Diagnostic and prognostic value of heart-type fatty acid-binding protein in the early hours of acute myocardial infarction.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a cytosolic protein that is released into the bloodstream when the myocardium is injured. The aim was to determine the diagnostic and prognostic value of H-FABP in patients with suspected acute myocardial infarction (AMI) within the first 3-6 hours after the onset of chest pain. METHODS AND RESULTS: A consecutive series of 165 patients with chest pain lasting less than 6 hours were enrolled in a forward observational design in the emergency department.The diagnostic validity of H-FABP was evaluated according to sensitivity, specificity, and predictive values, likelihood ratios, ROC curves, and multivariate logistic regression analyses. The prognostic value of H-FABP at 6 months was checked using survival curves and the multivariate Cox proportional hazards model. The sensitivity of H-FABP was 81% (95% CI: 69.2-92.9). Its area under the ROC curve: 0.729 (95% CI: 0.63-0.83) and negative likelihood ratio (0.38; 95% CI: 0.22-0.65) were significantly better than both troponin (cTnI) and CK-MB, whereas its specificity, 53% (95% CI: 41.1-64.8), was lower than that of the other markers. Increased H-FABP added diagnostic information as it demonstrated independent association with AMI by logistic regression analysis. Increased H-FABP and cTnI were both strong and independent predictors of outcome in the 6-month follow-up (hazard ratio: 2.18; 95% CI: 1.07-4.42; and 2.34; 95% CI: 0.98-5.59, respectively). CONCLUSIONS: H-FABP is, within 6 hours and also within 3 hours, more sensitive than the other markers in the early diagnosis of AMI and it is an independent prediction factor of events within 6 months.

A comparison of the effectiveness of two online haemodiafiltration modalities: mixed versus post-dilution.

INTRODUCTION: Haemodiafiltration (HDF) with high reinfusion volumes is the most effective technique for clearing uraemic toxins. There are various modalities depending on the location where the replacement volume is administered in the extracorporeal circuit: pre-dilution, mixed or mid-dilution and post-dilution, in which the infusion is carried out pre-dilution, pre- and post-dilution simultaneously and post-dilution, respectively. OBJECTIVE: Compare the clearance of small, medium-sized and protein-bound molecules and the convective volume administered in online HDF (OL-HDF) in post-dilution and mixed (pre-post-dilution) infusion. MATERIAL AND METHOD: A prospective, randomised, crossover study comparing post-dilution and mixed OL-HDF. Patients (n=8) were randomly assigned to receive 6 sessions in each technique. We conducted 89 sessions, of which 68 were at a scheduled time (ST) and 21 at an effective time (ET). We determined the reduction rate (RR) percentages for various substances and the infusion volumes. The RR study was performed using ET. RESULTS: The KT value obtained was greater with post-dilution OL-HDF [68 (8.1) compared to 64.9 (8.8) litres] (P=.009) when patients were dialysed at ST. This difference disappeared when dialysis was performed at ET. The difference between ST and ET was greater in mixed HDF than in post-dilution HDF [10.3 (7.4) compared to 6.5 (3.1) minutes, P=.02]. We found no differences in the RR of the substances analysed. CONCLUSION: Mixed OL-HDF is not inferior to post-dilution OL-HDF either in the clearance of small and medium-sized molecules or in the clearance of protein-bound molecules at the same ET.

Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART.

UNLABELLED: Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4(+) T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks) on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002). Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002), served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4(+) and CD8(+) cellular activation (CD38 and HLA-DR) together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4(+) T cells and B cells with reduction of CD8(+) T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4(+) and CD8(+) T cells were accompanied by increases of CD4(+) and CD8(+) T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite, absent or partial in the OBS population. These findings support the use of Tat immunization to intensify HAART efficacy and to restore immune homeostasis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00751595.

