Initial experience with a homemade "hybrid-tome" for needle-knife precut in patients with difficult biliary cannulation.

Background and study aims Current clinical guidelines recommend needle-knife precut (NKP) as the primary and best method for performing a biliary cannulation (BC) when simple techniques fail and the criteria are met for difficult BC (DBC). However, many endoscopists avoid or defer early NKP in favor of alternative, simpler techniques that have not been shown to be either safer or more effective. Our goal is to test a device that provides the needle-knife papillotome (NKPT) with traction capability and which can facilitate the learning and execution of NKP. Patients and methods This was a descriptive bicentric observational study of a personal cohort of patients undergoing early NKP to analyse the efficacy and safety of the technique with a "hybrid-tome" (HT) built using the isolated core of a NKPT and a conventional canulotome. Results Over a 4-year period, we performed 43 NKPs with the HT, achieving BC in one or two steps in all cases. The 100 % technical success was matched by a 95 % clinical success rate. We recorded 11 adverse events (23 %): five hemorrhages, four pancreatitis, and two cholangitis. In addition to the objective data, we confirmed that HT facilitates alignment with the duodenal papilla and the execution of pre-cutting, especially if the papilla is intradiverticular or hidden by folds. Conclusions The HT tested seems to help trained endoscopists to perform NKP, especially in some anatomic situations, which can improve compliance with the guidelines recommended for early NKP in patients with DBC.

Flexible endoscopic treatment of Zenker's diverticulum: thirteen years' experience in Spain.

INTRODUCTION: Flexible endoscopic treatment is one of the alternative approaches for the management of Zenker's diverticum. The present paper shows our short-term and long-term results with flexible endoscopic cricopharyngeal myotomy/septotomy. PATIENTS AND METHODS: A retrospective analysis of our experience in patients with Zenker's diverticulum treated using a flexible endoscope, assisted by a flexible diverticuloscope, between 2002 and 2015. Myotomy/septotomy was performed with a needle-knife papillotome under deep sedation or general anesthesia. RESULTS: Among the 64 patients treated, two died within 10 days of surgery from causes not directly related to the procedure, and one presented with pharyngo-esophageal perforation, which recovered with conservative management at 47 days after admission. Four additional patients were lost to short-term follow-up. Among the 57 remaining patients, 52 had complete relief of dysphagia after 6 weeks. Eleven of these had recurrent symptoms on the mid and the long term. Eight were retreated with the same flexible endoscopic technique, one with a hybrid endoscopic approach, one with classical open surgery and one refused retreatment. After a mean follow-up of 2 years and a half, 33 of 37 patients reported absent or minimal dysphagia, controllable with punctual dietary restrictions. CONCLUSIONS: Flexible endoscopic treatment for Zenker's diverticulum is effective and safe. It represents an option on an equal footing to rigid endoscopy and classical open surgery and may also be used when the latter two are technically impracticable or contraindicated.

Phenotype and prognostic correlations of the converter region mutations affecting the ß myosin heavy chain.

OBJECTIVES: The prognostic value of genetic studies in cardiomyopathies is still controversial. Our objective was to evaluate the outcome of patients with cardiomyopathy with mutations in the converter domain of ß myosin heavy chain (MYH7). METHODS: Clinical characteristics and survival of 117 affected members with mutations in the converter domain of MYH7 were compared with 409 patients described in the literature with mutations in the same region. RESULTS: Twenty-five mutations were evaluated (9 in our families including 3 novel (Ile730Asn, Asp717Gly and Arg719Pro)). Clinical diagnoses were hypertrophic (n=407), dilated (n=15), non-compaction (n=4) and restrictive (n=5) cardiomyopathies, unspecified cardiomyopathy (n=11), sudden death (n=50) and 35 healthy carriers. One hundred eighty-four had events (cardiovascular death or transplant). Median event-free survival was 50±2 years in our patients and 53±3 years in the literature (p=0.27). There were significant differences in the outcome between mutation: Ile736Thr had fewer events than other mutations in the region (p=0.01), while Arg719Gln (p<0.01) had reduced event-free survival. CONCLUSIONS: Mutations in the converter region are generally associated with adverse prognosis although there are differences between mutations. The identification of a mutation in this particular region provides important prognostic information that should be considered in the clinical management of affected patients.

p.D1690N Nav1.5 rescues p.G1748D mutation gating defects in a compound heterozygous Brugada syndrome patient.

