Detección de nuevos marcadores asociados a daño por reperfusión y fibrosis en infarto de miocardio validados histopatológicamente mediante análisis multivariante de resonancia magnética multimodal

La resonancia magnética cardiovascular (RMC) con realce tardío es la técnica de referencia para la evaluación no invasiva del daño cardíaco después de un infarto de miocardio (IM). Sin embargo, la interpretación de estas imágenes en términos de daño tisular es aún complicado y el uso de agentes de contraste en esta técnica está contraindicado en un amplio sector de la población con insuficiencia renal crónica. La microscopía de resonancia magnética (MRM) proporciona un nivel de detalle comparable al objetivo macroscópico de la microscopía óptica. Por ello, podría ser una herramienta muy útil en la interpretación de la imagen de RMC y en la identificación de nuevos marcadores de imagen de resonancia en el IM. El objetivo de la presente Tesis Doctoral es caracterizar, utilizando la MRM e histopatología correlativa, el tejido miocárdico en las regiones remota, adyacente e infartada en corazones porcinos con IM en fase aguda (1 semana) y en fase crónica (1 mes), y de corazones sanos mediante MRM multisecuencia sin hacer uso de ningún agente de contraste exógeno. Se estableció un grupo control (n= 3 animales) y dos grupos experimentales de IM: 90 min de isquemia seguida de 1 semana tras reperfusión (IM en fase aguda, n= 6 animales) o 1 mes tras reperfusión (IM en fase crónica, n= 5 animales). La MRM se realizó en un espectrómetro de campo ultra alto de eje vertical de 14,1 Tesla (Bruker Avance III 600). Las distintas regiones representativas del corazón infartado (remoto, adyacente e infarto) se analizaron mediante varias secuencias de RMN: imágenes potenciadas en T1, imágenes potenciadas en T2,imágenes potenciadas en T2*, mapeo T2, mapeo T2* y coeficiente de difusión aparente (ADC). Los cortes histopatológicos de las mismas muestras adquiridas con MRM permitieron identificar estructuras y relieves que contribuyeron a realizar una caracterización adecuada del tejido a estudio. Las imágenes de MRM revelaron diferencias de intensidad de señal para los diferentes componentes estructurales y anatómicos del tejido de IM en fase aguda y los de IM en fase crónica (valor p<0,05), pudiendo identificar con un elevado grado de detalle tanto el tipo de región al que pertenecían como el grado de daño tisular. Los modelos multivariantes permitieron clasificar con precisión las regiones de interés (IM en fase aguda: especificidad 93 % y sensibilidad 80 %; IM en fase crónica: especificidad 100 % y sensibilidad 98 %). Los mapas probabilísticos basados en nuestros modelos de análisis discriminante de mínimos cuadrados parciales (PLS-DA) delinearon claramente las regiones remotas e infartadas. Estos resultados ilustran el potencial de MRM contrastada con histopatología correlativa como plataforma para explorar nuevos biomarcadores de RMN sin uso de agentes de contraste exógenos tras un IM

High content and dispersion of Gd in bimodal porous silica: T2 contrast agents under ultra-high magnetic fields

Silica-based UVM-7-type bimodal mesoporous materials with high gadolinium content (∞ ≥ Si/Gd ≥ 13) have been synthesized through a one-pot surfactant-assisted procedure from hydroalcoholic solution using a cationic surfactant as template, and starting from atrane complexes of Gd and Si as inorganic precursors. The novel synthetic pathway developed in the study preserves the UVM-7-type architecture while optimizing the dispersion of the Gd-guest species at the nanoscale and even at atomic level. It has been determined that the number of Gd atoms forming clusters is always less than 10. The behaviour under exposure to ultra-high magnetic fields reveals a significant increase in the transversal relaxivity value when compared with related materials in the bibliography. Their activity as T2 instead of T1 contrast agents is discussed and explained considering the high Gd-dispersion and concentration, nature of the materials as well as due to the high magnetic fields used, typical of MRM studies. The absence of toxicity has been confirmed in preliminary cell cultures “in vitro” and the degradation of the solids studied under biological conditions. Results suggest that the atrane route could be a suitable synthesis approach for the preparation of Gd containing contrast agents

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Cross-sectional versus retrospective cohort design

Background Adverse events (AEs) epidemiology is the first step to improve practice in the healthcare system. Usually, the preferred method used to estimate the magnitude of the problem is the retrospective cohort study design, with retrospective reviews of the medical records. However this data collection involves a sophisticated sampling plan, and a process of intensive review of sometimes very heavy and complex medical records. Cross-sectional survey is also a valid and feasible methodology to study AEs. Objectives The aim of this study is to compare AEs detection using two different methodologies: cross-sectional versus retrospective cohort design. Setting Secondary and tertiary hospitals in five countries: Argentina, Colombia, Costa Rica, Mexico and Peru. Participants The IBEAS Study is a cross-sectional survey with a sample size of 11 379 patients. The retrospective cohort study was obtained from a 10% random sample proportional to hospital size from the entire IBEAS Study population. Methods This study compares the 1-day prevalence of the AEs obtained in the IBEAS Study with the incidence obtained through the retrospective cohort study. Results The prevalence of patients with AEs was 10.47% (95% CI 9.90 to 11.03) (1191/11 379), while the cumulative incidence of the retrospective cohort study was 19.76% (95% CI 17.35% to 22.17%) (215/1088). In both studies the highest risk of suffering AEs was seen in Intensive Care Unit (ICU) patients. Comorbid patients and patients with medical devices showed higher risk. Conclusion The retrospective cohort design, although requires more resources, allows to detect more AEs than the cross-sectional design.publishersversionpublishe

Children living with HIV in Europe: do migrants have worse treatment outcomes?

International audienceTo assess the effect of migrant status on treatment outcomes among children living with HIV in Europe

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

International audienceIn human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

BACKGROUND: In human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. METHODS: Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children &lt;18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. RESULTS: Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P &lt; .001). CONCLUSIONS: One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders