The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design.

The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience's MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: <7.1 kPa (F0-F1), 7.1-9.4 kPa (F2; significant fibrosis), 9.5-12.4 kPa (F3; advanced fibrosis), and ≥12.5 kPa (F4; cirrhosis). All HCV genotypes were analyzed. The median of follow-up time was 47.9 months. Baseline liver stiffness measurement (LSM) values did not show significant statistical differences for IL7RA genotypes (p>0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p<0.001) and higher odds of progression to advanced fibrosis [adjusted OR = 4.46 (95%CI = 1.87; 10.62); p = 0.001], and progression to cirrhosis [adjusted OR = 3.92 (95%CI = 1.30; 11.77); p = 0.015]. Regarding IL7RA rs987106 and rs3194051 polymorphisms, we did not find significant results except for the relationship between IL7RA rs987106 and the increase in LSM values [adjusted OR = 1.12 (95%CI = 1.02; 1.23); p = 0.015]. The IL7RA rs6897932 polymorphism seems to be related to increased risk of liver fibrosis progression in HCV-infected patients. Thus, the rs6897932 polymorphism could be related to the physiopathology of CHC and might be used to successfully stratify the risk of CHC progression.

Liver stiffness measurement predicts liver-related events in patients with chronic hepatitis C: A retrospective study.

The management of patients with chronic hepatitis C (CHC) depends on their clinical stage. Thus, noninvasive early recognition of patients with CHC at high risk for developing liver-related events (LREs) is important because it ensures optimal preventative management strategies may be employed that can affect the course of CHC disease. Our aim was to determine whether liver stiffness measurement (LSM) in hepatitis C virus (HCV)-infected patients is associated with a risk of LREs, particularly in cirrhotic patients. We carried out a retrospective study on 343 HCV-infected patients stratified according to cirrhosis (LSM<12.5 kPa vs. LSM≥12.5 kPa), and the cirrhotic patient group (LSM≥12.5 kPa) was divided according to risk of esophageal varices (LSM <25 kPa vs. LSM≥25 kPa). For all patients, each incremental unit in the natural logarithm (Ln) of LSM was associated with 14.76 times higher risk of developing LREs (p<0.001). Patients with cirrhosis (LSM≥12.5 kPa) had a higher risk of LREs than patients without cirrhosis (LSM<12.5 kPa) [adjusted hazard ratio (aHR) = 30.97; p<0.001]. When only cirrhotic patients were analyzed (n = 60), each incremental unit in the Ln of LSM was associated with 10.56 times higher risk of developing LREs (p = 0.010). Patients with LSM≥25 kPa had a greater risk for LRE development compared to those with LSM<25 kPa (aHR = 3.65; p = 0.045). The AUROC for predicting the onset of LREs was 0.876 in all patients and 0.729 in cirrhotic patients. In conclusion, LSM was associated with an increased risk of developing LREs in HCV-infected patients, even within the group of cirrhotic patients.

CXCL9-11 polymorphisms are associated with liver fibrosis in patients with chronic hepatitis C: a cross-sectional study.

BACKGROUND AND AIMS: CXCL9-11 polymorphisms are related to various infectious diseases, including hepatitis C virus (HCV) infection. In this study, we analyzed the association between CXCL9-11 polymorphisms and liver fibrosis in HCV-infected patients. METHODS: We performed a cross-sectional study in 389 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using the Sequenom's MassARRAY platform. The primary outcome variable was the liver stiffness measurement (LSM). We established three cut-offs of LSM: LSM ≥ 7.1 kPa (F ≥ 2-significant fibrosis), LSM ≥ 9.5 kPa (F ≥ 3-advanced fibrosis), and LSM ≥ 12.5 kPa (F4-cirrhosis). RESULTS: Recessive, overdominant and codominant models of inheritance showed significant values, but the overdominant model was the best fitting our data. In this case, CXCL9 rs10336 AG, CXCL10 rs3921 CG and CXCL11 rs4619915 AG were mainly associated with lower values of LSM [(adjusted GMR (aGMR) = 0.85 (p = 0.005), aGMR = 0.84 (p = 0.003), and aGMR = 0.84 (p = 0.003), respectively]. Patients with CXCL9 rs10336 AG genotype had lower odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 0.59 (p = 0.016)], advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 0.54 (p = 0.010)], and cirrhosis (LSM ≥ 12.5 kPa) [aOR = 0.56 (p = 0.043)]. Patients with CXCL10 rs3921 CG or CXCL11 rs4619915 AG genotypes had lower odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 0.56 (p = 0.008)], advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 0.55 (p = 0.013)], and cirrhosis (LSM ≥ 12.5 kPa) [aOR = 0.57 (p = 0.051)]. Additionally, CXCL9-11 polymorphisms were related to lower liver stiffness under a codominant model of inheritance, being the heterozygous genotypes also protective against hepatic fibrosis. In the recessive inheritance model, the CXCL9 rs10336 AA, CXCL10 rs3921 CC and CXCL11 rs4619915 AA were associated with higher LSM values [(adjusted GMR (aGMR) = 1.19 (p = 0.030), aGMR = 1.21 (p = 0.023), and aGMR = 1.21 (p = 0.023), respectively]. Moreover, patients with CXCL9 rs10336 AA genotype had higher odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 1.83 (p = 0.044)] and advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 1.85 (p = 0.045)]. Furthermore, patients with CXCL10 rs3921 CC or CXCL11 rs4619915 AA genotypes had higher odds of advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 1.89 (p = 0.038)]. CONCLUSIONS: CXCL9-11 polymorphisms were related to likelihood of having liver fibrosis in HCV-infected patients. Our data suggest that CXCL9-11 polymorphisms may play a significant role against the progression of CHC and could help prioritize antiviral therapy.

