Safety and effectiveness of direct-acting antiviral drugs in the treatment of hepatitis C in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) management in Inflammatory Bowel Disease (IBD) is uncertain. The ECCO guidelines 2021 recommended HCV treatment but warn about the risk of IBD reactivation. We aimed to evaluate 1) the effectiveness and safety of direct-acting antivirals (DAAs) in IBD; 2) the interaction of DAAs with IBD drugs. METHODS: Multicentre study of IBD patients and HCV treated with DAAs. Variables related to liver diseases and IBD, as well as adverse events (AEs) and drug interactions, were recorded. McNemar's test was used to assess differences in the proportion of active IBD during the study period. RESULTS: We included 79 patients with IBD and HCV treated with DAAs from 25,998 IBD patients of the ENEIDA registry. Thirty-one (39.2 %) received immunomodulators/biologics. There were no significant differences in the percentage of active IBD at the beginning (n = 11, 13.9 %) or at the 12-week follow-up after DAAs (n = 15, 19 %) (p = 0.424). Sustained viral response occurred in 96.2 % (n = 76). A total of 8 (10.1 %) AEs occurred and these were unrelated to activity, type of IBD, liver fibrosis, immunosuppressants/biologics, and DAAs. CONCLUSIONS: We demonstrate a high efficacy and safety of DAAs in patients with IBD and HCV irrespective of activity and treatment of IBD.

Low-dose chest CT for preoperative screening for SARS-CoV-2 infection.

INTRODUCTION: This study aimed to evaluate the role of chest computed tomography (CT) in complementing reverse transcription polymerase chain reaction (RT-PCR) in asymptomatic candidates for elective surgery in the context of the COVID-19 pandemic. MATERIAL AND METHODS: We prospectively included 464 asymptomatic patients who underwent a triple screening workup for SARS-CoV-2 infection (health questionnaire, RT-PCR, and low-dose chest CT) during the 48 h prior to undergoing elective surgery. A positive RT-PCR and/or CT findings suggestive of COVID-19 (CO-RADS 4/5) were considered diagnostic criteria for SARS-CoV-2 infection. RESULTS: Most patients (64.7%) underwent otorhinolaryngology surgery. No patients had positive RT-PCR results or symptoms suggestive of SARS-CoV-2 in the health questionnaire. Only 22 (4.7%) had signs compatible with lung infection; in 20 of these, the CT findings were atypical or indeterminate for COVID-19 (CO-RADS 2/3) and in 2 they were compatible with COVID-19 pneumonia in resolution. In the immediate postoperative period, no cases of SARS-CoV-2 infection were confirmed. CONCLUSION: In our series of asymptomatic patients, low-dose CT did not add any value to the results of RT-PCR and a health questionnaire in preoperative screening for SARS-CoV-2.

High-efficiency grating coupler for an ultralow-loss Si3N4-based platform.

Integrated silicon nitride waveguides of 100 nm height can achieve ultralow propagation losses below 0.1 dB/cm at the 1550 nm wavelength band but lack the scattering strength to form efficient grating couplers. An enhanced grating coupler design based on an amorphous silicon layer on top of silicon nitride is proposed and demonstrated to improve the directionality of the coupler. The fabrication process is optimized for a self-alignment process between the amorphous silicon and silicon nitride layers without increasing waveguide losses. Experimental coupling losses of 5 dB and a 3 dB bandwidth of 75 nm are achieved with both regular and focusing designs.

[Low-dose chest CT for preoperative screening for SARS-CoV-2 infection]. / TC torácica de baja dosis de radiación como técnica de cribado preoperatorio de infección por SARS-CoV-2.

