RESUMEN
OBJECTIVES: Although widely recommended, data on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) efficacy in HIV-1-infected children/adolescents are mainly extrapolated from studies in adults and one paediatric trial in which subjects have good treatment adherence. This study aimed to provide data about the risk of virological failure (VF) and acquired genotypic resistance in children and adolescents receiving BIC/FTC/TAF in a real-world setting. METHODS: This retrospective monocentric study included 74 paediatric patients who received BIC/FTC/TAF during ≥6 months in 2019-2023. VF was defined as not achieving a plasma viral load <50 copies/mL within 6 months of BIC/FTC/TAF initiation or as experiencing virological rebound ≥50 copies/mL. RESULTS: Most patients were antiretroviral therapy (ART)-experienced (93.2%), previously exposed to integrase inhibitors (85.1%) and displayed viral suppression at baseline (67.6%). Their median age was 11.2 years [interquartile range (IQR): 8.8-15.2]. BIC/FTC/TAF introduction reduced treatment burden in most ART-experienced subjects. Genotypic susceptibility score of BIC/FTC/TAF was ≥2 in all cases. Median follow-up was 40 months (IQR: 21-46). VF occurred in 28 people (37.8%), more frequently in the case of VF versus viral suppression at baseline (68% vs. 26%, P = 0.02). BIC/FTC/TAF was interrupted for suspected intolerance in only one case (1.4%). Nucleoside reverse transcriptase inhibitor (NRTI) mutation (T69D/N) emerged in one patient (3.6% of VF) after 47 months of continuous detectable viraemia while on ART. No acquisition of mutations in the integrase gene was observed. CONCLUSION: Because of its high genetic barrier to resistance, BIC/FTC/TAF could be especially useful in the paediatric population, in which the risk of poor treatment adherence and VF is high.
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Alanina , Amidas , Fármacos Anti-VIH , Infecciones por VIH , Piperazinas , Piridonas , Tenofovir , Adolescente , Adulto , Niño , Humanos , Fármacos Anti-VIH/uso terapéutico , Combinación de Medicamentos , Emtricitabina/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Tenofovir/análogos & derivadosRESUMEN
OBJECTIVES: The aim of the study was to carry out a comparison of the safety and efficacy of dolutegravir-based regimens among age groups of HIV-1-infected paediatric and young adult patients. PATIENTS AND METHODS: This retrospective monocentric study included 109 patients infected since childhood who began receiving dolutegravir between January 2014 and December 2017. The patients were divided into three groups according to age at the time of dolutegravir initiation: 5-11, 12-17 and 18-25 years old. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) < 50 HIV-1 RNA copies/mL within 3 months of dolutegravir initiation (for patients with detectable viraemia at baseline), and maintaining virological suppression (PVL < 50 copies/mL) until the last follow-up visit (for all patients). RESULTS: Most of the subjects were antiretroviral-experienced (91.7%) and virologically suppressed at baseline (66.7%, 54.9% and 56.0% in the 5-11, 12-17 and 18-25 year age groups, respectively). Median follow-up was 24 months (range 6-54 months). Sustained virological success throughout follow-up was observed in 79.8% of patients, with similar rates among age groups (87.9%, 72.5% and 84.0%, respectively; P = 0.22). With reinforced measures to improve adherence, undetectable PVL was obtained at the last visit in 88.1% of patients, with similar proportions among age groups (93.9%, 84.3% and 88.0%, respectively; P = 0.51). No emergence of resistance mutations was observed in the 22 patients with virological failure. Dolutegravir was well tolerated; only one patient stopped treatment for severe drug-related side effects. CONCLUSIONS: The virological efficacy and safety of dolutegravir were similar among the three age groups. Because of its high genetic barrier to resistance, dolutegravir could be especially useful in the paediatric population, in which the risk of poor treatment adherence is high.
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/administración & dosificación , VIH-1/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Adolescente , Distribución por Edad , Niño , Preescolar , Femenino , Infecciones por VIH/virología , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de Integrasa VIH/farmacología , VIH-1/genética , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Masculino , Cumplimiento de la Medicación , Oxazinas , Piperazinas , Piridonas , Estudios Retrospectivos , Resultado del Tratamiento , Carga Viral/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and review the literature. OBJECTIVES: To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID. METHODS: We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature. RESULTS: Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red-brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma-like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia-telangiectasia (52%), combined immunodeficiency (24%), cartilage-hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus. CONCLUSION: Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID.
