Julián Torre-Cisneros

Hospital Universitario Reina Sofía, Cordoue, Andalusia, Spain

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Publications (134)477.77 Total impact

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    ABSTRACT: BACKGROUND: It is necessary to develop a safe alternative to isoniazid for tuberculosis prophylaxis in liver transplant recipients. This study was designed to investigate the efficacy and safety of levofloxacin. METHODS: An open-label, prospective, multicenter, randomized study was conducted to compare the efficacy and safety of levofloxacin (500 mg q24h for 9 months) initiated in patients awaiting liver transplantation and isoniazid (300 mg q24h for 9 months) initiated post-transplant when liver function was stabilized. Efficacy was measured by tuberculosis incidence at 18 months after transplantation. All adverse events related to the medication were recorded. RESULTS: CONSORT guidelines were followed in order to present the results. The safety committee suspended the study through a safety analysis when 64 patients had been included (31 in the isoniazid arm and 33 in the levofloxacin arm). The reason for suspension was an unexpected incidence of severe tenosynovitis in the levofloxacin arm (18.2%). Although the clinical course was favorable in all cases, tenosynovitis persisted for 7 weeks in some patients. No patients treated with isoniazid, developed tenosynovitis. Only 32.2% of patients randomized to isoniazid (10/31) and 54.5% of patients randomized to levofloxacin (18/33, P = .094) completed prophylaxis. No patient developed tuberculosis during the study follow-up (median 270 days). CONCLUSIONS: Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a high incidence of tenosynovitis that limits its potential utility.
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    ABSTRACT: The emergence and spread of carbapenemase-producing Enterobacteriaceae is an important and very concerning problem. There is an urgent need of new antibimicrobials for treating these infections. Currently there are some options in the pipeline. Several new beta-lactamase and carbapenemase inhibitors as avibactam and MK-7655, combined with old or new betalactams are a very interesting option. Some combinations as ceftazidime-avibactam are in the late stages of clinical development and could reach the market in the next years. New aminoglycosides as plazomicin, tetracycline derivates as eravacycline, and several other new molecules as monosulfactams are currently in different stages of development. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
    Enfermedades Infecciosas y Microbiología Clínica 12/2014; 32S4:56-60. DOI:10.1016/S0213-005X(14)70175-2 · 1.88 Impact Factor
  • Journal of Infection 11/2014; 4453(14):334-335. DOI:10.1016/j.jinf.2014.11.010 · 4.02 Impact Factor
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    ABSTRACT: BACKGROUND & AIM The seroprevalence of the hepatitis E virus (HEV) and its chronicity rate in the HIV-infected population has not been well established. As a result, the magnitude of this emerging disease in this population cannot be established. METHODS: Prospective study that included HIV-infected patients followed up between September 2012 and May 2013. All included patients were tested for anti-HEV IgG/IgM. In patients with confirmed anti-HEV IgG/IgM positivity, RT-PCR was performed. In patients where HEV RNA was amplified, a second RT-PCR assay was performed 6 months later to identify transient or chronic HEV infections. RESULTS: Eight hundred and ninety-four HIV-infected patients were enrolled in the study. Of these patients, 399 (44.6%) were monoinfected with HIV; 462 (51.6%) were co-infected with HIV/HCV; 12 (1.3%) were co-infected with HIV/HBV; and 21 (2.3%) were co-infected with HIV/HCV/HBV. In 88 patients, anti-HEV IgG/IgM was detected (seroprevalence: 9.8% [95% CI: 8.02%-11.9%]). In five patients (0.5%; 95% CI: 0.2%-1.2%), HEV RNA was detected; 5.7% (95% CI: 2.1%-12.1%) of the patients were anti-HEV IgG/IgM positive. None of these patients showed detectable HEV RNA six months later. CONCLUSION: HEV infection is frequent in HIV-infected patients but developing a chronic HEV infection may be considered an uncommon liver disease in this population.
