Role and Diagnostic Performance of Host Epigenome in Respiratory Morbidity after RSV Infection: The EPIRESVi Study.

Background: Respiratory syncytial virus (RSV) infection has been associated with the subsequent development of recurrent wheezing and asthma, although the mechanisms involved are still unknown. We investigate the role of epigenetics in the respiratory morbidity after infection by comparing methylation patterns from children who develop recurrent wheezing (RW-RSV), subsequent asthma (AS-RVS), and those experiencing complete recovery (CR-RSV). Methods: Prospective, observational study of infants aged < 2 years with RSV respiratory infection admitted to hospital and followed-up after discharge for at least three years. According to their clinical course, patients were categorized into subgroups: RW-RSV (n = 36), AS-RSV (n = 9), and CR-RSV (n = 32). The DNA genome-wide methylation pattern was analyzed in whole blood samples, collected during the acute phase of the infection, using the Illumina Infinium Methylation EPIC BeadChip (850K CpG sites). Differences in methylation were determined through a linear regression model adjusted for age, gender and cell composition. Results: Patients who developed respiratory sequelae showed a statistically significant higher proportion of NK and CD8T cells (inferred through a deconvolution approach) than those with complete recovery. We identified 5,097 significant differentially methylated positions (DMPs) when comparing RW-RSV and AS-RVS together against CR-RSV. Methylation profiles affect several genes involved in airway inflammation processes. The most significant DMPs were found to be hypomethylated in cases and therefore generally leading to overexpression of affected genes. The lead CpG position (cg24509398) falls at the gene body of EYA3 (P-value = 2.77×10-10), a tyrosine phosphatase connected with pulmonary vascular remodeling, a key process in the asthma pathology. Logistic regression analysis resulted in a diagnostic epigenetic signature of 3-DMPs (involving genes ZNF2698, LOC102723354 and RPL15/NKIRAS1) that allows to efficiently differentiate sequelae cases from CR-RSV patients (AUC = 1.00). Enrichment pathway analysis reveals the role of the cell cycle checkpoint (FDR P-value = 4.71×10-2), DNA damage (FDP-value = 2.53×10-2), and DNA integrity checkpoint (FDR P-value = 2.56×10-2) in differentiating sequelae from CR-RSV patients. Conclusions: Epigenetic mechanisms might play a fundamental role in the long-term sequelae after RSV infection, contributing to explain the different phenotypes observed.

¿La pregabalina es un fármaco seguro? Insuficiencia cardiaca asociada a pregabalina / Does pregabalin is a safe drug? Heart failure associated with pregabalin

En los estudios clínicos en los que se ha utilizado pregabalina para el dolor neuropático se concluye que es un fármaco seguro. Sin embargo durante la experiencia postcomercialización se han notificado casos de insuficiencia cardiaca congestiva

In all clinical studies that pregabalin has been used for the treatment of neuropathic pain it is concluded that it is a drug insurance. However, during the post-marketing experience they have been reported cases of congestive heart failure

Bloqueo más radiofrecuencia térmica de los nervios esplácnicos. A propósito de un caso / Radiofrequency thermal and splanchnics nerves block

El dolor crónico con etiología multifactorial, requiere un tratamiento multidisciplinario, donde además del manejo farmacológicos y no farmacológico se encuentra el intervencionista, siendo la radiofrecuencia una de las herramientas disponibles

Chronic pain has a multifactorial etiology and requires multidisciplinary treatment, where the interventionist is in addition to pharmacological and non-pharmacological management, radio frequency being one of the tools available

Cirugía de cono en la enfermedad de Ebstein. Primeros casos / The cone technique for Ebstein Repair. First cases

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Beating-heart aortic arch surgery in neonates and infants.

