PubMed | Hospital Universitario La Paz, University Hospital Cruces, University of the Basque Country, San Sebastián University and 2 more.
Type: Journal Article | Journal: Pharmacogenomics | Year: 2016
Vincristine is an important component of acute lymphoblastic leukemia (ALL) treatment protocols that can cause neurotoxicity. Patients treated with LAL/SHOP protocols often suffer from vincristine-related neurotoxicity in early phases of treatment. Recently, a genome-wide association study connected a SNP in CEP72, involved in vincristine pharmacodynamics, with neurotoxicity during later phases of therapy, which was not replicated during induction phase. These results, together with previous studies indicating that polymorphisms in pharmacokinetic genes are associated with drug toxicity, suggest that changes in the activity or levels of vincristine transporters or metabolizers could work as predictors of vincristine-related neurotoxicity in early phases of treatment in pediatric ALL.We analyzed 150 SNPs in eight key genes involved in vincristine pharmacokinetics and in 13 miRNAs that regulate them. We studied their correlation with neurotoxicity during induction phase in 152 ALL patients treated with LAL/SHOP protocols.The strongest associations with neurotoxicity were observed for two SNPs in ABCC2. The genotypes rs3740066 GG and rs12826 GG were associated with increased neurotoxicity.Polymorphisms in ABCC2 could be novel markers for vincristine-related neurotoxicity in pediatric ALL in early phases.
Ruiz I.,University Hospital Donostia |
Martin-Arruti M.,University Hospital Donostia |
Martin-Arruti M.,University of the Basque Country |
Lopez-Lopez E.,University of the Basque Country |
Garcia-Orad A.,University of the Basque Country
Gynecologic Oncology | Year: 2014
Objective Endometrial carcinomas of the endometrioid type (EEC) are associated with a good prognosis. However, about 20% of them recur and new prognostic markers are needed. Microsatellite instability (MSI), associated with mismatch repair (MMR) deficiency, is a frequent alteration in EECs that has been associated with prognosis. However, its prognostic impact on EECs remains unclear. The aim of the present study was to clarify the relationship between MMR deficiency and outcome in a large cohort of well classified EECs. Methods A total of 212 EEC samples were analyzed by immunohistochemistry for the MMR genes MLH-1, MSH-2, MSH-6 and PMS-2. Kaplan-Meier survival analysis and log-rank tests were performed to study the prognostic significance of dMMR taking into account clinical and pathological parameters. Results We observed no association between MMR deficiency and OS or PFS in our 212 EEC patients (p-value = 0.6565 and 0.4380, respectively). When we performed the analysis in different FIGO-stage groups, we did not find association between MMR and OS or PFS in stages I, I/II or III/IV. When we analyzed the specific group of patients with lymphatic invasion separately, MMR expression was not associated with OS or PFS either. Conclusions MMR deficiency does not seem to be a good prognostic marker in endometrioid type endometrial carcinomas. © 2014 Elsevier Inc. All rights reserved.
Obeso J.A.,University of Navarra |
Obeso J.A.,CIBER ISCIII |
Rodriguez-Oroz M.C.,CIBER ISCIII |
Rodriguez-Oroz M.C.,University Hospital Donostia |
And 4 more authors.
The Lancet | Year: 2014
Summary The basal ganglia were originally thought to be associated purely with motor control. However, dysfunction and pathology of different regions and circuits are now known to give rise to many clinical manifestations beyond the association of basal ganglia dysfunction with movement disorders. Moreover, disorders that were thought to be caused by dysfunction of the basal ganglia only, such as Parkinson's disease and Huntington's disease, have diverse abnormalities distributed not only in the brain but also in the peripheral and autonomic nervous systems; this knowledge poses new questions and challenges. We discuss advances and the unanswered questions, and ways in which progress might be made. © 2014 Elsevier Ltd.
