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Cruz-Gonzalez F.,Hospital Universitario Of Salamanca | Cruz-Gonzalez F.,University of Salamanca | Cruz-Gonzalez F.,Complejo Asistencial Universitario Of Salamanca | Cabrillo-Estevez L.,Hospital Universitario Of Salamanca | And 4 more authors.
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2014

Background: To determine whether gene polymorphisms of the vascular endothelial growth factor A (VEGF A) and its receptor (VEGFR) influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration. Methods: This prospective cohort study included 94 patients (94 eyes) with exudative age-related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (SUSTAIN). Injections were administered monthly during 3 months to all the patients diagnosed of neovascular AMD; reinjections were made when a patient lost 5 letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 μm in central subfield retinal thickness measured by OCT. Genotypes (VEGF A (rs 699947, rs833061) and VEGFR (rs 2071559)) were analyzed using TaqMan probes. Best-corrected visual acuity (BCVA), subjective improvement, and macular thickness measured with OCT values were compared with VEGF A and VEGFR genotypes. Multiple regression analysis was used to assess the statistical significance. Results: We found statistically significant differences in allelic distribution of VEGF A rs833061 polymorphism in relation with the response to intravitreal ranibizumab regarding to visual acuity improvement [p=0,.34; OR: 1.619 (1.098-2.386)]. Patients carrying "protector" genotype CC had higher probability of best corrected visual acuity improvement. When we analyzed VEGF A rs699947 polymorphism we found that patients expressing AA genotype had a higher chance of increasing their best corrected visual acuity [p:0,022; OR 1,532 (1,015-2,313)]. We did not find statistically significant differences reagarding VEGFR rs2071559 polymorphism and treatment response. Conclusions: Polymorphisms of VEGF A seem to influence the different response to antiangiogenic treatment in patients with AMD in our population, although further investigation is needed to know the mechanisms of this relationship. © Springer-Verlag 2014. Source

Gonzalez-Calle V.,Complejo Asistencial Universitario Of Salamanca
Leukemia | Year: 2016

The diagnosis of smoldering multiple myeloma (SMM) includes patients with a heterogeneous risk of progression to active multiple myeloma (MM): some patients will never progress, whereas others will have a high risk of progression within the first 2 years. Therefore, it is important to improve risk assessment at diagnosis. We conducted a retrospective study in a large cohort of SMM patients, in order to investigate the role of Bence Jones (BJ) proteinuria at diagnosis in the progression to active MM. We found that SMM patients presenting with BJ proteinuria had a significantly shorter median time to progression (TTP) to MM compared with patients without BJ proteinuria (22 vs 88 months, respectively; hazard ratio=2.3, 95% confidence interval=1.4–3.9, P=0.002). We also identified risk subgroups based on the amount of BJ proteinuria: ⩾500 mg/24 h, <500 mg/24 h and without it, with a significantly different median TTP (13, 37 and 88 months, P<0.001). Thus, BJ proteinuria at diagnosis is an independent variable of progression to MM that identifies a subgroup of high-risk SMM patients (51% risk of progression at 2 years) and ⩾500 mg of BJ proteinuria may allow, if validated in another series, to reclassify these patients to MM requiring therapy before the end-organ damage development.Leukemia advance online publication, 27 May 2016; doi:10.1038/leu.2016.123. © 2016 Macmillan Publishers Limited Source

Casas Ferreira A.M.,University of Salamanca | Moreno Cordero B.,University of Salamanca | Crisolino Pozas T.P.,Complejo Asistencial Universitario Of Salamanca | Perez Pavon J.L.,University of Salamanca
Journal of Chromatography A | Year: 2016