OBJECTIVES: Aortic arch repair has been shifted from deep hypothermia plus circulatory arrest to cerebral perfusion at tepid temperatures. A step forward is a simultaneous brain-coronary perfusion, allowing beating-heart arch surgery. METHODS: A 'Y' cannula from the arterial line delivers oxygenated blood to brain and heart. The arch is repaired on a beating heart at 25°C. Intracardiac repair is performed after running cardioplegia through the root line. Fifty patients are classified into 3 groups: A, Norwood (8 neonates); B, aortic arch (14 children) and C, aortic arch plus intracardiac repair (28 patients). Associated anomalies in Group C are as follows: ventricular septal defect (10), arterial switch (5), atrial septal defect (4), cor triatriatum (3), aortic commissurotomy (2), comprehensive repair (2), ostium primum (1) and Yasui (1). RESULTS: The mean bypass time was 161 ± 54.44 (range 93-312) min. Mean brain-coronary perfusion was 37.26 ± 10.54 (18-60) min. Mean coronary ischaemia was 31 ± 32.40 (0-160) min. The heart was not arrested in Group B patients. Follow-up was complete for a mean of 30 (1-48) months. Four patients died in the postoperative period. Two required angioplasty for recoarctation. CONCLUSIONS: Selective brain-coronary perfusion is feasible and easy to switch to conventional cardioplegia delivery. Coronary ischaemia can be notably reduced and even 0 min in isolated arch surgery.

Myocarditis, flail tricuspid valve, and normal rhythm: an exceptional form of neonatal cardiac lupus.

Neonatal cardiac lupus is a rare, passively acquired autoimmune disease. We report a case of in utero myocarditis, confirmed postnatally, with papillary muscle rupture and severe tricuspid regurgitation after birth in the absence of conduction disturbances. Tricuspid repair was successfully performed with polytetrafluoroethylene neochordae. In this article, we discuss the pathophysiology, medical and surgical management, and implications at follow-up in this unique scenario.

Pediatric Heart Transplantation With Lecompte Maneuver Owing to Extremely Oversized Donor Allograft.

The techniques and outcomes of heart transplantation in the pediatric population continue to improve over the years, although the supply of organs remains limited. Donor-to-recipient size matching is critical, especially in neonates and small infants. We present a novel strategy for heart transplantation that includes the Lecompte maneuver because of the features of the donor allograft available in a 8-month-old patient with a cardiac fibroma. We discuss the basis principles for extending the indication of this procedure to exceptional transplantation scenarios and describe the results at long-term follow-up.

How to set-up a program of minimally-invasive surgery for congenital heart defects.

BACKGROUND: Mid-line sternotomy is the commonest incision for cardiac surgery. Alternative approaches are becoming fashionable in many centres, amidst some reluctance because of learning curves and overall complexity. Our recent experience in starting a new program on minimally invasive pediatric cardiac surgery is presented. The rationale for a stepwise onset and the short-medium term results for a three-year span are displayed. METHODS: A three-step schedule is planned: First, an experienced surgeon (A) starts performing simple cases. Second, new surgeons (B, C, D, E) are introduced to the minimally invasive techniques according to their own proficiency and skills. Third, the new adopters are enhanced to suggest and develop further minimally invasive approaches. Two quality markers are defined: conversion rate and complications. RESULTS: In part one, surgeon A performs sub-mammary, axillary and lower mini-sternotomy approaches for simple cardiac defects. In part two, surgeons B, C, D and E are customly introduced to such incisions. In part three, new approaches such as upper mini-sternotomy, postero-lateral thoracotomy and video-assisted mini-thoracotomy are introduced after being suggested and developed by surgeons B, C and E, as well as an algorithm to match cardiac conditions and age/weight to a given alternative approach. The conversion rate is one out of 148 patients. Two major complications were recorded, none of them related to our alternative approach. Four minor complications linked to the new incision were registered. The minimally invasive to mid-line sternotomy ratio rose from 20% in the first year to 40% in the third year. CONCLUSIONS: Minimally invasive pediatric cardiac surgery is becoming a common procedure worldwide. Our schedule to set up a program proves beneficial. The three-step approach has been successful in our experience, allowing a tailored training for every new surgeon and enhancing the enthusiasm in developing further strategies on their own. Recording conversion-rates and complications stands for quality standards. A twofold increase in minimally invasive procedures was observed in two years. The short-medium term results after three years are excellent.

Split-graft technique in neonatal heart transplant for aortic atresia.

We describe a neonate with aortic atresia and hypoplastic aorta, listed for heart transplant after extracorporeal membrane oxygenation resuscitation and ductal stenting. The donor aorta was detached from the graft, after an isolated arch reconstruction prior to the transplant itself in a routine fashion. To the best of our knowledge, this is the first reported case of neonatal arch reconstruction before transplantation performed with grafts from the same donor in a split-way strategy.