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Granuloma/diagnóstico , Granuloma/patología , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/patología , Anomalías Múltiples/diagnóstico , Ataxia Telangiectasia/etiología , Niño , Preescolar , Femenino , Granuloma/complicaciones , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico , Humanos , Hidrocolpos/complicaciones , Hidrocolpos/diagnóstico , Lactante , Masculino , Polidactilia/complicaciones , Polidactilia/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/complicaciones , Inmunodeficiencia Combinada Grave/complicaciones , Inmunodeficiencia Combinada Grave/diagnóstico , Enfermedades de la Piel/complicaciones , Úlcera Cutánea/etiología , Enfermedades Uterinas/complicaciones , Enfermedades Uterinas/diagnósticoRESUMEN
Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has been introduced as an identification procedure for bacteria and fungi. The MALDI-TOF MS-based analysis of resistance to ß-lactam antibiotics has been applied to detect hydrolysis of carbapenems by different bacterial strains. However, the detection of enzymatic carbapenem degradation by MALDI-TOF MS lacks well-standardized protocols and several methods and models of interpretation using different calculations of ratio-of-peak intensities have been described in the literature. Here, we used faropenem and ertapenem hydrolysis as model compounds. In an attempt to propose a universal protocol, the hydrolysis was regularly monitored during 24 h using well-characterized bacterial strains producing different types of carbapenemases (KPC, IMP, NDM, VIM, and OXA-48). Variable responses and different timing for detectable hydrolysis, depending on the enzyme produced, were observed. KPC degrades its template antibiotics very quickly (15 min for some KPC producers) compared to other types of enzymes (more than 90 min for other enzymes). Prior bacterial lysis was shown to be of no interest in the modulation or optimization of the hydrolytic kinetics. The adequate detection of carbapenem hydrolysis would, therefore, require several MALDI-TOF MS readouts for the timely detection of rapid hydrolysis without missing slow hydrolysis. This enzymatic constraint limits the implementation of a standard protocol in routine microbiology laboratories.
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Antibacterianos/metabolismo , Proteínas Bacterianas/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , beta-Lactamasas/análisis , Ertapenem , Hongos , Humanos , Hidrólisis , Cinética , Factores de Tiempo , beta-Lactamas/metabolismoRESUMEN
BACKGROUND: Stroke guidelines emphasize the importance of adequate vascular risk factor assessment and management in transient ischemic attack (TIA) and ischemic stroke patients, but it is not clear how these guidelines are applied in routine clinical practice. The limited data that are available indicate that TIA and ischemic stroke patients often do not receive the recommended interventions. The aim of this study was to investigate practice variations in long-term secondary stroke prevention in The Netherlands. METHODS: Between June and December 2013, an invitation for a web-based survey was sent to 90 Dutch neurologists with a special interest in stroke neurology. This web-based survey contained questions regarding the organization of outpatient care for TIA and ischemic stroke patients after initial hospital assessment, pharmacologic treatment, and nonpharmacologic strategies for long-term secondary prevention. RESULTS: In total, 84 (93%) neurologists completed the survey. Although nearly all respondents reported that they follow-up TIA and ischemic stroke patients after initial hospital assessment, the number of follow-up visits and the follow-up duration were variable. A similar variation was found in treatment targets levels for both blood pressure and low-density lipoprotein cholesterol. Regarding nonpharmacologic strategies for long-term secondary stroke prevention, most respondents inform their TIA and ischemic stroke patients about the importance of smoking cessation. There is considerably less attention for the other lifestyle risk factors. CONCLUSIONS: We found considerable practice variation in long-term secondary stroke prevention. These variations may have an impact on the risk for stroke recurrence and cardiovascular disease in general.
