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Objetivos de este website de Epidemiología Molecular de Enfermedades Infecciosas (EMEI)

Este portal de EMEI pretende ser una plataforma de divulgación:

– Científica en el área de la Epidemiología Molecular de Enfermedades Infecciosas aplicada a pacientes infectados por distintos microorganismos que producen infecciones víricas (SIDA, hepatitis C, etc.) ó infecciones bacterianas (sepsis, etc.).

– De las actividades científicas (artículos científicos, comunicaciones a congresos, etc.) realizadas por el grupo de investigación formado en torno a la Unidad de Infección Viral e Inmunidad del Centro Nacional de Microbiología (Instituto de Salud Carlos III, Majadahoda, Madrid), cuyo responsable es el Dr. Salvador Resino García

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EMEI- Últimos artículos científicos publicados:

  • Soluble Adhesion Molecules in Patients Coinfected with HIV and HCV: A Predictor of Outcome. -
    Related Articles

    Soluble Adhesion Molecules in Patients Coinfected with HIV and HCV: A Predictor of Outcome.

    PLoS One. 2016;11(2):e0148537

    Authors: Aldámiz-Echevarría T, Berenguer J, Miralles P, Jiménez-Sousa MA, Carrero A, Pineda-Tenor D, Díez C, Tejerina F, Pérez-Latorre L, Bellón JM, Resino S

    Abstract
    BACKGROUND: Higher serum levels of adhesion molecules (sICAM-1 and sVCAM-1) are associated with advanced liver fibrosis in patients coinfected with human immunodeficiency virus and hepatitis C virus. We assessed the relationship between serum levels of adhesion molecules and liver-related events (LRE) or death, in coinfected patients.
    METHODS: We studied clinical characteristics and outcomes of 182 coinfected patients with a baseline liver biopsy (58 with advanced fibrosis) and simultaneous plasma samples who were followed for median of 9 years. We used receiver-operating characteristic (ROC) curves to calculate optimized cutoff values (OCV) of sICAM-1 and sVCAM-1, defined as the values with the highest combination of sensitivity and specificity for LRE. We used multivariate regression analysis to test the association between OCVs of sICAM-1 and sVCAM-1 and outcomes. The variables for adjustment were age, HIV transmission category, liver fibrosis, baseline CD4+ T-cell counts, antiretroviral therapy, and sustained virologic response (SVR).
    RESULTS: During the study period 51 patients had SVR, 19 had LRE, and 16 died. The OCVs for LRE were 5.68 Log pg/mL for sICAM-1 and 6.25 Log pg/mL for sVCAM-1, respectively. The adjusted subhazard ratio (aSHR) (95% confidence interval [CI]) of death or LRE, whichever occurred first, for sICAM-1 and sVCAM-1 > OCV were 3.98 ([1.14; 13.89], P = 0.030) and 2.81 ([1.10; 7.19], respectively (P = 0.030).
    CONCLUSIONS: Serum levels of sICAM-1 and sVCAM-1 can serve as markers of outcome in HIV/HCV-coinfected patients. Therapies targeting necroinflammatory damage and fibrogenesis may have a role in the management chronic hepatitis C.

    PMID: 26849641 [PubMed - as supplied by publisher]

  • IL15 polymorphism is associated with advanced fibrosis, inflammation-related biomarkers and virologic response in HIV/HCV coinfection. -
    Related Articles

    IL15 polymorphism is associated with advanced fibrosis, inflammation-related biomarkers and virologic response in HIV/HCV coinfection.

    Liver Int. 2016 Feb 2;

    Authors: Jiménez-Sousa MA, Berenguer J, Rallón N, Pineda-Tenor D, Echevarria TA, Soriano V, García-Álvarez M, Vazquez-Morón S, Restrepo C, Carrero A, Benito JM, Resino S

