26 results on '"M. Bendavid"'
Search Results
2. Population Pharmacokinetics of Intravenous and Oral Acyclovir and Oral Valacyclovir in Pediatric Population To Optimize Dosing Regimens
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Coralie Briand, S Winter, M. Bendavid, Zeynep Demir, Carmen Capito, Mehdi Oualha, Naïm Bouazza, Sana Boujaafar, S Abdalla, Sihem Benaboud, Yi Zheng, Frantz Foissac, Agathe Béranger, Déborah Hirt, Inès Gana, and J-M Tréluyer
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viruses ,Acyclovir ,Administration, Oral ,Renal function ,Population pharmacokinetics ,Pharmacology ,medicine.disease_cause ,Antiviral Agents ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Humans ,Medicine ,Pharmacology (medical) ,Dosing ,Child ,0303 health sciences ,medicine.diagnostic_test ,030306 microbiology ,business.industry ,virus diseases ,Valine ,Liter ,Prodrug ,Infectious Diseases ,Herpes simplex virus ,Therapeutic drug monitoring ,Valacyclovir ,business - Abstract
Acyclovir is an antiviral currently used for the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. This study aimed to characterize the pharmacokinetics (PK) of acyclovir and its oral prodrug valacyclovir to optimize dosing in children. Children receiving acyclovir or valacyclovir were included in this study. PK were described using nonlinear mixed-effect modeling. Dosing simulations were used to obtain trough concentrations above a 50% inhibitory concentration for HSV or VZV (0.56 mg/liter and 1.125 mg/liter, respectively) and maximal peak concentrations below 25 mg/liter. A total of 79 children (212 concentration-time observations) were included: 50 were taking intravenous (i.v.) acyclovir, 22 were taking oral acyclovir, and 7 were taking both i.v. and oral acyclovir, 57 for preventive and 22 for curative purposes. A one-compartment model with first-order elimination best described the data. An allometric model was used to describe body weight effect, and the estimated glomerular filtration rate (eGFR) was significantly associated with acyclovir elimination. To obtain target maximal and trough concentrations, the more suitable initial acyclovir i.v. dose was 10 mg/kg of body weight/6 h for children with normal renal function (eGFR ≤ 250 ml/min/1.73 m(2)) and 15 to 20 mg/kg/6 h for children with augmented renal clearance (ARC) (eGFR > 250 ml/min/1.73 m(2)). The 20-mg/kg/8 h dose for oral acyclovir and valacyclovir produced effective concentrations in more than 75% of children; however, a 15-mg/kg/6 h dose, if possible, is preferred. These doses should be prospectively confirmed, and therapeutic drug monitoring could be used to refine them individually. (This study has been registered at ClinicalTrials.gov under identifier NCT02539407.)
- Published
- 2020
3. Severe and fatal forms of COVID-19 in children
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Mehdi Oualha, Elodie Salvador, M. Vedrenne, L. de Saint Blanquat, L. Dupic, F. Lesage, C. Heilbronner, Alice Corsia, David Drummond, Florence Moulin, C. de Marcellus, M. Bendavid, G. Chéron, Y. Pinhas, Marion Grimaud, Romain Berthaud, Judith Chareyre, François Angoulvant, Jacques Fourgeaud, Laureline Berteloot, Sylvain Renolleau, Julie Toubiana, Pierre Frange, M. Castelle, Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)
- Subjects
Male ,Paris ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Coronavirus disease 2019 (COVID-19) ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Pneumonia, Viral ,coronavirus ,India ,Comorbidity ,Disease ,Severity of Illness Index ,Article ,Betacoronavirus ,03 medical and health sciences ,COVID-19 Testing ,0302 clinical medicine ,Risk Factors ,030225 pediatrics ,medicine ,Extracorporeal membrane oxygenation ,Humans ,Pediatrics, Perinatology, and Child Health ,030212 general & internal medicine ,Renal replacement therapy ,Disease management (health) ,Child ,Pandemics ,Demography ,Retrospective Studies ,Mechanical ventilation ,Past medical history ,Clinical Laboratory Techniques ,SARS-CoV-2 ,business.industry ,COVID-19 ,Infant ,Prognosis ,3. Good health ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Disease Progression ,Female ,Observational study ,Coronavirus Infections ,business ,Scientific Letter - Abstract
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.