BACKGROUND: We identified 2 compound heterozygous mutations (p.D1690N and p.G1748D) in the SCN5A gene encoding cardiac Na(+) channels (Nav1.5) in a proband diagnosed with Brugada syndrome type 1. Furthermore, in the allele encoding the p.D1690N mutation, the p.H558R polymorphism was also detected. OBJECTIVE: The purpose of this study was to analyze the functional properties of the mutated channels as well as the putative modulator effects produced by the presence of the polymorphism. METHODS: Wild-type and mutated human Nav1.5 channels were expressed in Chinese hamster ovary cells and recorded using whole-cell patch-clamp technique. RESULTS: Separately, both p.D1690N and p.G1748D mutations produced a marked reduction in peak Na(+) current density (>80%), mainly due to their limited trafficking toward the membrane. Furthermore, p.G1748D mutation profoundly affected channel gating. Both p.D1690N and p.G1748D produced a marked dominant negative effect when cotransfected with either wild-type or p.H558R channels. Conversely, p.H558R was able to rescue defective trafficking of p.D1690N channels toward the membrane when both polymorphism and mutation were in the same construct. Surprisingly, cotransfection with p.D1690N, either alone or together with the polymorphism (p.H558R-D1690N), completely restored the profound gating defects exhibited by p.G1748D channels but only slightly rescued their trafficking. CONCLUSIONS: Our results add further support to the hypothesis that Nav1.5 subunits interact among them before trafficking toward the membrane and suggest that a missense mutation can "rescue" the defective gating produced by another missense mutation.

Análisis de la tasa de detección mediante ecografía de fetos con crecimiento intrauterino restringido y pequeño para la edad gestacional / Detection rate by ultrasound in fetuses with intrauterine growth restriction and small for gestational age

Objetivo: Analizar la tasa de detección de fetos pequeños para la edad gestacional (PEG) y crecimiento intrauterino restringido (CIR) mediante exploración ecográfica. Método: Estudio retrospectivo de casos y controles. Recién nacidos (RN) de gestaciones únicas a término (entre la semana 37-42) en el Hospital Universitario San Cecilio entre 2009 y 2010. Grupo casos: 98 RN a término con peso al nacer < 2500 g, con peso fetal estimado (PFE) por ecografía en el III trimestre. Grupo control: 100 RN durante el mismo período con peso al nacer entre 3000-4000 g, con PFE por ecografía en el III trimestre obtenido de forma aleatoria. Resultados: La tasa de detección de CIR tipo I fue de un 11,1 por ciento con una incidencia del 0,1 por ciento y la tasa de detección de pequeños para edad gestacional fue de un 56,5 por ciento con una incidencia del 2 por ciento respecto al total de RN. Conclusión: En nuestra experiencia la EPF mediante ecografía en fetos con peso bajo el p10 tiene un error de 6 por ciento respecto al peso neonatal, esto permite una adecuada identificación de fetos con PEG y CIR.

Objective: To analyze the detection rate of small for gestational age (SGA) fetuses and intrauterine growth restriction (IUGR) fetuses by ultrasound exploration. Methods: Cases and controls retrospective study. Material: Newborn (NB) of singleton pregnancies at term (between 37 and 42 weeks) at the Hospital Universitario San Cecilio between 2009 and 2010 both inclusive. Cases group: 98 at term NB with a birth weight < 2500 g; and an estimated fetal weight (EFW) by ultrasound in the 3rd trimester. Controls Group: 100 NB during the same period of time with birth weight between 3000-4000g, with EFW by ultrasound in the 3rd trimester randomly extracted. Results: The detection rate of small for gestational age infants born was 56.5 percent with 2 percent of incidence and the detection rate of intrauterine growth restriction type I was 11.1 percent with 0.1 percent of incidence within the total number of newborns in the period from 2009 to 2010. Conclusion: In our experience, EPF ultrasound in fetuses with weight below the 10th percentile has an error of 6 percent compared to birth weight, this allows proper identification of fetuses with SGA and IUGR.

Severe cardiac conduction disturbances and pacemaker implantation in patients with hypertrophic cardiomyopathy.

The aims of this study were to determine the prevalence of severe cardiac conduction disturbances in a cohort of 451 patients with hypertrophic cardiomyopathy and to describe the characteristics of, and outcomes in, those who required a permanent pacemaker. A pacemaker was implanted in 48 patients (11%): 20 had sinus node dysfunction and 28 had an atrioventricular conduction disturbance. Primary bradyarrhythmia (which was not related to iatrogenic atrioventricular block or therapeutic ablation of the atrioventricular node) was the reason for permanent pacemaker implantation in 36 patients (8%). In 18% of cases, at least one other family member had a permanent pacemaker. In this patient series, a high prevalence of severe cardiac conduction disturbance leading to permanent pacemaker implantation was observed. Severe cardiac conduction disturbance in hypertrophic cardiomyopathy may also have a familial component.