    Abstract
    BACKGROUND & AIMS: IL15 is an essential cytokine in both innate and adaptive immune response against HCV infection. The aim was to analyze whether IL15 rs10833 is associated with liver disease severity and response to pegylated-interferon-alpha plus ribavirin (pegIFN-alpha/RBV) therapy in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients.
    METHODS: A retrospective study was performed in 315 patients who started pegIFN-alpha/RBV therapy. Liver fibrosis stage was characterized in 286 patients. IL15 rs10833 and IL28B rs12980275 were genotyped by GoldenGate.The primary outcomes were: a) advanced liver fibrosis evaluated by liver biopsy (F3-F4) or transient elastography (liver stiffness values ≥9.5 Kpa); b) sustained virological response (SVR). The secondary outcome variable was the levels of serum biomarkers of inflammation.
    RESULTS: Patients with rs10833 AA genotype had increased odds of having advanced fibrosis (adjusted odds ratio (aOR)=2.30; p=0.019), particularly in males (aOR=2.24; p=0.040), patients with HCV-RNA <500,000 IU/mL (aOR=5.14; p=0.018) and patients with IL28B rs12980275 AG/GG genotypes (aOR=2.51; p=0.046). Moreover, rs10833 AA genotype was significantly associated with higher levels of HGF (adjusted arithmetic mean ratio (aAMR)=1.50; p=0.016), sICAM-1 (aAMR=1.57; p=0.025) and sVCAM-1 (aAMR=1.56; p=0.007). Finally, patients with rs10833 AA genotype had increased odds of achieving SVR (aOR=3.12; p=0.006), particularly in males (aOR=3.69; p=0.005), GT1/4 patients (aOR=3.59; p=0.006), patients with advanced fibrosis (aOR=4.64; p=0.021), HCV-RNA ≥500,000 IU/mL (aOR=3.92; p=0.007) and patients with IL28B rs12980275 AG/GG genotype (aOR=2.98; p=0.041).
    CONCLUSIONS: The presence of IL15 rs10833 AA genotype in HIV/HCV-coinfected patients was associated with advanced liver fibrosis, inflammation-related biomarkers and increased rates of SVR to pegIFN-alpha/RBV therapy. This article is protected by copyright. All rights reserved.

    PMID: 26836972 [PubMed - as supplied by publisher]

  • Impact of patatin-like phospholipase domain-containing 3 gene polymorphism (rs738409) on severity of liver disease in HIV/hepatitis C virus-coinfected patients. -
    Related Articles

    Impact of patatin-like phospholipase domain-containing 3 gene polymorphism (rs738409) on severity of liver disease in HIV/hepatitis C virus-coinfected patients.

    AIDS. 2016 Jan 28;30(3):465-70

    Authors: Jiménez-Sousa MA, Berenguer J, García-Álvarez M, Gutierrez-Rivas M, Aldámiz-Echevarria T, Tejerina F, Diez C, Vázquez-Morón S, Resino S

    Abstract
    OBJECTIVE: To analyze the association between patatin-like phospholipase domain-containing 3 gene (PNPLA3) rs738409 polymorphism and severity of liver disease in HIV/hepatitis C virus-coinfected patients.
    METHODS: We performed a cross-sectional study of 215 patients who underwent a liver biopsy. PNPLA3 rs738409 polymorphism was genotyped using GoldenGate assay. The outcome variables were as follows: advanced fibrosis (F ≥3 and FIB-4 ≥3.25), rapid fibrosis progression (FPR ≥0.10 fibrosis units/year), severe activity grade (A≥3), and steatosis (fatty hepatocytes ≥10%). The genetic association analysis was carried out according to an additive genetic model through logistic regressions adjusted by the most significant covariables.
    RESULTS: Overall, 21.4% had F at least 3, 8.9% had FIB-4 at least 3.25, 11.4% had A at least 3, 60.6% had steatosis, and 32.5% had FPR at least 0.10. For each rs738409 G allele, we found an increased frequency of patients with advanced fibrosis (F at least 3) (0% CC, 18.5% CG, and 25.2% GG; P = 0.049) and FIB-4 at least 3.25 (0% CC, 3.8% CG, and 13.2% GG; P = 0.016). Furthermore, for each rs738409 G allele, the odds of having F at least 3 increased 2.15 times (95% confidence interval=1.07; 4.35; P = 0.029) and having FIB-4 at least 3.25 increased 8.77 times (95% of confidence interval = 1.11; 69.0; P = 0.039). Note that rs738409 G allele carriers tended to higher likelihood of having FPR at least 0.10, but statistical significance was not reached (P = 0.054). Finally, we did not find any association for A at least 3 and liver steatosis.
    CONCLUSION: PNPLA3 rs738409 polymorphism was associated with the severity of liver fibrosis in patients coinfected with HIV and hepatitis C virus, suggesting that this polymorphism might also play a significant role in the progression of hepatic fibrosis in this group of patients.

    PMID: 26760234 [PubMed - in process]

  • CXCL12 rs1029153 Polymorphism Is Associated with the Sustained Virological Response in HIV/Hepatitis C Virus-Coinfected Patients on Hepatitis C Virus Therapy. -
    Related Articles

    CXCL12 rs1029153 Polymorphism Is Associated with the Sustained Virological Response in HIV/Hepatitis C Virus-Coinfected Patients on Hepatitis C Virus Therapy.

