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.

Flow cytometric analysis of duodenal intraepithelial lymphocytes (celiac lymphogram): A diagnostic test for celiac disease.

Celiac disease (CD) diagnosis in adults and certain cases of children mainly relies on the assessment of histopathological features in duodenal biopsies. However, none of the histological findings that characterize CD are pathognomonic. This, in addition to the clinical heterogeneity of the disease and the presence of seronegative forms, makes the diagnosis of CD still a challenge. A hallmark of the celiac mucosa is the elevated number of TCRγδ intraepithelial lymphocytes (IEL) in the epithelium, which may remain increased even long after gluten withdrawal. Active disease is also characterized by the decreased CD3- IEL subset. The use of flow cytometry enables a precise cell counting and phenotyping, allowing the ascertainment of both TCRγδ+ and CD3- IEL subsets, what is known as the "IEL lymphogram." Although determination of this lymphogram has become a routine evaluation tool in numerous hospitals, standardization of the technical method will guarantee an accurate performance in order to become a pivotal technique for CD diagnosis. Here we describe the protocol to process duodenal biopsies in order to obtain the IELs from the mucosa and to characterize lymphocyte populations by flow cytometry to obtain the IEL lymphogram.

Initial results of the implementation of an ambulatory mini percutaneous nephrolithotomy program.

OBJECTIVE: To present our program for ambulatory mini percutaneous nephrolithotomy (mini-PCNL) and evaluate its initial results. MATERIAL AND METHODS: We analyzed the implementation of the protocol into the clinical practice with the first 30 outpatient mini-PCNL cases performed in our center between April 2021 and September 2022. Demographic characteristics, perioperative variables, complications and need for unplanned health care, stone-free rate (SFR), stone type and patient satisfaction with the major ambulatory surgery (MAS) process were collected. RESULTS: A total of 30 patients with a mean age of 60.2 ±â€¯11.6 years who met the inclusion criteria underwent surgery. The mean stone size was 15 mm [range: 5-20]. No intraoperative complications were recorded. All patients except one were discharged the same day of surgery as planned. In the month following discharge, the rate of complications, emergency department (ED) revisits or hospital readmissions rates were 0%. Stone-free-rate (SFR) at 3 months was 83%. Overall satisfaction with the whole perioperative process was assessed with the EVAN-G questionnaire, obtaining 124.3 points out of a maximum of 150, which is equivalent to a 78.6% level of satisfaction. CONCLUSION: Ambulatory mini-PCNL can be implemented as a treatment option in centers with experience in endourology, an established MAS Unit, and strictly selected patients. Our initial results show an adequate safety profile and high overall satisfaction perceived by patients undergoing the ambulatory approach.

Preliminary results of the implementation of robotic radical prostatectomy in a major ambulatory surgery regimen.

OBJECTIVE: To report our initial experience with robotic radical prostatectomy as an outpatient procedure. MATERIAL AND METHODS: Retrospective analysis of patients who underwent RRP as MAS (Major Ambulatory Surgery) at our center between March 2021 and May 2022. We collected baseline patient characteristics, intraoperative outcomes and postoperative data (need for unplanned medical care and complications at one month after surgery). Oncologic characteristics at disease diagnosis (PSA, staging, ISUP, MRI) and postoperative pathologic outcomes were collected. RESULTS: We identified a total of 35 patients with an average age of 60,8 ± 6,88 years and a BMI of 27 ± 2,9 Kg/m2. All patients had a low anesthetic risk and 25.71% had undergone previous abdominal surgery. The surgical time was 151,66 ± 42,15 min and the average blood loss was 301,2 ± 184,38 mL. Two patients (5.7%) were admitted for one night and 7 patients (20%) consulted the emergency department in the following month, of which 3 (8.57%) were readmitted. We recorded one intraoperative complication, seven mild postoperative complications (Clavien I-II) and one severe complication (Clavien IIIb). The severe complication occurred on the eighth postoperative day and was not related to the procedure being ambulatory. CONCLUSION: The absence of serious complications in the immediate postoperative period supports RRP in MAS as a safe technique for selected patients.

Dimensions of household food waste focused on family and consumers.