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Ataque Isquémico Transitorio/terapia , Cuidados a Largo Plazo/tendencias , Pautas de la Práctica en Medicina/tendencias , Prevención Secundaria/tendencias , Accidente Cerebrovascular/terapia , Anticolesterolemiantes/uso terapéutico , Antihipertensivos/uso terapéutico , Adhesión a Directriz/tendencias , Encuestas de Atención de la Salud , Humanos , Internet , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/etiología , Países Bajos , Guías de Práctica Clínica como Asunto , Calidad de la Atención de Salud/tendencias , Recurrencia , Medición de Riesgo , Factores de Riesgo , Conducta de Reducción del Riesgo , Cese del Hábito de Fumar , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
Scarce data exist on allogeneic hematopoietic stem cell transplantation (HSCT) outcomes in hepatitis B virus (HBV)-naïve recipients from HBV-experienced donors. Long-term follow-up is herein reported for 17 allogeneic HSCT performed in 13 HBV-naïve children from HBc-antibodies-positive donors between 2006 and 2012. Four donors were HBs-antigen-positive, with detectable but low viremia in 2 cases (<2 log10IU/ml). HBV-DNA was undetectable in all transplanted cell products. Recipients' HBV prophylaxis consisted of pre-transplant vaccination, polyvalent immune globulins, specific anti-HBV immune globulins, and/or oral lamivudine in 3, 12, 8, and 8 children, respectively. No case of HBV transmission occurred based on negative close monitoring of recipients' HBV serology and plasma HBV-DNA during a median follow-up of 22 months. In case of undetectable viremia in the donor, prophylaxis with vaccination and/or immune globulins in the recipient seems to be sufficient and lamivudine prophylaxis might be unnecessary to prevent viral transmission. In case of undetectable viremia in the donor, a systematic screening of HBV DNA in the stem cell product might be unnecessary to confirm the low risk of viral transmission. Prior exposure to HBV in the donor should not be considered a contraindication to HSCT.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/normas , Anticuerpos contra la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Donantes de Tejidos/estadística & datos numéricos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Viremia/sangreRESUMEN
Our objective was to study relations between non-disclosure of HIV to partner, socio demographics and prevention of HIV mother-to-child transmission (PMTCT), among HIV-infected pregnant women enrolled in the French Perinatal Cohort (ANRS-EPF-CO1) from 2005 to 2009 (N = 2,952). Fifteen percent of the women did not disclose their HIV status to their partner. Non-disclosure was more frequent in women diagnosed with HIV infection late in pregnancy, originating from Sub-Saharan Africa or living alone, as well as when the partner was not tested for HIV. Non-disclosure was independently associated with non optimal PMTCT: late initiation of antiretroviral therapy, detectable viral load at delivery and lack of neonatal prophylaxis. Nonetheless, the rate of transmission did not differ according to disclosure status. Factors associated with non-disclosure reflect vulnerability and its association with non optimal PMTCT is a cause for concern although the impact on transmission was limited in this context of universal free access to care.
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Consejo , Seropositividad para VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Madres , Complicaciones Infecciosas del Embarazo/prevención & control , Parejas Sexuales , Revelación de la Verdad , Adulto , Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa , Escolaridad , Femenino , Francia/epidemiología , Seropositividad para VIH/psicología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Masculino , Madres/psicología , Aceptación de la Atención de Salud , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/psicología , Atención Prenatal/estadística & datos numéricos , Parejas Sexuales/psicología , Esposos , Encuestas y Cuestionarios , Carga ViralRESUMEN
The molecular basis of X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) has remained elusive. Here we report hypomorphic mutations in the gene IKBKG in 12 males with EDA-ID from 8 kindreds, and 2 patients with a related and hitherto unrecognized syndrome of EDA-ID with osteopetrosis and lymphoedema (OL-EDA-ID). Mutations in the coding region of IKBKG are associated with EDA-ID, and stop codon mutations, with OL-EDA-ID. IKBKG encodes NEMO, the regulatory subunit of the IKK (IkappaB kinase) complex, which is essential for NF-kappaB signaling. Germline loss-of-function mutations in IKBKG are lethal in male fetuses. We show that IKBKG mutations causing OL-EDA-ID and EDA-ID impair but do not abolish NF-kappaB signaling. We also show that the ectodysplasin receptor, DL, triggers NF-kappaB through the NEMO protein, indicating that EDA results from impaired NF-kappaB signaling. Finally, we show that abnormal immunity in OL-EDA-ID patients results from impaired cell responses to lipopolysaccharide, interleukin (IL)-1beta, IL-18, TNFalpha and CD154. We thus report for the first time that impaired but not abolished NF-kappaB signaling in humans results in two related syndromes that associate specific developmental and immunological defects.