- Published
- 2020
4. Réforme de la maquette du diplôme d’études spécialisées de pédiatrie : vision des juniors
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B. Girard, H. Foucambert, M. Bendavid, M. Bacquet, A. Morand, and M.-C. Ploton
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03 medical and health sciences ,Medical education ,0302 clinical medicine ,030225 pediatrics ,Political science ,Pediatrics, Perinatology and Child Health ,MEDLINE ,030212 general & internal medicine - Published
- 2016
5. [Teaching pediatrics to residents via conventional lectures in France: A national survey from students]
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B, Girard, M, Bendavid, J-C, Faivre, J, Salleron, T, Debillon, O, Claris, B, Chabrol, C, Schweitzer, and V, Gajdos
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Adult ,Cross-Sectional Studies ,Surveys and Questionnaires ,Teaching ,Humans ,Internship and Residency ,Curriculum ,France ,Personal Satisfaction ,Child ,Pediatrics ,Retrospective Studies - Abstract
To assess the point of view of young physicians training in pediatrics in France on their theoretical courses during residency.A free-access electronic anonymous survey was sent three times by e-mail to the 1215 residents in pediatrics, from July to October 2015.Fifty-seven percent of French residents in pediatrics responded to the survey. It was established that they took part in six (range, 3-10) half-days of specific theoretical teaching in pediatrics from November 2014 to mid-April 2015. Only 54% participated in more than 75% of regional theoretical training. The main self-declared reason for their absence was that they could not leave their clinical activities. Fifty-three per cent of the residents took part in additional training, 45% of them because they found the primary theoretical training insufficient. The overall quality of the theoretical teaching was rated 5 (range, 3-7) out of 10. Eighty-five percent of residents expected to be evaluated on their knowledge during their residency.In pediatrics, additional training is individually undertaken because they deemed their initial training insufficient during their residency. An evaluation of knowledge is requested by residents. The reform of the national residency program must take into account these results in redesigning the theoretical training in pediatrics, integrating innovative teaching techniques to daily practice, for example.
- Published
- 2017
6. [Reform of the model of specialized pediatric diploma: Vision of the juniors]
- Author
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M, Bacquet, M, Bendavid, H, Foucambert, B, Girard, A, Morand, and M-C, Ploton
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Education, Medical, Graduate ,Humans ,France ,Pediatrics - Published
- 2016
7. Nirsevimab and Hospitalization for RSV Bronchiolitis.
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Assad Z, Romain AS, Aupiais C, Shum M, Schrimpf C, Lorrot M, Corvol H, Prevost B, Ferrandiz C, Giolito A, Valtuille Z, Bendavid M, Cohen JF, Toubiana J, de Pontual L, Delande CF, Levy M, See P, Cohen R, Levy C, Angoulvant F, Lenglart L, Gits-Muselli M, Biran V, Diallo K, Alemede O, El Hebil MM, Durrmeyer X, Labouret G, Casanovas N, Hallak B, Maréchal O, Jung C, Bréhin C, and Ouldali N
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- Female, Humans, Infant, Infant, Newborn, Male, Case-Control Studies, Hospitalization statistics & numerical data, Logistic Models, Prospective Studies, Respiratory Syncytial Virus, Human, Respiration, Artificial, Antibodies, Monoclonal, Humanized therapeutic use, Antiviral Agents therapeutic use, Bronchiolitis, Viral drug therapy, Bronchiolitis, Viral etiology, Bronchiolitis, Viral therapy, Bronchiolitis, Viral virology, Respiratory Syncytial Virus Infections complications, Respiratory Syncytial Virus Infections drug therapy, Respiratory Syncytial Virus Infections therapy
- Abstract
Background: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear., Methods: We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed., Results: The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%])., Conclusions: In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.)., (Copyright © 2024 Massachusetts Medical Society.)
- Published
- 2024
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8. Pharmacokinetic of ceftazidime-avibactam in a critically ill patient under high-volume continuous venovenous haemodiafiltration: A first paediatric case report.
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Collignon C, Benaboud S, Gana I, Bendavid M, Fournier B, Oualha M, and de Marcellus C
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- Adult, Humans, Female, Child, Infant, Ceftazidime pharmacokinetics, Anti-Bacterial Agents, Critical Illness therapy, Drug Combinations, Microbial Sensitivity Tests, Continuous Renal Replacement Therapy, Sepsis drug therapy, Azabicyclo Compounds
- Abstract
Ceftazidime-avibactam is a novel cephalosporin/B-lactamase inhibitor developed in the context of increasing resistance. This case reports the pharmacokinetics of ceftazidime-avibactam in a critically ill child under continuous renal replacement (CRRT) therapy for fluid overload. The patient was a 6-month-old female with sepsis due to bloodstream infection to Stenotrophomonas maltophilia following stem cell transplantation for severe combined immunodeficiency. CRRT was started on Day 2. Concentrations have been monitored using liquid chromatography-tandem mass spectrometry. Treatment was given every 8 h with a 2 h infusion of 30-7,5 mg/kg and did not reach pharmacokinetic/pharmacodynamic targets. Total clearance was respectively 1.7 and 3.02 L/h, with CRRT clearance respectively 28.8%-60% for ceftazidime and 14%-33% for avibactam. Those clearances are higher than reported in adult literature leading to a risk of treatment failure and emerging resistance. This supports the benefit of monitoring antimicrobial therapy under CRRT and the necessity to assess higher dosing or continuous infusion of ceftazidime-avibactam., (© 2024 British Pharmacological Society.)