    AIDS Res Hum Retroviruses. 2015 Dec 1;

    Authors: Pineda-Tenor D, Jiménez-Sousa MA, Rallón N, Berenguer J, Soriano V, Aldámiz-Echevarria T, García-Álvarez M, Diez C, Fernández-Rodríguez A, Benito JM, Resino S

    Abstract
    The immune response against HIV and hepatitis C virus (HCV) infection partly depends on chemokine-mediated recruitment of specific T cells. CXCL12 polymorphisms have been associated with AIDS progression and survival, but there are no data related to HCV infection. The aim of this study was to determine whether CXCL12 polymorphisms are related so as to achieve sustained virological response (SVR) after HCV therapy with pegylated-interferon-alpha/ribavirin (pegIFN-α/ribavirin) in HIV/HCV-coinfected patients. We carried out a retrospective study in 319 naive patients who started HCV treatment. The CXCL12 (rs266093, rs1029153, and rs1801157) and IL28B (rs12980275) polymorphisms were genotyped by using the GoldenGate assay. Genetic data were analyzed under an additive inheritance model. The overall rates of the SVR were 54.9% (175/319) and 41.5% (90/217) in GT1/4 patients and 83.2% (84/101) in GT2/3 patients. Patients with a favorable CXCL12 rs1029153 T allele had higher SVR rates than patients with the rs1029153 CC genotype (44% CC, 49% CT, and 61.3% TT; p = 0.025). No significant results for the rs266093 and rs1801157 polymorphisms were found. Patients harboring the favorable rs1029153 T allele had significantly increased odds of achieving SVR [adjusted odds ratio (aOR) = 1.55; 95% confidence interval (95% CI) = 1.01; 2.40; p = 0.047]. Moreover, no significant association was found when the study population was stratified by HCV genotype (data not shown), possibly due to the low number of patients in each group. In conclusion, in this study we found that the favorable CXCL12 rs1029153 T allele seems to be related so as to achieve an SVR in HIV/HCV-coinfected patients on pegIFN-α/ribavirin therapy.

    PMID: 26499461 [PubMed - as supplied by publisher]

  • Toll-like receptor 8 (TLR8) polymorphisms are associated with non-progression of chronic hepatitis C in HIV/HCV coinfected patients. -
    Related Articles

    Toll-like receptor 8 (TLR8) polymorphisms are associated with non-progression of chronic hepatitis C in HIV/HCV coinfected patients.

    Infect Genet Evol. 2015 Dec;36:339-44

    Authors: Fernández-Rodríguez A, Berenguer J, Jiménez-Sousa MA, García-Álvarez M, Aldámiz-Echevarría T, Pineda-Tenor D, Diez C, de la Barrera J, Bellon JM, Briz V, Resino S

    Abstract
    Toll-like receptor 8 (TLR8) polymorphisms have been related to hepatitis C virus (HCV) infection. The aim was to estimate the association of TLR8 polymorphisms with HCV-related outcomes in HIV/HCV coinfected patients. We performed a cross-sectional study of 220 patients who underwent a liver biopsy. TLR8 polymorphisms were genotyped using GoldenGate® assay. The outcome variables were non-fibrosis (F0), mild-inflammation (A0/A1), and non-steatosis [fatty hepatocytes (FH) <10%]. Logistic regression analysis was used to compare the outcome variables according to TLR8 polymorphisms. Four polymorphisms were analyzed (rs1013151, rs5744069, rs17256081 and rs3764880rs1013151). Female patients had higher frequency of TLR8 major alleles at rs17256081 and rs101315, and minor alleles at rs3764880 and rs5744069. Male patients had higher frequency of TLR8 minor alleles except for rs3764880, where major alleles were higher (p<0.01). Two TLR8 polymorphisms (rs1013151 and rs5744069) were significantly associated with non-fibrosis (F0) [adjusted odds ratio (aOR)=4.42 (95% of confidence interval (95%CI)=1.54; 12.68) (p=0.006) and aOR=4.76 (95%CI=1.69; 13.37) (p=0.003); respectively]. When data were stratified by gender, rs1013151 and rs5744069 polymorphisms remained significant for male patients [adjusted odds ratio (aOR)=4.49 (95%CI=1.08; 18.62) (p=0.039) and aOR=6.17 (95%CI=1.45; 26.20) (p=0.014); respectively]. When data were stratified by major HCV genotypes, patients infected with HCV genotype 1 (GT1) had significant values for both rs1013151 and rs5744069 polymorphisms [aOR=5.79 (95%CI=1.44; 23.32) (p=0.013) and aOR=8.01 (95%CI=2.16; 35.65) (p=0.005); respectively]. Finally, none of the TLR8 polymorphisms were significantly associated with mild-inflammation or non-steatosis. In conclusion, TLR8 polymorphisms seem to be related to non-progression of liver fibrosis in HIV/HCV coinfected patients, particularly in males and those patients infected with GT1.