Rendimiento diagnóstico de la procalcitonina y la proteína C reactiva para predecir meningitis bacteriana en los ancianos en urgencias / Diagnostic usefulness of procalcitonin and C-reactive protein in the Emergency Department for predicting bacterial meningitis in the elderly

OBJETIVOS: Analizar y comparar la capacidad de la procalcitonina (PCT) y la proteína C reactiva (PCR) para detectar meningitis bacteriana (MB) en los ancianos (mayores de 74 años). MÉTODOS: Estudio observacional, prospectivo, descriptivo y analítico de pacientes ≥ 1 año diagnosticados de meningitis aguda (MA) en un servicio de urgencias (SU) desde septiembre de 2009 hasta julio de 2014. RESULTADOS: Se incluyeron 220 casos diagnosticados de MA con una edad media de 30 ± 26 años, el 62% varones (136). De ellos, 83 pacientes de 1-14 años (17 con MB), 111 pacientes de 15-74 años (32 con MB) y 26 casos ≥ 75 años (17 con MB). Para predecir MB la PCT obtiene la mayor área bajo la curva ROC (ABC-ROC), de 0,972 (IC 95%: 0,946-0,998, p < 0,001), y con un punto de corte ≥ 0,52 ng/ml se consigue una sensibilidad del 93% y una especificidad del 86%, y para los pacientes ≥ 75 años una sensibilidad del 96% y una especificidad del 75% con el mismo ABC-ROC de 0,972. La PCR consigue un ABC-ROC de 0,888 y con punto de corte ≥ 54,4 mg/l una sensibilidad de 91% y una especificidad de 78%, y para los pacientes ≥ 75 años solo un ABC-ROC de 0,514 con una sensibilidad de 97% y una especificidad del 43%. CONCLUSIONES: En todos los pacientes con MA en SU la PCT consigue un gran rendimiento diagnóstico para sospechar la etiología bacteriana, mayor que la PCR y leucocitos. Además, en los pacientes ancianos la PCR no tiene utilidad

OBJECTIVES: To analyse and compare procalcitonin (PCT) and C-reactive protein (CRP) as tools for detecting bacterial meningitis (BM) in the elderly (> 74 years of age). METHODS: A prospective, observational, descriptive, analytical study of 220 consecutive patients aged ≥ 1 year and diagnosed with acute meningitis in an emergency department between September 2009 and July 2014. RESULTS: A total of 220 patients (136 [62%] male) were studied. The mean age was 30 ± 26 years, with BM being diagnosed in 17/83 patients from 1 to 14 years of age, 32/111 from 15 to 74 years of age, and 17/26 patients ≥ 75 years of age. PCT had the highest area under the receiver operating characteristic curve (AUC) (0.972; 95% CI, 0.946-0,998; P < .001) to predict bacterial meningitis. With a cut-off of ≥ 0.52 ng/mL, PCT achieved 93% sensitivity and 86% specificity, and for patients over 75 years of age 96% sensitivity and 75% specificity, with the same AUC (0.972). The AUC for CRP was 0.888, and a ≥ 54,4 mg/L cut-off achieved 91% sensitivity and 78% specificity, and for patients over 75 years of age an AUC of only 0.514 achieved with 97% sensitivity and 43% specificity. CONCLUSIONS: For all patients with acute meningitis in the emergency department, PCT has a high diagnostic power, outperforming CRP and Leukocytes for detection of bacterial etiology, but CPR is of not useful in the elderly

[Diagnostic usefulness of procalcitonin and C-reactive protein in the Emergency Department for predicting bacterial meningitis in the elderly]. / Rendimiento diagnóstico de la procalcitonina y la proteína C reactiva para predecir meningitis bacteriana en los ancianos en urgencias.

OBJETIVES: To analyse and compare procalcitonin (PCT) and C-reactive protein (CRP) as tools for detecting bacterial meningitis (BM) in the elderly (>74 years of age). METHODS: A prospective, observational, descriptive, analytical study of 220 consecutive patients aged ≥1year and diagnosed with acute meningitis in an emergency department between September 2009 and July 2014. RESULTS: A total of 220 patients (136 [62%] male) were studied. The mean age was 30±26years, with BM being diagnosed in 17/83 patients from 1 to 14years of age, 32/111 from 15 to 74years of age, and 17/26 patients ≥75years of age. PCT had the highest area under the receiver operating characteristic curve (AUC) (0.972; 95%CI, 0.946-0,998; P<.001) to predict bacterial meningitis. With a cut-off of ≥0.52ng/mL, PCT achieved 93% sensitivity and 86% specificity, and for patients over 75years of age 96% sensitivity and 75% specificity, with the same AUC (0.972). The AUC for CRP was 0.888, and a ≥54,4mg/L cut-off achieved 91% sensitivity and 78% specificity, and for patients over 75years of age an AUC of only 0.514 achieved with 97% sensitivity and 43% specificity. CONCLUSIONS: For all patients with acute meningitis in the emergency department, PCT has a high diagnostic power, outperforming CRP and Leukocytes for detection of bacterial etiology, but CPR is of not useful in the elderly.

Valores de referencia y cribado universal de la función tiroidea en el primer trimestre de la población de mujeres gestantes del área de Toledo / Reference values and universal screening of thyroid function in the first trimester of the population of pregnant women in Toledo (Spain)

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Pseudohipoaldosteronismo tipo 1 secundario a reflujo vesicoureteral: una urgencia endocrinológica / Pseudohypoaldosteronism type 1 secondary to vesicoureteral reflux: An endocrinologic emergency

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