    Journal of Infection 11/2014; 4453(14):331-334. DOI:10.1016/j.jinf.2014.10.016 · 4.02 Impact Factor
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    ABSTRACT: Antimicrobial therapy for sepsis caused by carbapenem- and colistin-resistant Klebsiella pneumoniae is not well established. We hypothesized that the early use of gentamicin in cases due to susceptible organisms would decrease the crude mortality rate of this infection.
    Journal of Antimicrobial Chemotherapy 10/2014; 70(3). DOI:10.1093/jac/dku432 · 5.44 Impact Factor
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    ABSTRACT: Despite administration of annual influenza vaccination, influenza-associated complications in transplant recipients continue to be an important cause of hospitalization and death. Although influenza vaccination has been proven to be the most effective measure to reduce influenza infection after transplantation, transplant recipients are still vulnerable to influenza infections, with lower serological responses to vaccination compared to the general population. In order to assess the efficacy and safety of an alternative immunization scheme for solid organ transplant recipients, the TRANSGRIPE1-2Study Group aimed to test a booster dose administration 5 weeks after the standard vaccination. The primary objective of this trial was to compare short-term and long-term neutralizing antibody immunogenicity of a booster dose of influenza vaccination to the standard single-dose immunization scheme. Secondary objectives included the evaluation of the efficacy and/or safety, cellular immune response, incidence of influenza infection, graft rejection, retransplant and mortality rates.
    Trials 08/2014; 15(1):338. DOI:10.1186/1745-6215-15-338 · 2.12 Impact Factor
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    ABSTRACT: Optimizing HCV genotype 1 therapy in terms of response prediction and tailoring treatment is undoubtedly the cornerstone of treating HIV co-infected patients in clinical practice. Accordingly, our aim was to analyze the predictive value of HCV viral decline for sustained virological response (SVR), measured at a time point as early as week 2 of therapy with pegylated interferon alpha-2a plus ribavirin (Peg-IFN/RBV).
    PLoS ONE 06/2014; 9(6):e99468. DOI:10.1371/journal.pone.0099468 · 3.53 Impact Factor
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    ABSTRACT: We determined the characteristics of posttransplant tuberculosis and the impact of rifampin-based antituberculosis regimens on outcomes in the current era. Patients comprised 64 transplant recipients with tuberculosis, divided into 2 consecutive cohorts: an earlier cohort (cases occurring from 2003 to 2007) and a later cohort (cases from 2008 to 2011). Patients from the later versus earlier era had tuberculosis develop later after transplant (odds ratio, 1.01; 95% CI, 1.00-1.02; P= .05), were more likely to be liver transplant recipients (odds ratio, 4.52; 95% CI, 1.32-15.53; P= .02), and were more likely to receive tacrolimus-based immunosuppression (odds ratio, 3.24; 95% CI, 1.14-9.19; P= .03). Mortality rate was 10% in the later cohort and 21% in the earlier cohort (P= .20). Rifampin-based treatment was less likely to be used in patients with prior rejection (P= .04). However, neither rejection rate (P= .71) nor mortality (P= .93) after tuberculosis differed between recipients who received rifampin and recipients who did not. Thus, notable changes have occurred in the epidemiological characteristics of tuberculosis in transplant recipients. Overall mortality rate has improved, with about 90% of the patients now surviving after tuberculosis.