Gutierrez-Camino A.,University of the Basque Country |
Martin-Guerrero I.,University of the Basque Country |
Lopez-Lopez E.,University of the Basque Country |
Echebarria-Barona A.,University Hospital Cruces |
And 5 more authors.
Pharmacogenetics and Genomics | Year: 2016
Vincristine is a component of acute lymphoblastic leukemia (ALL) treatment with the potential to induce peripheral neuropathy. Recently, the CEP72 rs924607 TT genotype was found to be associated with vincristine-induced toxicity during the continuation phase in pediatric ALL patients treated on the Total XIIIB and COG AALL0433 protocols at St Jude Children's Research Hospital and Children's Oncology Group. This finding could provide a base for safer dosing of vincristine. Nevertheless, there are variations in vincristine regimens among ALL treatment protocols and phases in different populations. Therefore, the aim of this study was to determine whether the CEP72 rs924607 TT genotype is a useful marker of vincristine neuropathy during induction therapy among Spanish children with B-ALL treated on the LAL-SHOP protocols. No association was found between neurotoxicity during the induction phase and the rs924607 TT genotype. This lack of association could be because of population differences and/or differences in neurotoxicity etiology between induction and continuation phases of treatment. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
PubMed | Foundation University and University Hospital Donostia
Type: Journal Article | Journal: Revista da Escola de Enfermagem da U S P | Year: 2013
The aim of this study was to analyze the discourse of health managers on aspects related to delay in tuberculosis diagnosis. This was a qualitative research study, conducted with 16 Family Health Unit managers. The empirical data were obtained through semi-structured interviews. The analysis was based on the theoretical framework of the French school of discourse analysis. According to the managers statements, the delay in tuberculosis diagnosis is related to patient and health service aspects. As for patient aspects, managers report fear, prejudice and lack of information as factors that may promote a delayed diagnosis. Regarding health service aspects, structural problems and lack of professional skills were reported. The discourse of managers should be considered to qualify tuberculosis control actions and to prevent delays in diagnosis.
Predictive value of interim 18F-FDG-PET/CT for event-free survival in patients with diffuse large B-cell lymphoma homogenously treated in a phase II trial with six cycles of R-CHOP-14 plus pegfilgrastim as first-line treatment
Gonzalez-Barca E.,Hospital Duran i Reynals |
Canales M.,Hospital Universitario La Paz |
Cortes M.,Institute of Diagnosis by Image IDI |
Vidal M.J.,University Hospital Donostia |
And 9 more authors.
Nuclear Medicine Communications | Year: 2013
OBJECTIVE: The predictive value of interim PET/computed tomography (I-PET/CT) in diffuse large B-cell lymphoma (DLBCL) is controversial. Our aim was to evaluate the predictive value of I-PET/CT for an event-free survival. PATIENTS AND METHODS: We analyzed patients with DLBCL included in a prospective clinical trial who were treated with six cycles of dose-dense R-CHOP followed by pegfilgrastim and who had undergone an I-PET/CT (after two cycles) and a final PET [F-PET/CT (60 days after the sixth cycle)]. Event was defined as nonresponse, relapse, or death. RESULTS: A total of 69 patients were included. Their median age was 60 years; 54% were male, 25% had bulky disease, and 67% had an International Prognostic Index of 0-2. The median follow-up duration was 28.8 months. I-PET/CT was positive in 34 (49%) patients and F-PET/CT was positive in 12 (17.4%). The 3-year event-free survival was 86% for patients who were I-PET/CT negative as against 64% for those who were I-PET/CT positive (P=0.036). The negative and positive predictive values, sensitivity, and specificity of I-PET/CT for an event were 83, 32, 65, and 56%, respectively. In a multivariate analysis including baseline characteristics, I-PET/CT, and F-PET/CT, F-PET/CT was the only significant predictor (P<0.0005). CONCLUSION: In patients with DLBCL treated with dose-dense R-CHOP plus pegfilgrastim, a negative I-PET/CT is highly predictive of a favorable outcome and a positive I-PET/CT is of limited clinical value. These results do not support treatment intensification after a short course of chemotherapy based solely on a positive I-PET/CT. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