Comparación de la eficacia de dos modalidades de hemodiafiltración en línea: mixta frente a posdilucional / A comparison of the effectiveness of two online haemodiafiltration modalities: mixed versus post-dilution

Introducción: La hemodiafiltración (HDF) con altos volúmenes de reinfusión es la técnica más eficaz en la depuración de toxinas urémicas. Existen distintas modalidades dependiendo del lugar donde se administra el volumen de sustitución en el circuito extracorpóreo: predilucional, mixta o mid-dilucional y posdilucional, en las que la infusión se realiza pre, de forma simultánea pre y pos, y posdilucional, respectivamente. Objetivo: Comparar la depuración de moléculas pequeñas, medianas y unidas a proteínas y el volumen convectivo administrado en HDF en línea (HDF-OL) con infusión posdilucional y mixta (pre-posdilucional). Material y métodos: Estudio prospectivo, aleatorizado y cruzado, comparando HDF-OL posdilucional y mixta. Los pacientes (n = 8) fueron asignados aleatoriamente para recibir 6 sesiones en cada técnica. Se realizaron 89 sesiones, de las cuales 68 fueron a tiempo programado (TP) y 21 a tiempo efectivo (TE). Se determinaron los porcentajes de reducción (RR) de distintas sustancias y los volúmenes de infusión. El estudio de los RR se realizó con TE. Resultados: El KT obtenido fue mayor con HDF-OL posdilucional [68 (8,1) frente a 64,9 (8,8) litros] (p = 0,009) cuando los pacientes se dializaron a TP. Esta diferencia desaparecía cuando la diálisis se realizaba a TE. La diferencia entre el TP-TE fue mayor en la HDF mixta con respecto a la HDF posdilucional [10,3 (7,4) frente a 6,5 (3,1) minutos, p = 0,02]. No encontramos diferencias en los RR de las sustancias analizadas. Conclusión: La HDF-OL mixta no es inferior a la posdilucional ni en la depuración de moléculas pequeñas y medianas ni en las unidas a proteínas a igual TE (AU)

Introduction: Haemodiafiltration (HDF) with high reinfusion volumes is the most effective technique for clearing uraemic toxins. There are various modalities depending on the location where the replacement volume is administered in the extracorporeal circuit: pre-dilution, mixed or mid-dilution and post-dilution, in which the infusion is carried out pre-dilution, pre- and post-dilution simultaneously and post-dilution, respectively. Objective: Compare the clearance of small, medium-sized and protein-bound molecules and the convective volume administered in online HDF (OL-HDF) in post-dilution and mixed (pre-post-dilution) infusion. Material and method: A prospective, randomised, crossover study comparing post-dilution and mixed OL-HDF. Patients (n=8) were randomly assigned to receive 6 sessions in each technique. We conducted 89 sessions, of which 68 were at a scheduled time (ST) and 21 at an effective time (ET). We determined the reduction rate (RR) percentages for various substances and the infusion volumes. The RR study was performed using ET. Results: The KT value obtained was greater with post-dilution OL-HDF [68 (8.1) compared to 64.9 (8.8) litres] (P=.009) when patients were dialysed at ST. This difference disappeared when dialysis was performed at ET. The difference between ST and ET was greater in mixed HDF than in post-dilution HDF [10.3 (7.4) compared to 6.5 (3.1) minutes, P=.02]. We found no differences in the RR of the substances analysed. Conclusion: Mixed OL-HDF is not inferior to post-dilution OL-HDF either in the clearance of small and medium-sized molecules or in the clearance of protein-bound molecules at the same ET (AU)

Set-point de sodio en hemodiálisis: ¿es lo que vemos en la clínica? / Sodium set-point in haemodialysis: is it what we see clinically?