    Progress in transplantation (Aliso Viejo, Calif.) 03/2014; 24(1):37-43. DOI:10.7182/pit2014398 · 0.69 Impact Factor
  • Medicina Clínica 01/2014; 142(2):87–88. DOI:10.1016/j.medcli.2013.07.006 · 1.25 Impact Factor
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    ABSTRACT: It is not known whether the probability of achieving sustained virological response (SVR) can be determined on the basis of the magnitude of HCV viral decline over the first 4 weeks of Peg-IFN/RBV treatment of HIV/HCV co-infected patients who fail to achieve a rapid virological response (RVR). HIV patients co-infected with HCV genotype 1 naïve to Peg-IFN/RBV treatment were included. HCV viral decline from baseline to week 4 was graded. The positive predictive value (PPV) for SVR was evaluated according to the magnitude of HCV viral decline at week 4. One hundred and fifty patients were included. Thirty-four (22.6%) patients achieved RVR, 33 of these (PPV [CI 95%]; 97.05% [86.34-99.85]) achieved SVR. In those patients who did not achieve RVR, the probability to achieving SVR was graded according to the magnitude of viral decline at week 4 (>2 log10 [55.5%], >2.5 log10 [73.3%] and >3 log10 [75%]). The combination of undetectable and magnitude of decline (>2.5 log10) had a PPV for SVR of 89.8% (CI 95%; 0.794-0.964). The combination of undetectable HCV viral load andmagnitude of decline at week 4 has a high PPV for SVR and identified ahigher number of potential Peg-IFN/RBV responders.
    The Journal of infection 11/2013; DOI:10.1016/j.jinf.2013.11.009 · 4.02 Impact Factor
  • Medicina Clínica 10/2013; · 1.25 Impact Factor
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    ABSTRACT: To evaluate the IL28B effect on hepatitis C virus (HCV) decline during first weeks of treatment according to HCV-1 subtypes. Patients coinfected with HIV/HCV genotype 1 and naive to peginterferon-alpha-2a and ribavirin (Peg-IFN-alpha-2a/RBV) were included. Plasma HCV-RNA was measured at baseline, and then at weeks 1, 2, and 4. HCV-1 subtype (1a or 1b) was determined. HCV viral decline was analyzed according to HCV-1 subtype between baseline and week 1, week 2 and week 4 of treatment. Additionally, we analyzed the effect of the IL28B (rs12979860) genotype on HCV viral decline with HCV-1a and HCV-1b genotype patients (CC versus non-CC). Two hundred and six patients were included in the study, of whom 113 (54.8%) and 93 (45.2%) were infected by HCV-1a and 1b genotypes, respectively. No differences were found between HCV-1 subtypes in terms of HCV viral decline or rapid virological response rate. The effect of the IL28B-CC genotype on HCV viral decline was observed only among patients infected with HCV-1b at all time points analyzed (week 1: CC 1.53 ± 0.33, non-CC 0.27 ± 0.24, P <0.001; week 2: CC 1.81 ± 0.39, non-CC 0.74 ± 0.39, P = 0.002; week 4: CC 2.97 ± 0.53, non-CC 1.2 ± 0.61, P < 0.001). Our study suggests that the effect associated with the impact of the IL28B-CC genotype on HCV decline during the first weeks of treatment with Peg-IFN-alpha-2a/RBV differs according to HCV-1 subtype and may be limited to HCV-1b patients.
    AIDS (London, England) 07/2013; 27(12):1941-7. DOI:10.1097/QAD.0b013e328360ea1e · 6.56 Impact Factor
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    ABSTRACT: Several studies have reported that a significant number of HIV patients not co-infected with HCV/HBV develop liver damage of uncertain origin (LDUO). The objective of our study was to evaluate the incidence of and risk factors for the development of LDUO in HIV infected patients not co-infected with HCV/HBV. Prospective longitudinal study that included HIV-infected patients free of previous liver damage and viral hepatitis B or C co-infections. Patients were followed up at 6-monthly intervals. Liver stiffness was measured at each visit. Abnormal liver stiffness (ALS) was defined as a liver stiffness value greater than 7.2 kPa at two consecutive measurements. For patients who developed ALS, a protocol was followed to diagnose the cause of liver damage. Those patients who could not be diagnosed with any specific cause of liver disease were diagnosed as LDUO and liver biopsy was proposed. 210 patients matched the inclusion criteria and were included. 198 patients completed the study. After a median (Q1-Q3) follow-up of 18 (IQR 12-26) months, 21 patients (10.6%) developed ALS. Of these, fifteen patients were diagnosed as LDUO. The incidence of LDUO was 7.64 cases/100 patient-years. Histological studies were performed on ten (66.6%) patients and all showed liver steatosis. A higher HOMA-IR value and body mass index were independently associated with the development of LDUO. We found a high incidence of LDUO in HIV-infected patients associated with metabolic risk factors. The leading cause of LDUO in our study was non-alcoholic fatty liver disease.