Introduction: This study aimed to evaluate the role of chest computed tomography (CT) in complementing reverse transcription polymerase chain reaction (RT-PCR) in asymptomatic candidates for elective surgery in the context of the COVID-19 pandemic. Material and methods: We prospectively included 464 asymptomatic patients who underwent a triple screening workup for SARS-CoV-2 infection (health questionnaire, RT-PCR, and low-dose chest CT) during the 48 hours prior to undergoing elective surgery. A positive RT-PCR and/or CT findings suggestive of COVID-19 (CO-RADS 4 / 5) were considered diagnostic criteria for SARS-CoV-2 infection. Results: Most patients (64.7%) underwent otorhinolaryngology surgery. No patients had positive RT-PCR results or symptoms suggestive of SARS-CoV-2 in the health questionnaire. Only 22 (4.7%) had signs compatible with lung infection; in 20 of these, the CT findings were atypical or indeterminate for COVID-19 (CO-RADS 2 / 3) and in 2 they were compatible with COVID-19 pneumonia in resolution. In the immediate postoperative period, no cases of SARS-CoV-2 infection were confirmed. Conclusion: In our series of asymptomatic patients, low-dose CT did not add any value to the results of RT-PCR and a health questionnaire in preoperative screening for SARS-CoV-2.

Serial voiding urosonography in posterior urethral valve diagnosis and management in pediatric patients. / Urosonografía miccional seriada en el diagnóstico y manejo de las válvulas de uretra posterior en pacientes pediátricos.

OBJECTIVES: Report our experience with the use of contrast-enhanced serial voiding urosonography (SVU) for posterior urethral valve (PUV) patient diagnosis and management. MATERIAL AND METHODS: Descriptive retrospective study in 0- to 14-year-old patients with suspected PUV at SVU performed as a first contrast-enhanced urinary tract test with subsequent cystoscopic study. Variables were analyzed using SPSSv22. RESULTS: 18 patients were studied (median age: 6 months). Most patients (15) presented posterior urethral dilatation (mean diameter: 9.56 mm) and a >2 mm gap between proximal and distal urethra. 13 cases had bladder thickening and 9 had VUR. 15 PUV cases, 1 case of distal urethral mucocele, and 1 case of bladder diverticulum obstructing the urethra were diagnosed. Complete PUV resection was performed in 10 patients (66.6%) at the first cystoscopy. The control SVU detected one case of recurrence due to persistence of posterior urethral dilatation. The recurrence case and the 5 incomplete resection cases were treated with a second cystoscopy and resection. The youngest patients required a third resection and cutting balloon dilatation due to residual stenosis. Mean creatinine levels at diagnosis were 0.28 mg/dl. CONCLUSIONS: Serial voiding urosonography (SVU) is a useful complementary test in pediatric patients with posterior urethral valve. Its dynamic nature and its advantages - absence of irradiation, safety, and high sensitivity - make it an ideal imaging test for PUV diagnosis and follow-up.

OBJETIVOS: Comunicar nuestra experiencia con la utilización de la urosonografía miccional seriada (UMS) para el diagnóstico y manejo de pacientes con válvulas de uretra posterior (VUP). MATERIAL Y METODOS: Estudio retrospectivo descriptivo en pacientes entre 0 a 14 años con sospecha de VUP en UMS realizada como primera prueba contrastada de la vía urinaria y con estudio cistoscópico posterior. Las variables se analizaron utilizando SPSSv22. RESULTADOS: Fueron estudiados 18 pacientes (edad mediana de 6 meses). La mayoría de los pacientes (15) presentaban dilatación de la uretra posterior (diámetro medio de 9,56 mm) y diferencia entre uretra proximal y distal mayor de 2 mm. Trece casos tenían engrosamiento vesical y 9 RVU. Se diagnosticaron 15 casos de VUP, 1 caso de mucocele de uretra distal y 1 divertículo vesical que obstruía uretra. Se consiguió resección completa de las VUP en 10 pacientes (66,6%) en la primera cistoscopia. La UMS de control detectó un caso de resección incompleta por persistencia de dilatación de uretra posterior. Este caso y los 5 conocidos con resección incompleta se sometieron a una segunda cistoscopia y resección. El menor de los pacientes requirió una tercera resección y dilatación con balón de corte por estenosis residual. La creatinina media al diagnóstico fue 0,28 mg/dl. CONCLUSIONES: La urosonografía miccional seriada (UMS) es una prueba complementaria útil en pacientes pediátricos con válvulas de uretra posterior. Su carácter dinámico y ventajas: ausencia de irradiación, seguridad y alta sensibilidad; la convierten en una prueba de imagen ideal para el diagnóstico y seguimiento de VUP.