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Displasia Ectodérmica/genética , Displasia Ectodérmica/inmunología , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunología , FN-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Adolescente , Niño , Preescolar , Codón de Terminación/genética , Displasia Ectodérmica/metabolismo , Ectodisplasinas , Ligamiento Genético , Humanos , Quinasa I-kappa B , Inmunidad Celular , Síndromes de Inmunodeficiencia/metabolismo , Lactante , Masculino , Proteínas de la Membrana/metabolismo , Mutación , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Síndrome , Cromosoma X/genéticaRESUMEN
BACKGROUND. Increasing numbers of children perinatally infected with human immunodeficiency virus (HIV) are reaching adolescence, largely because of advances in treatment over the past 10 years, but little is known about their current health status. We describe here the living conditions and clinical and immunovirologic outcomes at last evaluation among this pioneering generation of adolescents who were born before the introduction of prophylaxis for vertical transmission and whose infections were diagnosed at a time when treatment options were limited. METHODS. The eligible population consisted of HIV-1-infected children who were born before December 1993 and who were included at birth in the prospective national French Perinatal Cohort (EPF/ANRS CO10). RESULTS. Of the 348 eligible children, 210 (60%; median age, 15 years) were still alive and regularly followed up. Current treatment was highly active antiretroviral therapy (HAART) in 77% and 2 nucleoside analogues in 5.0%; 16% had stopped treatment, and 2% had never been treated. The median CD4 cell count was 557 cells/microL, and 200 cells/microL was exceeded in 94% of patients. The median viral load was 200 copies/mL. Viral load was undetectable in 43% of the adolescents and in 54.5% of those receiving HAART. Median height, weight, and body mass index were similar to French reference values for age, and school achievement was similar to nationwide statistics. Better immunologic status was associated with being younger and with having begun HAART earlier. Undetectable viral load was associated with maternal geographic origin and current HAART. CONCLUSIONS. Given the limited therapeutic options available during the early years of these patients' lives and the challenge presented by treatment adherence during adolescence, the long-term outcomes among this population are encouraging.
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Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , VIH-1/aislamiento & purificación , Adolescente , Recuento de Linfocito CD4 , Niño , Preescolar , Estudios de Cohortes , Femenino , Francia , Infecciones por VIH/patología , Infecciones por VIH/virología , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Estudios Longitudinales , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: Management of pregnant women with human immunodeficiency virus (HIV) type 2 infection remains unclear because of its low prevalence and important differences from HIV-1. METHODS: Pregnant women monoinfected with HIV-2 or HIV-1 and their infants enrolled in the prospective, national, multicenter French Perinatal Cohort between 1986 and 2007. RESULTS: Overall, 2.6% (223/8660) of mothers were infected with HIV-2, and they accounted for 3.1% (367/ 11841) of the total births. Most were born in sub-Saharan Africa. A higher proportion of HIV-2-infected mothers than HIV-1-infected mothers had no symptoms, had received no antiretroviral therapy at conception (85.9% vs 66.7%), and had received no antiretroviral therapy during pregnancy (42.8% vs 19.9%), particularly highly active antiretroviral therapy (HAART) (79.7% vs 46.1%), and they had higher CD4 cell counts near delivery (median, 574 vs 452 cells/mm3; P < .01). If antiretroviral therapy was used, it was started at a later gestational age for HIV- 2-infected mothers (median, 28 vs 25 weeks; P < .01). HIV-2-infected mothers were more likely to deliver vaginally (67.9% vs 49.3%) and to breastfeed (3.6% vs 0.6%; P < .01), and their infants less frequently received postexposure prophylaxis. In the period 2000-2007, the proportion with viral load <100 copies/mL at delivery was 90.5% of HIV-2-infected mothers, compared with 76.2% of HIV-1-infected mothers (P=.1). There were 2 cases of transmission: 1 case in 1993 occurred following maternal primary infection, and the other case occurred postnatally in 2002 and involved a mother with severe immune deficiency. The mother-to-child transmission rate for HIV-2 was 0.6% (95% confidence interval, 0.07%-2.2%). CONCLUSIONS: Care for HIV-2-infected pregnant women rests on expert opinion. The mother-to-child transmission residual rate (0.07%-2.2%) argues for systematic treatment: protease inhibitor-based HAART for women requiring antiretrov