    PLoS ONE 07/2013; 8(7):e68953. DOI:10.1371/journal.pone.0068953 · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: Globalization and migration patterns have increased the number of donors from countries with high incidence rates of tuberculosis (TB) in low incidence countries, with the subsequent increase in risk of TB transmission to the recipients. METHODS: Retrospective cohort study, including all actual deceased donors in Spanish hospitals between January 1998 and June 2011 and all the recipients who had received an organ from donors identified as TB cases. RESULTS: Six actual donors were identified as TB cases, representing an annual incidence of 30.6 cases/100,000 donors (95% CI, 4-58). Two cases did not become utilized donors, because TB was detected in the organ recovery and were therefore excluded. Annual incidence in utilized donors was 23 cases/100,000 donors (95% CI, 6-59). Annual incidence of the Spanish population in the same period was 17.5 cases/100,000 inhabitants (95% CI, 17-18). Annual incidence in actual donors belonging to the Romanian immigrant community was 2353 cases/100,000 donors (95% CI, 286-8242). Variations in the prophylactic strategy utilized in recipients were observed. TB was transmitted to three recipients (27.3% transmission), two of whom developed active TB. CONCLUSIONS: Incidence of TB in actual donors is greater than that of the general population (P<0.001). The risk of immigrant communities should be grouped according to the real incidence in donors. Transmissibility of TB is high; therefore, transplant teams should be immediately informed when TB donor transmission is suspected to prevent TB in the recipient.
    Transplantation 06/2013; DOI:10.1097/TP.0b013e3182977adf · 3.78 Impact Factor
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    ABSTRACT: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR) 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6). Rapid and sustained virological response (RVR and SVR) rates were also analyzed. Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week1: p = 0.01; week2: p = 0.038; week 4: p = 0.03). Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031). With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week1: p<0.001; week2: p = 0.01; week 4: p = 0.02), RVR (p = 0.015) and SVR (p = 0.029) than those not carrying KIR3DS1. Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.
    PLoS ONE 04/2013; 8(4):e61992. DOI:10.1371/journal.pone.0061992 · 3.53 Impact Factor
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    ABSTRACT: Objetivo Estimar la relación coste-utilidad de valganciclovir durante 200 días (VGC 200) frente a valganciclovir durante 100 días (VGC 100) en pacientes que han recibido un trasplante renal de alto riesgo (TRAR) D+/R−, desde la perspectiva del Sistema Nacional de Salud (SNS) en España. Métodos Se desarrolló un modelo de Markov para simular la historia natural de la progresión de la enfermedad por citomegalovirus en una cohorte de 10.000 pacientes durante 10 años. Los datos de la enfermedad se obtuvieron del ensayo IMPACT (año 1) y de la mejor evidencia científica disponible (años 2–10). Los costes unitarios (€ de 2010) se obtuvieron del Catálogo de Medicamentos y de la base de datos e-Salud. Los valores de utilidad se tomaron de la literatura. Se aplicó una tasa de descuento del 3 % para costes y resultados. Los resultados se expresaron como coste incremental de VGC 200 frente a VGC 100 por año de vida ajustado por calidad (AVAC) ganado. Se realizó un análisis de sensibilidad (AS) univariante y multivariante. Resultados VGC 200 proporciona mejores resultados que VGC 100 (5,002 AVAC frente a 4,764 AVAC; 0,238 AVAC ganados por paciente). El coste promedio por paciente fue de 109.012,11 € con VGC 200 y de 110.305,14 € con VGC 100 (ahorro de costes de 1.293,03 € por paciente). Los resultados del AS muestran la robustez del análisis. Conclusiones La administración de VGC 200 días frente a VGC 100 días en pacientes que han recibido un TRAR D+/R− es una estrategia eficiente desde la perspectiva del SNS en España.