Batista Procedure for a Coronary Anomaly in an Infant: Long-Term Follow-Up.

A partial left ventriculectomy (Batista operation) is extremely unusual in infants. Follow-up data are unknown. We report the findings at long-term follow-up in an infant after the Batista procedure, following reimplantation of an anomalous coronary artery. The initial approach and options for management are discussed, along with late cardiac remodeling. doi: 10.1111/jocs.12775 (J Card Surg 2016;31:556-558).

Combined Ablation and Exclusion of the Left Atrial Appendage in a Pediatric Patient: A Minimally Invasive Simplified Approach.

We present the first reported case of totally video-assisted thoracoscopic surgery for combined ablation and external exclusion without appendectomy of the left atrial appendage. We encourage the use of video-assisted thoracoscopic surgery for a combined procedure of epicardial radiofrequency ablation and external exclusion without appendectomy to achieve a safe and complete electrical isolation of the left atrial appendage in children with focal atrial tachycardia. In our opinion, the external exclusion of the appendage has several advantages: it presents minimal risk of bleeding (especially in the pediatric population), and the clip can be retrieved if the circumflex artery is distorted.

End-stage ischemic heart failure and Williams-Beuren syndrome: A unique scenario for pediatric heart transplantation.

WBS is a rare disorder caused by mutations in the chromosomal sub-band 7q11.23 involving the elastin gene. The clinical features (craniofacial, developmental, and cardiovascular abnormalities) are variable. The association with cardiac anomalies is a well-recognized feature, and SVAS is the most common cardiac defect found. End-stage ischemic heart disease is unusual in this setting but when it occurs, OHT remains the final therapeutic option. This decision can be difficult to determine, and it must be tailored to the individual patient based on the clinical status and concomitant cardiovascular and multisystem lesions. To date, no cases of OHT in patients with WBS have been described. We present a 14-month-old patient with WBS who developed severe LV dysfunction secondary to ischemia following a complex staged surgery for SVAS repair. He underwent successful OHT with no post-operative complications, and at three-month follow-up, he remains asymptomatic on standard immunosuppressive therapy. This case constitutes the first demonstration that OHT may be indicated for extended survival in selected children with WBS and we discuss the basic principles for extending the indication for OHT to this scenario as well as the particularities for post-transplant care.

[15 years of minimally invasive paediatric cardiac surgery; development and trends]. / 15 años de cirugía cardiaca infantil miniinvasiva; evolución y tendencias.

INTRODUCTION: The minimally invasive approach is seldom reported in paediatric cardiac surgery. Teams gathering experience are scarce, with programs focused on simple cases. The experience is presented on a series of over 200 cases operated on in the past 15 years. MATERIAL AND METHODS: A sub-mammary approach program was started in 2000, which was gradually extended to include more complex and younger patients. The axillary incision was adopted in 2009, following the same steps. In 2013, the mini-sternotomy incision was introduced, increasing our armamentarium. From July 2000 until December 2014, 203 patients were operated on. The sub-mammary approach was used in 102 cases, axillary in 50 patients, mini-sternotomy in 44, postero-lateral thoracotomy in 4 cases, and upper mini-sternotomy in 3. RESULTS: By diagnosis, ostium secundum atrial septal defect was the most common (128), followed by sinus venosus (20), ventricular septal defect (20), ostium primum (16), and others (19). One patient was converted to sternotomy. No neurological events were detected. The mean age was 7.8/3.7 and 1.8 years, and the mean weight was 28.1/16.1 and 9.4 Kg. in the sub-mammary, axillary and mini-sternotomy approaches, respectively. The aesthetic results were excellent. CONCLUSIONS: Based on our 15 years of experience, minimally invasive surgery is safe and yields excellent cosmetic results. The gradual introduction of alternative approaches (sub-mammary, axillary, mini-sternotomy) allowed us to set-up guidelines and learning curves. The wide range of incisions enables the most appropriate one to be selected depending on age/weight and cardiac condition.

Orthotopic Heart Transplantation in an Adult Patient with Heterotaxy Syndrome: Surgical Implications.