[Two decades of experience in endovascular treatment of varicocele in pediatric age]. / Dos décadas de experiencia en el tratamiento endovascular del varicocele en la edad pediátrica.

OBJECTIVES: To present our experience of 23 years in the treatment of varicocele by embolization in pediatric age. MATERIAL AND METHODS: Observational descriptive study of all patients with varicocele treated by embolization after phlebography, by indication of the pediatric surgery service between 1995 and 2017. We performed descriptive statistical analysis and comparison between pain and testicular asymmetry before and after treatment (SPSSv22). RESULTS: Embolization was performed in 113 patients with left varicocele. The mean age of diagnosis was 12.4 years (5.2-15.5). The main clinical manifestations were: incidental finding (46.7%), increase in scrotal volume (28%) and testicular pain (15.9%). 61.5% were grade 3 and 38.5% grade 2. The selective embolization procedure was performed at an average age of 13.6 years (8-18). There were no serious complications of the procedure or reactive hydrocele. The overall success rate of endovascular treatment was 93.8%. In 85 patients (75.2%) a single procedure was performed and in 21, two procedures (18.6%). Only 4 patients required surgical intervention. The pain disappeared in all cases in which it presented and the testicular asymmetry decreased from 44.7% pre-treatment to 21.2% post-treatment (p<0.05). CONCLUSIONS: Endovascular treatment through embolization allows a selective varicocele management, after venous mapping, with an adequate effectiveness, without altering the arterial flow of the testicle or producing hydrocele. It is a minimally invasive treatment that could be considered the first choice in varicoceles of children and adolescents.

OBJETIVOS: Presentar nuestra experiencia de 23 años en el tratamiento del varicocele mediante embolización en la edad pediátrica. MATERIAL Y METODOS: Estudio descriptivo observacional de todos los pacientes con varicocele tratados mediante embolización previa flebografía, por indicación del servicio de cirugía pediátrica entre los años 1995 a 2017. Realizamos análisis estadístico descriptivo y comparación entre dolor y asimetría testicular previa y posterior al tratamiento (SPSSv22). RESULTADOS: Se realizó embolización en 113 pacientes con varicocele izquierdo. La edad media de diagnóstico fue de 12,4 años (5,2-15,5). Las manifestaciones clínicas principales fueron: hallazgo incidental (46,7%), aumento de volumen escrotal (28%) y dolor testicular (15,9%). El 61,5% eran de grado 3 y el 38,5% de grado 2. El procedimiento de embolización selectiva se realizó a una edad media de 13,6 años (8-18). No se presentaron complicaciones graves del procedimiento ni hidrocele reactivo. En 85 pacientes (75,2%) se realizó un único procedimiento y en 21, dos procedimientos (18,6%). La tasa de éxito global del tratamiento endovascular fue de 93,8%. Solo 4 pacientes requirieron intervención quirúrgica. El dolor desapareció en todos los casos en que se presentaba y la asimetría testicular disminuyó del 44,7% pretratamiento al 21,2% postratamiento (p<0,05). CONCLUSIONES: El tratamiento endovascular mediante embolización permite un manejo selectivo del varicocele, previo mapeo venoso, con una adecuada efectividad, sin alterar el flujo arterial del testículo ni producir hidrocele. Es un tratamiento poco invasivo que se puede considerar de primera elección en varicoceles de niños y adolescentes.

[Video-urodynamic evaluation with cystosonography for the study of lower urinary tract dysfunction and other uropathies in children]. / Videourodinamia con cistosonografía para estudio de la disfunción miccional y otras uropatías en niños.