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Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-2/aislamiento & purificación , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/virología , Adulto , Estudios de Cohortes , Femenino , Francia , Humanos , EmbarazoRESUMEN
OBJECTIVES: To assess the outcome of HIV-infected individuals attending one of the largest French pediatric HIV centers in 2016-2017 and to compare the rates of antiretroviral coverage and virological suppression with the UNAIDS targets. PATIENTS AND METHODS: The clinical and immuno-virological status of 163 HIV-1-infected children and adolescents attending Necker Hospital in Paris, France, were investigated. Virological suppression was defined as an HIV-1 viral load<50 copies/mL for at least six months. All genotypic resistance tests performed since birth were analyzed. RESULTS: Most patients were born in Sub-Saharan African countries (41.7%) or in France (38.0%). Their median age was 14 years [IQR 7.3-17.0]. Although 33.7% of individuals had a history of AIDS-defining clinical event(s), 86.5% of children/adolescents were free from HIV-related symptoms at their most recent evaluation. Antiretroviral coverage was high (98.2%; mainly including one integrase inhibitor [42.3%] or one protease inhibitor [23.9%]). At the last visit, most patients (82.8%) had normal CD4T lymphocytes counts (≥25%). Although 61.7% of antiretroviral-experienced children had resistance to≥1 drug class and 9.2% had triple-class resistance, 80.3% of patients receiving antiretrovirals for≥6 months (126/157) were virologically suppressed. International adoptees were more frequently virologically suppressed than other patients (96.0% versus 74.6%, P=0.02). CONCLUSIONS: Antiretroviral coverage exceeded the second UNAIDS 90 target aimed at ending the AIDS epidemic. The rate of virological suppression, one of the highest reported in children in high-income countries, is approaching the third UNAIDS 90 target and the rate observed in French HIV-infected adults on antiretrovirals.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Carga Viral/efectos de los fármacos , Viremia/tratamiento farmacológico , Adolescente , África del Sur del Sahara/etnología , Fármacos Anti-VIH/farmacología , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Niño , Niño Adoptado , Preescolar , Farmacorresistencia Viral , Emigrantes e Inmigrantes , Femenino , Francia/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Lactante , Recién Nacido , Masculino , Factores Socioeconómicos , Tailandia/etnología , Vietnam/etnología , Viremia/epidemiología , Viremia/virologíaRESUMEN
OBJECTIVES: Antiretroviral therapy has dramatically improved the survival of HIV-infected children. Nevertheless, side effects comparable to those found in adults have been encountered, such as facial lipoatrophy, which can have a negative impact on the self-esteem of otherwise healthy adolescents. Cosmetic surgical procedures in adolescents raise psychological issues which need to be specifically addressed and which have never been previously reported in this population. We evaluated the patient satisfaction, safety and cosmetic results of HIV-infected adolescents who experienced autologous fat transplants for the correction of facial lipoatrophy. METHODS: We report the results of plastic surgery using autologous fat transplants (Coleman's Lipostructure) in six HIV-infected adolescents with facial lipoatrophy: three boys and three girls, aged 14-19 years. RESULTS: The quantity of reinjected fat on each side of the face varied from 5 to 12 mL within a single procedure. All the patients reported being satisfied or very satisfied with the cosmetic results and reported a positive impact on their daily life. CONCLUSIONS: With well-trained surgeons and carefully selected indications, corrective surgery of facial lipoatrophy in HIV-infected adolescents can provide immediate and long-lasting benefits in terms of physical appearance and psychological wellbeing, and should be considered as a component of comprehensive care.