    PMID: 26455634 [PubMed - in process]

  • Relationship between ITPA polymorphisms and hemolytic anemia in HCV-infected patients after ribavirin-based therapy: a meta-analysis. -
    Related Articles

    Relationship between ITPA polymorphisms and hemolytic anemia in HCV-infected patients after ribavirin-based therapy: a meta-analysis.

    J Transl Med. 2015;13:320

    Authors: Pineda-Tenor D, García-Álvarez M, Jiménez-Sousa MA, Vázquez-Morón S, Resino S

    Abstract
    BACKGROUND: There is growing evidence that variations in the gene encoding inosine triphosphate pyrophosphohydrolase (ITPase), known as inosine triphosphatase (ITPA), are related to hemolytic anemia, which is frequently observed among hepatitis C virus (HCV)-infected patients receiving ribavirin (RBV)-based therapy. We performed a meta-analysis of all eligible studies assessing ITPA gene polymorphisms related to RBV-induced hemolytic anemia in HCV-infected patients published in PubMed, Embase and the Cochrane library prior to the end of 2014.
    METHODS: Three outcomes were evaluated: (1) hemoglobin decline, (2) severe anemia, and (3) RBV dose reduction or treatment discontinuation. Pooled odds ratio (OR) and 95 % confidence interval (95 % CI) were estimated by either fixed or random effects models.
    RESULTS: Twenty-nine studies were selected from the literature search: 20 references involving 6533 individuals for hemoglobin decline, 13 references on 3764 patients for severe anemia, and 16 references on 3918 patients for RBV dose reduction or discontinuation. Significant associations with hemoglobin decline were found for rs1127354 CC [OR = 12.84 (95 % CI 7.44; 22.17)], rs7270101 AA [OR = 3.41 (95 % CI 2.08; 5.59)] and rs6051702 AA [OR = 4.43 (95 % CI 2.80; 7.00)] genotypes. Moreover, significant associations with hemoglobin decline were also found for absent [OR = 6.01 (95 % CI 4.84; 7.46)] and mild [OR = 4.68 (95 % CI 2.83; 7.74)] ITPase deficiency haplotypes. The ITPA rs1127354 CC genotype and absent ITPase deficiency haplotype were also associated with severe anemia {[OR = 7.77 (95 % CI 5.03; 12.00)] and [OR = 4.79 (95 % CI 1.69; 13.56)], respectively}. Additionally, the rs1127354 CC genotype showed significant association with RBV dose reduction or stopping treatment (OR = 2.24; 95 % CI 1.79; 2.81).
    CONCLUSIONS: ITPA polymorphisms increase the likelihood of developing hemolytic anemia for HCV-infected patients on RBV-based therapy, particularly rs1127354 CC and rs7270101 AA genotypes, suggesting the utility of screening for ITPA polymorphisms to avoid hematological toxicity and increase adherence to RBV-based therapy.

    PMID: 26438033 [PubMed - in process]

  • IL7RA polymorphisms predict the CD4+ recovery in HIV patients on cART. -
    Related Articles

    IL7RA polymorphisms predict the CD4+ recovery in HIV patients on cART.

    Eur J Clin Invest. 2015 Nov;45(11):1192-9

    Authors: Guzmán-Fulgencio M, Berenguer J, Jiménez-Sousa MA, Micheloud D, García-Álvarez M, Bellón JM, Aldámiz-Echevarría T, García-Broncano P, Catalán P, Diez C, Pineda-Tenor D, Resino S

    Abstract
    BACKGROUND: The IL7RA polymorphisms have recently been associated with CD4+ T-cell decline in untreated HIV-infected subjects and CD4+ T-cell recovery in patients on combination antiretroviral therapy (cART). The aim of this study was to evaluate whether IL7RA polymorphisms are associated with CD4+ T-cell recovery in HIV-infected patients on long-term cART.
    STUDY DESIGN: We performed a retrospective study in 151 naïve cART patients with severe immunodeficiency (CD4+ counts ≤200 cells/mm(3) ). IL7RA polymorphisms' genotyping was performed using Sequenom's MassARRAY platform. The outcome variable was the time to achieve the first value of CD4+ count ≥500 cells/mm(3) during the follow-up.
    RESULTS: Two different trends of CD4+ T-cell recovery were found in Kaplan-Meier analysis. During the first 48 months, 60 of 151 (39·7%) of the patients reached CD4+ T-cell values ≥500 cells/mm(3) , and no differences were observed between IL7RA genotypes. After the first 48 months of follow-up, 27 of 151 (17·8%) of the patients reached CD4+ T-cell values ≥500 cells/mm(3) , with a different pattern of CD4+ recovery depending on IL7RA genotype. Patients with rs10491434 TT genotype and rs6897932 TT genotype were more likely of achieving CD4+ value ≥500 cells/mm(3) than patients with rs10491434 CT/CC genotype (adjusted hazard ratio (aHR) = 3·59; P = 0·005) and patients with rs6897932 CC/CT genotype (aHR = 11·7; P < 0·001).
    CONCLUSIONS: The IL7RA polymorphisms seem to be associated with CD4+ T-cell recovery in HIV-infected patients who started cART with severe immunodeficiency, in the second phase of CD4+ T-cell recovery after long-term cART.