OBJECTIVES: To assess the utility of a new modality of video-urodynamic for study of lower urinary tract dysfunction and other uropathies in kids, replacing voiding cystourethrography by echo-enhanced cystosonography, without ionizing radiations. MATERIAL AND METHODS: Prospective study with simultaneous performance of filling cystometry and cystosonography in 43 kids during the last two years. The sonographic contrast was infused trough the urodynamic catheter. RESULTS: 18 girls and 25 boys, with an average age of 6.18 years (between 2 months and 14 years). The most frequent indication was micturition disfunction in boys and vesicoureteral reflux follow-up in girls. 60,5% presented urodynamic alterations, predominating low bladder accommodations (N = 9), mixed detrusor overactivity (N = 5) and bladder sphincter dyssynergia (N = 4). 15 children had vesicoureteral reflux: 8 passive, 5 active (associated with contractile activity of the detrusor or in the voiding phase) and two mixed. Urethral pathology was seen in two males (urethral valves and stenosis) and two girls (spinning top urethra). A statistically significant relationship was found between the presence of vesicoureteral reflux and other variables: bladder capacity (t = 4.98; p <0.005), detrusor activity (t = 3; p = 0.005), sex (t = 2.543; p = 0.015) and high post-void residual volume (t = 3.75; p <0.005), so that it was more frequent in girls with big bladders, with detrusor activity and high post-void residue. CONCLUSIONS: Cystosonography can replace conventional cystourethrography as an imaging test associated with urodynamics. With this type of exploration we have been able to indicate the treatment to our patients, subjecting them to a single catheterization and without exposing them to ionizing radiation.

OBJETIVOS: Valorar la utilidad de una nueva modalidad de videourodinamia sin radiaciones ionizantes en el estudio de disfunciones miccionales y otras uropatías en niños, sustituyendo cistouretrografía miccional seriada por cistosonografía o urosonografía miccional. MATERIAL Y METODOS: Estudio prospectivo con realización simultánea de cistomanometría de llenado y cistosonografía en 43 niños durante los dos últimos años. El contraste sonográfico fue infundido a través del catéter de urodinamia. RESULTADOS: 18 niñas y 25 niños, con edades de entre 2 meses y 14 años (media de 6,18 años). La indicación más frecuente en los varones fue disfunción miccional y en las niñas seguimiento de reflujo. El 60,5% presentaba alteraciones urodinámicas, predominando baja acomodación vesical (N = 9), hiperactividad del detrusor mixta (N = 5) y disinergia vésico-esfinteriana (N = 4). 15 niños tenían reflujo: 8 pasivos, 5 activos (asociados a actividad contráctil del detrusor o en fase miccional) y dos mixtos. Se vio patología uretral en dos varones (valvas de uretra posterior y estenosis uretral) y dos niñas (uretra en peonza). Se encontró relación estadísticamente significativa entre presencia de reflujo vesicoureteral y otras variables: capacidad vesical (t = 4,98; p <0,005), actividad del detrusor (t = 3; p = 0,005), sexo (t = 2,553; p = 0,015) y residuo postmiccional alto (t = 3,75; p <0,005), siendo más frecuente en niñas con vejigas grandes, con actividad del detrusor y residuo postmiccional alto. CONCLUSIONES: La UMS puede sustituir a la cistouretrografía convencional como prueba de imagen asociada a la urodinamia. Con este tipo de exploración hemos podido indicar un tratamiento a nuestros pacientes, sometiéndolos a un único sondaje y sin exponerlos a radiaciones ionizantes.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Extracolonic Cancer in Inflammatory Bowel Disease: Data from the GETECCU Eneida Registry.

OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. EXCLUSION CRITERIA: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

Fish consumption in mid-childhood and its relationship to neuropsychological outcomes measured in 7-9 year old children using a NUTRIMENTHE neuropsychological battery.

BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFA), particularly n-3 LCPUFA, play a central role in neuronal growth and the development of the human brain. Fish is the main dietary source of n-3 LCPUFA. To assess the relation between fish consumption, estimated dietary n-3 LCPUFA intake and cognition and behaviour in childhood in a multi-centre European sample. METHODS: Children from 2 European studies, CHOP and NUHEAL, were assessed at 8 and 7.5 years of age, respectively. Different outcomes of neuropsychological development (assessed with the standardized NUTRIMENTHE Neuropsychological Battery (NNB) consisting of 15 subtests) were related with outcomes from a food-frequency questionnaire (FFQ) focussing on the consumption of fish. RESULTS: A total of 584 children completed the FFQ and the neuropsychological tests. We found no associations with calculated DHA or EPA intakes for any of the neuropsychological domains. Children who consumed 2 fish meals per week including one of fatty fish, showed no substantive differences in the cognitive domains from the children who did not. However negative associations with fatty fish consumption were found for social problems (p = 0.019), attention problems (p = 0.012), rule-breaking problems (p = 0.019) and aggressive behaviour problems (p = 0.032). No association was observed with internalizing problems. Higher levels of externalizing problems (p = 0.018) and total problems (p = 0.018) were associated with eating less fatty fish. CONCLUSIONS: Children who consumed 2 fish meals per week including one of fatty fish were less likely to show emotional and behavioural problems than those who did not.

Voiding urosonography with second-generation contrast as a main tool for examining the upper and lower urinary tract in children. Pilot Study.

INTRODUCTION: In this series, we analyse the diagnostic efficacy of serial voiding urosonography (VUS) with second-generation contrast, combined harmoniously and specifically with contrast technology, in the examination of the urinary tract in children. This examination includes the diagnosis and follow-up for vesicoureteral reflux (VUR) and urethral disorders, mainly those of the posterior urethral valve (PUV). PATIENTS AND METHODS: After obtaining informed consent, a prospective study was conducted using urosonography with second-generation contrast (sulphur hexafluoride microbubbles, SonoVue®) from November 2014 to October 2015 (1 year) in paediatric patients with suspected VUR or PUV impairment. For patients with a high suspicion of VUR and in cases of PUV, we also conducted simultaneous voiding cystourethrography (VCUG). RESULTS: We studied 40 patients (80 renal units) between the ages of 2 months and 13 years (median age, 14 months). The indication for the test was a suspected VUR (36 patients, group A) and PUV follow-up (4 patients, group B). The test was correlated with VCUG in 16 patients (12 cases with high suspicion of VUR in group A and with 4 cases of PUV in group B). The visualisation of the urethra was appropriate in cases of dilation or urethral stricture. For 3 of these patients with bilateral VUR demonstrated in the serial VUS, the VCUG showed only unilateral VUR in 2 of the patients and no VUR in 1 of the patients (κ=.73). DISCUSSION: We have shown that the visualisation of the urethra is no longer a limitation and that serial VUS can be superior to conventional VCUG in diagnosing VUR.

Comparative genetic study of intratumoral heterogenous MYCN amplified neuroblastoma versus aggressive genetic profile neuroblastic tumors.

Intratumoral heterogeneous MYCN amplification (hetMNA) is an unusual event in neuroblastoma with unascertained biological and clinical implications. Diagnosis is based on the detection of MYCN amplification surrounded by non-amplified tumor cells by fluorescence in situ hybridization (FISH). To better define the genetic features of hetMNA tumors, we studied the Spanish cohort of neuroblastic tumors by FISH and single nucleotide polymorphism arrays. We compared hetMNA tumors with homogeneous MNA (homMNA) and nonMNA tumors with 11q deletion (nonMNA w11q-). Of 1091 primary tumors, 28 were hetMNA by FISH. Intratumoral heterogeneity of 1p, 2p, 11q and 17q was closely associated with hetMNA tumors when analyzing different pieces for each case. For chromosome 2, 16 cases showed 2p intact, 4 focal gain at 2p24.3 and 8 MNA. The lengths of the smallest regions of overlap (SROs) for 2p gains and 1p deletions were between the SRO lengths observed in homMNA and nonMNA w11q- tumors. Co-occurrence of 11q- and +17q was frequently found with the largest SROs for both aberrations. The evidence for and frequency of different genetic subpopulations representing a hallmark of the hetMNA subgroup of NB indicates, on one hand, the presence of a considerable genetic instability with different SRO of either gains and losses compared with those of the other NB groups and highlights and, on the other hand, the need for multiple sampling from distant and macroscopically and microscopically distinct tumor areas. Narrowing down the different SRO for both deletions and gains in NB groups would be crucial to pinpointing the candidate gene(s) and the critical gene dosage with prognostic and therapeutic significance. This complexity of segmental chromosomal aberration patterns reinforces the necessity for a larger cohort study using FISH and pangenomic techniques to develop a suitable therapeutic strategy for these patients.