Food waste produced in homes represents the largest fraction of food waste generated along the food chain. Therefore, adequate prevention measures based on the quantitative and qualitative dimensions of the problem need to be put in place to reduce waste. The objective of the review was to identify areas of interest in relation to the food waste in households, considering the family unit as a whole as well as individual family members. Quantifying the problem is an important aspect in order to know its scope and dimension, but prevention also involves knowing the causes in a home. This is a complex issue, which, on a family level, is related to socioeconomic status, educational level, composition and number of members of the household as well as culinary and buying food habits. Individual variables such as age, sex, values, awareness, lifestyle and time spent on food preparation were included to characterize consumers. The focus of the problem is also important because most consumers consider food waste from a social perspective, without being aware of the serious environmental and economic problems. Habits and customs of consumers are considered the leading cause of food waste in homes and knowledge of this issue raises consumer awareness as a preventive tool.

The immune status against tetanus and diphtheria in healthcare workers in Catalonia.

The objective was to investigate the immune status against tetanus and diphtheria of healthcare workers in Catalonia. A cross-sectional multicentre study was conducted in seven health centres. Blood samples were obtained, and demographic and clinical variables collected. 509 health workers were included. The prevalence of protective antibodies against tetanus was 94.7% (95% CI: 92.3-96.4) overall and 85.1% (95% CI: 74.5-92.0) in workers aged ≥55 years. The prevalence of protective antibodies against diphtheria was 68.6% (95% CI: 64.3-72.5%) overall and 29.7% (95% CI: 19.9-41.6) in workers aged ≥55 years. Protection against tetanus in healthcare workers is high, but should be improved in workers aged ≥55 years. Protection against diphtheria has improved in healthcare workers over the past decade (68.6% vs 46.5%) but should be improved in all ages, especially in workers aged ≥55 years.

[Mental development trajectories of a group of preterm babies from 1 to 30 months of age]. / Trayectorias de desarrollo mental de un grupo de bebes prematuros de 1 a 30 meses.

INTRODUCTION: This research falls within the category of longitudinal studies assessing the evolution of prematurely born infants with the use of standardized tests. AIMS: To analyze the trajectory of the mental development of a group of premature infants and to identify if gestational age is a significant predictor of their evolution. SUBJECTS AND METHODS: 359 prematurely born infants were assessed at three stages of their development (between 1-9 months, 10-18 months and 19-30 months of age), using the Bayley Scales of Infant DEVELOPMENT. To analyze the trajectory of the sample mental development, a linear mixed model procedure was applied. RESULTS: The trajectories of the mental development of these children conform to a model of the quadratic development curve. The results show that gestational age is a significant predictor of the initial score that explains 34% of the total interindividual variability. CONCLUSIONS: Children with lowest initial scores are those who most increase them with age, an important fact for the prediction of premature newborns future development. This fact should be taken into account regarding negative prognoses in the first year of life.

TITLE: Trayectorias de desarrollo mental de un grupo de bebes prematuros de 1 a 30 meses.Introduccion. Esta investigacion se inscribe en los estudios de corte longitudinal para evaluar la evolucion de los recien nacidos prematuros con el uso de pruebas estandarizadas. Objetivos. Analizar la trayectoria del desarrollo mental de un grupo de recien nacidos prematuros e identificar si la edad gestacional es un predictor significativo de su evolucion. Sujetos y metodos. Se evaluo a 359 recien nacidos prematuros en tres momentos de su desarrollo (entre 1 y 9 meses, entre 10 y 18 meses, y entre 19 y 30 meses de edad), utilizando las escalas Bayley de desarrollo infantil. Para analizar la trayectoria del desarrollo mental de la muestra se aplico el procedimiento de modelos lineales mixtos. Resultados. Las trayectorias del desarrollo mental de estos niños se ajustan a un modelo de la curva de desarrollo cuadratica. Los resultados muestran que la edad gestacional es un predictor significativo de la puntuacion inicial que explica el 34% del total de la variabilidad interindividual. Conclusiones. Los niños con puntuaciones iniciales mas bajas son los que mas incrementan sus puntuaciones con la edad, un dato importante de cara a la prediccion del futuro desarrollo de los prematuros y que previene sobre la realizacion de pronosticos negativos en el primer año de vida.

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.

Human intestinal pro-inflammatory CD11chighCCR2+CX3CR1+ macrophages, but not their tolerogenic CD11c-CCR2-CX3CR1- counterparts, are expanded in inflammatory bowel disease.