    PMID: 26402121 [PubMed - in process]

  • Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study. -
    Related Articles

    Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study.

    J Transl Med. 2015;13:206

    Authors: Guzmán-Fulgencio M, Berenguer J, Jiménez-Sousa MA, Pineda-Tenor D, Aldámiz-Echevarria T, García-Broncano P, Carrero A, García-Álvarez M, Tejerina F, Diez C, Vazquez-Morón S, Resino S

    Abstract
    BACKGROUND: Interleukin-7 (IL-7) is a critical factor for T cell development and for maintaining and restoring homeostasis of mature T cells. Polymorphisms at α-chain of the IL-7 receptor (IL7R or CD127) gene are related to evolution of HIV-infection, but there are no data concerning the evolution of hepatitis C virus (HCV) infection. The aim of this study was to analyze the association between IL7R polymorphisms and severe liver disease in HCV/HIV coinfected patients.
    METHODS: We performed a cross-sectional study in 220 naïve patients who underwent a liver biopsy. IL7R polymorphisms (rs6897932, rs987106 and rs3194051) were genotyped using the GoldenGate(®) assay. The outcome variables were: (a) liver biopsy: advanced fibrosis (F ≥ 3), severe activity grade (A3); (b) non-invasive indexes: advanced fibrosis (APRI ≥1.5 and FIB-4 ≥3.25). Logistic regression analysis was used to investigate the association between IL7R polymorphisms and outcome variables. This test gives the differences between groups and the odds ratio (OR) for liver disease.
    RESULTS: Patients with rs6897932 CC genotype had higher likelihood of having A3 than patients with rs6897932 CT/TT (adjusted odds ratio (aOR) = 4.16; p = 0.026). Patients with rs987106 TT genotype had higher odds of having F ≥ 3 (aOR = 3.09; p = 0.009) than rs987106 AA/AT carriers. Finally, patients with rs3194051 AA genotype had higher odds of having severe liver fibrosis (F ≥ 3; APRI ≥1.5, and FIB4 ≥3.25) than patients with rs3194051 AG/GG genotype [aOR = 2.73 (p = 0.010); aOR = 2.52 (p = 0.029); and aOR = 4.01 (p = 0.027); respectively]. The CTA haplotype (comprised of rs6897932, rs987106, and rs3194051) carriers had higher odds of having F ≥ 3 (aOR = 1.85; p = 0.012), APRI ≥1.5 (aOR = 1.94; p = 0.023), and FIB4 ≥3.25 (aOR = 2.47; p = 0.024). Conversely, the CAG haplotype carriers had lower odds of having F ≥ 3 (aOR = 0.48; p = 0.011), APRI ≥1.5 (aOR = 0.48; p = 0.029), and FIB4 ≥3.25 (aOR = 0.29; p = 0.010).
    CONCLUSIONS: The presence of IL7R polymorphisms seems to be related to severe liver disease in HIV/HCV coinfected patients, because patients with unfavorable IL7R genotypes (rs6897932 CC, rs987106 TT, and rs3194051AA) had a worse prognosis of CHC.

    PMID: 26123260 [PubMed - in process]

  • Pneumocystis pneumonia in HIV-positive patients in Spain: epidemiology and environmental risk factors. -
    Related Articles

    Pneumocystis pneumonia in HIV-positive patients in Spain: epidemiology and environmental risk factors.

    J Int AIDS Soc. 2015;18:19906

    Authors: Alvaro-Meca A, Palomares-Sancho I, Diaz A, Resino R, De Miguel AG, Resino S