Current concepts on microscopic colitis: evidence-based statements and recommendations of the Spanish Microscopic Colitis Group.

BACKGROUND: Microscopic colitis (MC) is an underdiagnosed inflammatory bowel disease. AIM: To develop an evidence-based clinical practice guide on MC current concepts. METHODS: Literature search was done on the Cochrane Library, EMBASE and MEDLINE electronic databases, which were consulted covering the period up until March 2015. Work groups were selected for each of the reviewed topics, with the purpose of drafting the initial statements and recommendations. They subsequently underwent a voting process based on the Delphi method. Each statement/recommendation was accompanied by the result of the vote the level of evidence, and discussion of the corresponding evidence. The grade of recommendation (GR) using the GRADE approach was established for diagnosis and treatment recommendations. RESULTS: Some key statements and recommendations are: advancing age increases the risk of developing MC, mainly in females. The symptoms of MC and IBS-D may be similar. If MC is suspected, colonoscopy taking biopsies is mandatory. Treatment with oral budesonide is recommended to induce clinical remission in patients with MC. Oral mesalazine is not recommended in patients with collagenous colitis for the induction of clinical remission. The use of anti-TNF-alpha drugs (infliximab, adalimumab) is recommended for the induction of remission in severe cases of MC that fail to respond to corticosteroids or immunomodulators, as an alternative to colectomy. CONCLUSIONS: This is the first consensus paper on MC based on GRADE methodology. This initiative may help physicians involved in care of these patients in taking decisions based on evidence.

Randomised clinical trial: colestyramine vs. hydroxypropyl cellulose in patients with functional chronic watery diarrhoea.

BACKGROUND: Idiopathic bile acid malabsorption (BAM) has been suggested as a cause of chronic watery diarrhoea, with a response to colestyramine in 70% of patients. However, the efficacy of this drug has never been investigated in placebo-controlled trials. AIM: To evaluate the efficacy of colestyramine as compared with hydroxypropyl cellulose in the treatment of functional chronic watery diarrhoea. METHODS: Patients with chronic watery diarrhoea were randomly assigned to groups given colestyramine sachets 4 g twice daily (n = 13) or identical hydroxypropyl cellulose sachets (n = 13) for 8 weeks. The primary end-point was clinical remission defined as a mean of 3 or fewer stools per day during the week before the visit, with less than 1 watery stool per day. A secondary end-point was the reduction in daily watery stool number. SeHCAT test was performed in all patients, but an abnormal test was not a prerequisite to be included. RESULTS: All included patients had a SeHCAT 7-day retention ≤20%. There were no statistical differences in the percentage of patients in clinical remission at week 8 between colestyramine and hydroxypropyl cellulose with either intention-to-treat (53.8% vs. 38.4%; P = 0.43) or per-protocol (63.6% vs. 38.4%; P = 0.22) analyses. However, the mean per cent decrease in watery stool number was significantly higher with colestyramine than with hydroxypropyl cellulose (-92.4 ± 3.5% vs. -75.8 ± 7.1%; P = 0.048). The rate of adverse events related to study drugs did not differ between groups. CONCLUSIONS: Colestyramine (4 g twice daily) is effective and safe for short-term treatment of patients with chronic watery diarrhoea presumably secondary to BAM. Clinical Trials Register number EudraCT 2009-011149-14.

Differential patterns of recurrence and specific survival between luminal A and luminal B breast cancer according to recent changes in the 2013 St Gallen immunohistochemical classification.

