RÉSUMÉ
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.
Sujet(s)
Alanine , Amides , Agents antiVIH , Infections à VIH , Pipérazines , Pyridones , Ténofovir , Adolescent , Adulte , Enfant , Humains , Agents antiVIH/usage thérapeutique , Association médicamenteuse , Emtricitabine/usage thérapeutique , Composés hétérocycliques 3 noyaux/usage thérapeutique , Infections à VIH/traitement médicamenteux , Études rétrospectives , Ténofovir/analogues et dérivésRÉSUMÉ
OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.
Sujet(s)
Betacoronavirus , Infections à coronavirus/diagnostic , Infections à coronavirus/mortalité , Pneumopathie virale/diagnostic , Pneumopathie virale/mortalité , Adolescent , Betacoronavirus/isolement et purification , COVID-19 , Dépistage de la COVID-19 , Enfant , Enfant d'âge préscolaire , Techniques de laboratoire clinique , Comorbidité , Infections à coronavirus/épidémiologie , Infections à coronavirus/thérapie , Évolution de la maladie , Femelle , Humains , Nourrisson , Mâle , Pandémies , Paris/épidémiologie , Pneumopathie virale/épidémiologie , Pneumopathie virale/thérapie , Pronostic , Études rétrospectives , Facteurs de risque , SARS-CoV-2 , Indice de gravité de la maladieRÉSUMÉ
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.
Sujet(s)
Agents antiVIH/usage thérapeutique , Infections à VIH/traitement médicamenteux , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Charge virale/effets des médicaments et des substances chimiques , Virémie/traitement médicamenteux , Adolescent , Afrique subsaharienne/ethnologie , Agents antiVIH/pharmacologie , Thérapie antirétrovirale hautement active , Numération des lymphocytes CD4 , Enfant , Enfant adopté , Enfant d'âge préscolaire , Résistance virale aux médicaments , Émigrants et immigrants , Femelle , France/épidémiologie , Infections à VIH/épidémiologie , Infections à VIH/virologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/isolement et purification , Humains , Nourrisson , Nouveau-né , Mâle , Facteurs socioéconomiques , Thaïlande/ethnologie , Vietnam/ethnologie , Virémie/épidémiologie , Virémie/virologieRÉSUMÉ
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.
Sujet(s)
Infections à VIH/traitement médicamenteux , Inhibiteurs de l'intégrase du VIH/administration et posologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/effets des médicaments et des substances chimiques , Composés hétérocycliques 3 noyaux/administration et posologie , Adolescent , Répartition par âge , Enfant , Enfant d'âge préscolaire , Femelle , Infections à VIH/virologie , Inhibiteurs de l'intégrase du VIH/effets indésirables , Inhibiteurs de l'intégrase du VIH/pharmacologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/génétique , Composés hétérocycliques 3 noyaux/effets indésirables , Composés hétérocycliques 3 noyaux/pharmacologie , Humains , Mâle , Adhésion au traitement médicamenteux , Oxazines , Pipérazines , Pyridones , Études rétrospectives , Résultat thérapeutique , Charge virale/effets des médicaments et des substances chimiques , Jeune adulteRÉSUMÉ
Three cases of Bacillus cereus infection or colonization occurred in the same region in France, and milk from the milk bank was suspected as a possible common source of contamination. All Batches delivered to the three cases complied with the requirements of the bacteriological reference method recommended by good practices guidelines. Still, a retrospective analysis with a more sensitive method showed one batch to contain B. cereus, however straincomparison revealed no epidemiological link betweenisolates from patients and those from the milk. Consequently, in accordance with the precautionary principle, we developed a new sensitive method for the screening of pasteurized milk for pathogenic bacteria. From January 1 to August 31, 2017, 2526 samples of pasteurized milk were prospectively included in the study. We showed that a 20 mL sample of pasteurized milk incubated for 18 h at 37 °C under aerobic conditions was favoring the detection of B. Cereus. The nonconformity rate was 6.3% for the reference method and 12.6% for the improved method (p < 0.0001). Nonconformity was due to the presence of B. cereus in 88.5% of cases for the improved method and 53% of cases for the reference method (p < 0.0001). Thus our new method is improves the microbiological safety of the product distributed and only moderately increases the rate of bacteriological nonconformity .