    Abstract
    INTRODUCTION: Specific environmental factors may play a role in the development of Pneumocystis pneumonia (PCP) in HIV-positive patients. The aim of this study was to estimate the PCP incidence and mortality in hospitalized HIV-positive patients in Spain during the combination antiretroviral therapy (cART) era (1997 to 2011), as well as to analyze the climatological factors and air pollution levels in relation to hospital admissions and deaths.
    METHODS: We carried out a retrospective study. Data were collected from the National Hospital Discharge Database and the State Meteorological Agency of Spain. A case-crossover analysis was applied to identify environmental risk factors related to hospitalizations and deaths. For each patient, climatic factors and pollution levels were assigned based on readings from the nearest meteorological station to his or her postal code.
    RESULTS: There were 13,139 new PCP diagnoses and 1754 deaths in hospitalized HIV-positive patients from 1997 to 2011. The PCP incidence (events per 1000 person-years) dropped from 11.6 in 1997 to 2000, to 5.4 in 2004 to 2011 (p<0.001). The mortality (events per 10,000 person-years) also decreased from 14.3 in 1997 to 2000, to 7.5 in 2004 to 2011 (p<0.001). Most hospital admissions and deaths occurred in the winter season and the fewest occurred in the summer, overlapping respectively with the lowest and highest temperatures of the year in Spain. Moreover, lower temperatures prior to PCP admission, as well as higher concentrations of NO2 and particulate matter up to 10 m in size (PM10) at the time of admission were associated with higher likelihoods of hospital admission due to PCP when two weeks, one month, 1.5 months or two months were used as controls (p<0.01). Furthermore, higher concentrations of ozone at one month (p=0.007), 1.5 months (p<0.001) and two months (p=0.006) prior to admission were associated with higher likelihoods of hospital admission with PCP. For PCP-related deaths, lower temperatures prior to admission and higher concentrations of atmospheric PM10 at the time of admission were related to higher likelihood of death when two weeks, one month and 1.5 months were used as controls (p<0.05).
    CONCLUSIONS: PCP was a significant health problem in the cART era (1997 to 2011), and PCP epidemiology was adversely influenced by colder climatological factors and higher ambient air pollution levels.

    PMID: 25997453 [PubMed - in process]

  • Trends in nontuberculous mycobacterial disease in hospitalized subjects in Spain (1997-2010) according to HIV infection. -
    Related Articles

    Trends in nontuberculous mycobacterial disease in hospitalized subjects in Spain (1997-2010) according to HIV infection.

    HIV Med. 2015 Sep;16(8):485-93

    Authors: Álvaro-Meca A, Rodríguez-Gijón L, Díaz A, Gil Á, Resino S

    Abstract
    OBJECTIVES: The aim of the study was to estimate the incidence of nontuberculous mycobacterial (NTM) disease and the rate of NTM disease-related mortality and to analyse trends in these variables according to HIV infection.
    METHODS: We performed a retrospective study for the period 1997-2010 using data from the Minimum Basic Data Set (MBDS) provided by the Spanish Ministry of Health. The exposure variables were: (i) HIV infection (HIV positive versus HIV negative); (ii) calendar period in relation to widespread use of combination antiretroviral therapy (cART) [1997-1999 (early cART period), 2000-2003 (middle cART period) and 2004-2010 (late cART period)]. The outcome variables were (i) new NTM disease diagnosis and (ii) mortality.
    RESULTS: A total of 3729 cases of incident NTM disease were collected in MBDS, 1795 in the HIV-negative group and 1934 in the HIV-positive group, among whom 602 deaths occurred, 223 in the HIV-negative group and 379 in the HIV-positive group. The incidence of NTM disease and the rate of NTM disease-related mortality were 1000-fold higher in the HIV-positive group than in the HIV-negative group. Regarding the incidence of NTM disease, in the HIV-negative group the incidence increased from 2.91 to 3.97 events per 1,000,000 patient-years from 1997-1999 to 2004-2010 (P < 0.001), while in the HIV-positive group the incidence decreased from 2.29 to 0.71 events per 1000 patient-years from 1997-1999 to 2004-2010 (P < 0.001). Regarding mortality, in the HIV-negative group mortality increased from 2.63 to 4.26 events per 10,000,000 patient-years from 1997-1999 to 2000-2003 (P = 0.059), and then the rate stabilized at around 3.87 events per 10,000,000 patient-years in 2004-2010 (P = 0.128), while in the HIV-positive group mortality decreased from 4.28 to 1.39 events per 10,000 patient-years from 1997-1999 to 2004-2010 (P < 0.001).
    CONCLUSIONS: HIV infection was associated with a higher NTM disease incidence and higher NTM disease-related mortality than in the general population, but these rates decreased in the HIV-positive group from 1997-1999 to 2004-2010, whereas the NTM disease incidence increased in the HIV-negative group.

    PMID: 25854195 [PubMed - in process]

  • Reply: To PMID 24975775. -
    Related Articles

    Reply: To PMID 24975775.

    Hepatology. 2015 Nov;62(5):1643

    Authors: Pineda-Tenor D, García-Álvarez M, Jiménez-Sousa MA, Fernández-Rodríguez A, Resino S

    PMID: 25807876 [PubMed - indexed for MEDLINE]

  • TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients. -
    Related Articles

    TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients.

