Relationship between CD38 expression on peripheral blood T-cells and monocytes, and response to antiretroviral therapy: a one-year longitudinal study of a cohort of chronically infected ART-naive HIV-1+ patients

BACKGROUND: HIV-1 infection has been associated with high expression of CD38 on peripheral blood (PB) CD8+ and CD4+ T-cells, which has been related with poor prognosis in untreated HIV-1+ patients. In turn, CD38 expression on PB monocytes from HIV-1+ individuals and its behavior after starting antiretroviral therapy (ART) have been poorly studied. METHODS: CD38 expression on PB CD8+ and CD4+ T-lymphocytes and monocytes was prospectively analyzed in 30 ART-naive HIV-1+ patients, using a quantitative multiparameter flow cytometry approach. Patients were tested prior to therapy, and at weeks +2, +4, +8, +12, and +52 after ART. RESULTS: Prior to ART, CD38 expression was significantly increased on PB CD8+ and CD4+ T-cells and monocytes; despite a significant decrease after ART, CD38 expression remained abnormally high on PB CD8+ T-cells and monocytes, even after one year of therapy, in the absence of detectable plasma viral load. The ART-induced early changes on CD38 expression by PB T-cells and monocytes differed among the cell subsets analyzed and patient groups, probably reflecting an interaction between the direct effects of therapy and a redistribution of the PB compartments of T-cells and monocytes. Hierarchical clustering analysis showed that the overall pattern of changes in CD38 expression observed early after starting ART was predictive of a better response to therapy, not only for PB CD8+ T-cells, but also for CD4+ T-cells and monocytes. Accordingly, those HIV-1+ patients, who experienced a more pronounced increase in CD38 expression on both PB CD4+ T-cells and monocytes after 2 weeks of ART, showed a more rapid viral clearance, which might reflect decreased HIV-1 replication in lymph nodes and other tissues, and a partial restoration of hematopoiesis. CONCLUSIONS: Combined quantitative measurement of CD38 expression on PB monocytes, and CD8+ and CD4+ T-cells is a more useful tool for monitoring HIV-1+ patients under ART, rather than quantitation of CD38 expression on PB CD8+ T-lymphocytes alone.     

Continuous versus interrupted sutures for repair of episiotomy or second-degree perineal tears: a randomised controlled trial

Objective  To evaluate the repair techniques of continuous and interrupted methods for episiotomy or perineal tears.
Design  A randomised controlled trial.
Setting  The Hospital Universitario Principe de Asturias, a state hospital belonging to the community of Madrid.
Sample  Four hundred forty-five women who had undergone vaginal deliveries with episiotomies or second-grade tearing of the perineum between September 2005 and July 2007.
Methods  One group was repaired with continuous, nonlocking sutures involving the vagina, perineum, and subcutaneous tissues. The other group had continuous, locking sutures of the vagina, interrupted sutures in the perineal muscles, and interrupted transcutaneous sutures. The threads used for stitching were identical in both groups.
Main outcome measures  The participants were questioned regarding the sensation of pain and the use of painkillers on the second and the tenth days, and 3 months postpartum.
Results  When comparing the group with continuous suture to the group with interrupted sutures, the differences included less repair time (1 minute; P = 0.017) and less suture material used (relative risk [RR], 3.2, 95% CI: 2.6–4.0). The comparison of pain on the second and tenth days, and 3 months postpartum were not statistically different between the two techniques (RR, 1.08, 95% CI: 0.74–1.57; RR, 0.96, 95% CI: 0.59–1.55; and RR, 0.68, 95% CI: 0.19–2.46, respectively).
Conclusions  Although we did not demonstrate that one technique was better than the other in the incidence of pain in the short or long term, we showed that episiotomy and perineal tear repairs with continuous suturing were quicker and used less suture material without an increase in complication than interrupted suturing.     