A novel methodology for the determination of ornithine, putrescine, cadaverine, spermidine and gamma-amino butyric acid in urine samples has been developed. The method uses in situ aqueous derivatization followed by automated microextraction by packed sorbent coupled to a gas chromatography-mass spectrometry system equipped with a programmed temperature vaporizer. This instrumental configuration minimizes sample manipulation due to from the mixing of the reagents, the process is completely automated. The analytes were derivatized using ethyl chloroformate as derivatization reagent. The reaction occurred in aqueous medium and was carried out in 1 min in the vial of an autosampler used to perform microextraction by packed sorbent. The parameters affecting derivatization, extraction and separation were optimized in order to obtain maximum sensitivity. Calibration curves were obtained for five calibration levels in three different matrices. All the calibration models displayed good linearity, with R2 values higher than 0.95. The validity of the models was checked using ANOVA, and it was observed that they did not exhibit any lack of fit. Repeatability and reproducibility was evaluated, with values below 15% in both cases. LOD and LOQ values were found to be in the low μg/L level. Influence of the matrix was confirmed, thus quantification was performed using the standard additions method and normalization to IS. The method developed was applied to the analysis of these compounds in urine samples from healthy individuals and cancer diagnosed patients (Internal Medicine Unit of the Virgen de la Vega Hospital, Salamanca, Spain). Significant differences (Mann-Whitney U test) were observed for putrescine and ornithine concentrations. © 2016 Elsevier B.V. Source

Otero M.J.,Complejo Asistencial Universitario Of Salamanca | Moreno-Gomez A.M.,ISMP Espana | Agra Y.,Direccion General de Salud Publica
European Journal of Internal Medicine | Year: 2014

Background Patients with chronic diseases often receive multiple medications and are associated with increased vulnerability to medication errors. Identifying high-alert medications for them would help to prioritize the interventions with greatest impact for improving medication safety. The aim of this study was to develop a list of high-alert medications for patients with chronic illnesses (HAMC list) that would prove useful to the Spanish National Health Service strategies on chronicity.Methods The RAND/UCLA appropriateness method was used. Drug classes/drugs candidates to be included on the HAMC list were identified from a literature search in MedLine, bulletins issued by patient safety organizations, incidents recorded in Spanish incident reporting systems, and previous lists. Eighteen experts in patient/medication safety or in chronic diseases scored candidate drugs for appropriateness according to three criteria (evidence, benefit and feasibility of implementing safety practices). Additionally they rated their priority of inclusion on a Likert scale.Results The final HAMC list includes 14 drug classes (oral anticoagulants, narrow therapeutic range antiepileptics, antiplatelets - including aspirin -, antipsychotics, β-blockers, benzodiazepines and analogues, corticosteroids long-term use, oral cytostatics, oral hypoglycemic drugs, immunosuppressants, insulins, loop diuretics, nonsteroidal anti-inflammatory drugs, and opioid analgesics), and 4 drugs or pairs of drugs (amiodarone/ dronedarone, digoxin, oral methotrexate and spironolactone/eplerenone).Conclusions An initial list of high-alert medications for patients with chronic diseases has been developed, which can be built into the medication management strategies for chronicity to guide the implementation of efficient safety strategies and to identify those patients at greater risk for preventable adverse drug events. © 2014 European Federation of Internal Medicine. Source

Mateos M.-V.,Complejo Asistencial Universitario Of Salamanca
Expert Opinion on Orphan Drugs | Year: 2016

Introduction: Multiple myeloma remains an incurable disease; the introduction of novel drugs has improved outcomes but patients become eventually refractory.Areas covered: Monoclonal antibodies targeting multiple myeloma-related antigens can complement currently available therapies. SLAMF7, a cell surface glycoprotein receptor that is a member of the signaling lymphocytic activation molecule (SLAM) family, is highly and nearly uniformly expressed in myeloma cells and Natural Killer (NK) cells, but is not detected on normal solid tissues or on hematopoietic stem cells. Elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. It has been shown to be effective in preclinical studies and in the clinical setting, although only stabilization of the disease was reported when used as a single-agent. Its combination with antimyeloma therapies was positive and several trials have confirmed this hypothesis. The results of these trials in terms of efficacy and safety will be covered in this review.Expert opinion: Elotuzumab, plus lenalidomide and dexamethasone, is the first immunostimulatory monoclonal antibody demonstrating a benefit in progression free survival in a large phase 3 study in patients with relapsed or relapsed and refractory disease, representing a new standard of care for this patient population. © 2016 Taylor & Francis. Source

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