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Guerra J.L.L.,University of Seville | Guerra J.L.L.,Grupo IMO | Matute R.,Grupo IMO | Puebla F.,San Carlos Clinical Hospital | And 12 more authors.
Tumori | Year: 2015

Aims and background: The objective of this study was to assess the influence of ethnicity on toxicity in patients treated with dynamic arc radiation therapy (ART) for prostate cancer (PC). Methods: From June 2006 to May 2012, 162 cT1-T3 cN0 cM0 PC patients were treated with ART (primary diagnosis, n = 125; post-prostatectomy/brachytherapy biochemical recurrence, n = 26; adjuvant post-prostatectomy, n = 11) at 2 institutions. Forty-five patients were Latin Americans and 117 were Europeans. The dose prescribed to the prostate ranged between 68 Gy and 81 Gy. Results: The median age was 69 years (range 43-87 years). The median follow-up was 18 months (range 2-74 months). Overall, only 3 patients died, none due to a cancer-related cause. Biochemical recurrence was seen in 7 patients. The rates of acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicities were 19.7% and 17%, respectively. Only 1 patient experienced acute grade 3 GI toxicity, whereas 11 patients (6.7%) experienced acute grade 3 GU toxicity. Multivariate analysis showed that undergoing whole pelvic lymph node irradiation was associated with a higher grade of acute GI toxicity (OR: 3.46; p = 0.003). In addition, older age was marginally associated with a higher grade of acute GI toxicity (OR: 2.10; p = 0.074). Finally, ethnicity was associated with acute GU toxicity: Europeans had lowergrade toxicity (OR: 0.27; p = 0.001). Conclusions: Our findings suggest an ethnic difference in GU toxicity for PC patients treated with ART. In addition, we found that ART is associated with a very low risk of severe toxicity and a low recurrence rate. © 2015 INTM, Italy. Source

Castellano D.,University of Cordoba, Spain | Gonzlaez-Larriba J.L.,San Carlos Clinical Hospital | Anton-Aparicio L.M.,University of La Coruna | Cassinello J.,University of Guadalajara | And 3 more authors.
Expert Opinion on Pharmacotherapy | Year: 2011

Objective: Vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) correlate with poor prognosis in castration-resistant prostate cancer (CRPC). Sunitinib has shown activity in CRPC and at the time of this analysis there was no standard therapy for docetaxel-refractory CRPC. Methods: We present a case series data collection of 19 patients with a median age of 73 years, CRPC and rising prostate-specific antigen (PSA). Patients received sunitinib 37.5 mg continuous daily dose. One cycle comprised a 4-week period. Patients were evaluated by CT scan every 8 weeks and PSA was monitored every 4 weeks. Results: Median Eastern Cooperative Oncology Group (ECOG) performance status score was 2. Patients received a median of two previous treatment lines for the hormone-refractory setting. Baseline median PSA was 280 ng/ml. Patients received a median of 16 weeks of therapy (4 48+). One patient achieved a partial response (5%) and 12 (66.7%) achieved stable disease for at least 3 months according to RECIST criteria. Median progression-free survival was 4 months. PSA declined > 50% in 5/19 (26.3%) and stabilized in 7/19 (37%) patients. Frequent adverse events were grade 3 asthenia (21%), grade 3 diarrhea (10%) and grade 3 hand-foot syndrome (15.7%). Conclusions: Activity with sunitinib was observed in highly pretreated docetaxel-refractory CRPC with acceptable tolerability. Additional studies should confirm the role of antiangiogenic agents in this setting. © 2011 Informa UK, Ltd. Source

Fernandez Lopez M.,Fuenlabrada University Hospital | Fernandez Lopez M.,Rey Juan Carlos University | Ruiz Giardin J.M.,Fuenlabrada University Hospital | San Martin Lopez J.V.,Fuenlabrada University Hospital | And 4 more authors.
Malaria Journal | Year: 2015

Background: Arrival of inmigrants from malaria endemic areas has led to a emergence of cases of this parasitic disease in Spain. The objective of this study was to analyse the high incidence rate of imported malaria in Fuenlabrada, a city in the south of Madrid, together with the frequent the lack of chemoprophylaxis, for the period between 2004 and 2014. Both pregnant women and HIV risk groups have been considered. Methods: Retrospective descriptive study of laboratory-confirmed malaria at the Fuenlabrada University Hospital, in Madrid, during a 10-year period (2004-2014). These data were obtained reviewing medical histories of the cases. Relevant epidemiological, clinical and laboratory results were analysed, with focus on the following risk groups: pregnant women and individuals with HIV. Results: A total of 185 cases were diagnosed (90.3 % Plasmodium falciparum). The annual incidence rate was 11.9/100,000 inhabitants/year. The average age was 30.8 years (SD: 14.3). Infections originating in sub-Saharan Africa comprised the 97.6 % of the cases. A total of 85.9 % were Visiting Friends and Relatives. Only a 4.3 % completed adequate prophylaxis. A total of 14.28 % of the fertile women were pregnant, and 8 cases (4.3 %) had HIV. None of them in these special groups completed prophylaxis. Conclusions: The incidence rate in Fuenlabrada is higher than in the rest of Spain, due to the large number of immigrants from endemic areas living in the municipality. However, the results are not representative of all the country. It seems to be reasonable to implement prevention and pre-travel assessment programs to increase chemoprophylaxis. Pregnancy tests and HIV serology should be completed for all patients to improve prophylactic methods. © 2015 Fernández López et al. Source

Perez de Diego R.,University Institute of La Paz | Sanchez-Ramon S.,San Carlos Clinical Hospital | Lopez-Collazo E.,University Institute of La Paz | Martinez-Barricarte R.,Rockefeller University | And 7 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of eachof the components of the CBM complex to human immunity. © 2015 American Academy of Allergy, Asthma & Immunology. Source

Torres J.M.,Hospital Universitario La Paz | Torres J.M.,University Institute of La Paz | Martinez-Barricarte R.,Rockefeller University | Garcia-Gomez S.,University Institute of La Paz | And 36 more authors.
Journal of Clinical Investigation | Year: 2014

Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain-containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of-function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient's myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB-mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects. © 2014, American Society for Clinical Investigation. All rights reserved. Source

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