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1.
AIDS ; 33(15): 2289-2298, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31764094

RESUMO

BACKGROUND: We aimed to characterize the impact of antiretroviral therapy (ART) initiation on gastrointestinal-associated lymphoid tissue at various sites along the gastrointestinal site. METHODOLOGY: Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV to 33 treatment-naive HIV participants at baseline and after 9 months ART. Tissue was digested for immunophenotyping. Inflammatory, bacterial translocation and intestinal damage markers were measured in plasma. RESULTS: Twenty-six HIV patients completed follow-up. The lowest reconstitution of CD4 T cells and the lowest CD4/CD8 ratio during ART compared with blood were observed in the duodenum with the rectum being either intermediate or approaching blood levels. Regulatory T cells were in higher proportions in the duodenum than the rectum and neither declined significantly during ART. Several correlations with biomarkers of microbial translocation were observed including increases in lipoteichoic acid levels, which reflects Gram-positive bacterial translocation, correlated with increases in %CD4 T cells in the duodenum (Rho 0.773, P = 0.033), and with decreases in duodenal regulatory T-cell populations (Rho -0.40, P = 0.045). CONCLUSION: HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with Gram-positive bacteria.

2.
J Viral Hepat ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31515866

RESUMO

HIV co-infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV-infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co-infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV-co-infected patients and age- and sex-matched vertically HCV-mono-infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty-seven co-infected patients were compared with 67 matched HCV-mono-infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co-infected vs 20% mono-infected had progressed to advanced fibrosis (P = .617). Peg-IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P-value < .001). At treatment initiation, co-infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P < .001), and 47.1% vs 7.1% showed advanced fibrosis (P < .003), with no differences in hard-to-treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P = .122). In vertically HIV/HCV-co-infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg-IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct-acting antivirals against HCV for vertically co-infected patients.

3.
AIDS ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31483371

RESUMO

BACKGROUND: We aimed to characterize the impact of ART initiation on GALT at various sites along the gastrointestinal site. METHODOLOGY: Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV and 33 treatment-naïve HIV subjects at baseline and after 9-months ART. Tissue was digested for immunophenotyping. Inflammatory, bacterial translocation and intestinal damage markers were measured in plasma. RESULTS: Twenty-six HIV subjects completed follow-up. The lowest reconstitution of CD4 T-cells and the lowest CD4/CD8 ratio during ART compared to blood were observed in the duodenum with the rectum being either intermediate or approaching blood levels. Regulatory T-cells (Treg) were in higher proportions in the duodenum than the rectum and neither declined significantly during ART. Several correlations with biomarkers of microbial translocation were observed including increases in LTA levels, which reflects gram-positive bacterial translocation, correlated with increases in %CD4 T-cells in duodenum (Rho 0.773, P = 0.033), and with decreases duodenal Treg populations (Rho -0.40, P = 0.045). CONCLUSIONS: HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with gram positive bacteria.

4.
PLoS One ; 14(8): e0220552, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31381604

RESUMO

BACKGROUND: Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. METHODS: Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. RESULTS: 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). CONCLUSIONS: CD4/CD8 >1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1).

5.
World J Pediatr ; 15(5): 492-498, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31286425

RESUMO

BACKGROUND: Studies investigating health-related quality of life (HRQoL) in youth with perinatally acquired HIV (PHIV+) are scarce. This study aimed to compare HRQoL of PHIV+ to sociodemographic-matched youth not living with HIV (HIV-), Spanish general youth population, and to explore associations between sociodemographic variables, drug consumption, and HRQoL. METHODS: PHIV+ youth were randomly selected from CoRISpe database (Cohort of the Spanish Pediatric HIV Network). HRQoL was evaluated by SF-12v2. RESULTS: Thirty-nine PHIV+ youth (mean age: 23.36 years, SD = 3.83) and thirty-nine HIV- youth (mean age: 22.97 years, SD = 3.80) participated in this study. PHIV+ obtained lower scores in SF-12 physical health subscale (PCS) than HIV- (P = 0.001) and Spanish general youth population (P = 0.006). PHIV+ had lower scores on the mental health subscale (MCS) than the Spanish general youth population (P < 0.001). PHIV+ who were at school obtained better scores than those were not at school. PHIV+ youth who had used cocaine and cannabis had lower scores in MCS (P = 0.002). CONCLUSIONS: There is a need for HRQoL management in the associated medical follow-up.

