellular assays. MAIN RESULTS: We identified pathogenic variants in EVC/EVC2 in affected individuals from 41 of the 43 families with EvC. Patients from each of the two remaining families were found with a homozygous splicing variant in WDR35 and a de novo heterozygous frameshift variant in GLI3, respectively. The phenotype of these patients showed a remarkable overlap with EvC. A novel EVC2 C-terminal truncating variant was identified in the family with WAD. Deep phenotyping of the cohort recapitulated 'classical EvC findings' in the literature and highlighted findings previously undescribed or rarely described as part of EvC. CONCLUSIONS: This study presents the largest cohort of living patients with EvC to date, contributing to better understanding of the full clinical spectrum of EvC. We also provide comprehensive information on the EVC/EVC2 mutational landscape and add GLI3 to the list of genes associated with EvC-like phenotypes.

Comparación de la eficacia y seguridad de flecainida y dronedarona como terapias antiarrítmicas para mantenimiento de ritmo sinusal en fibrilación auricular / Comparison of the efficacy and safety of dronedarone and flecainide as maintenance antiarrhythmic therapy for sinus rhythm in atrial fibrillation

Resumen Introducción y objetivos: Dronedarona y flecainida son antiarrítmicos de primera elección para reducir recurrencias de fibrilación auricular (FA), sin existir estudios que los comparen entre sí. Nuestro objetivo es comparar la eficacia en cuanto a prevención de recurrencias y seguridad de ambos fármacos. Métodos: Estudio retrospectivo en el que se incluyeron 123 pacientes de forma consecutiva en tratamiento con flecainida o dronedarona desde octubre de 2010 hasta febrero de 2013 por FA paroxística (76.4%) y FA persistente (23.6%). Se realizó cardioversión eléctrica en un 7.3% de los pacientes y farmacológica en un 16.3%. La mediana (rango intercuartílico) de seguimiento fue de 301 días (92-474), con una media de 2.8 revisiones por paciente. Se realizó análisis de tiempo hasta el primer evento mediante Kaplan-Meier y regresión de Cox ajustada por un índice de propensión. Resultados: De entre los 123 sujetos incluidos con FA, 71 fueron tratados con flecainida y 52 con dronedarona. Durante el seguimiento se registraron 36 recurrencias y 20 efectos adversos. Se documentaron un 36.6% de recurrencias en los pacientes tratados con flecainida en comparación con un 21% en los tratados con dronedarona (p = 0.073). En el análisis multivariante, dronedarona se mostró al menos tan eficaz como flecainida para prevenir recurrencias de FA (HR: 0.53, IC 95%: 0.20-1.44, p = 0.221) y demostró un perfil de seguridad comparable al de flecainida (HR: 0.68, IC 95%: 0.18-2.53, p = 0.566). Conclusiones: Según nuestra experiencia, dronedarona resulta al menos tan eficaz como flecainida para el mantenimiento de ritmo sinusal, con un buen perfil de tolerabilidad, a pesar de pautarse en pacientes con un perfil clínico más desfavorable.

Abstract Introduction and objectives: Dronedarone and flecainide are the first pharmacological choice to reduce recurrence of atrial fibrillation (AF); however, there are no studies comparing them. A study was performed to compare the efficacy in terms of recurrence of AF and safety of both drugs. Methods: A retrospective cohort study was conducted that included 123 consecutive patients treated with flecainide or dronedarone due to paroxysmal AF (76.4%) or persistent AF (23.6%), from October 2010 to February 2013. Electrical cardioversion was performed in 7.3% of patients and pharmacological cardioversion in 16.3%. The median (interquartile range) follow-up was 301 days (92-474) with a mean of 2.8 reviews per patient. Time to first event analysis was performed using Kaplan-Meier and Cox regression, adjusted for propensity score. Results: Of the 123 consecutive patients with AF included, 71 were on dronedarone and 52 on flecainide. During the follow-up, there were 36 AF recurrences and 20 safety events. There were recurrences in 36.6% of patients treated with flecainide, compared with 21% of those receiving dronedarone (P = .073). Dronedarone showed to be at least as effective as flecainide in preven- ting recurrence of atrial fibrillation (HR: 0.53, 95% CI: 0.20-1.44, P = .221), and demonstrated an acceptable safety profile when compared with flecainide (HR: 0.68, 95% CI: 0.18-2.53, P = .566). Conclusions: In our experience, dronedarone has been at least as effective and safe as flecainide, despite it was most frequently prescribed in patients with worse baseline risk profile.