Sujet(s)
Bacillus cereus/isolement et purification , Contamination des aliments/prévention et contrôle , Sécurité des aliments/méthodes , Lactariums , Lait humain/microbiologie , Contamination des aliments/analyse , France , Humains , Pasteurisation , Études rétrospectivesRÉSUMÉ
Cytomegalovirus (CMV) infection is a common complication in immunocompromised patients, especially after hematopoietic stem cell or solid organ transplantation. Therapeutic antiviral options [(val)ganciclovir, foscarnet, cidofovir] are still limited and can expose to severe toxicities. Moreover, prolonged antiviral drug exposure and ongoing viral replication are key factors in the development of antiviral drug resistance. After many years of few tangible advances in terms of new antiviral drugs, we are now experiencing an exciting period characterized by a series of phase III clinical trials incorporating three novel agents: maribavir, brincidofovir, and letermovir. This article summarizes the current state of the prevention and treatment of CMV infections as well as data of investigational drugs in clinical development.
Sujet(s)
Acétates/usage thérapeutique , Antiviraux/usage thérapeutique , Benzimidazoles/usage thérapeutique , Infections à cytomégalovirus/traitement médicamenteux , Cytosine/analogues et dérivés , Phosphonates/usage thérapeutique , Quinazolines/usage thérapeutique , Ribonucléosides/usage thérapeutique , Cytosine/usage thérapeutique , Ganciclovir/usage thérapeutique , HumainsRÉSUMÉ
Vaccination is an effective strategy to decrease infections in transplant recipients. Children after intestinal transplantation carry a high risk of infection due to increased immunosuppression. In a series of 22 children after intestinal transplantation, we studied the vaccination schedules and the antibodies against vaccine-preventable diseases before transplantation, and at one and five yr after transplantation. We reviewed whether the vaccination schedules were complete, and we analysed the factors that may influence serological immunity and the incidence of disease in patients with deficient immunity. All patients completed the recommended vaccination schedules for DTaP-IPV and HBV. After transplantation, the negative antibodies against vaccine-preventable diseases were mostly related to an antirejection therapy: for DTaP-IPV: four of four patients with no antibody had been treated for rejection, for HBV: two of five, HAV: three of four, MMR: three of seven, and VZV: three of four. A post-transplantation varicella infection was followed by acute rejection, with probability for a relationship between both events. We observed 50% of varicella cases in unvaccinated children, highlighting the importance of pretransplant vaccination. Waning immunogenicity mediated by antibodies against vaccine-preventable disease after transplantation indicated a need for boosters. The recommendations should be regularly enforced, as the reliance on routine immunizations schedules is not adequate in immunocompromised patients.
Sujet(s)
Maladies intestinales/complications , Maladies intestinales/chirurgie , Intestins/transplantation , Transplantation/méthodes , Vaccination , Varicelle/prévention et contrôle , Enfant , Enfant d'âge préscolaire , Diphtérie/prévention et contrôle , Vaccin diphtérie-tétanos-coqueluche/administration et posologie , Femelle , Survie du greffon , Hépatite A/prévention et contrôle , Hépatite B/prévention et contrôle , Humains , Calendrier vaccinal , Sujet immunodéprimé , Immunosuppression thérapeutique/effets indésirables , Immunosuppresseurs/usage thérapeutique , Mâle , Rougeole/prévention et contrôle , Oreillons/prévention et contrôle , Poliomyélite/prévention et contrôle , Vaccin antipoliomyélitique inactivé/administration et posologie , Rubéole/prévention et contrôle , Tétanos/prévention et contrôle , Résultat thérapeutique , Coqueluche/prévention et contrôleRÉSUMÉ
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.