6.
Eur J Clin Microbiol Infect Dis ; 38(11): 2097-2102, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31359255

RESUMO

According to many guidelines, gentamicin is the empirical parenteral treatment for children with community-acquired urinary tract infection (CA-UTI). However, increasing resistance rates are reported. The purpose of this study is to analyze risk factors for presenting with a UTI caused by a community-acquired gentamicin-resistant Escherichia coli in children in our hospital and to describe their clinical outcome. A retrospective case-control local study was performed in a tertiary care hospital from January 2014 to December 2016. Cases and controls were children below 14 years old diagnosed in the Emergency Department with febrile CA-UTI caused by gentamicin-resistant and gentamicin-susceptible febrile E. coli strains, respectively. During the study period, 54 cases were included and compared with 98 controls. Patients with chronic conditions were more likely to present with a UTI due to gentamicin-resistant E. coli (OR 3.27; 95% CI 1.37-7.8, p < 0.05), as well as children receiving antibiotic prophylaxis (OR 3.5; 95% CI 1.2-10.1, p < 0.05). Cases had longer hospital stays than controls (5.8 ± 5 days vs. 4.4 ± 4 days, p = 0.017). Gentamicin-resistant strains associated higher rates of cefuroxime (29% vs. 3%), cefotaxime (27% vs. 0%), and quinolone resistance (40.7% vs. 6%) (p < 0.01) and produced more frequently extended-spectrum beta-lactamases (ESBL) (20% vs. 0%, p < 0.01) and carbapenemases (7.4% vs. 0%; p = 0.015). All gentamicin-resistant strains were amikacin-sensitive. The presence of chronic conditions and antibiotic prophylaxis could be potential risk factors for gentamicin-resistant E. coli CA-UTI in children. Simultaneous resistance to cephalosporins, quinolones, and ESBL/carbapenemase production is frequent in these strains.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30929024

RESUMO

Data for a total of 57 patients vertically coinfected with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) and 365 HIV-monoinfected patients were compared until their transition to adult care. No differences regarding the dynamics of CD4 and/or CD8 T-cell counts during childhood were found. The coexistence of HCV does not increase the risk of disease progression in vertically HIV-infected patients.

8.
Pediatr Pulmonol ; 54(6): 873-880, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30838805

RESUMO

OBJECTIVE: Respiratory tract infections are among the most common causes of morbidity and mortality worldwide. Acute bronchiolitis (AB) is the leading cause of hospital admission among infants. Clinical scores have proven to be inaccurate in predicting prognosis. Our aim was to build a score based on findings of lung ultrasound (LU) performed at admission, to stratify patients at risk of needing respiratory support (non-invasive and invasive ventilation). STUDY DESIGN: Prospective, multicenter study including infants <6 months of age admitted with AB. Point-of-care LU was performed on admission, and a score was calculated based on ultrasound findings (presence and localization of B lines, B line confluence and/or consolidations) and clinical data. Main outcome was need of respiratory support. RESULTS: A total of 145 patients were included in the study, with a median age of 1.7 months [IQR: 1.2-2.8], 47.6% were female. Mean duration of symptoms prior to admission was 3.1 days (SD 1.8). Fifty-six patients (39%) required non-invasive ventilation (NIV), 14 (9.7%) were transferred to PICU, and 3 needed invasive ventilation (3/145). Identification of at least one posterior consolidation >1 cm was the main factor associated to NIV (RR 4.4; [CI95%1.8-10.8]) The LU score built according to the findings on admission showed an AUC: 0.845(CI95%:0.78-0.91). A score ≥3.5 showed a sensitivity of 89.1% (CI95%:78.2-94.9%) and specificity of 56% (CI95%: 45.3-66.1%) CONCLUSIONS: Among infants below 6 months of age admitted with AB, point-of-care LU was a helpful tool to identify patients at risk of needing respiratory support.