Experiencia única con macitentán y sildenafilo en el tratamiento de la enfermedad venooclusiva pulmonar / The first experience of pulmonary veno-occlusive disease treatment with macitentan and sildenafil

No disponible

Pericarditis recurrente como presentación en enfermedad de Still del adulto / Recurrent pericarditis as the presenting form of adult Still's disease

No disponible

Impacto pronóstico a largo plazo de la anticoagulación en pacientes en hemodiálisis con fibrilación auricular / Long-term prognostic impact of anticoagulation on patients with atrial fibrillation undergoing hemodialysis

INTRODUCCIÓN Y OBJETIVOS: La evidencia de la eficacia y seguridad de la anticoagulación oral con dicumarínicos en pacientes en hemodiálisis con fibrilación auricular (FA) es controvertida. El objetivo de nuestro estudio es evaluar las implicaciones a nivel pronóstico a largo plazo de la anticoagulación con dicumarínicos en una cohorte de pacientes con FA no valvular en programa de hemodiálisis debido a insuficiencia renal terminal. MÉTODOS: Estudio observacional retrospectivo con inclusión consecutiva de 74 pacientes en hemodiálisis con FA. El periodo de inclusión fue de enero de 2005 a octubre de 2016. Las variables principales fueron mortalidad por todas las causas, reingresos no programados y sangrados. RESULTADOS: La edad media fue de 75 ± 10 años; el 66,2% fueron hombres y 43 pacientes (58,1%) recibieron acenocumarol. Durante una mediana de seguimiento de 2,40 años (IQR = 0,88-4,15), el acenocumarol no demostró beneficio en supervivencia [HR = 0,76, IC 95% (0,35-1,66), p = 0,494]. Sin embargo, los pacientes anticoagulados presentaron más riesgo de hospitalizaciones cardiovasculares recurrentes [IRR=3,94, IC 95% (1,06-14,69), p = 0,041]. Hubo una tendencia a un aumento de hospitalizaciones repetidas de causa isquémica en los pacientes anticoagulados [IRR = 5,80, IC 95% (0,86-39,0), p = 0,071]. Se observó una tendencia estadística hacia un mayor riesgo de sangrados totales recurrentes en los anticoagulados [IRR = 4,43, IC 95% (0,94-20,81), p = 0,059]. CONCLUSIONES: En el presente estudio, la anticoagulación oral con acenocumarol en pacientes en hemodiálisis con FA no supuso un aumento de la supervivencia, y sin embargo, se asoció con un mayor riesgo de hospitalizaciones de causa cardiovascular y una tendencia a mayor riesgo de sangrados totales

INTRODUCTION AND OBJECTIVES: Evidence for the efficacy and safety of oral anticoagulation with dicumarines in patients with atrial fibrillation (AF) on hemodialysis is controversial. The aim of our study is to evaluate the long-term prognostic implications of anticoagulation with dicumarines in a cohort of patients with non-valvular AF on a hemodialysis program due to end-stage renal disease. METHODS: Retrospective, observational study with consecutive inclusion of 74 patients with AF on hemodialysis. The inclusion period was from January 2005 to October 2016. The primary variables were all-cause mortality, non-scheduled readmissions and bleeding during follow-up. RESULTS: Mean age was 75 ± 10 years; 66.2% were men and 43 patients (58.1%) received acenocoumarol. During a median follow-up of 2.40 years (IQR = 0.88-4.15), acenocoumarol showed no survival benefit [HR = 0.76, 95% CI (0.35-1.66), p = 0.494]. However, anticoagulated patients were at increased risk of recurrent cardiovascular hospitalizations [IRR = 3.94, 95% CI (1.06-14.69), p = 0.041]. There was a trend towards an increase in repeated hospitalizations of ischemic cause in anticoagulated patients [IRR = 5.80, 95% CI (0.86-39.0), p = 0.071]. There was a statistical trend towards a higher risk of recurrent total bleeding in patients treated with acenocoumarol [IRR = 4.43, 95% CI (0.94-20.81), p = 0.059]. CONCLUSIONS: In this study, oral anticoagulation with acenocoumarol in patients with AF on hemodialysis did not increase survival. However, it was associated with an increased risk of hospitalizations of cardiovascular causes and a tendency to an increased risk of total bleeding