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- 2024
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9. Severe and fatal neonatal infections linked to a new variant of echovirus 11, France, July 2022 to April 2023.
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Grapin M, Mirand A, Pinquier D, Basset A, Bendavid M, Bisseux M, Jeannoël M, Kireche B, Kossorotoff M, L'Honneur AS, Robin L, Ville Y, Renolleau S, Lemee V, Jarreau PH, Desguerre I, Lacaille F, Leruez-Ville M, Guillaume C, Henquell C, Lapillonne A, Schuffenecker I, and Aubart M
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- Infant, Newborn, Humans, Male, Female, Enterovirus B, Human genetics, France epidemiology, Echovirus Infections diagnosis, Echovirus Infections epidemiology, Enterovirus Infections diagnosis, Enterovirus Infections epidemiology, Enterovirus, Communicable Diseases
- Abstract
We report nine severe neonatal infections caused by a new variant of echovirus 11. All were male, eight were twins. At illness onset, they were 3-5 days-old and had severe sepsis and liver failure. This new variant, detected in France since April 2022, is still circulating and has caused more fatal neonatal enterovirus infections in 2022 and 2023 (8/496; 1.6%, seven associated with echovirus 11) compared with 2016 to 2021 (7/1,774; 0.4%). National and international alerts are warranted.
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- 2023
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10. A new step in understanding stem cell mobilization in patients with Fanconi anemia: A bridge to gene therapy.
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Diana JS, Manceau S, Leblanc T, Magnani A, Magrin E, Bendavid M, Couzin C, Joseph L, Soulier J, Cavazzana M, and Lefrère F
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- Antigens, CD34 metabolism, Genetic Therapy methods, Granulocyte Colony-Stimulating Factor, Hematopoietic Stem Cell Mobilization methods, Humans, Fanconi Anemia chemically induced, Fanconi Anemia genetics, Fanconi Anemia therapy, Hematopoietic Stem Cell Transplantation methods, Heterocyclic Compounds
- Abstract
Background: Fanconi anemia (FA) is an inherited disorder characterized clinically by congenital abnormalities, progressive bone marrow failure (BMF), and a predisposition to malignancy. Gene therapy (GT) of FA, via the infusion of gene-corrected peripheral blood (PB) autologous hematopoietic stem cells (HSCs), may constitute a cure for BMF. GT bypasses the donor restrictions and adverse events associated with allogenic HSC transplantation. However, adequate harvesting of PB-HSCs is a crucial determinant of successful engraftment in gene therapy. Harvesting the low numbers of HSCs in patients with FA is particularly challenging., Study Design and Methods: This open-label phase I/II trial evaluates the feasibility and safety of co-administration of G-CSF and plerixafor in patients with FA for the mobilization and harvesting of peripheral HSCs, intending to use them in a gene therapy trial. Patients with mutations in the FANCA gene received two subcutaneous injections of G-CSF (6 μg/kg × 2/d from D1 to D8. Plerixafor (0.24 mg/kg/d) was administered 2 h before apheresis (from D5 onward)., Results: CD34
+ cells were mobilized for four patients quickly but transiently after the plerixafor injection. One patient had a CD34+ cell count of over 100/μl; the mobilization peaked 2 h after the injection and lasted for more than 9 h. There were no short-term adverse events associated with the mobilization or harvesting procedures., Conclusion: Our data in patients with FA show that the mobilization of HSCs with G-CSF and plerixafor is safe and more efficient in younger individuals without BMF., (© 2021 AABB.)- Published
- 2022
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11. Sustained remission after haploidentical bone marrow transplantation in a child with refractory systemic juvenile idiopathic arthritis.
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Morelle G, Castelle M, Pinto G, Breton S, Bendavid M, Boussard C, Mouy R, Bader-Meunier B, Semeraro M, Faye A, Cavazzana M, Neven B, Blanche S, Quartier P, and Moshous D
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- Female, Humans, Infant, Remission Induction, Arthritis, Juvenile surgery, Bone Marrow Transplantation methods
- Abstract
Background: Some patients with systemic juvenile idiopathic arthritis (SJIA) and severe, refractory disease achieved remission through intensive immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (HSCT). However, disease relapsed in most cases. More recently selected SJIA patients received allogenic HSCT from a HLA-identical sibling or a HLA matched unrelated donor. While most transplanted patients achieved sustained SJIA remission off-treatment, the procedure-related morbidity was high., Case Report: A girl presented SJIA with a severe disease course since the age of 15 months. She was refractory to the combination of methotrexate and steroids to anti-interleukin (IL)-1, then anti-IL-6, tumor necrosis factor alpha inhibitors, and thalidomide. Given the high disease burden and important treatment-related toxicity the indication for a haploidentical HSCT from her mother was validated, as no HLA matched donor was available. The patient received a T replete bone marrow graft at the age of 3.7 years. Conditioning regimen contained Rituximab, Alemtuzumab, Busulfan, and Fludarabine. Cyclophosphamide at D + 3 and + 4 post HSCT was used for graft-versus-host-disease prophylaxis, followed by Cyclosporin A and Mycophenolate Mofetil. Post HSCT complications included severe infections, grade 3 intestinal graft-versus-host-disease, autoimmune thyroiditis, and immune thrombocytopenia. Three years after HSCT, the child is alive and well, notwithstanding persistent hypothyroidy requiring substitution. Immune thrombocytopenia had resolved. Most importantly, SJIA was in complete remission, off immunosuppressive drugs., Conclusion: Allogenic HSCT may be a therapeutic option, even with a HLA haplo-identical alternative donor, in patients with inflammatory diseases such as SJIA. Despite increased experience with this treatment, the risk of life-threatening complications restrains its indication to selected patients with severe, refractory disease.
