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Rodrigo F.G.-M.,Complejo Hospitalario Universitario Insular Materno Infantil Of Las Palmas | Henriquez G.G.,Complejo Hospitalario Universitario Insular Materno Infantil Of Las Palmas | Aloy J.F.,Hospital Clinic de Barcelona | Perez A.G.-A.,Hospital Sant Joan de Deu de Barcelona
Neonatology | Year: 2014

Background: Chorioamnionitis is a recognized risk factor of preterm delivery; however, controversy still persists concerning the relationship between maternal inflammation and neonatal morbidity and mortality.Objective: To determine the incidence of clinical chorioamnionitis and its relationship to morbidity and mortality among very-low-birth-weight (VLBW) infants.Methods: This was a retrospective analysis of prospectively collected data of VLBW neonates ≤ 32 weeks' gestational age (GA) admitted to collaborating units in the Spanish SEN1500 Network between January 2008 and December 2011. Clinical chorioamnionitis was defined by obstetricians based on clinical findings, and neonatal outcomes were compared between exposed and non-exposed infants by multivariate logistic regression analysis.Results: During the study period, 11,464 VLBW newborns were admitted to our units and 10,026 were ≤ 32 weeks' GA. Among them, 8,330 (83.1%) had complete data and were included. Of these, 1,480 (17.8%) were exposed to maternal clinical chorioamnionitis. The incidence was higher at lower GA and, after adjusting for confounding factors, exposed infants had higher risks of early- onset neonatal sepsis (EONS) (10.0 vs. 2.8%; aOR 3.102; 95% CI 2.306-4.173; p < 0.001) and necrotizing enterocolitis (NEC) (11.2 vs. 7.7%; aOR 1.300; 95% CI 1.021-1.655; p < 0.033), but lower risks of patent ductus arteriosus (PDA) (43.2 vs. 34.9%; aOR 0.831; 95% CI 0.711-0.971; p < 0.02) and late-onset bacterial sepsis (LONS) (36.6 vs. 32.5%; aOR 0.849; 95% CI 0.729- 0.989; p < 0.035). There were no differences in mortality between the groups.Conclusions: The incidence of maternal clinical chorioamnionitis is inversely related to GA at delivery, and in VLBW infants ≤ 32 weeks' GA it is associated with higher risks of EONS and NEC, but lower risks of PDA and LONS. We did not found differences in survival. © 2014 S. Karger AG, Basel.

Ramaswamy V.,Hospital for Sick Children | Ramaswamy V.,Labatt Brain Tumour Research Center | Ramaswamy V.,University of Toronto | Remke M.,Hospital for Sick Children | And 59 more authors.
The Lancet Oncology | Year: 2013

Background: Recurrent medulloblastoma is a therapeutic challenge because it is almost always fatal. Studies have confirmed that medulloblastoma consists of at least four distinct subgroups. We sought to delineate subgroup-specific differences in medulloblastoma recurrence patterns. Methods: We retrospectively identified a discovery cohort of all recurrent medulloblastomas at the Hospital for Sick Children (Toronto, ON, Canada) from 1994 to 2012 (cohort 1), and established molecular subgroups using a nanoString-based assay on formalin-fixed paraffin-embedded tissues or frozen tissue. The anatomical site of recurrence (local tumour bed or leptomeningeal metastasis), time to recurrence, and survival after recurrence were assessed in a subgroup-specific manner. Two independent, non-overlapping cohorts (cohort 2: samples from patients with recurrent medulloblastomas from 13 centres worldwide, obtained between 1991 and 2012; cohort 3: samples from patients with recurrent medulloblastoma obtained at the NN Burdenko Neurosurgical Institute [Moscow, Russia] between 1994 and 2011) were analysed to confirm and validate observations. When possible, molecular subgrouping was done on tissue obtained from both the initial surgery and at recurrence. Results: Cohort 1 consisted of 30 patients with recurrent medulloblastomas; nine with local recurrences, and 21 with metastatic recurrences. Cohort 2 consisted of 77 patients and cohort 3 of 96 patients with recurrent medulloblastoma. Subgroup affiliation remained stable at recurrence in all 34 cases with available matched primary and recurrent pairs (five pairs from cohort 1 and 29 pairs from cohort 2 [15 SHH, five group 3, 14 group 4]). This finding was validated in 17 pairs from cohort 3. When analysed in a subgroup-specific manner, local recurrences in cohort 1 were more frequent in SHH tumours (eight of nine [89%]) and metastatic recurrences were more common in group 3 and group 4 tumours (17 of 20 [85%] with one WNT, p=0·0014, local vs metastatic recurrence, SHH vs group 3 vs group 4). The subgroup-specific location of recurrence was confirmed in cohort 2 (p=0·0013 for local vs metastatic recurrence, SHH vs group 3 vs group 4,), and cohort 3 (p<0·0001). Treatment with craniospinal irradiation at diagnosis was not significantly associated with the anatomical pattern of recurrence. Survival after recurrence was significantly longer in patients with group 4 tumours in cohort 1 (p=0·013) than with other subgroups, which was confirmed in cohort 2 (p=0·0075), but not cohort 3 (p=0·70). Interpretation: Medulloblastoma does not change subgroup at the time of recurrence, reinforcing the stability of the four main medulloblastoma subgroups. Significant differences in the location and timing of recurrence across medulloblastoma subgroups have potential treatment ramifications. Specifically, intensified local (posterior fossa) therapy should be tested in the initial treatment of patients with SHH tumours. Refinement of therapy for patients with group 3 or group 4 tumours should focus on metastases. Funding: Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, Garron Family Chair in Childhood Cancer Research at The Hospital for Sick Children and The University of Toronto. © 2013 Elsevier Ltd.