Therapy With m‐TOR Inhibitors Decreases the Response to the Pandemic Influenza A H1N1 Vaccine in Solid Organ Transplant Recipients

Concern has been raised regarding the response to vaccination in solid organ transplant recipients (SOTR) undergoing immunosuppressant regimens and the possibility of rejection related to the immune response associated with pandemic influenza H1N1–2009 vaccination. The goal of this study was to assess the immunogenicity, efficacy and safety of the pandemic vaccine in SOTR. We performed a multicenter prospective study in SOTR receiving the pandemic vaccine. Immunological response was determined in serum 5 weeks after vaccination by microneutralization assays, and immunoglobulins were measured by ELISA. Three hundred and forty‐six SOTR were included. Preexisting seroprotection was detected in 13.6% of cases and rates of seroconversion and seroprotection after vaccination were 73.1% and 82.9%, respectively. Patients with baseline antibody titers had better geometric mean titers (GMT)‐post after pandemic vaccination (339.4 vs. 121.4, p < 0.001). Younger age, liver disease and m‐TOR inhibitor therapy were independently associated with lower seroprotection and GMT‐post. There were no major adverse effects or rejection episodes. Pandemic vaccine was safe in SOTR and elicited an adequate response, although lower than in healthy individuals. This is the first study describing a decreased response after vaccination in patients receiving mTOR inhibitors who presented lower seroprotection rates and lower GMT‐post.     

HLA-G polymorphism influences the susceptibility to HCV infection in sickle cell disease patients

Despite its well known monogenic etiopathogenesis, sickle cell disease (SCD) is characterized by a striking variability of clinical presentation. There is growing evidence that genetic factors may be involved in this variability. Human leukocyte antigen (HLA)-G is a non-classical HLA molecule which was shown to be expressed at sites of inflammation and in inflammatory diseases. Besides its large and highly polymorphic promoter region, the 3' UTR region seems also to play an important role on regulating HLA-G expression. We investigated the influence of the 14 pb (rs1704) and the +3142 (rs1063320) HLA-G polymorphisms in 93 SCD patients in order to evaluate its potential role on clinical parameters. Twenty-one patients presented an HCV infection. Among all SCD patients 16 (22.2%) were homozygous for the +3142C genotype, none of them hepatitis C (HCV) positive. Controlling for blood transfusions in the last year, the C allele represented a dose dependent protection effect for HCV infection (PR = 0.41; 95% CI: 0.24–0.71). The +3142C allele was also underrepresented among patients with history of respiratory-tract infections. Our results support a role of the +3142 polymorphism in the susceptibility to infections, in particular to HCV infection, and suggest a possible interference of the HLA-G molecule in the response to infections, among SCD patients.     

Monogenic human obesity: role of the leptin-melanocortin system in the regulation of food intake and body weight in humans

Human obesity is a disorder of multifactorial origin in which genetic and environmental factors are involved. To understand the mechanisms regulating energy intake and fat accumulation in the body, it is important to study the genetic alterations causing monogenic obesity. Most of the genes involved in monogenic obesity are associated with the leptin-melanocortin system; hence the importance of studying this system by analysing natural mutations in mice. Previous studies have described mutations in leptin and its receptor, proopiomelanocortin and prohormone convertase 1 associated with human obesity of monogenic origin. The aim of this study is to provide an updated review of the main characteristics and functioning of the leptin-melanocortin system, and its implications and potentialities in regulating food intake and body weight.     

Sesgos de confusión por indicación y gravedad en estudios observacionales

Observational studies are subject to biases that may lead to misinterpretation of the results. This study aimed to determine the influence of omeprazole treatment on the duration of sick leave in patients with ankle sprains treated with non-steroidal anti-inflammatory drugs. We used the Ibermutuamur database. Contrary to our expectations, sick leave was longer in patients who received omeprazole than in those who did not. These findings were probably due to the influence of a bias due to confounding by severity, given that patients who received omeprazole had a worse kind of ankle sprain; however, a bias due to confounding by indication cannot be excluded. To avoid the influence of these systematic errors, biases should be monitored from the design stage to the data analysis stage.