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- 2021
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12. Population Pharmacokinetics of Intravenous Ganciclovir and Oral Valganciclovir in a Pediatric Population To Optimize Dosing Regimens.
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Nguyen T, Oualha M, Briand C, Bendavid M, Béranger A, Benaboud S, Tréluyer JM, Zheng Y, Foissac F, Winter S, Gana I, Boujaafar S, Lopez V, Berthaud R, Demir Z, Bouazza N, and Hirt D
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- Administration, Oral, Antiviral Agents therapeutic use, Child, Humans, Valganciclovir therapeutic use, Cytomegalovirus Infections drug therapy, Ganciclovir therapeutic use
- Abstract
Ganciclovir is indicated for curative or preventive treatment of cytomegalovirus (CMV) infections. This study aimed to characterize ganciclovir pharmacokinetics, following intravenous ganciclovir and oral valganciclovir administration, to optimize dosing schemes. All children aged <18 years receiving ganciclovir or valganciclovir were included in this study. Pharmacokinetics were described using nonlinear mixed-effect modeling. Monte Carlo simulations were used to optimize the dosing regimen to maintain the area under the concentration-time curve (AUC) in the preventive or therapeutic target. Among the 105 children (374 concentration-time observations) included, 78 received intravenous (i.v.) ganciclovir, 19 received oral valganciclovir, and 6 received both drugs. A two-compartment model with first-order absorption for valganciclovir and first-order elimination best described the data. An allometric model was used to describe the bodyweight (BW) effect. Estimated glomerular filtration rate (eGFR) and medical status of critically ill children were significantly associated with ganciclovir elimination. Recommended doses were adapted for prophylactic treatment. To obtain a therapeutic exposure, doses should be increased to 40 mg/kg of body weight/day oral or 15 to 20 mg/kg/day i.v. in children with normal eGFR and to 56 mg/kg/day oral or 20 to 25 mg/kg/day i.v. in children with augmented eGFR. These doses should be prospectively confirmed, and therapeutic drug monitoring could be used to refine them individually. (This study has been registered at ClinicalTrials.gov under identifier NCT02539407.)., (Copyright © 2021 American Society for Microbiology.)
- Published
- 2021
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13. Population Pharmacokinetics of Intravenous and Oral Acyclovir and Oral Valacyclovir in Pediatric Population To Optimize Dosing Regimens.
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Abdalla S, Briand C, Oualha M, Bendavid M, Béranger A, Benaboud S, Tréluyer JM, Zheng Y, Capito C, Demir Z, Foissac F, Winter S, Gana I, Boujaafar S, Bouazza N, and Hirt D
- Subjects
- Administration, Oral, Antiviral Agents, Child, Humans, Valacyclovir, Acyclovir, Valine
- Abstract
Acyclovir is an antiviral currently used for the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. This study aimed to characterize the pharmacokinetics (PK) of acyclovir and its oral prodrug valacyclovir to optimize dosing in children. Children receiving acyclovir or valacyclovir were included in this study. PK were described using nonlinear mixed-effect modeling. Dosing simulations were used to obtain trough concentrations above a 50% inhibitory concentration for HSV or VZV (0.56 mg/liter and 1.125 mg/liter, respectively) and maximal peak concentrations below 25 mg/liter. A total of 79 children (212 concentration-time observations) were included: 50 were taking intravenous (i.v.) acyclovir, 22 were taking oral acyclovir, and 7 were taking both i.v. and oral acyclovir, 57 for preventive and 22 for curative purposes. A one-compartment model with first-order elimination best described the data. An allometric model was used to describe body weight effect, and the estimated glomerular filtration rate (eGFR) was significantly associated with acyclovir elimination. To obtain target maximal and trough concentrations, the more suitable initial acyclovir i.v. dose was 10 mg/kg of body weight/6 h for children with normal renal function (eGFR ≤ 250 ml/min/1.73 m
2 ) and 15 to 20 mg/kg/6 h for children with augmented renal clearance (ARC) (eGFR > 250 ml/min/1.73 m2 ). The 20-mg/kg/8 h dose for oral acyclovir and valacyclovir produced effective concentrations in more than 75% of children; however, a 15-mg/kg/6 h dose, if possible, is preferred. These doses should be prospectively confirmed, and therapeutic drug monitoring could be used to refine them individually. (This study has been registered at ClinicalTrials.gov under identifier NCT02539407.)., (Copyright © 2020 American Society for Microbiology.)- Published
- 2020
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14. Severe and fatal forms of COVID-19 in children.