    J Clin Virol. 2015 Apr;65:62-7

    Authors: Jiménez-Sousa MA, Rallón N, Berenguer J, Pineda-Tenor D, López JC, Soriano V, Guzmán-Fulgencio M, Cosín J, Retana D, García-Álvarez M, Miralles P, Benito JM, Resino S

    Abstract
    BACKGROUND: Toll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response.
    OBJECTIVES: To analyze the association between Toll-like receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response to pegylated interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/HCV coinfected patients.
    STUDY DESIGN: We performed a retrospective study in 321 naïve patients treated with pegIFNα/RBV. Genotyping was performed by using the GoldenGate(®) assay with VeraCode(®). The outcome variables were early virologic response (EVR) and sustained virologic response (SVR).
    RESULTS: In a multivariate analysis, rs3775291 A allele decreased the likelihood of achieving EVR (aOR = 0.20; p = 0.018) and SVR (aOR = 0.38; p = 0.024). Regarding rs13126816, the percentage of EVR decreased with each minor A allele (p = 0.034) in HCV-GT2/3 patients, although no significant association was obtained in the multivariate analysis (p = 0.076). Regarding TLR3 haplotypes (comprised of rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of achieving EVR (p = 0.030), whereas GG haplotype increased the likelihood (p = 0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR (p = 0.019, p = 0.043 and p = 0.070 for all, GT2/3 and GT1/4 patients, respectively). Besides, GT1/4 patients with GA haplotype had lower odds of achieving SVR (p = 0.039).
    CONCLUSIONS: Our study shows the first evidence that two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV therapy response in HCV/HIV coinfected patients.

    PMID: 25766991 [PubMed - indexed for MEDLINE]

  • Single nucleotide polymorphisms of CXCL9-11 chemokines are associated with liver fibrosis in HIV/HCV-coinfected patients. -
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    Single nucleotide polymorphisms of CXCL9-11 chemokines are associated with liver fibrosis in HIV/HCV-coinfected patients.

    J Acquir Immune Defic Syndr. 2015 Apr 1;68(4):386-95

    Authors: Pineda-Tenor D, Berenguer J, García-Álvarez M, Guzmán-Fulgencio M, Carrero A, Aldámiz-Echevarria T, Tejerina F, Diez C, Jiménez-Sousa MA, Fernández-Rodríguez A, Munoz-Fernandez MA, Resino S

    Abstract
    BACKGROUND: CXCR3A-associated chemokines (CXCL9-11) are implicated in the pathogenesis of hepatitis C virus (HCV) infection. We analyzed the association between CXCL9-11 polymorphisms and significant liver fibrosis in human immunodeficiency virus (HIV)/HCV-coinfected patients.
    METHODS: We performed a cross-sectional study in 220 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using GoldenGate assay. Three outcome variables related to liver fibrosis were studied: (1) F ≥ 2; (2) APRI ≥ 2; and (3) FIB-4 ≥ 3.25.
    RESULTS: The percentage of patients with significant liver fibrosis (F ≥ 2, APRI ≥ 2, and FIB-4 ≥ 3.25) was significantly higher for CXCL9 rs10336 TT (P = 0.046, P = 0.010, and P = 0.046, respectively), CXCL10 rs3921 GG (P = 0.046, P = 0.011, and P = 0.049, respectively), and CXCL11 rs4619915 AA (P = 0.035, P = 0.014, and P = 0.057, respectively) genotypes. Moreover, the greater likelihood of having significant liver fibrosis (F ≥ 2, APRI ≥ 2, and FIB-4 ≥ 3.25) was found in carriers of CXCL9 rs10336 TT and CXCL10 rs3921 GG [adjusted odds ratio (aOR) > 2 (P < 0.05)]. These trends were significantly more pronounced in patients infected with HCV-genotype 1 (GT1) [aOR > 3 (P < 0.05)]. Moreover, TGA haplotype showed higher odds for having values of APRI ≥ 2 (aOR = 2.4; P = 0.012) when we considered all patients. This elevated risk for significant liver fibrosis was better represented in patients infected with HCV-GT1, where TGA haplotype had increased odds for having values of F ≥ 2 (aOR = 1.9; P = 0.045), APRI ≥ 2 (aOR = 3.2; P = 0.009), and FIB-4 ≥ 3.25 (aOR = 3.3; P = 0.026).
    CONCLUSIONS: The homozygosity for the minor alleles CXCL9 rs10336 (T), CXCL10 rs3921 (G), and CXCL11 rs4619915 (A) is associated with the higher likelihood of significant liver fibrosis in HIV-infected patients coinfected with HCV-GT1.

    PMID: 25559603 [PubMed - indexed for MEDLINE]

  • Transcriptomic correlates of organ failure extent in sepsis. -
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    Transcriptomic correlates of organ failure extent in sepsis.