Shern J.F.,U.S. National Institutes of Health | Chen L.,U.S. National Institutes of Health | Chmielecki J.,The Broad Institute of MIT and Harvard | Chmielecki J.,Dana-Farber Cancer Institute | And 26 more authors.
Cancer Discovery | Year: 2014

Despite gains in survival, outcomes for patients with metastatic or recurrent rhabdomyosarcoma remain dismal. In a collaboration between the National Cancer Institute, Children's Oncology Group, and Broad Institute, we performed whole-genome, whole-exome, and transcriptome sequencing to characterize the landscape of somatic alterations in 147 tumor/ normal pairs. Two genotypes are evident in rhabdomyosarcoma tumors: those characterized by the PAX3 or PAX7 fusion and those that lack these fusions but harbor mutations in key signaling pathways. The overall burden of somatic mutations in rhabdomyosarcoma is relatively low, especially in tumors that harbor a PAX3/7 gene fusion. In addition to previously reported mutations in NRAS, KRAS, HRAS, FGFR4, PIK3CA, and CTNNB1, we found novel recurrent mutations in FBXW7 and BCOR, providing potential new avenues for therapeutic intervention. Furthermore, alteration of the receptor tyrosine kinase/ RAS / PIK3CA axis affects 93% of cases, providing a framework for genomics-directed therapies that might improve outcomes for patients with rhabdomyosarcoma. © 2014 American Association for Cancer Research.

Rives S.,Hospital Sant Joan de Deu de Barcelona | Rives S.,University of Barcelona | Estella J.,Hospital Sant Joan de Deu de Barcelona | Gomez P.,Hospital Reina Sofia | And 17 more authors.
British Journal of Haematology | Year: 2011

Philadelphia-chromosome acute lymphoblastic leukaemia (Ph+ ALL) is a subgroup of ALL with very high risk of treatment failure. We report here the results of the Sociedad Española de Hematología y Oncología Pediátricas (SEHOP/SHOP) in paediatric Ph+ ALL treated with intermediate-dose imatinib concurrent with intensive chemotherapy. The toxicities and outcome of these patients were compared with historical controls not receiving imatinib. Patients with Ph+ ALL aged 1-18years were enrolled in three consecutive ALL/SHOP trials (SHOP-94/SHOP-99/SHOP-2005). In the SHOP-2005 trial, imatinib (260mg/m2 per day) was given on day-15 of induction. Allogeneic haematopoietic stem-cell transplantation (HSCT) from a matched related or unrelated donor was scheduled in first complete remission (CR1). Forty-three patients were evaluable (22 boys, median age 6.8years, range, 1.2-15). Sixteen received imatinib whereas 27 received similar chemotherapy without imatinib. Seventeen of 27 and 15 of 16 patients in the non-imatinib and imatinib cohort, respectively, underwent HSCT in CR1. With a median follow-up of 109 and 39months for the non-imatinib and imatinib cohorts, the 3-year event-free survival (EFS) was 29.6% and 78.7%, respectively (P=0.01). These results show that, compared to historical controls, intermediate dose of imatinib given concomitantly with chemotherapy and followed by allogeneic HSCT markedly improved early EFS in paediatric Ph+ ALL. © 2011 Blackwell Publishing Ltd.

Tomas E.P.,Parc Tauli Hospital | Hurtado G.,Institute Of Neuropsiquiatria I Addiccions | Noguer S.,Servei de Psiquiatria i Psicologia | Domenech C.,Parc Tauli Hospital | And 7 more authors.
International Journal of Social Psychiatry | Year: 2012

Background: Despite their proven efficacy, family work interventions on families of patients with schizophrenia are not being implemented in routine clinical practice in contexts where expressed emotion levels among caregivers are relatively high. Aims: This study aimed to explore the effectiveness of a family work intervention in a Mediterranean environment in Catalonia, Spain. Method: Participants were 23 patients and 35 key relatives in five different clinical settings. The family intervention was provided by 10 trained health care professionals during a nine-month period. A six-month follow-up was also conducted. Results: Statistically significant improvements were found in patients' clinical status, global functioning and social functioning levels, as well as in caregivers' burden of care. These results were maintained during follow-up. Conclusion: This is the first study to explore the effectiveness of family intervention in a high-expressed emotion context in Catalonia. The findings add weight to the growing literature supporting these interventions in different cultural settings. © 2011 The Author(s).

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