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Oualha M, Bendavid M, Berteloot L, Corsia A, Lesage F, Vedrenne M, Salvador E, Grimaud M, Chareyre J, de Marcellus C, Dupic L, de Saint Blanquat L, Heilbronner C, Drummond D, Castelle M, Berthaud R, Angoulvant F, Toubiana J, Pinhas Y, Frange P, Chéron G, Fourgeaud J, Moulin F, and Renolleau S
- Subjects
- Adolescent, COVID-19, COVID-19 Testing, Child, Child, Preschool, Clinical Laboratory Techniques, Comorbidity, Coronavirus Infections epidemiology, Coronavirus Infections therapy, Disease Progression, Female, Humans, Infant, Male, Pandemics, Paris epidemiology, Pneumonia, Viral epidemiology, Pneumonia, Viral therapy, Prognosis, Retrospective Studies, Risk Factors, SARS-CoV-2, Severity of Illness Index, Betacoronavirus isolation & purification, Coronavirus Infections diagnosis, Coronavirus Infections mortality, Pneumonia, Viral diagnosis, Pneumonia, Viral mortality
- Abstract
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., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2020
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15. Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children.
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Grimaud M, Starck J, Levy M, Marais C, Chareyre J, Khraiche D, Leruez-Ville M, Quartier P, Léger PL, Geslain G, Semaan N, Moulin F, Bendavid M, Jean S, Poncelet G, Renolleau S, and Oualha M
- Abstract
Background: A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020., Results: 20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25-55); troponin, 269 ng/mL (31-4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1-10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge., Conclusions: Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.
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- 2020
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16. Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide for Primary Immunodeficiencies and Inherited Disorders in Children.
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Neven B, Diana JS, Castelle M, Magnani A, Rosain J, Touzot F, Moreira B, Fremond ML, Briand C, Bendavid M, Levy R, Morelle G, Vincent M, Magrin E, Bourget P, Chatenoud L, Picard C, Fischer A, Moshous D, and Blanche S
- Subjects
- Adolescent, Autoimmune Diseases epidemiology, Autoimmune Diseases prevention & control, Child, Child, Preschool, Female, Genetic Diseases, Inborn epidemiology, Graft vs Host Disease epidemiology, Graft vs Host Disease prevention & control, Humans, Infant, Male, Primary Immunodeficiency Diseases epidemiology, Tissue Donors, Cyclophosphamide administration & dosage, Genetic Diseases, Inborn therapy, Hematopoietic Stem Cell Transplantation, Primary Immunodeficiency Diseases therapy, Transplantation Conditioning
- Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for some inherited disorders, including selected primary immunodeficiencies (PIDs). In the absence of a well-matched donor, HSCT from a haploidentical family donor (HIFD) may be considered. In adult recipients high-dose post-transplant cyclophosphamide (PTCY) is increasingly used to mitigate the risks of graft failure and graft-versus-host disease (GVHD). However, data on the use of PTCY in children (and especially those with inherited disorders) are scarce. We reviewed the outcomes of 27 children transplanted with an HIFD and PTCY for a PID (n = 22) or osteopetrosis (n = 5) in a single center. The median age was 1.5 years (range, .2 to 17). HSCT with PTCY was a primary procedure (n = 21) or a rescue procedure after graft failure (n = 6). The conditioning regimen was myeloablative in most primary HSCTs and nonmyeloablative in rescue procedures. After a median follow-up of 25.6 months, 24 of 27 patients had engrafted. Twenty-one patients are alive and have been cured of the underlying disease. The 2-year overall survival rate was 77.7%. The cumulative incidences of acute GVHD grade ≥ II, chronic GVHD, and autoimmune disease were 45.8%, 24.2%, and 29.6%, respectively. There were 2 cases of grade III acute GVHD and no extensive cGVHD. The cumulative incidences of blood viral replication and life-threatening viral events were 58% and 15.6%, respectively. There was evidence of early T cell immune reconstitution. In the absence of an HLA-identical donor, HIFD HSCT with PTCY is a viable option for patients with life-threatening inherited disorders., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