    J Infect. 2015 May;70(5):445-56

    Authors: Almansa R, Heredia-Rodríguez M, Gomez-Sanchez E, Andaluz-Ojeda D, Iglesias V, Rico L, Ortega A, Gomez-Pesquera E, Liu P, Aragón M, Eiros JM, Jiménez-Sousa MÁ, Resino S, Gómez-Herreras I, Bermejo-Martín JF, Tamayo E

    Abstract
    OBJECTIVES: Sepsis is characterised by the frequent presence of organ failure and marked immunologic alterations. We studied the association between the extent of organ failure and the transcriptomic response of septic patients.
    METHODS: Gene expression profiles in the blood of 74 surgical patients with sepsis were compared with those of 30 surgical patients with no sepsis. Differentially expressed genes were assessed for their correlation with the sequential organ failure (SOFA) score.
    RESULTS: The expression levels of a group of genes participating in the cell cycle (HIST1H1C, CKS2, CCNA2, CDK1, CCNB2, CIT, CCNB1, AURKA, RAD51), neutrophil protease activity (ELANE, ADORA3, MPO, MMP8, CTSG), IL-1R and IL-18R response correlated directly with SOFA and mortality. Genes involved in T cell (LCK, CD3G, CD3D, ZAP70, ICOS, CD3E, CD28, IL2RB, CD8B, CD8A, CD40LG, IL23A, CCL5, SH2D1A, ITK, CD247, TBX21, GATA3, CCR7, LEF1, STAT4) and NK cell immunity (CD244, KLRK1, KLRD1) were inversely associated with SOFA and mortality.
    CONCLUSIONS: The extent of organ failure in sepsis correlates directly with the existence of imbalanced innate and adaptive responses at the transcriptomic level. Quantification of the expression levels of the genes identified here could contribute to the simultaneous assessment of disease severity and immunological alterations in sepsis.

    PMID: 25557485 [PubMed - indexed for MEDLINE]

  • FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients. -
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    FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.

    BMC Med. 2014;12:198

    Authors: Pineda-Tenor D, Berenguer J, Jiménez-Sousa MA, García-Alvarez M, Aldámiz-Echevarria T, Carrero A, Vázquez-Morón S, García-Broncano P, Diez C, Tejerina F, Guzmán-Fulgencio M, Resino S

    Abstract
    BACKGROUND: The Fat Mass and Obesity-Associated Protein (FTO) gene rs9939609 single nucleotide polymorphism (SNP) has been associated with obesity, metabolic syndrome, insulin resistance (IR), and type 2 diabetes mellitus in the general population. The aim of our study was to examine for the first time the association of the rs9939609 polymorphism with metabolic disturbances, liver disease and virologic response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) in human immunodeficiency virus (HIV)/HCV coinfected patients.
    METHODS: We carried out a cross-sectional study in 261 patients, of whom 178 were subsequently treated with pegIFNα/RBV therapy. FTO rs9939609 and IFNL3 rs12980275 polymorphisms were genotyped by GoldenGate®. The main outcomes were: 1) metabolic disturbances: insulin resistance (homeostatic model assessment (HOMA-IR)) and overweight (body mass index (BMI)); 2) liver disease (Metavir score): significant fibrosis (F ≥2) and steatosis (>10% fatty hepatocytes); and 3) virologic response to HCV treatment: sustained virologic response (SVR).
    RESULTS: The rs9939609 AA genotype was associated with higher values of BMI (adjusted arithmetic mean ratio (aAMR) = 1.08; 95% confidence interval (95%CI) = 1.03 to 1.14; P = 0.002) and HOMA-IR (aAMR = 1.32; 95%CI = 1.03 to 1.69; P = 0.027). Patients with an rs9939609 AA genotype had higher likelihoods of achieving values of BMI ≥27.5 kg/m2 (adjusted odds ratio (aOR) = 3.46; 95%CI =1.17 to 10.21; P = 0.024), HOMA-IR ≥2.5 (aOR = 2.09; 95%CI = 1.02 to 4.32; P = 0.045), significant fibrosis (aOR = 2.34; 95%CI =1.02 to 5.36; P = 0.045) and steatosis (aOR = 3.65; 95%CI = 1.29 to 10.36; P = 0.015). The rs9939609 AT/AA genotype decreased the likelihood of achieving SVR (aOR = 0.58; 95%CI = 0.34 to 0.99; P = 0.044). A decision tree was performed with the genotypes of HCV, IFNL3 and FTO. The incorporation of rs9939609 significantly improves the prediction of SVR (P <0.05). The overall accuracy was 68.2%.
    CONCLUSIONS: Patients carrying the unfavourable AT/AA genotype of rs9939609 polymorphism had higher odds of metabolic disturbances and a lower likelihood of achieving successful virologic response to HCV therapy.

    PMID: 25367448 [PubMed - indexed for MEDLINE]