9.
An. pediatr. (2003. Ed. impr.) ; 89(5): 314.e1-314.e6, nov. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-177123

RESUMO

La investigación clínica es la piedra angular para el desarrollo de la Medicina, y, en el ámbito de la Pediatría, supone un reto adicional debido a las peculiaridades que diferencian a los niños de los adultos. A pesar del enorme impacto de la salud infantil en el resto de la vida, nuestra sociedad aún no está suficientemente concienciada sobre la importancia de la investigación pediátrica, que, en general, se encuentra también muy alejada del día a día de quienes nos dedicamos a esta profesión. Desde la Asociación Española de Pediatría (AEP) se ha creado una plataforma específica de investigación -INVEST-AEP- para dar respuesta específica a los retos de la investigación en el seno de nuestra sociedad. En este artículo se retrata el escenario actual de la investigación pediátrica en España y se objetivan las metas alcanzadas en los últimos años, gracias al esfuerzo de los pediatras investigadores. Además, se realiza un análisis en profundidad sobre las barreras cotidianas que dificultan el desarrollo amplio y competitivo de la investigación pediátrica, como la falta de incentivación y ausencia de formación específica de pre y posgrado, la elevada carga asistencial o la falta de infraestructuras y financiación específicas. Definimos la misión, visión y valores de INVEST-AEP para tratar de diseñar una "hoja de ruta" para la investigación pediátrica española de los próximos años


Research is the cornerstone of medical progress. Paediatric research has its own nuances and represents an additional challenge due to the intrinsic characteristics of the paediatric population compared with adults. Despite the tremendous importance of childhood health and its impact during adulthood, society is still not convinced about the importance of conducting research in paediatrics. This also applies to paediatricians themselves, who think about research as a discipline that does not directly involve them. The Spanish Academy of Paediatrics has developed a specific research platform- INVEST-AEP- to try to help and answer the challenges associated with paediatric research in the society This article reflects the current status of paediatric research in Spain, and the goals achieved over the last few years due to the effort of paediatric researchers. In addition, a deeper analysis is provided as regards: a) the barriers that represent a hurdle for the development of broad and competitive paediatric research in our day to day work; b) the limited incentives and specific pre- and post-doctoral training; c) the high clinical burden for paediatricians or; d) the lack of specific infrastructure and dedicated funding for paediatrics. The mission, vision and values of INVEST-AEP are to develop an accessible roadmap for the development and implementation of paediatric research in Spain for the next few years


Assuntos
Pesquisa , Pediatria , Prioridades em Saúde , Sociedades Médicas/normas , Espanha
10.
An Pediatr (Barc) ; 89(5): 314.e1-314.e6, 2018 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-30309723

RESUMO

Research is the cornerstone of medical progress. Paediatric research has its own nuances and represents an additional challenge due to the intrinsic characteristics of the paediatric population compared with adults. Despite the tremendous importance of childhood health and its impact during adulthood, society is still not convinced about the importance of conducting research in paediatrics. This also applies to paediatricians themselves, who think about research as a discipline that does not directly involve them. The Spanish Academy of Paediatrics has developed a specific research platform- INVEST-AEP- to try to help and answer the challenges associated with paediatric research in the society This article reflects the current status of paediatric research in Spain, and the goals achieved over the last few years due to the effort of paediatric researchers. In addition, a deeper analysis is provided as regards: a) the barriers that represent a hurdle for the development of broad and competitive paediatric research in our day to day work; b) the limited incentives and specific pre- and post-doctoral training; c) the high clinical burden for paediatricians or; d) the lack of specific infrastructure and dedicated funding for paediatrics. The mission, vision and values of INVEST-AEP are to develop an accessible roadmap for the development and implementation of paediatric research in Spain for the next few years.