17. Intermediate autosomal recessive osteopetrosis with a large noncoding deletion in SNX10: A case report.
- Author
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Baer S, Schaefer É, Michot C, Fischbach M, Morelle G, Bendavid M, Castelle M, Moshous D, and Collet C
- Subjects
- Child, Female, Humans, Base Sequence, Genes, Recessive, Genetic Diseases, Inborn diagnostic imaging, Genetic Diseases, Inborn genetics, Osteopetrosis congenital, Osteopetrosis diagnostic imaging, Sequence Deletion, Sorting Nexins genetics
- Published
- 2019
- Full Text
- View/download PDF
18. Rescue of recurrent deep intronic mutation underlying cell type-dependent quantitative NEMO deficiency.
- Author
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Boisson B, Honda Y, Ajiro M, Bustamante J, Bendavid M, Gennery AR, Kawasaki Y, Ichishima J, Osawa M, Nihira H, Shiba T, Tanaka T, Chrabieh M, Bigio B, Hur H, Itan Y, Liang Y, Okada S, Izawa K, Nishikomori R, Ohara O, Heike T, Abel L, Puel A, Saito MK, Casanova JL, Hagiwara M, and Yasumi T
- Subjects
- Female, Fibroblasts metabolism, Fibroblasts pathology, Humans, Immunologic Deficiency Syndromes genetics, Immunologic Deficiency Syndromes metabolism, Immunologic Deficiency Syndromes pathology, Macrophages metabolism, Macrophages pathology, Male, Ectodermal Dysplasia genetics, Ectodermal Dysplasia metabolism, Ectodermal Dysplasia pathology, Frameshift Mutation, I-kappa B Kinase deficiency, I-kappa B Kinase metabolism, Incontinentia Pigmenti genetics, Incontinentia Pigmenti metabolism, Incontinentia Pigmenti pathology, Introns
- Abstract
X-linked dominant incontinentia pigmenti (IP) and X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) are caused by loss-of-function and hypomorphic IKBKG (also known as NEMO) mutations, respectively. We describe a European mother with mild IP and a Japanese mother without IP, whose 3 boys with EDA-ID died from ID. We identify the same private variant in an intron of IKBKG, IVS4+866 C>T, which was inherited from and occurred de novo in the European mother and Japanese mother, respectively. This mutation creates a new splicing donor site, giving rise to a 44-nucleotide pseudoexon (PE) generating a frameshift. Its leakiness accounts for NF-κB activation being impaired but not abolished in the boys' cells. However, aberrant splicing rates differ between cell types, with WT NEMO mRNA and protein levels ranging from barely detectable in leukocytes to residual amounts in induced pluripotent stem cell-derived (iPSC-derived) macrophages, and higher levels in fibroblasts and iPSC-derived neuronal precursor cells. Finally, SRSF6 binds to the PE, facilitating its inclusion. Moreover, SRSF6 knockdown or CLK inhibition restores WT NEMO expression and function in mutant cells. A recurrent deep intronic splicing mutation in IKBKG underlies a purely quantitative NEMO defect in males that is most severe in leukocytes and can be rescued by the inhibition of SRSF6 or CLK.
- Published
- 2019
- Full Text
- View/download PDF
19. Blacklisting variants common in private cohorts but not in public databases optimizes human exome analysis.
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Maffucci P, Bigio B, Rapaport F, Cobat A, Borghesi A, Lopez M, Patin E, Bolze A, Shang L, Bendavid M, Scott EM, Stenson PD, Cunningham-Rundles C, Cooper DN, Gleeson JG, Fellay J, Quintana-Murci L, Casanova JL, Abel L, Boisson B, and Itan Y
- Subjects
- Cohort Studies, Female, Humans, Male, Databases, Nucleic Acid, Exome, Genetic Variation, Genome, Human, Sequence Analysis, DNA, Software
- Abstract
Computational analyses of human patient exomes aim to filter out as many nonpathogenic genetic variants (NPVs) as possible, without removing the true disease-causing mutations. This involves comparing the patient's exome with public databases to remove reported variants inconsistent with disease prevalence, mode of inheritance, or clinical penetrance. However, variants frequent in a given exome cohort, but absent or rare in public databases, have also been reported and treated as NPVs, without rigorous exploration. We report the generation of a blacklist of variants frequent within an in-house cohort of 3,104 exomes. This blacklist did not remove known pathogenic mutations from the exomes of 129 patients and decreased the number of NPVs remaining in the 3,104 individual exomes by a median of 62%. We validated this approach by testing three other independent cohorts of 400, 902, and 3,869 exomes. The blacklist generated from any given cohort removed a substantial proportion of NPVs (11-65%). We analyzed the blacklisted variants computationally and experimentally. Most of the blacklisted variants corresponded to false signals generated by incomplete reference genome assembly, location in low-complexity regions, bioinformatic misprocessing, or limitations inherent to cohort-specific private alleles (e.g., due to sequencing kits, and genetic ancestries). Finally, we provide our precalculated blacklists, together with ReFiNE, a program for generating customized blacklists from any medium-sized or large in-house cohort of exome (or other next-generation sequencing) data via a user-friendly public web server. This work demonstrates the power of extracting variant blacklists from private databases as a specific in-house but broadly applicable tool for optimizing exome analysis., Competing Interests: Conflict of interest statement: A.T. has coauthored multiple papers with J.F. and J.G.G. M.W. coauthored a 2017 paper with J.G.G.
