Influence of the Co-Administration of Heptavalent Conjugate Vaccine PCV7-TT on the Immunological Response Elicited by VA-MENGOC-BC® and Heberpenta®-L in Rabbits

Finlay Vaccine Institute is developing a new heptavalent conjugate vaccine against Streptococcus pneumoniae. As infants are the target population, PCV7-TT will be necessarily co-administered with other vaccines, and then, the interactions represent a concern. The aim of this work is to evaluate the possible immunological interferences in rabbits as animal experimental model. Rabbits were immunized with Heberpenta®-L, VA-MENGOC-BC®, and PCV7-TT. Blood samples were taken fourteen days after final immunization for obtaining sera. Antibody responses to all antigens were evaluated by indirect ELISA. Functional responses against diphtheria and tetanus toxoid were done by in vivo seroneutralization assay. No interference was observed by PCV7-TT over the humoral response against diphtheria toxoid and meningococcal antigens (p > 0.05). A nonstatistically significant reduction (p > 0.05) was observed in the case of the humoral response against Haemophilus influenzae type b oligosaccharide. Concomitant administration of Heberpenta®-L and PCV7-TT increased twice the antibody titers as well as the protective activity against tetanus toxoid, but no statistical differences were found. The co-administration did not induce a reduction in the percent of responders against pneumococcal polysaccharides contained in PCV7-TT vaccine. Concomitant administration of PCV7-TT did not induce interferences over the evaluated antigens of Heberpenta®-L and VA-MENGOC-BC®. Also, no interference was observed on the immune response elicited by PCV7-TT. These preclinical results suggest that PCV7-TT will not result in a serious problem over the immune response elicited by the licensed vaccines Heberpenta®-L and VA-MENGOC-BC®. However, the clinical interference could be strictly studied during clinical trials in infants.     

Direct‐acting antivirals are effective and safe in HCV/HIV‐coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study

Direct‐acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV‐coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV‐coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV‐monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV‐coinfected patients had a median (IQR) CD4 T‐cell count of 366 (256‐467) cells/µL. HIV‐RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV‐RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon‐free regimens with DAAs for post‐LT recurrence of HCV infection in HIV‐infected individuals were highly effective and well tolerated, with results comparable to those of HCV‐monoinfected patients.     

Association of cell-free plasma DNA with perioperative mortality in patients with suspected acute mesenteric ischemia

BackgroundDiagnosing patients with acute mesenteric ischemia (AMI) in the emergency ward is challenging. This study assesses the usefulness of plasma DNA in patients with clinically suspected AMI.Methods130 consecutive patients who underwent laparotomy were studied. Cell-free plasma DNA was measured by real-time quantitative PCR assay for the β-globin gene. The primary endpoint was the accuracy of plasma DNA for predicting 30-day mortality.ResultsSurgery revealed AMI in 99 patients and alternative diagnoses in 31 patients. Forty-six patients with AMI died (46.6%) as compared to 6 (19.4%) in the non-AMI group (p < 0.05). The DNA concentration at admission was significantly higher in patients with AMI (median 7340 GE/ml, versus, 2735 GE/ml, p < 0.01) and in AMI patients who died (8830 GE/ml, versus 4970 GE/ml, p < 0.05). The area under the ROC curves for plasma DNA as a marker for mesenteric ischemia and independent predictor for 30-day mortality were 0.708 (95% CI 0.701–0.890) and 0.815 (95% CI 0.735–0.894). Multiple logistic regression analysis showed that the risk of hospital mortality increased 1.52-fold for every 1000 GE/ml increase in plasma DNA.ConclusionsPlasma DNA levels may be a useful biomarker in predicting the outcome of patients with AMI.     

Factors at de novo donor‐specific antibody initial detection associated with allograft loss: a multicenter study

We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor‐specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death‐censored allograft loss were assessed by Cox proportional modeling. Death‐censored allograft survival was 77.0% (87/113) during a median follow‐up of 2.2 (IQR 1.2–3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6–15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1–13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post‐transplant (years) until donor‐specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody‐mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA.     

La comunicación y la satisfacción de las primíparas en un servicio público de salud

Objective

To analyze first-time mothers communication with health professionals, and to explore satisfaction, needs and expectation towards healthcare services.

Method

Qualitative design using in-deep interviews and phenomenology was used. First-time mothers from Huercal-Overa (Almería) were intentionally selected in 2010 and were included in the study. A hermeneutic analysis was performed.

Results

Six meta-categories were obtained. Saturation of information was found with nine interviews. The meta-categories were the following: 1) Health professionals; 2) Pregnancy, partum and postpartum; 3) Communication; 4) Child nutrition; 5) Feelings; 6) Others. The mothers perceived as exciting this new experience and expressed feelings of fear, anguish and high sensitiveness. These feelings are increased by the information received from the family circle and the professionals which is referred low and contradictory. All professionals were positively considered, specially the midwife. The following negative experiences were identified: contractions, dilation and delivery. The end of the stay at the hospital was considered early and the time for consultation was short for the mothers. There is a demand about more information on breast feeding. Mothers wish health professionals to respect their decisions.

Conclusions

The study found some areas for improvement in the communication between firs-time mothers and health professionals which could be taken into account in satisfaction promotion plans in regards to healthcare services.     

Genistein restores caveolin-1 and AT-1 receptor expression and vascular function in large vessels of ovariectomized hypertensive rats

OBJECTIVE: The soy-derived phytoestrogen genistein improves endothelial function in postmenopausal women and ovariectomized (OVX) normotensive rats. We hypothesized that genistein would improve vascular reactivity involving changes in endothelial nitric oxide synthase (NOS) expression and its regulatory proteins (caveolin and calmodulin), angiotensin II receptor, and/or oxidative status in OVX spontaneously hypertensive rats (SHRs). DESIGN: After ovariectomy or sham operation, 23-week-old female SHRs received either 17beta-estradiol (2 mg/kg/wk SC), genistein (10 mg/kg/d by gavage), or placebo. RESULTS: In OVX rats, final body weight was increased and uterus weight was decreased, and these values were reduced and increased, respectively, by 17beta-estradiol but unaffected by genistein. Acetylcholine-induced endothelium-dependent vasorelaxation was significantly blunted in aortas from OVX placebo SHRs. The contractions induced by the NOS inhibitor L-NAME and angiotensin II in OVX placebo were lower and higher, respectively, than in sham rats. Estradiol and genistein restored these functional changes. Aortic endothelial NOS and calmodulin-1 expression were unchanged, whereas caveolin-1 and angiotensin II receptor expression was increased in OVX rats. Estradiol and genistein treatment did not modify endothelial NOS, but normalized caveolin-1 and angiotensin II receptor and increased calmodulin-1 expression. Vascular superoxide production was increased in OVX placebo and normalized by both estradiol and genistein. CONCLUSIONS: Genistein prevented all cardiovascular changes induced by estrogen depletion in SHRs to a similar extent as estradiol but had no uterotrophic effect. The present findings may help to explain the potential benefits of genistein as a therapeutic agent for preventing menopausal vascular complications, especially in hypertensive women.