Although macrophages (Mϕ) maintain intestinal immune homoeostasis, there is not much available information about their subset composition, phenotype and function in the human setting. Human intestinal Mϕ (CD45+HLA-DR+CD14+CD64+) can be divided into subsets based on the expression of CD11c, CCR2 and CX3CR1. Monocyte-like cells can be identified as CD11chighCCR2+CX3CR1+ cells, a phenotype also shared by circulating CD14+ monocytes. On the contrary, their Mϕ-like tissue-resident counterparts display a CD11c-CCR2-CX3CR1- phenotype. CD11chigh monocyte-like cells produced IL-1ß, both in resting conditions and after LPS stimulation, while CD11c- Mϕ-like cells produced IL-10. CD11chigh pro-inflammatory monocyte-like cells, but not the others, were increased in the inflamed colon from patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Tolerogenic IL-10-producing CD11c- Mϕ-like cells were generated from monocytes following mucosal conditioning. Finally, the colonic mucosa recruited circulating CD14+ monocytes in a CCR2-dependent manner, being such capacity expanded in IBD. Mϕ subsets represent, therefore, transition stages from newly arrived pro-inflammatory monocyte-like cells (CD11chighCCR2+CX3CR1+) into tolerogenic tissue-resident (CD11c-CCR2-CX3CR1-) Mϕ-like cells as reflected by the mucosal capacity to recruit circulating monocytes and induce CD11c- Mϕ. The process is nevertheless dysregulated in IBD, where there is an increased migration and accumulation of pro-inflammatory CD11chigh monocyte-like cells.

Our experience in the management of prostate cancer in renal transplant recipients. / Nuestra experiencia en el manejo del cáncer de próstata en pacientes trasplantados renales.

INTRODUCTION AND OBJECTIVES: The management of Prostate cancer (PCa) in renal transplant recipients (RTR) is challenging and remain controversial. Currently there is no consensus about this condition. The aim of the study was to analyse our experience in the diagnosis and management of PCa in RTR. METHOD: Retrospective monocentric study of a prospective and consecutive database from 2003-2017. Inclusion of RTR diagnosed of PCa. Staging and treatment in agreement with the contemporary guidelines. The main outcome measures included clinical staging, type of treatment, oncological outcomes and follow-up. RESULTS: 1,330 renal transplants were performed (787 males), diagnosed of PCa in 33 RTR (4.2%), mean age 66years±6.3 (51-78). Median PSA was 8.8ng/ml and PSA ratio 0.19. Mean time between renal transplantation and PCa diagnosis 130months±90 (2-236). TREATMENTS: Radical prostatectomy (RP) (n=22; 66.7%), Radiation therapy (RT) with Androgen deprivation therapy (ADT) (n=7; 21.2%), Active surveillance (n=3; 9.1%), ADT (n=1; 3%). No graft loss neither impaired renal function due to PCa treatment was reported. After RP two patients (9.1%) presented biochemical recurrence treated with RT. Remission of the 100%. Mean follow-up was 61months±37 (6-132). CONCLUSIONS: PCa in renal transplant patients can be managed with the same therapeutic options as in the general population. Active surveillance should also be provided in RTR despite being under immunosuppressive therapy.

Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

OBJECTIVES: To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. METHODS: Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. RESULTS: Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. CONCLUSIONS: Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

Dietary Assesment of Free-Living Elderly Spanish People with Disabilities.

Nutritional research in elderly disabled is difficult in noninstitutionalized people. The dietary intake of a noninstitutionalized disabled population of the eastern region of Spain was evaluated to detect possible nutritional deviations. A total of 329 participants aged 65 and over were recruited. Most participants were overweight. Carbohydrates did not reach 50% of total Kcal/day. Insufficient micronutrient intakes and high consumption of simple carbohydrates and saturated fats (SFA) were found. A decreasing trend of water intake (p < .05) as well as an increasing trend of alcohol consumption (p < .05) with increasing age was found. The area of residence had a relevant impact on nutritional, dietary, and anthropometric characteristics of our population.

Coats' disease with macular oedema responsive to aflibercept and argon laser. / Enfermedad de Coats con edema macular sensible al aflibercept y láser argón.

CLINICAL CASE: A 14 year-old boy with Coats' disease in his right eye, presented with a visual acuity (VA) of 0.1, micro-aneurysms, exudates, a macular oedema of 959 microns, and peripheral telangiectasias. After 12 months follow-up with 6 ranibizumab injections and 3 sessions of argon laser photocoagulation, the macular oedema remained and VA was 0.2. Following 4 aflibercept injections and another 2 laser sessions, he had a good foveal slope and a VA of 0.5, with no recurrences in the last 12 months. DISCUSSION: Treatment with aflibercept and argon laser was effective in our patient with stage 2B Coats' disease and macular oedema unresponsive to ranibizumab.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Serological survey of hepatitis B immunity in healthcare workers in Catalonia (Spain).