    Pharmacoeconomics - Spanish Research Articles 04/2013; 10(1). DOI:10.1007/s40277-013-0002-y
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    ABSTRACT: OBJECTIVES: The aim of this study was to determine the epidemiology and clinical impact of infections in patients awaiting heart transplantation. METHODS: We evaluated all patients considered for a heart transplant in our center over a period of 18 months over a period of 18 months from 2007 to 2009. The patients were followed up for 8 months or until death, transplant, or loss to follow-up. RESULTS: Ninety patients were included in the study. During follow-up, 25 infections were recorded in 22 heart transplant candidates (24.4%). Respiratory infections were the most frequent infection (12 bronchitis; 48.0%), followed by skin and soft tissue infections (four infections; 16.0%), intra-abdominal infections (four infectious diarrhea; 16.0%), bacteremia (three infections; 12.0%), and urinary tract infections (two infections; 2.0%). Age, comorbidity, sex, and diabetes were not found to be risk factors for infection. Twenty-four patients (26.7%) were transplanted during follow-up. Infection before transplantation was not associated with an increased risk of mortality or a higher rate of infection in the immediate post-transplant period. CONCLUSIONS: Infections are common in heart transplant candidates, affecting almost 25% of them. Respiratory tract infections are the most frequent type of infection. However, they are not associated with increased mortality in the immediate post-transplant period.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 03/2013; 17(9). DOI:10.1016/j.ijid.2013.01.021 · 2.33 Impact Factor
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    ABSTRACT: INTRODUCTION: Pegylated interferon plus ribavirin (Peg-IFN/RBV) therapy leads to improvements in liver stiffness measurements (LSM) in hepatitis C virus (HCV)-infected patients. However, the rate of LSM return to normal values in response to Peg-IFN/RBV is unclear. Thus, our aim was to assess the probability and factors associated with LSM normalization in HCV-infected patients receiving Peg-IFN/RBV. METHODS: This prospective observational longitudinal study included 160 HCV-infected patients, 111 (69%) with human immunodeficiency virus and receiving Peg-IFN/RBV, with baseline LSM ≥7kPa. The outcome variable was LSM normalization, i.e. a stable decrease in LSM below 7kPa after starting Peg-IFN/RBV. RESULTS: After starting Peg-IFN/RBV, 56 [35%, 95% confidence interval (95% CI): 28-42%] patients showed LSM normalization. The probability of LSM normalization was 21% (95% CI: 13.2-32.4%) at 12 months, and 51.3% (95% CI: 39.9-63.9%) at 24 months after Peg-INF/RBV initiation for individuals with sustained virological response (SVR), and 8.3% (95% CI: 4-16.6%) at 12 months and 11.3% (95% CI: 6-20.7%) at 24 months for those without SVR (p<0.001). For individuals with LSM ≥7kPa 24 weeks after the pre-planned end of treatment, LSM normalizations were only observed among those with SVR. Achievement of SVR [Hazard ratio (HR, 95% CI): 6.84 (3.39-13.81)] and lack of baseline cirrhosis [HR (95% CI): 4.17 (1.69-10)] were independently associated with LSM normalization after starting Peg-IFN/RBV. CONCLUSIONS: LSM normalizations during Peg-IFN/RBV treatment are more likely, and occur earlier among patients with SVR. In addition, LSM normalizations continue 24 weeks after the scheduled end of therapy, but only among individuals who reach SVR.