Modified techniques for orthotopic heart transplantation are mandatory when complex congenital anomalies are associated in adult patients. An unusual case of a heterotaxy syndrome and dilated cardiomyopathy following mitral ring annuloplasty is presented in a 62-year-old male. Orthotopic cardiac transplantation was performed by using a modified operative strategy: selective peripheral and central venous cannulation according to the thoraco-abdominal venous challenges, biatrial technique, and preservation of venous drainage via the native coronary sinus. We discuss the anatomical features of heterotaxy in adult patients and surgical approaches when heart transplantation is needed.

Evolución del impacto de la cardiopatía isquémica en la reincorporación laboral de trabajadores españoles / Evolution of ischemic cardiopathy impact on spanish workers on their return to work

INTRODUCCIÓN: La cardiopatía isquémica es una de las principales causas de morbimortalidad en los países desarrollados dificultando la vuelta al trabajo de estos pacientes. Pretendemos estudiar la evolución de la incapacidad Temporal y Permanente en trabajadores españoles que causan baja por cardiopatía isquémica, así como analizar las variables que influyen en la reincorporación laboral. MATERIAL Y MÉTODOS: Estudio observacional retrospectivo de cohortes con pacientes menores 65 años que sufrieron un infarto agudo de miocardio (IAM) entre Enero de 2000 y mayo de 2011. Se recogieron datos clínicos, demográficos, socioeconómicos y laborales para analizar su relación con la reincorporación laboral. RESULTADOS: Se seleccionaron un total de 5067 pacientes, el 94% varones, y con una edad media de 54,3 años. Un total de 3.679 pacientes (72,6%) se reincorporaron a su actividad laboral tras el infarto, mientras que 1261 (24,9%) obtuvieron la incapacidad laboral permanente. La mayores tasas de incapacidad laboral se observan en los pacientes > 50 años, en los que han sufrido un mayor daño cardiaco (FEVI < 50%), en aquellos con un mayor número de arterias coronarias obstruidas y los que fueron revascularizados mediante cirugía. En cuanto a las variables socioeconómicas se reincorporan menos los trabajadores con salarios más bajos, los trabajadores por cuenta ajena y los que realizan trabajos en los que predomina la carga física y manual frente a las profesiones en que predomina el trabajo intelectual. No encontramos diferencias con respecto a la tasa de reincorporación entre hombres y mujeres o en función del diagnóstico que motivó la baja (síndrome coronario agudo vs. angina). Observamos que la tasa de reincorporación laboral se ha incrementado de forma progresiva en la última década. (Desde tasas de reincorporación del 60% en el 2000-2002 a tasas superiores al 80% a partir de 2010) Este incremento se observa en todos los sectores ocupacionales como en todos los tramos etarios en los que se distribuye la muestra CONCLUSIONES: En nuestro estudio se observa un aumento progresivo en los últimos años en el porcentaje de pacientes que se reincorporan al trabajo. Las variables que mejor predicen la reincorporación laboral tras sufrir una baja por cardiopatía isquémica son viables clínicas como la extensión del daño miocárdico (FEVI <50%/FEVI >50%) y el procedimiento de revascularización empleado (percutáneo/cirugía) así como las variables socioeconómicas referentes al tipo de trabajo (autónomo/cuenta ajena), ocupación profesional (carga física/carga intelectual) y la edad del trabajador