Healthcare workers (HCW) are exposed to preventable infectious diseases, notably hepatitis B (HB). The aim of this study was to determine the immunity of HCW against hepatitis B. We made a seroprevalence study using a self-administered survey and obtained blood samples. Antibodies against the HB surface antigen (anti-HBs) and against the HB core antigen (anti-HBc) were studied. The odds ratio (OR) and 95% confidence intervals (CI) were calculated. The adjusted OR were calculated using logistic regression. Of the 644 HCW who participated (29.7% physicians, 38.7% nurses, 13.4% other clinical workers and 18.3% non-clinical workers), 46.4% were primary care workers and 53.6% hospital workers. The overall prevalence of anti-HBs was 64.4%. HCW aged <25 y had a significantly higher prevalence (86.7%) than those aged 35-44 y (adjusted OR 3.40; 95% CI 1.06-10.90). The prevalence of anti-HBc was 4.1%, and increased with age. Significant differences were found for HCW aged >44 y with respect to those aged 25-34 y. 75.6% of HCW stated they were vaccinated, but only 39.3% had a vaccination card. In HCW who stated they were unvaccinated, 10.8% had a vaccinated serological pattern (anti-HBc-negative and anti-HBs -positive). Written, updated vaccination records are essential to reliably determine the vaccination status.

Chronic diarrhoea: Definition, classification and diagnosis / Diarrea crónica: definición, clasificación y diagnóstico

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.

La diarrea crónica es un síntoma de presentación frecuente, tanto en las consultas de medicina de familia como en las de digestivo. Se estima que >5% de la población sufre diarrea crónica y que cerca del 40% de estos sujetos son mayores de 60 años. El clínico se enfrenta con frecuencia a la necesidad de decidir cuál es el mejor enfoque diagnóstico de estos pacientes y elegir entre las múltiples pruebas diagnósticas existentes. En 2014 la Societat Catalana de Digestologia creó un grupo de trabajo con el objetivo principal de crear algoritmos diagnósticos en base a la práctica clínica y evaluar las pruebas diagnósticas disponibles y la evidencia científica para su utilización. Para clasificar la evidencia científica y la fuerza de las recomendaciones se utilizó el sistema GRADE. Se han establecido 28 recomendaciones y 6 algoritmos diagnósticos. Se describen los criterios de derivación desde medicina primaria a digestivo de un paciente con diarrea crónica.

Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.

BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients. METHODS: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: (XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and D'Amico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D'Amico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002). CONCLUSIONS: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.

Conservative treatment of retinoblastoma: a prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy.

PurposeIntraocular retinoblastoma treatments often combine chemotherapy and focal treatments. A first prospective protocol of conservative treatments in our institution showed the efficacy of the use of two courses of chemoreduction with etoposide and carboplatin, followed by chemothermotherapy using carboplatin as a single agent and diode laser. In order to decrease the possible long-term toxicity of chemotherapy due to etoposide, a randomized neoadjuvant phase II protocol was conducted using vincristine-carboplatin vs etoposide-carboplatin.Patients and methodsThe study was proposed when initial tumor characteristics did not allow front-line local treatments. Patients included in this phase II noncomparative randomized study of neoadjuvant chemotherapy received vincristin-carboplatin (new arm) vs etoposide-carboplatin (our reference arm). They were subsequently treated by local treatments and chemothermotherapy. Primary end point was the need for secondary enucleation or external beam radiotherapy (EBRT) not exceeding 40% at 2 years.ResultsA total of 65 eyes in 55 children were included in the study (May 2004 to August 2009). Of these, 32 eyes (27 children) were treated in the arm etoposide-carboplatin and 33 eyes (28 children) in the arm vincristin-carboplatin. At 2 years after treatment, 23/33 (69.7%) eyes were treated and salvaged without EBRT or enucleation in the arm vincristin-carboplatin and 26/32 (81.2%) in the arm etoposide-carboplatin.ConclusionEven if the two treatment arms could be considered as sufficiently active according to the study decision rules, neoadjuvant chemotherapy by two cycles of vincristine-carboplatin followed by chemothermotherapy appear to offer less optimal local control than the etoposide-carboplatin combination.