INTRODUCTION: In 2011, the St Gallen panel introduced several changes in breast cancer classification, thereby creating the luminal B Her2- subtype. In 2013, the panel also included Ki67 overexpression and PR <20 % as risk factors, while excluding GH3 in the absence of increased Ki67. We compared the classification of 2011 modified with the new 2013 St Gallen classification. PATIENTS AND METHOD: Consecutive breast cancer patients referred to the Breast Unit of the University Hospital Mútua Terrassa and Hospital of Terrassa for surgical treatment of either primary or recurrent tumors were prospectively included between 1997 and 2014. Eventually, 1,874 cases were included for the four-subtype analysis. The median follow-up was of 66 months. RESULTS: Using the 2013 St Gallen classification no significant differences were found in specific mortality rates between luminal A and B subtypes. There were significant differences at 5, 10, and, 15 years if we excluded luminal A GH3 patients in the absence of increased Ki67 (p = 0.004, 0.005, and 0.007). Luminal A sub-type patients showed significantly less distant metastases than the rest, including luminal B Her2- patients (p < 0.001). Also, luminal B patients showed significantly less distant metastases than pure Her2 (0.05) and triple negative (TN) (p < 0.001). There were no differences between pure Her2 and TN patients (0.055), neither among the different luminal B sub-types. CONCLUSION: GH3, PR, and Ki67 may all be discriminatory factors for metastasis and specific mortality. Therefore, we suggest including GH3 in the luminal B subtype in the absence of Ki67.

A study comparing two consecutive historical periods in breast cancer with a focus on surgical treatment, loco-regional recurrence, distant metastases and mortality.

BACKGROUND AND AIM: Recent introduction of breast units, mass-screening programmes (SP) and sentinel node biopsy (SNB) has impacted on the clinical care of breast cancer patients (BC), resulting in a significant increase of breast-conserving surgery with the goal of achieving completely free margins and good cosmetic outcome, along with significantly less axillary morbidity. In order to ascertain the combined impact of SP and SNB on BC patients, we have reviewed the primary therapeutic approach of patients diagnosed with invasive breast carcinoma in our centre, both before and after implementation of the two new procedures. METHODS: 1,942 patients operated for BC between 1997 and 2013 in two clinical centres. Two historical periods were considered: before and after the advent of the Breast Unit in our institutions and the concurrent implementation of SP and SNB (September 2002). RESULTS: Rates of breast-conserving surgery and re-operations improved in the second period. Intraoperative margin re-excision increased in the second period. Breast-conserving surgery decreased in parallel to stage: from 79 % for stage I to 31 % for stage III. The Cox analysis, including stage as adjusted for all significant variables, showed statistically significant differences in favour of the initial stages but only for specific mortality, not overall mortality. CONCLUSIONS: Combined implementation of breast units, SP, and SNB have resulted in a significant improvement of BC treatment leading to increased rates of breast-conserving surgery and decreased disease recurrence and mortality.

Impact of surveillance of hepatitis b and hepatitis c in patients with inflammatory bowel disease under anti-TNF therapies: multicenter prospective observational study (REPENTINA 3).