PubMed | University Hospital Donostia and Laboratory Hospital Galdakao Usansolo
Type: Journal Article | Journal: International journal of laboratory hematology | Year: 2016
The aim of this study was to perform a verification of the hematology analyzer Sysmex XN-2000 by comparing with the previous XE-5000. This study assessed the precision and carryover on the XN-2000 and the systematic error between the both counters according to desirable biological variability criterion and a flag comparison study.Within-run precision and between-batch precision were measured according to the ICSH guidelines. A comparative study was performed analyzing two hundred and six samples of peripheral blood from patients. The statistical study was conducted using the Passing-Bablok and Bland-Altman analyses. The leucocyte flag comparison was made by measuring the efficiency rate.Between-batch precision was lower than that recommended by the biological variability criterion and manufacturer specifications. The comparison gave nonagreement results for neutrophil and basophil counts according to the criterion of biological variability. Erythroblasts and immature granulocytes showed nonagreement, but there is no available biological variation database for these parameters to compare with. Nevertheless, excellent absolute agreement was found for red blood cell parameters, and for platelet, lymphocyte, monocyte, and eosinophil counts.The global results obtained for the precision, comparability, and efficiency provide a satisfactory integration of the XN-2000 in the core laboratory routine and accomplish an optimal reliability.
Ramirez J.M.,University of Cordoba, Spain |
Nunez V.M.,University of Cordoba, Spain |
Lancho C.,University of Cordoba, Spain |
Lancho C.,University Hospital Donostia |
And 2 more authors.
Journal of Strength and Conditioning Research | Year: 2015
The power production is force-velocity related. We hypothesized that speed-based training of lower limb using half-squat can lead to absolute and relative power improvements in concentric movement with the same external load. One group of 19 soccer players (age 24.4 years, SD 3.7 years) participated in a pretest-posttest power training protocol, consistent in 2 training sessions per week during 10 weeks, targeted to work the leg power by performing half-squat with a fixed external load (mean 71.7, SD 5.4) at 65% of 1 repetition maximum. Measurements of power (absolute [in watt] and relative [in watt per kilogram]), force (in Newton), and velocity (in meter per second) (mean and peak) were made from a concentric movement of a half-squat exercise with a fixed external load. The training protocol increased relative power (mean 47.5, SD 47.5, p < 0.001) and absolute power (mean 169.2, SD 95.5, p < 0.001). Also, number of repetitions (mean 2.9, SD 2.4, p < 0.01), force (mean 66.6, SD 36.7, p < 0.001), and velocity (mean 0.1, SD 0.1, p < 0.001) were increased. However, only improved velocity was related to the changes in absolute (r 0.939, p < 0.001) and relative (r 0.757, p < 0.001) power. The speed-based training combined with moderate to high external load can lead to an improvement of absolute and relative power in concentric phases of half-squat in soccer players. This could be important for improving the performance of the players in the field. © 2015 National Strength and Conditioning Association.
Arana M.E.,University Hospital Donostia |
De Zarate J.M.M.O.,University Hospital Donostia
BMJ Case Reports | Year: 2015
Nocardia fusca was first described in 1983; however, to date, no report of human infection has been done. In this work, we report the first case of N. fusca isolation during an episode of acute exacerbation in a patient with chronic obstructive pulmonary disease. The extent of the role of N. fusca as human pathogen still has to be determined. © 2015 BMJ Publishing Group.
PubMed | University Hospital Donostia
Type: | Journal: BMJ case reports | Year: 2015
Nocardia fusca was first described in 1983; however, to date, no report of human infection has been done. In this work, we report the first case of N. fusca isolation during an episode of acute exacerbation in a patient with chronic obstructive pulmonary disease. The extent of the role of N. fusca as human pathogen still has to be determined.