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Tejido Adiposo/trasplante , Fármacos Anti-VIH/efectos adversos , Técnicas Cosméticas , Síndrome de Lipodistrofia Asociada a VIH/cirugía , Estavudina/efectos adversos , Adolescente , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Imagen Corporal , Niño , Cara , Femenino , Infecciones por VIH/tratamiento farmacológico , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Síndrome de Lipodistrofia Asociada a VIH/psicología , Humanos , Masculino , Satisfacción del Paciente , Calidad de Vida , Autoimagen , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate inter-reader agreement and diagnostic accuracy of chest radiography (CXR) in the diagnosis of tuberculosis (TB) in children with human immunodeficiency virus (HIV) infection. DESIGN: HIV-infected children with clinically suspected TB were enrolled in a prospective study conducted in Burkina Faso, Cambodia, Cameroon and Viet Nam from April 2010 to December 2014. Three readers-a local radiologist, a paediatric pulmonologist and a paediatric radiologist-independently reviewed the CXRs. Inter-reader agreement was then assessed using the κ coefficient. Diagnostic accuracy of CXR was assessed in culture-confirmed cases and controls. RESULTS: A total of 403 children (median age 7.3 years, interquartile range 3.5-9.7; 49.6% males) were enrolled. Inter-reader agreement was as follows: between local radiologist and paediatric pulmonologist, κ = 0.36 (95%CI 0.27-0.45); local radiologist and paediatric radiologist, κ = 0.16 (95%CI 0.08-0.24); and paediatric pulmonologist and paediatric radiologist, κ = 0.30 (95%CI 0.21-0.40). Among 51 cases and 151 controls, after a consensus, CXR had a sensitivity of 71.4% (95%CI 58.8-84.1) and a specificity of 50.0% (95%CI 41.9-58.1). Alveolar opacities and enlarged lymph nodes on CXR had limited specificity for TB (64.7% and 70.2%, respectively). Miliary and/or nodular opacities patterns on CXR were more specific to TB (specificity 94.3%). CONCLUSION: CXR showed poor-to-fair inter-reader agreement and limited diagnostic accuracy for TB in HIV-infected children, likely due to comorbidities. Radiological criteria for this specific population require further investigation.
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Radiografía Torácica/economía , Tuberculosis Pulmonar/diagnóstico por imagen , Burkina Faso/epidemiología , Cambodia/epidemiología , Camerún/epidemiología , Niño , Preescolar , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Recursos en Salud , Humanos , Masculino , Estudios Prospectivos , Sensibilidad y Especificidad , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/epidemiología , Vietnam/epidemiologíaRESUMEN
Pearson's marrow-pancreas syndrome (McKusick No. 26056) is a fatal disorder of hitherto unknown etiology involving the hematopoietic system, exocrine pancreas, liver, and kidneys. The observation of high lactate/pyruvate molar ratios in plasma and abnormal oxidative phosphorylation in lymphocytes led us to postulate that Pearson's syndrome belongs to the group of mitochondrial cytopathies. Since rearrangements of the mitochondrial genome between direct DNA repeats were consistently found in all tissues tested, our results show that this disease is in fact a multisystem mitochondrial disorder, as suggested by the clinical course of the patients. Based on these observations, we would suggest giving consideration to the hypothesis of a defect of oxidative phosphorylation in elucidating the origin of other syndromes, especially those associated with an abnormal oxidoreduction status in plasma.
