RESUMO
Neutralizing antibody (NAb) activity against the viral capsid of adeno-associated viral (AAV) vectors decreases transduction efficiency, thus limiting transgene expression. Several reports have mentioned a variation in NAb prevalence according to age, AAV serotype, and, most importantly, geographic location. There are currently no reports specifically describing the anti-AAV NAb prevalence in Latin America. Here, we describe the prevalence of NAb against different serotypes of AAV vectors (AAV1, AAV2, and AAV9) in Colombian patients with heart failure (HF) (referred to as cases) and healthy individuals (referred to as controls). The levels of NAb were evaluated in serum samples of 60 subjects from each group using an in vitro inhibitory assay. The neutralizing titer was reported as the first dilution inhibiting ≥50% of the transgene signal, and the samples with neutralizing titers at ≥1:50 dilution were considered positive. The prevalence of NAb in the case and control groups were similar (AAV2: 43% and 45%, respectively; AAV1 33.3% in each group; AAV9: 20% and 23.2%, respectively). The presence of NAb for two or more of the serotypes analyzed was observed in 25% of the studied samples, with the largest amount in the positive samples for AAV1 (55-75%) and AAV9 (93%), suggesting serial exposures, cross-reactivity, or coinfection. Moreover, patients in the HF group exhibited more common combined seropositivity for NAb against AAV1 d AAV9 than those in the control group (91.6% vs. 35.7%, respectively; p = 0.003). Finally, exposure to toxins was significantly associated with the presence of NAb in all regression models. These results constitute the first report of the prevalence of NAb against AAV in Latin America, being the first step to implementing therapeutic strategies based on AAV vectors in this population in our region.
Assuntos
Anticorpos Neutralizantes , Insuficiência Cardíaca , Humanos , Sorogrupo , América Latina , Anticorpos Antivirais , Dependovirus/genética , Prevalência , Insuficiência Cardíaca/epidemiologia , Vetores Genéticos/genética , Transdução GenéticaRESUMO
BACKGROUND: Heart transplant (HT) remains the most frequently indicated therapy for patients with end-stage heart failure that improves prognosis in Chagas cardiomyopathy (CCM). However, the lack of benznidazole therapy and availability of RT-PCR follow-up in many centers is a major limitation to perform this life-saving intervention, as there are concerns related with the risk of reactivation. We aimed to describe the outcomes of a cohort of patients with CCM who underwent HT using a conventional protocol with mycophenolate mofetil, without benznidazole prophylaxis or RT-PCR follow-up. METHODS: Retrospective cohort study. Between 2008 and 2018, 43 patients with CCM underwent HT. A descriptive analysis to characterize outcomes as rejection, infectious and neoplastic complications and a survival analysis was carried out. RESULTS: Median of follow-up was 4.3 (IR 4.28) years. Survival at 1 month, 1 year, and 5 years was 95%, 85%, and 75%, respectively, infections being the main cause of death (60%). Reactivations occurred in only three patients (7.34%) and were not related to mortality. CONCLUSION: This cohort showed a favorable survival and a low reactivation rate without an impact on mortality. Our results suggest that performing HT in patients with CCM following conventional guidelines and recommendations for other etiologies is a safe approach.
Assuntos
Cardiomiopatia Chagásica , Insuficiência Cardíaca , Transplante de Coração , Cardiomiopatia Chagásica/tratamento farmacológico , Cardiomiopatia Chagásica/cirurgia , Estudos de Coortes , Transplante de Coração/efeitos adversos , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVE: Disease and hospitalization generate stress, which can affect the response to treatment. Humor has been used in many hospitals to decrease stress. The aim of this study was to evaluate the impact of a humor therapy program on stress levels in pediatric inpatients. METHODS: In the first phase, an intervention and a control group were studied over 2 consecutive 3-month periods; the interventions were performed by a team of artists trained in humor therapy. Salivary cortisol levels were measured by enzyme-linked immunosorbent assay, and the Weisz test, a pictorial chart that determines subjective stress perception, and the Parker test, which assesses objective stress, were applied. In the second phase, salivary cortisol levels were measured and the Weisz test was administered before and after the interventions. RESULTS: A total of 306 patients were recruited into this study: 198 in the first phase (94 in the intervention group and 104 in the nonintervention group) and 108 in the second phase. There were no differences between groups regarding age, sex, or medical diagnosis. The children in the intervention group presented lower cortisol levels, lower scores on the Parker test, and higher scores on the Weisz test than children in the nonintervention group. In the second phase, the children showed lower salivary cortisol levels and higher scores on the Weisz test after the intervention. CONCLUSIONS: Humor therapy has beneficial effects on stress and cortisol levels in pediatric inpatients. This supports the implementation and reinforcement of these therapies in pediatric hospitals.