AIMS: Assess IBD patients starting anti-TNF for the impact of preventive measures in HBV and/or HCV, and the predictive response factors to HBV vaccination. METHODS: Multicenter prospective study including 389 IBD patients. Four interventions were established: I-1) anti-HBs <100IU/L: HBV vaccination with double doses at 0-1-2months, and revaccination if titres <100IU/L (seroprotection defined as anti-HBs10-100IU/L and effective vaccination anti-HBs >100IU/L); I-2) anti-HBs >100IU/L (previous effective vaccination): monitoring levels; I-3) anti-HBc and/or HCV+: analysis every two months; I-4) HBsAg+: start anti-virals. RESULTS: I-1 and I-2) For first vaccination, effective vaccination and seroprotection were obtained in 26.4% and 43.5%, and for revaccination 31.3% and 44.4%, respectively. Predictive factors of effective vaccination were age ≤30years (OR=2.2) and being vaccinated simultaneously with anti-TNF (OR=5.2) instead of late vaccination, whereas age ≤30years (OR=2.6) and anti-TNF monotherapy (OR=2.4) were predictive for seroprotection. 80.8% of patients previously vaccinated maintained titres at 29months follow-up. The only factor related to maintaining titres was previous vaccination versus achieving effective vaccination during anti-TNF (HR=2.49); I-3 and I-4) HBV-DNA + without reactivation was detected in 7% of 29 anti-HBc. No reactivation was found in the remaining HCV (n=5) or HBsAg (n=4) patients. CONCLUSIONS: 1) Response to vaccination/revaccination is low in patients with anti-TNF. Young patients vaccinated at the beginning of anti-TNF and receiving it as a monotheraphy showed better response. 2) Long-lasting effective vaccination is greatest in patients previously vaccinated. 3) Following-up the established surveillance and/or preventive anti-viral therapy seems to be safe in HBV and HCV patients.

Comparison of childhood size and dietary differences at age 4 years between three European countries.

BACKGROUND/OBJECTIVES: Obesity in childhood is very common in Europe. It may be linked to diet, and intakes of protein and polyunsaturated fatty acids (PUFA) have been investigated. The study aims to investigate child size and dietary differences at the age of 4 years between three European countries and to assess dietary adequacy. SUBJECTS/METHODS: A total of 161 4-year-old children from Spain, Germany and Hungary, whose mothers participated in a pregnancy micronutrient supplementation trial, were included in this analysis. Child size was assessed by standardised anthropometry and diet calculated from parent-completed food frequency questionnaires. Adequacy of the diet was evaluated using US guidelines. RESULTS: The Spanish children had a higher mean body mass index (BMI) (16.4±1.5) compared with German (15.7±1.0) and Hungarian children (14.9±1.4, P<0.01). In Spanish children, dietary intakes were higher in animal protein density, particularly from dairy foods, were little different in total protein density and slightly lower in n-6 PUFA density compared with the intakes in the other groups. Dietary intakes of most children (% contribution to energy) were higher than those recommended for protein, saturated fat and added sugar. CONCLUSIONS: Spanish children had a higher mean BMI compared with German and Hungarian children. Diets taken by Spanish children may be more obesogenic than those taken by German or Hungarian children. In the present study, many children in all three countries were consuming diets that were high in protein, saturated fat and sugar.

[Demands and expectations of parents who refuse vaccinations and perspective of health professional on the refusal to vaccinate]. / Demandas y expectativas de padres y madres que rechazan la vacunación y perspectiva de los profesionales sanitarios sobre la negativa a vacunar.

OBJECTIVES: To examine the opinions, beliefs and attitudes about vaccination, of parents who decide not to vaccinate their children. To determine the opinions and attitudes of the health professionals on the behaviour towards childhood vaccination. METHOD: Qualitative research based on semi-structured interviews and focal groups in Granada, Spain, including parents who chose to not vaccinate their children, and healthcare professionals who can provide a technical point of view. An analysis was made of the semantic content, and answers were categorized in thematic units. RESULTS: The parents argued on the benefit of suffering vaccine-preventable diseases in a natural way, without non-natural, aggressive or toxic products. Vaccination was considered unnecessary, if given adequate hygienic-sanitary conditions, effectiveness unproven and more dangerous than the diseases they prevent, especially the polyvalent vaccines. They believed that vaccination programs are moved by biased studies and interests other than prevention. Health care professionals believe that they had fears without scientific basis, which requires improving information systems. CONCLUSIONS: Non-vaccinators are unaware of the benefit/risk ratio between the vaccination and the individual risk for preventable diseases, and ask for informed consent. Health care professionals believe that non-vaccinators' arguments are not correctly contrasted and expose the existence of failures in actual vaccination coverage and information registration systems. It was suggested to centralize registers and compare them in schools, working with local leaders and reporting regularly on the status of vaccine-preventable diseases.