11.
Clin Infect Dis ; 2018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29788075

RESUMO

Background: While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, their clinical implications in HIV-infected subjects initiating ART at advanced HIV disease remain unclear. Methodology: Pilot multicenter randomized, placebo-controlled, double-blind study in which 78 HIV-infected, ART-naive subjects with <350 CD4 T-cells/µl or AIDS were randomized to either daily PMT25341 (a mixture of prebiotics, probiotics, oligonutrients, DHA, EPA, GLA, and aminoacids) or placebo for 48 weeks, each in combination with first-line ART. Primary endpoints were changes in CD4 T-cell counts and CD4/CD8 ratio from baseline to week 48 and safety. Secondary endpoints were changes in markers of T-cell activation, bacterial translocation, inflammation, and microbiota composition (Clinicaltrials.gov: NCT00870363). Results: Fifty-nine participants completed the follow-up with a mean CD4+ T-cell count of 221108/µl and mean CD4/CD8 ratio of 0.260.19. PMT25341 was well tolerated; without grade 3-4 adverse effects attributable to the intervention. While most of the assessed biomarkers improved during the follow-up in both arms, PMT25341-treated subjects did not experience any significant change, compared to placebo-treated subjects, in median CD4+ T-cell count change (226 cells/µl vs. 414, P=0.461) or CD4/CD8 ratio change (0.21 vs. 0.48, P=0.854). Similarly, we did not detect differences between treatment arms in the variations of %HLADR+CD38+ or %CD28- T-cells, sCD14, LTA, IL-6, CRP, TNF-⍺, sCD163, IP-10, IL-7, IL-10, or IL-17 or alpha and beta microbiota diversity. Conclusion: In HIV-infected patients initiating ART at advanced disease, the clear immunological benefits of ART were not enhanced by this nutritional intervention targeting the GALT and microbiota.

12.
AIDS ; 32(10): 1229-1237, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29683848

RESUMO

OBJECTIVE: In a recent blinded randomized study, we found that in HIV-infected individuals a short supplementation with prebiotics (scGOS/lcFOS/glutamine) ameliorates dysbiosis of total gut bacteria, particularly among viremic untreated patients. Our study goal was to determine the fraction of the microbiota that becomes active during the intervention and that could provide additional functional information. DESIGN: A total of six healthy individuals, and 16 HIV-infected patients comprising viremic untreated patients (n = 5) and antiretroviral therapy-treated patients that are further divided into immunological responders (n = 7) and immunological nonresponders (n = 4) completed the 6-week course of prebiotic treatment, including six patients receiving a placebo. METHODS: Alpha and beta diversity of potentially active and total gut microbiota was evaluated using shotgun proteomics and 16S rRNA gene sequencing. RESULTS: HIV infection decreased dormancy and increased alpha diversity of active bacteria in comparison with the healthy controls, whose richness was not further influenced by the prebiotic intervention. The effect of the prebiotics was most evident at the beta-diversity of active bacteria, particularly within viremic untreated patients. We found that the prebiotics did not only ameliorate dysbiosis of total bacteria in viremic untreated patients but also increased the abundance of active bacteria with strong immunomodulatory properties and amino acids metabolism, namely Bifidobacteriaceae, at similar levels to those in healthy individuals. This effect was attenuated in ART-treated individuals. CONCLUSION: The effect of prebiotics was greater among ART-naive HIV-infected individuals than in ART-treated patients and healthy controls. This highlights the importance of therapies aimed at manipulating the microbiome in this group of patients.