Sujet(s)
Aspergillose , Fongémie , Adolescent , Antifongiques/usage thérapeutique , Antigènes fongiques/sang , Antinéoplasiques/effets indésirables , Aspergillose/diagnostic , Aspergillose/traitement médicamenteux , Aspergillose/épidémiologie , Aspergillose/prévention et contrôle , Aspergillus/effets des médicaments et des substances chimiques , Aspergillus/immunologie , Aspergillus/isolement et purification , Enfant , Enfant d'âge préscolaire , ADN fongique/sang , Fongémie/diagnostic , Fongémie/traitement médicamenteux , Fongémie/épidémiologie , Fongémie/prévention et contrôle , Humains , Sujet immunodéprimé , Immunosuppresseurs/effets indésirables , Nourrisson , Tumeurs/complications , Tumeurs/traitement médicamenteux , Complications postopératoires/traitement médicamenteux , Complications postopératoires/microbiologie , Guides de bonnes pratiques cliniques comme sujet , Pronostic , Essais contrôlés randomisés comme sujet , Facteurs de risqueRÉSUMÉ
BACKGROUND: Human deficiency virus (HIV) protease inhibitors (PIs) are widely used drugs whose effects are pharmacologically enhanced by ritonavir, a potent cytochrome P450 inhibitor. We reported previously that prophylactic postnatal ritonavir-PI therapy in HIV-exposed neonates was associated with increases in plasma 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone sulfate (DHEA-S). AIMS: To further investigate adrenal function in neonates and adolescents given ritonavir-PI. METHODS: Adrenal function was assessed prospectively in 3 HIV-exposed neonates given short-term prophylactic treatment and 3 HIV-infected adolescents given long-term treatment. Plasma cortisol, 17-OHP, 17-OH-pregnenolone, DHEA-S, and androstenedione were measured before and after ACTH administration. RESULTS: None of the patients had clinical signs of adrenal dysfunction. The only neonate exposed to ritonavir-PI in utero had up to 3-fold increases in plasma 17-OHP. Increases in 17-OH-pregnenolone of up to 3.1-fold were noted in 4 of the 6 patients, and all 6 patients had elevations in DHEA-S (up to 20.4-fold increase) and/or DHEA (up to 4.7-fold) and/or androstenedione (up to 5.2-fold). All these parameters improved after treatment completion. CONCLUSION: Neonates and adolescents given ritonavir-PI exhibit a similar adrenal dysfunction profile consistent with an impact on multiple adrenal enzymes. These abnormalities require evaluation, given the potentially long exposure times.
Sujet(s)
Glandes surrénales/effets des médicaments et des substances chimiques , Agents antiVIH/pharmacologie , Infections à VIH/traitement médicamenteux , Inhibiteurs de protéases/pharmacologie , Ritonavir/pharmacologie , 17alpha-Hydroxypregnénolone/sang , 17alpha-Hydroxyprogestérone/sang , Adolescent , Glandes surrénales/physiopathologie , Agents antiVIH/usage thérapeutique , Déhydroépiandrostérone/sang , Sulfate de déhydroépiandrostérone/sang , Femelle , Infections à VIH/sang , Infections à VIH/physiopathologie , Humains , Hydrocortisone/sang , Nouveau-né , Mâle , Inhibiteurs de protéases/usage thérapeutique , Ritonavir/usage thérapeutique , Jeune adulteRÉSUMÉ
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.
Sujet(s)
Transplantation de cellules souches hématopoïétiques/effets indésirables , Transplantation de cellules souches hématopoïétiques/normes , Anticorps de l'hépatite B/immunologie , Virus de l'hépatite B/immunologie , Donneurs de tissus/statistiques et données numériques , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Nourrisson , Mâle , Études rétrospectives , Virémie/sangRÉSUMÉ
Nocardiosis is a rare opportunistic infection caused by Nocardia spp., an aerobic actinomycete, that mainly affects patients with cell-mediated immunity defects, such as transplant recipients. Despite recent progress regarding Nocardia identification and changes in taxonomic assignment, many challenges remain for the diagnosis or management of nocardiosis. This opportunistic infection affects 0.04 to 3.5 % of patients with solid organ or hematopoietic stem cell transplantation, depending on the organ transplanted, cytomegalovirus (CMV) infection, corticosteroids dose and calcineurin inhibitors level. Nocardiosis diagnosis relies on appropriate clinical, radiological and microbiological workup that includes the sampling of an accessible involved site and molecular microbiology tools. In parallel, extensive clinical and radiological evaluations are mandatory, including brain imaging, even in the absence of neurological signs. In transplanted patients, differential diagnosis is challenging, with co-infections reported in 20 to 64 % of cases. As the antibiotic susceptibility pattern varies among species, the antimicrobial regimen before species identification should rely on the association of antibiotics active on all species of Nocardia. Bactericidal antibiotics are required in cases of severe or disseminated disease. Furthermore, in transplant recipients, combination therapy is difficult to manage because of cumulative toxicity and interactions with immunosuppressive agents. Because of a high recurrence rate, antibiotic therapy should be prescribed for 6 to 12 months.