The R820W mutation in the MYBPC3 gene, associated with hypertrophic cardiomyopathy in cats, causes hypertrophic cardiomyopathy and left ventricular non-compaction in humans.

BACKGROUND: The R820W mutation in the MYBPC3 gene has been associated with the development of hypertrophic cardiomyopathy (HCM) in rag-doll cats, but had not been described in humans. AIMS: To describe the phenotype associated with the R820W mutation identified in a human family. METHODS: The R820W was identified by direct sequencing of the MYBPC3 gene in a 47 year old woman with HCM and left ventricular non-compaction (LVNC). Clinical and genetic studies of the R820W mutation were performed in her family. RESULTS: The index patient was homozygous for the mutation and had no additional mutations in the main sarcomeric genes (MYH7, TNNT2, TNNI3, and TPM1). She had HCM with LVNC and normal systolic function. One brother had died suddenly at age 43 years. Another brother diagnosed of LVNC with severe systolic dysfunction and a cardiac arrest was also homozygous for the mutation. One heterozygous 31 year old sister, and three heterozygous sons of the index (ages 14, 20 and 23 years old) were clinically unaffected. The father of the index was apparently healthy and her mother had atrial fibrillation and an electrocardiographic diagnosis of left ventricular hypertrophy at age 86 years. CONCLUSION: The R820W mutation in the MYBPC3 gene, previously associated with HCM in rag-doll cats, causes both HCM and LVNC in homozygous human carriers, with mild or null clinical expression in heterozygous carriers.

Eficacia de la tromboprofilaxis obstétrica / Efficacy of obstetrical tromboprophylaxis

Valorar la incidencia de enfermedad tromboembólica durante el embarazo, parto y puerperio en gestantes con riesgo y la efectividad de las tromboprofilaxis. Seguimiento de 2 727 gestantes con parto durante un año. Se realiza análisis descriptivo de nuestra población, de los factores de riesgo y de la duración de la tromboprofilaxis, analizando su relación con la incidencia de eventos tromboembólicos. Hospital Universitario San Cecilio de Granada, España. Nuestras gestantes tienen pocos factores de riesgo: cesárea, anemia posquirúrgica, tabaquismo, hipertensión inducida por el embarazo o previa, diabetes, cardiopatía y trombofilia, siendo la cesárea y la anemia los más frecuentes. La tromboprofilaxis postcesárea con nadroparina cálcica 0,4 diaria durante su hospitalización ha sido efectiva. No hubo ningún tromboembolismo. En nuestra población, con un adecuado control obstétrico y profilaxis con antiagregantes plaquetarios y/o heparinas de bajo peso molecular, se han evitado eventos tromboembólicos relacionados con el embarazo, parto puerperio.

[Effectiveness of maintenance azathioprine therapy without oral cyclosporine after severe attacks of ulcerative colitis refractory to endovenous steroids]. / Eficacia del mantenimiento con azatioprina sin ciclosporina oral tras un brote grave de colitis ulcerosa refractario a esteroides intravenosos.

INTRODUCTION: Intravenous (i.v.) cyclosporine (CsA) has proved effective in controlling acute attacks of ulcerative colitis unresponsive to IV steroids. After the initial response to i.v. CsA, two alternatives for maintaining remission have been proposed: either double or triple association with immunosuppressors. The aim of this study was to evaluate the effectiveness of i.v. CsA, its adverse effects, and the subsequent long-term effectiveness of azathioprine/6-mercaptopurine without oral CsA. MATERIAL AND METHODS: Intravenous CsA was administered for 10 days, at a dose of 4 mg/kg per day, to 20 patients diagnosed with a severe attack of ulcerative colitis who did not respond to IV steroid treatment. Patients who responded to CsA and could be discharged were administered azathioprine or 6-mercaptopurine associated with a decreasing dose of oral steroids, without oral CsA. RESULTS: Sixty per cent (12/20) of the patients showed clinical-biological improvement after CsA administration, thus avoiding colectomy, and were discharged from hospital. Nine of the 12 responders (three withdrew from the study) were followed-up long term. Of these nine patients, four (44.4%) underwent colectomy, all before the sixth month of discharge. All adverse effects were mild, except for one death. CONCLUSIONS: Intravenous CsA is effective in inducing remission of ulcerative colitis in severe attacks resistant to i.v. steroids. When treatment with azathioprine is administered without oral CsA, patients requiring colectomy need this procedure within the first 6 months of discharge.