- Published
- 2019
- Full Text
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20. Daratumumab in life-threatening autoimmune hemolytic anemia following hematopoietic stem cell transplantation.
- Author
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Schuetz C, Hoenig M, Moshous D, Weinstock C, Castelle M, Bendavid M, Shimano K, Tolbert V, Schulz AS, and Dvorak CC
- Subjects
- Anemia, Hemolytic, Autoimmune diagnosis, Anemia, Hemolytic, Autoimmune mortality, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Biomarkers, Child, Preschool, Combined Modality Therapy, Female, Humans, Infant, Male, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Young Adult, Anemia, Hemolytic, Autoimmune therapy, Antibodies, Monoclonal therapeutic use, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods
- Abstract
New-onset autoimmune hemolytic anemia (AIHA) occurs in 2% to 6% of pediatric patients post-hematopoietic stem cell transplantation (HSCT) and is a significant complication. Incomplete immune recovery following HSCT may predispose to immune dysregulation including autoimmune cytopenias. We describe an innovative therapy for AIHA refractory to proteasome inhibition. In potentially life-threatening AIHA in the context of HSCT, daratumumab may be an effective rescue therapy., (© 2018 by The American Society of Hematology.)
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- 2018
- Full Text
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21. Likely False-Positive Pneumococcal Antigen Test BinaxNOW Due to Parvimonas micra: A Four-Case Series.
- Author
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Ploton MC, Caseris M, Jost C, Picard Y, Gaschignard J, Pierron C, Canivez S, Le Dalour R, Bendavid M, Carol A, Bidet P, and Bonacorsi S
- Subjects
- Adolescent, Adult, Antigens, Bacterial metabolism, Child, Cross Reactions, False Positive Reactions, Female, Fusobacterium Infections immunology, Fusobacterium nucleatum immunology, Gram-Positive Bacterial Infections immunology, Humans, Immunoassay standards, Infant, Male, Pneumonia, Aspiration immunology, Pneumonia, Pneumococcal diagnosis, Streptococcus pneumoniae immunology, Empyema, Pleural immunology
- Abstract
We retrospectively report four cases from two hospitals of nonpneumococcal pleural empyema with a likely false-positive result on the pneumococcal antigen test BinaxNOW (PATB) (Alere) performed in pleural fluid samples in patients with aspiration pneumonia risk factors. To determine whether the positive reaction was due to cross-reactivity, we separately tested the isolates from the pleural fluid samples, along with collection and reference strains. All patients had polymicrobial aerobic and anaerobic positive cultures, including Parvimonas micra in every case. In all cases, 16S rDNA polymerase chain reaction sequencing yielded Fusobacterium nucleatum. Samples for culture and specific polymerase chain reaction were negative for Streptococcus pneumoniae. We found that the false-positive PATB finding was likely due to P micra, a previously unknown cross-reactivity. In case of aspiration pneumonia risk factors, a positive PATB result must be interpreted with caution because there can be a false positivity due to anaerobic infection or co-infection., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
22. [Teaching pediatrics to residents via conventional lectures in France: A national survey from students].
- Author
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Girard B, Bendavid M, Faivre JC, Salleron J, Debillon T, Claris O, Chabrol B, Schweitzer C, and Gajdos V
- Subjects
- Adult, Child, Cross-Sectional Studies, France, Humans, Personal Satisfaction, Retrospective Studies, Surveys and Questionnaires, Curriculum, Internship and Residency, Pediatrics education, Teaching
- Abstract
Objective: To assess the point of view of young physicians training in pediatrics in France on their theoretical courses during residency., Methods: A free-access electronic anonymous survey was sent three times by e-mail to the 1215 residents in pediatrics, from July to October 2015., Results: Fifty-seven percent of French residents in pediatrics responded to the survey. It was established that they took part in six (range, 3-10) half-days of specific theoretical teaching in pediatrics from November 2014 to mid-April 2015. Only 54% participated in more than 75% of regional theoretical training. The main self-declared reason for their absence was that they could not leave their clinical activities. Fifty-three per cent of the residents took part in additional training, 45% of them because they found the primary theoretical training insufficient. The overall quality of the theoretical teaching was rated 5 (range, 3-7) out of 10. Eighty-five percent of residents expected to be evaluated on their knowledge during their residency., Conclusion: In pediatrics, additional training is individually undertaken because they deemed their initial training insufficient during their residency. An evaluation of knowledge is requested by residents. The reform of the national residency program must take into account these results in redesigning the theoretical training in pediatrics, integrating innovative teaching techniques to daily practice, for example., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2017
- Full Text
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23. [Reform of the model of specialized pediatric diploma: Vision of the juniors].