    Enfermedades Infecciosas y Microbiología Clínica 02/2013; DOI:10.1016/j.eimc.2012.12.004 · 1.88 Impact Factor
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    ABSTRACT: BACKGROUND: Incidence, characteristics, and risk factors for tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (IRS) in solid-organ transplant (SOT) recipients are not known. METHODS: Patients are composed of 64 consecutive SOT recipients with TB followed for 12 months. IRS was defined based on previously proposed criteria. RESULTS: IRS developed in 14% (9/64) of the patients, a median of 47 days after the use of anti-TB therapy. Liver versus other types of organ transplant recipients (adjusted odds ratio [OR], 6.11; 95% confidence interval [CI], 1.08-34.86), prior cytomegalovirus infection (adjusted OR, 5.65; 95% CI, 0.93-34.47), and rifampin use (adjusted OR, 4.56; 95% CI, 0.74-27) were associated with a higher risk of IRS. The presence of more than one factor (liver transplantation, cytomegalovirus infection, and rifampin use) when compared with none of these factors conferred a 19-fold increase in the risk of IRS (P=0.01). Mortality at 1 year after diagnosis was 33.3% in patients with IRS and 17.2% in those without IRS (P=0.31). CONCLUSIONS: IRS was documented in 14% of the SOT recipients with TB. We determined clinically identifiable factors that may be useful in assessing the risk of tuberculosis-associated posttransplantation IRS.
    Transplantation 02/2013; DOI:10.1097/TP.0b013e31828719c8 · 3.78 Impact Factor
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    ABSTRACT: BACKGROUND: Experience with high-dose ganciclovir for the management of resistant cytomegalovirus (CMV) replication in transplant patients is limited despite its adoption as an effective therapy by some consensus documents. METHODS: We studied six cases of CMV replication in solid organ transplant patients whose genotypic testing showed mutations associated with different levels of resistance to ganciclovir. All were treated with high-dose intravenous ganciclovir (7.5-10 mg/kg/12 hr) or oral valganciclovir (1350-1800 mg/12 hr) corrected according to creatinine clearance. The virologic response was considered positive if the CMV plasma viral load was undetectable. Safety was evaluated by clinical assessment, including the review of vital signs and laboratory tests. RESULTS: All patients had asymptomatic replication, except one who had digestive disease. Four patients received universal prophylaxis with valganciclovir. Two patients received preemptive therapy with valganciclovir for individual episodes of replication. Two of the six patients received steroid boluses before the episode of replication by resistant CMV. All patients responded to treatment, including those with mutations associated with a high level of ganciclovir resistance. Four patients had neutropenia (<1.5 × 10/L), but only one received treatment. CONCLUSIONS: High-dose ganciclovir/valganciclovir can be an option in the treatment of resistant CMV replication and could be considered an alternative treatment in nonsevere patients for whom the use of foscarnet should be avoided. The toxicity of this regimen does not appear to limit its use.
    Transplantation 02/2013; DOI:10.1097/TP.0b013e31828555ac · 3.78 Impact Factor

Publication Stats

2k Citations
477.77 Total Impact Points

Institutions

  • 2000–2015
    • Hospital Universitario Reina Sofía
      Cordoue, Andalusia, Spain
  • 2009–2014
    • University of Cordoba (Spain)
      Cordoue, Andalusia, Spain
    • Instituto Maimónides de Investigación Biomédica de Córdoba
      Cordoue, Andalusia, Spain
    • Hospital Universitario 12 de Octubre
      Madrid, Madrid, Spain
    • Hospital Poniente, Almeria
      Unci, Andalusia, Spain
    • Hospital Regional Universitario de Málaga
      Málaga, Andalusia, Spain
  • 2012
    • Hospital Universitari de Bellvitge
      • Department of Infectious Diseases
      l'Hospitalet de Llobregat, Catalonia, Spain
    • Hospital General Universitario de Ciudad Real
      Ciudad Real, Castille-La Mancha, Spain
  • 2011
    • Universidad de Cantabria
      Santander, Cantabria, Spain
    • Hospital Universitari i Politècnic la Fe
      Valenza, Valencia, Spain
    • Universidad de Jaén
      Jaén, Andalusia, Spain
  • 2010
    • Hospital Son Dureta
      Palma, Balearic Islands, Spain
  • 2007–2008
    • University Hospital Vall d'Hebron
      • Department of Infectious Diseases
      Barcino, Catalonia, Spain
  • 2004–2008
    • Hospital Universitario Nuestra Señora de Valme
      Hispalis, Andalusia, Spain