14.
J Infect Dis ; 216(7): 813-818, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-28968888

RESUMO

Plasma, duodenal, and rectal tissue antiretroviral therapy (ART) drug concentrations, human immunodeficiency virus (HIV) RNA and HIV DNA copy numbers, and recovery of mucosal immunity were measured before and 9 months after initiation of 3 different ART regimens in 26 subjects. Plasma and tissue HIV RNA correlated at baseline and when 9-month declines were compared, suggesting that these compartments are tightly associated. Antiretroviral tissue:blood penetration ratios were above the 50% inhibitory concentration values in almost 100% of cases. There were no correlations between drug concentrations and HIV DNA/RNA. Importantly, no evidence was found for residual viral replication or deficient tissue drug penetration to account for delayed gastrointestinal-associated lymphoid tissue immune recovery.


Assuntos
Benzoxazinas/uso terapêutico , Cicloexanos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Tecido Linfoide/efeitos dos fármacos , Raltegravir Potássico/uso terapêutico , Triazóis/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/administração & dosagem , Cicloexanos/administração & dosagem , DNA Viral , Duodeno/efeitos dos fármacos , Duodeno/metabolismo , Feminino , Humanos , Tecido Linfoide/metabolismo , Masculino , Maraviroc , RNA Viral , Raltegravir Potássico/administração & dosagem , Reto/efeitos dos fármacos , Reto/metabolismo , Triazóis/administração & dosagem
18.
Pediatr Infect Dis J ; 36(6): 578-583, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28005690

RESUMO

BACKGROUND: Our aim was to determine the prevalence and risk factors associated with low bone mineral density (BMD) in vertically HIV-infected patients and to investigate whether low BMD is related to immune activation and senescence induced by HIV infection. METHODS: A cross-sectional study was performed in 98 vertically HIV-infected patients. BMD was measured by dual-energy radiograph absorptiometry at lumbar spine. Height adjustment of BMD Z score was performed using height-for-age Z score. T-cell immune activation and senescence were analyzed in a subgroup of 54 patients by flow cytometry. RESULTS: Median age was 15.9 years, 71.4% were Caucasian, 99% received antiretroviral therapy and 80.6% had undetectable viral load. Low BMD (BMD Z score ≤ -2) was present in 15.3% of cases, but after height adjustment in 4.1% of cases. Height-adjusted BMD Z score was positively correlated with body mass index Z score, CD4/CD8 ratio and nadir CD4, and inversely with duration of severe immunosuppression and parathyroid hormone values. In the multivariate model including age, gender, ethnicity, encephalopathy, Tanner stage, nadir CD4, duration of viral suppression, CD4 count, CD4/CD8 ratio, body mass index, cumulative duration of antiretroviral therapy, tenofovir and protease inhibitors exposure, nadir CD4 was independently associated to height-adjusted BMD Z score. No association was found between height-adjusted BMD Z score and T-cell activation or senescence. CONCLUSIONS: The prevalence of low BMD in vertically HIV-infected patients was low after height adjustment. Nadir CD4, but not T-cell activation or senescence, was an independent predictor for low BMD. Larger and prospective studies are needed to achieve better knowledge of the pathogenesis of low BMD in vertical HIV infection.


Assuntos
Densidade Óssea/imunologia , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Transmissão Vertical de Doença Infecciosa , Adolescente , Envelhecimento/imunologia , Estatura , Criança , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Humanos , Masculino , Fatores de Risco , Estatísticas não Paramétricas
19.
20.
AIDS ; 31(4): 591-594, 2017 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-27922858

RESUMO

Altered interplay between gut mucosa and dysbiotic bacteria during HIV infection seems to fuel chronic immune dysfunction and might explain the excess rates of human papillomavirus (HPV)-associated anal cancer in HIV-infected individuals. Here, we show in HIV-infected MSM undergoing screening for HPV-related cancer that specific fecal and mucosal bacteria are able to predict the existence of precancerous anal lesions. If confirmed, these bacterial biomarkers could be exploited either as diagnostic tools or therapeutic targets.


Assuntos
Neoplasias do Ânus/epidemiologia , Disbiose/complicações , Microbioma Gastrointestinal , Infecções por HIV/complicações , Microbiota , Infecções por Papillomavirus/complicações , Adulto , Neoplasias do Ânus/virologia , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Minorias Sexuais e de Gênero
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