Sujet(s)
Infections à Nocardia/épidémiologie , Nocardia/isolement et purification , Receveurs de transplantation , Transplantation/effets indésirables , Antibactériens/usage thérapeutique , Humains , Sujet immunodéprimé , Infections à Nocardia/diagnostic , Infections à Nocardia/traitement médicamenteuxRÉSUMÉ
During 2003-2010, 555 strains isolated from sexually-infected patients at the time of primary HIV-1 infection (PHI) were characterized. Tree topology revealed that 11.7% of PHIs segregated into transmission clusters. CXCR4-usage was identified in 27 strains (4.9%) and was significantly associated with subtype B (p 0.003) and low CD4 cell count (p 0.01). In clustered and unique PHIs, the prevalence of CXCR4-tropic strains was 1.5% and 5.3%, respectively (p 0.35). Our results are in line with the hypothesis of a mucosal bottleneck contributing to the high prevalence of CCR5 variants during PHI.
Sujet(s)
Infections à VIH/transmission , Infections à VIH/virologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/physiologie , Récepteurs CXCR4/métabolisme , Récepteur VIH/métabolisme , Tropisme viral , Adolescent , Adulte , Sujet âgé , Analyse de regroupements , Femelle , Infections à VIH/épidémiologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/classification , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/isolement et purification , Humains , Mâle , Adulte d'âge moyen , Prévalence , Jeune adulteRÉSUMÉ
Described for the first time in 1971, Schimke immuno-osseous dysplasia (SIOD) is an autosomal-recessive multisystem disorder that is caused by bi-allelic mutations of SMARCAL1, which encodes a DNA annealing helicase. To define better the dental anomalies of SIOD, we reviewed the records from SIOD patients with identified bi-allelic SMARCAL1 mutations, and we found that 66.0% had microdontia, hypodontia, or malformed deciduous and permanent molars. Immunohistochemical analyses showed expression of SMARCAL1 in all developing teeth, raising the possibility that the malformations are cell-autonomous consequences of SMARCAL1 deficiency. We also found that stimulation of cultured skin fibroblasts from SIOD patients with the tooth morphogens WNT3A, BMP4, and TGFß1 identified altered transcriptional responses, raising the hypothesis that the dental malformations arise in part from altered responses to developmental morphogens. To the best of our knowledge, this is the first systematic study of the dental anomalies associated with SIOD.
Sujet(s)
Artériosclérose/complications , Déficits immunitaires/complications , Syndrome néphrotique/complications , Ostéochondrodysplasies/complications , Embolie pulmonaire/complications , Malformations dentaires/étiologie , Allèles , Anodontie/étiologie , Artériosclérose/génétique , Prémolaire/malformations , Protéine morphogénétique osseuse de type 4/analyse , Techniques de culture cellulaire , Prolifération cellulaire , Survie cellulaire , Cellules cultivées , Helicase/analyse , Helicase/génétique , Fibroblastes/anatomopathologie , Humains , Déficits immunitaires/génétique , Molaire/malformations , Mutation/génétique , Syndrome néphrotique/génétique , Odontogenèse/génétique , Ostéochondrodysplasies/génétique , Maladies d'immunodéficience primaire , Embolie pulmonaire/génétique , Peau/cytologie , Germe dentaire/anatomopathologie , Racine dentaire/malformations , Dent de lait/malformations , Transcription génétique/génétique , Facteur de croissance transformant bêta-1/analyse , Protéine Wnt3A/analyseRÉSUMÉ
Chronic granulomatous disease (GCD) is characterized by severe infections, notably with Burkholderia cepacia complex (BCC). GCD is rarely complicated by lymphohistiocytic activation syndromes, most often secondary to bacterial or viral infections, in particular human herpes virus 6 (HHV-6). We describe the case of a 10-month-old boy who suffered from multiple organ failure due to a BCC infection and a lymphohistiocytic activation syndrome, leading to diagnosis of GCD. The initial search for HHV-6 was positive and the infection was treated, but the progression and viral sample analysis led to the chromosomal integration of the HHV-6 genome. The child's clinical condition was normal after bone marrow transplantation. This case describes a rare association between GCD and lymphohistiocytic activation syndrome and raises questions about the role played by chromosomal integration of the HHV-6 genome.