- Author
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Bacquet M, Bendavid M, Foucambert H, Girard B, Morand A, and Ploton MC
- Subjects
- France, Humans, Education, Medical, Graduate organization & administration, Pediatrics education
- Published
- 2016
- Full Text
- View/download PDF
24. European Young Pediatricians Association: Laying the Foundations for Collaboration, Integration, and Networking among Pediatricians of the Future.
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Gray S, Raschetti R, Beşer ÖF, Elicin PU, Aversa S, Pamuk G, Ozdil M, Berlese P, Ferreira-Magalhães M, Magner M, Ignat A, Lupu VV, Zsigmond B, Ghazaryan H, Rosenbaum S, Bendavid M, Bacquet M, Varga N, James D, Bon A, and Vecchio D
- Subjects
- Child, Child Health, Education, Medical, Europe, Humans, International Cooperation, Pediatrics education, Pediatrics trends, Societies, Medical, Pediatrics organization & administration, Physicians
- Published
- 2016
- Full Text
- View/download PDF
25. Kingella kingae Sequence Type 25 Causing Endocarditis with Multiple and Severe Cerebral Complications.
- Author
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Le Bourgeois F, Germanaud D, Bendavid M, Bonnefoy R, Desnous B, Beyler C, Blauwblomme T, Elmaleh M, Pierron C, Lorrot M, Bonacorsi S, and Basmaci R
- Subjects
- Amoxicillin therapeutic use, Anti-Bacterial Agents therapeutic use, Bacteremia diagnosis, Bacteremia drug therapy, Cerebrospinal Fluid microbiology, Ciprofloxacin therapeutic use, Drug Combinations, Endocarditis, Bacterial diagnosis, Endocarditis, Bacterial drug therapy, Female, Humans, Infant, Infectious Encephalitis diagnosis, Infectious Encephalitis drug therapy, Magnetic Resonance Imaging, Neisseriaceae Infections diagnosis, Neisseriaceae Infections drug therapy, Tomography, X-Ray Computed, Bacteremia microbiology, Endocarditis, Bacterial microbiology, Infectious Encephalitis microbiology, Kingella kingae isolation & purification, Neisseriaceae Infections microbiology
- Published
- 2016
- Full Text
- View/download PDF
26. Quantitative Shear-Wave Elastography of the Liver in Preterm Neonates with Intra-Uterine Growth Restriction.
- Author
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Alison M, Biran V, Tanase A, Bendavid M, Blouet M, Demené C, Sebag G, Tanter M, and Baud O
- Subjects
- Birth Weight, Cholestasis diagnostic imaging, Cholestasis mortality, Cholestasis physiopathology, Elasticity Imaging Techniques instrumentation, Female, Fetal Growth Retardation diagnostic imaging, Fetal Growth Retardation mortality, Fetal Growth Retardation physiopathology, Gestational Age, Humans, Infant, Infant, Newborn, Infant, Premature, Liver diagnostic imaging, Male, Reproducibility of Results, Survival Analysis, Cholestasis diagnosis, Elasticity Imaging Techniques methods, Fetal Growth Retardation diagnosis, Liver physiopathology
- Abstract
The feasibility and reproducibility of liver stiffness measurements using Supersonic Shear-wave Imaging (SSI) in preterm neonate have not been reported. Our aim was to determine if liver stiffness differs between intra-uterine growth restriction (IUGR) and appropriate for gestational age (AGA) preterm infants with/without cholestasis. We measured liver stiffness (in kPa) in 45 AGA and 18 IUGR preterm infants, and assessed reproducibility in 26 preterms using Intraclass Correlation Coefficients (ICC) and Bland-Altman tests. Liver stiffness values were compared between AGA and IUGR with and without cholestasis and correlated with birth weight. Measurements showed high reproducibility (ICC = 0.94-0.98 for intra-operator, 0.86 for inter-operator) with good agreement (95% limits: -1.24 to 1.24 kPa). During the first postnatal week, liver stiffness was higher in IUGR (7.50 ±1.53 kPa) than in AGA infants (5.11 ±0.80 kPa, p<0.001). After day 8, liver stiffness remained unchanged in AGA but increased progressively in IUGR infants (15.57 ±6.49 kPa after day 21). Liver stiffness was higher in IUGR neonates with cholestasis (19.35 ± 9.80 kPa) than without cholestasis (7.72 ± 1.27 kPa, p<0.001). In conclusion, quantitative liver SSI in preterms is feasible and reproducible. IUGR preterms who will develop cholestasis present high liver stiffness even at birth, before biological cholestasis occurs.
- Published
- 2015
- Full Text
- View/download PDF
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