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Anemia Sideroblástica/metabolismo , ADN Mitocondrial/genética , Insuficiencia Pancreática Exocrina/metabolismo , Mitocondrias/enzimología , Anemia Sideroblástica/genética , Anemia Sideroblástica/patología , Secuencia de Bases , Southern Blotting , Deleción Cromosómica , Insuficiencia Pancreática Exocrina/genética , Insuficiencia Pancreática Exocrina/patología , Femenino , Reordenamiento Génico , Humanos , Recién Nacido , Masculino , Datos de Secuencia Molecular , Oxidación-Reducción , Fosforilación Oxidativa , Secuencias Repetitivas de Ácidos Nucleicos , SíndromeRESUMEN
Complete interferon-gamma receptor 1 (IFNgammaR1) deficiency has been identified previously as a cause of fatal bacillus Calmette-Guérin (BCG) infection with lepromatoid granulomas, and of disseminated nontuberculous mycobacterial (NTM) infection in children who had not been inoculated with BCG. We report here a kindred with partial IFNgammaR1 deficiency: one child afflicted by disseminated BCG infection with tuberculoid granulomas, and a sibling, who had not been inoculated previously with BCG, with clinical tuberculosis. Both responded to antimicrobials and are currently well without prophylactic therapy. Impaired response to IFN-gamma was documented in B cells by signal transducer and activator of transcription 1 nuclear translocation, in fibroblasts by cell surface HLA class II induction, and in monocytes by cell surface CD64 induction and TNF-alpha secretion. Whereas cells from healthy children responded to even low IFN-gamma concentrations (10 IU/ml), and cells from a child with complete IFNgammaR1 deficiency did not respond to even high IFN-gamma concentrations (10,000 IU/ml), cells from the two siblings did not respond to low or intermediate concentrations, yet responded to high IFN-gamma concentrations. A homozygous missense IFNgR1 mutation was identified, and its pathogenic role was ascertained by molecular complementation. Thus, whereas complete IFNgammaR1 deficiency in previously identified kindreds caused fatal lepromatoid BCG infection and disseminated NTM infection, partial IFNgammaR1 deficiency in this kindred caused curable tuberculoid BCG infection and clinical tuberculosis.
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Mycobacterium bovis , Receptores de Interferón/deficiencia , Tuberculosis/inmunología , Adolescente , Vacuna BCG/efectos adversos , Preescolar , Femenino , Humanos , Lactante , Masculino , Proteínas de la Membrana , Mutación , Linaje , Receptor de Interferón alfa y beta , Receptores de Interferón/genética , Tuberculosis/etiología , Tuberculosis/genéticaRESUMEN
Limit of antiretroviral treatment success is the emergence of drug-resistant virus. As reported in adult population, prevalence of resistance was high in treated HIV-infected children with detectable HIV viral load. Resistance increased with number of prior antiretroviral treatments, particularly with protease inhibitors. Adolescent boys seem at greater risk to harbor multi-classes resistant virus. In HIV-infected newborns, prevalence of resistance was 20%. Most of resistance mutations detected were in accord to perinatal antiretroviral exposition. Principal mechanism of resistance acquisition in newborns was transmission of resistant viruses from mother to child with early archive in cellular reservoir and long term persistence with or without treatment. Consequences of long term therapeutic strategies in children are major.
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Antirretrovirales/uso terapéutico , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Adolescente , Niño , Preescolar , Francia , Humanos , Lactante , Recién NacidoRESUMEN
Adenovirus infections result in significant morbidity and mortality in allogeneic haematopoietic stem cell transplanted (hSCT) children. Adenovirus from species C and B account for more than 90% of adenoviruses recovered after hSCT. However, infections due to adenovirus A31 have been increasingly reported in recent years. Between April 2002 and April 2005, blood samples obtained every 2 weeks from 58 hSCT children were screened for adenovirus species A to C by quantitative real-time PCR. Phylogenetic analysis was realized after amplification and sequencing of the entire hexon gene. Fifteen cases of adenovirus infection with viraemia were recovered during this 3 years period. During spring/summer 2003, seven cases occurred and were due to an adenovirus species A. Phylogenetic analysis of the seven strains showed that they belonged to the A31 genotype and shared 100% homology. Clinical features of the seven HSCT children with A31 adenovirus viraemia are described. We describe here an epidemic spread of adenovirus genotype A31 in a paediatric haematology unit. Timing, location and hexon gene genotyping results highly suggested a nosocomial origin to this epidemic. The burden of adenovirus A31 infection needs to be further assessed in this context.