Sujet(s)
Infections à Burkholderia/complications , Burkholderia cepacia , ADN viral/génétique , Exanthème subit/complications , Exanthème subit/virologie , Granulomatose septique chronique/complications , Granulomatose septique chronique/diagnostic , Herpèsvirus humain de type 6/génétique , Histiocytose/complications , Intégration virale , Humains , Nourrisson , Mâle , SyndromeRÉSUMÉ
Medulloblastoma patients treated at the Institute Curie between 1980 and 2000 were reviewed. Only patients whose primary treatment included craniospinal radiation were considered. Surviving patients were identified and evaluated by means of self-report questionnaires using the Health Utility Index (HUI). Psychosocial functioning, employment, and other health-related indicators were recorded. Seventy-three patients were treated during the study period. At a median follow-up from diagnosis of 14.4 years, 49 patients were alive and 45 surviving patients could be contacted. Late sequelae were frequent, particularly neurological deficits (71%) and endocrine complications (52%). Impairments of psychosocial functioning, including employment, driving capacity, independent living, and marital status, were identified in most patients. Most long-term medulloblastoma survivors suffer persistent deficits in several domains, with a significant impact on their psychosocial functioning. These findings reinforce the importance of early intervention programs for all survivors in order to reduce the psychosocial impacts of their disease.
Sujet(s)
Tumeurs du cervelet/radiothérapie , Irradiation crânienne , Médulloblastome/radiothérapie , Qualité de vie , Tumeurs de la moelle épinière/radiothérapie , Adolescent , Tumeurs du cervelet/mortalité , Tumeurs du cervelet/psychologie , Enfant , Enfant d'âge préscolaire , Femelle , Études de suivi , État de santé , Humains , Nourrisson , Mâle , Médulloblastome/mortalité , Médulloblastome/psychologie , Pronostic , Tumeurs de la moelle épinière/mortalité , Tumeurs de la moelle épinière/psychologie , Enquêtes et questionnaires , Taux de survie , Survivants , Résultat thérapeutiqueRÉSUMÉ
Steroid sensitive idiopathic nephrotic syndrome is a T-cell disorder characterized by a functional renal impairment. Concluding a still relevant demonstration involving cellular immunity in the pathogenesis of the disease, R. Shalhoub in 1974 suggested a "special role for the thymus" based on the efficiency of steroids and alkylating agents, dramatic recoveries following measles, sensibility to bacterial infection due to a lack of cooperation between T and B cell and association to Hodgkin disease. As a matter of fact, the selected drugs based on medical empirism somehow enhance thymocytes apoptosis and negative selection of T cell, except cyclosporin. Steroids have been the first historical treatment of idiopathic nephrotic syndrome and have steadily been the first-line treatment for 50 years. Their unavoidable ability to induce rapid recovery of proteinuria and long-lasting or definite remission are dependent to a strict compliance to treatment. Indications of steroids-sparing treatments are not that clearcut in patients with steroids intoxication. Objectively, efficiency of levamisole and cyclophosphamide are much more limited than previously reported and cyclosporin nephrotoxicity might severely impair renal function following long-lasting treatment as well as it may paradoxically increase the activity of the disease. An alternate strategy to those currently adopted would use cyclosporin as the first-line steroids-sparing treatment during a very limited period, awaiting favourable ageing of patients and natural dampening activity of the disease to a full efficiency of alkylating agents. Compared to cyclophosphamide and cyclosporin, the relative safety of levamisole is encouraging to a more frequent uses. Its association to a full dose of prednisone in the treatment of the inaugural episode should be investigated. According to the limitations of those therapies, emerging drugs as mycophenolate might be worthwhile in the treatment of nephrotic patients.