BACKGROUND: Ischemic cardiopathy is one of the main causes of morbidity and mortality in developed countries. It affects the patients quality of life and interferes with their return to work, thus generating a significant economic cost. The aim of our study is to assess labor conditions of patients who suffered an acute myocardial infarction (AMI), highlighting the factors that could have an impact on their return-to-work time. MATERIALS AND METHODS: Observational retrospective study with patients under 65 years old who suffered an AMI between January 2000 and May 2011. Data concerning clinical, social, demographic and labor circumstances was collected to better understand its relation with the return to work. RESULTS: A total of 5.067 patients with Coronary Heart Disease (hereinafter referred to as CHD) were selected. 94% of the samples were men, under 54.3 years old. 3679 out of 5067 patients (72. 6%) returned to work after a heart infarct whereas 1261 (24.9%) did not return, obtaining the permanent incapacity to work. Among the clinical and patient factors, the main determinants were age (mostly <50 years), severity of AMI, poor left ventricular function (EF >50% / EF >50%) and revascularization procedures (percutaneous coronary interventions -PCI- and coronary artery bypass graft surgery, CABG). Regarding the economic and job-related factors three variables were found to be the strongest predictors of returning to work: job demands (physically demanding jobs vs. intellectually demanding jobs), incomes and job conditions (self-employment vs. employees). There were no significant differences on the returning-to-work rate between men or women or between sick leave due to an acute coronary syndrome or due to an angina. We observed that the return-to-work activity increased gradually from 2000-2011 (from rates of 60% in 2000-2002 to over 80% in 2010). This increase is present in all occupational activities as well as in all age ranges. CONCLUSION: In our study we observed a gradual increase of patients returning to work in recent years. The variables used to better predict the return-to-work time in a period of sick leave after a CHD episode are categorized as follows: clinic viable like the extent of myocardial damage (LVEF <50%/LVEF >50%) and the revascularization procedures (Percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery, CABG), socioeconomic variables related to the kind of job (self-employment vs. employees) and lastly labor conditions like job demands (physical-demanding jobs vs. intellectual-demanding jobs) or age

Surgical Management of Vascular Stents in Pediatric Cardiac Surgery: Clues for a Staged Partnership.

Complex cases undergo step surgical and percutaneous procedures, including stent deployment. Concerns arise on stent removal at latest surgery. Our initial experience is presented. Forty-six stents in 35 patients were partially or totally removed at surgery. Univentricular heart was diagnosed in 20 patients. Stents were previously deployed in: ductus (6), right ventricle outflow tract (12), atrial septal defect (4), right pulmonary artery (4), left pulmonary artery (16), inferior vena cava (2), superior vena cava (1) and ascending aorta (1). Surgical procedures performed: 9 transplants, 6 Fontan, 4 Glenn, 1 comprehensive repair (Norwood + Glenn), 1 Glenn takedown, 8 conduit replacement, 2 Fallot, 2 Rastelli, 1 ventricular septal defect closure and 1 iatrogenic aortopulmonary window. Five ductal stents were clipped. Eleven stents in right ventricle, four ones in atrial septal defect, two in right pulmonary artery, seven in the left pulmonary artery and two in inferior vena cava were completely removed. Two stents in right pulmonary artery, one in superior vena cava, one in ascending aorta and nine in the left pulmonary artery were partially retrieved. Handling the stents in ductus, right ventricle and atrial septal defect was straightforward. On the contrary, stent removal in the ductus (comprehensive case), pulmonary branches, both vena cavae or aorta required short periods of deep hypothermia with circulatory arrest. Surgery over stents is increasing in complex, step procedures. Univentricular hearts are most prevalent. Congenital transplant surgery faces new challenges. Stent removal at the time of surgery may require deep hypothermic circulatory arrest.

Truncus arteriosus, tricuspid atresia and partial anomalous pulmonary venous drainage: a unique form of univentricular heart.

We present the first reported case of truncus arteriosus, tricuspid atresia and partial anomalous pulmonary venous drainage into a retro-aortic innominate vein in a neonate in whom successful palliation was performed using a two-staged procedure. An early repair after presentation along with a re-routing of anomalous pulmonary venous drainage at the time of the second stage should be undertaken to optimize the patient's haemodynamic status prior to a Fontan completion.

Modified Fontan Conversion: An Alternative Technique for Adult Patients.

A need persists for Fontan conversion that provides alternative approaches for the individual anatomical challenges occurring in these unusual and complex adult patients. The pulmonary arteries present unique variations and the surgical technique needs to be intraoperatively addressed. We describe a technique for Fontan conversion for performing the distal anastomosis of the extracardiac conduit, allowing adequate matching to the pulmonary arteries and preserving an optimal flow into the Fontan circuit.

Atresia valvular aórtica o hipoplasia grave y comunicación interventricular: estrategias de corrección biventricular y resultados a medio plazo / Aortic valve atresia or severe hypoplasia and ventricular septal defect: surgical strategies for biventricular repair and mid-term results

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