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Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/virología , Adenovirus Humanos/genética , Infección Hospitalaria/epidemiología , Infección Hospitalaria/virología , Brotes de Enfermedades , Trasplante de Células Madre Hematopoyéticas , Infecciones por Adenovirus Humanos/terapia , Adenovirus Humanos/clasificación , Adenovirus Humanos/aislamiento & purificación , Adolescente , Niño , Preescolar , Infección Hospitalaria/terapia , Francia/epidemiología , Genotipo , Hospitales Pediátricos , Humanos , Lactante , Filogenia , Especificidad de la Especie , Trasplante Homólogo , Resultado del Tratamiento , Viremia/virologíaRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is a rare, often fatal, disease of early infancy. The diagnosis of HLH is frequently delayed or made at autopsy because no genetic or biologic marker has been identified. To improve the classification and treatment of HLH, the Histiocyte Society has established an 'International Registry for HLH'. Data collected included family history, clinical and laboratory features at the onset of illness, and treatment outcome. Stringent diagnostic criteria (ie fever, splenomegaly, cytopenia, hypertriglyceridemia, and/or hypofibrinogenemia, and hemophagocytosis without evidence of malignancy) were used for patient selection. One hundred and twenty-two patients (61 males, 61 females) were enrolled from 17 centers in 11 countries. The rate of parental consanguinity was 24%. A positive family history was reported in 49% of cases including two pairs of affected male twins. The median age at disease onset was 2.9 months, with no difference between familial and sporadic cases. Age at onset was similar in affected sibs from 10 of 14 families, but in four up to 3-year differences were observed. Hemophagocytosis was present at diagnosis in 75%. An associated infection (usually by common viral pathogens) was reported in 50 of the 122 (41%) cases, of which 25 had familial disease. Natural killer activity was impaired in 36 of 37 patients studied. Chromosome analysis was normal in all tested patients. A decreased frequency of HLA-B7 and B8 alleles and increased frequency of HLA-B21 and DQ3 were observed. The estimated 5-year survival (SE) was 21% (18.7) for all patients. It was 66% (37.8) for patients who received allogeneic bone marrow transplant and 10.1% (9.6) for patients treated with chemotherapy alone (P=0.0001). None of the previously proposed prognostic indicators (age, associated infection, cerebrospinal fluid pleocytosis, family history) correlated with treatment outcome.
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Histiocitosis de Células no Langerhans/epidemiología , Edad de Inicio , Análisis de Varianza , Distribución de Chi-Cuadrado , Preescolar , Salud de la Familia , Femenino , Antígenos HLA/análisis , Histiocitosis de Células no Langerhans/inmunología , Histiocitosis de Células no Langerhans/terapia , Humanos , Lactante , Células Asesinas Naturales/inmunología , Masculino , Pronóstico , Estudios Prospectivos , Sistema de Registros , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised adults and children, the number of which has been continuously increasing in the last decades. The purpose of our review was to provide epidemiological, clinical, and biological data and antifungal treatment options in the pediatric population. Several biological assays (galactomannan enzyme immunoassay, ß-D-glucan, detection of Aspergillus spp. DNA) have proven useful adjuncts for the diagnosis of IA in adult studies. However, data on these assays in children is limited by small sample sizes and sometimes conflicting results concerning their sensitivity/specificity. Pediatric treatment recommendations are mainly extrapolated from results of clinical trials performed in adults. It is thus necessary to develop new antifungal formulations specifically adapted to the pediatric population and to evaluate their pharmacokinetic/pharmacodynamic profile, their safety, and their effectiveness in infants and children.
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Aspergilosis , Fungemia , Adolescente , Antifúngicos/uso terapéutico , Antígenos Fúngicos/sangre , Antineoplásicos/efectos adversos , Aspergilosis/diagnóstico , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Aspergilosis/prevención & control , Aspergillus/efectos de los fármacos , Aspergillus/inmunología , Aspergillus/aislamiento & purificación , Niño , Preescolar , ADN de Hongos/sangre , Fungemia/diagnóstico , Fungemia/tratamiento farmacológico , Fungemia/epidemiología , Fungemia/prevención & control , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Lactante , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/microbiología , Guías de Práctica Clínica como Asunto , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
A boy with X-linked agammaglobulinemia experienced progressive global motor decline, cerebellar syndrome, and epilepsy. All standard polymerase chain reactions for neurotropic viruses were negative on cerebrospinal fluid and brain biopsy. Next-generation sequencing allowed fast identification of a new astrovirus strain (HAstV-VA1/HMO-C-PA), which led to tailor the patient's treatment, with encouraging clinical monitoring over 1 year.