Introducción: La natremia en los pacientes en hemodiálisis (HD) se considera constante, contrariamente a lo observado en la clínica diaria. Su relación con parámetros clínicos, de diálisis y con la distribución del agua corporal (AC) no está aclarada. Objetivos: Estudiar: 1) la variabilidad intrasujeto de la natremia, 2) la relación entre natremia y parámetros clínicos y dialíticos y 3) la relación entre natremia y distribución del AC por bioimpedancia. Material y métodos: Estudio observacional retrospectivo de 98 pacientes en HD crónica. Se recogieron características clínicas, de HD, natremia, glucemia y medidas de bioimpedancia. Resultados: Sesenta y tres varones y 35 mujeres de 69,6 (21-91) años con seguimiento de 23,2 (10) meses. Variabilidad: 1802 determinaciones de sodio: natremia media 138 (3,2) y corregida para glucemia: 139,1 (3,6) mEq/l, p < 0,0001. El coeficiente de variación (CV) intrasujeto fue 2 (0,8) % (rango: 1-5,6 %) y correlacionó negativamente con la natremia (r = -0,63, p < 0,0001). Parámetros clínicos: en diabéticos la natremia corregida era inferior a en no-diabéticos 138 (2,4) frente a 139 (2) mEq/l, p < 0,003, con CV de 2,3 (0,9) frente a 1,9 (0,7) % (p < 0,01) y desviación estándar de 3,2 (1,2) frente a 2,5 (0,9) mEq/l (p < 0,04). No encontramos diferencias según sexo, edad, tiempo en diálisis, cardiopatía, hepatopatía, fármacos, función renal residual ni mortalidad. Parámetros de HD: relación positiva entre natremia y conductividad del líquido de diálisis y negativa con ganancia de peso interdiálisis (GID). Bioimpedancia: no relación entre distribución AC y natremia. Conclusiones: La natremia varía en cada paciente y se relaciona positivamente con la conductividad y negativamente con la GID. En diabéticos la natremia es más baja y el CV es mayor. No existe relación entre natremia y la distribución del AC (AU)

Background: Natraemia in haemodialysis (HD) patients is considered constant contrary to daily clinical observations. Its relationship with clinical parameters, dialysis parameters and body water (BW) distribution is not clear. Objectives: The aims of this study were to know 1) the intraindividual variability of natraemia, 2) the relationship between natraemia and clinical and dialysis parameters and 3) the relationship between natraemia and BW distribution by bioimpedance. Material and Method: Observational retrospective study on 98 chronic HD patients. Clinical, HD and natraemia, glucose and bioimpedance data were collected. Results: We included 63 males and 35 females of 69.6 (21-91) years of age, with a follow-up of 23.2 (10) months. Variability: 1802 sodium measurements: mean natraemia 138 (3.2) mEq/l and corrected for glucose: 139.1 (3.6) mEq/l, p<.0001. Intraindividual coefficient of variation (CV) was 2% (0.8) (range 1-5.6%) and it correlated negatively with natraemia (r=-0.63, p<.0001). Clinical parameters: corrected natraemia was lower in diabetics than in non-diabetics 138 (2.4) compared with 139 (2) mEq/l, p<.003, CV 2.3 (0.9) compared with 1.9 (0.7)% (p<.01) and SD 3.2 (1.2) compared with 2.5 (0.9) mEq/l (p<.04). No differences according to gender, age, HD time, cardiac or liver disease, medication use, residual renal function or mortality were found. HD parameters: a positive relationship was found between natraemia and total dialysate conductivity and it was negative with interdialysis weight gain (IDG). - Bioimpedance: no relationship was found between natraemia and BW distribution. Conclusions: Natraemia varies in each patient and is related positively with conductivity and negatively with IDG. In diabetics natraemia is lower and CV is higher. There is no relationship between natraemia and BW distribution (AU)

Sequence conservation and antibody cross-recognition of clade B human immunodeficiency virus (HIV) type 1 Tat protein in HIV-1-infected Italians, Ugandans, and South Africans.

We determined immune cross-recognition and the degree of Tat conservation in patients infected by local human immunodeficiency virus (HIV) type 1 strains. The data indicated a similar prevalence of total and epitope-specific anti-Tat IgG in 578 serum samples from HIV-infected Italian (n=302), Ugandan (n=139), and South African (n=137) subjects, using the same B clade Tat protein that is being used in vaccine trials. In particular, anti-Tat antibodies were detected in 13.2%, 10.8%, and 13.9% of HIV-1-infected individuals from Italy, Uganda, and South Africa, respectively. Sequence analysis results indicated a high similarity of Tat from the different circulating viruses with BH-10 Tat, particularly in the 1-58 amino acid region, which contains most of the immunogenic epitopes. These data indicate an effective cross-recognition of a B-clade laboratory strain-derived Tat protein vaccine by individuals infected with different local viruses, owing to the high similarity of Tat epitopes.