Publications by authors named "Laureline Berteloot"

32 Publications

Sleep in children and young adults with interstitial and diffuse lung disease.

Sleep Med 2021 Jan 20;80:23-29. Epub 2021 Jan 20.

AP-HP, Hôpital Necker, Pediatric Noninvasive Ventilation and Sleep Unit, F-75015, Paris, France; Université de Paris, VIFASOM, F-75004, Paris, France. Electronic address:

Objective: Obstructive sleep apnea (OSA) is common in adult patients with interstitial lung disease (ILD). The aim of the study was to evaluate the prevalence of OSA and sleep quality in children and young adults with children's interstitial and diffuse lung disease (chILD).

Methods: A polysomnography (PSG) was performed in room air in all consecutive patients followed at a national reference centre between June 2018 and September 2019. Clinical and PSG data were collected.

Results: The PSG data of 20 patients (12 girls, median age 9 (range 0.5-20) years), were analyzed. Seven (35%) patients had pulmonary alveolar proteinosis (PAP), 5 (25%) a disorder of surfactant metabolism, 3 (15%) diffuse pulmonary hemorrhage, 4 (20%) chILD of unknown etiology and one patient had laryngeal and pulmonary sarcoidosis. The median obstructive apnea-hypnea index (OAHI) was normal at 0 events/hour, with a value > 4 events/hour being observed in 2 young adults: an 18-year-old male with PAP and a vital capacity of 27% predicted who had an OAHI of 10.7 events/hour, and a 20-year-old male with laryngeal and pulmonary sarcoidosis who had positional OSA with an OAHI of 19.5 events/hour. The median total sleep time, sleep efficiency, % of wake after sleep onset, and sleep stages were moderately disturbed.

Conclusions: Moderate or severe OSA was not observed in children <18 years with chILD. Mild or moderate OSA was observed in 2 young adults with PAP and sarcoidosis. As opposed to adults, OSA seems uncommon in children with chILD.
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http://dx.doi.org/10.1016/j.sleep.2021.01.020DOI Listing
January 2021

Endovascular stenting of blunt aortic isthmus rupture in a 5-year-old child.

Eur J Cardiothorac Surg 2021 Feb 4. Epub 2021 Feb 4.

Pediatric and Congenital Cardiology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris, France.

Blunt traumatic aortic tear is an extremely rare and life-threatening paediatric emergency. Percutaneous repair is highly debateable in children due to anatomic limitations. Herein, we report an important case of a 5-year-old boy diagnosed with grade 3 aortic isthmus disruption following fifth-floor defenestration. The 96-h control computerized tomography (CT) scan showed an increase in the pseudoaneurysm size with small active bleeding motivating endovascular covered stenting that was safely and efficiently performed with good outcomes.
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http://dx.doi.org/10.1093/ejcts/ezab029DOI Listing
February 2021

Life-Saving, Dose-Adjusted, Targeted Therapy in a Patient with a STAT3 Gain-of-Function Mutation.

J Clin Immunol 2021 Jan 11. Epub 2021 Jan 11.

Pediatric Immunohematology and Rheumatology Department, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), 149 rue de Sèvres, F-75015, Paris, France.

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http://dx.doi.org/10.1007/s10875-020-00914-3DOI Listing
January 2021

Arterial abnormalities identified in kidneys transplanted into children during the COVID-19 pandemic.

Am J Transplant 2020 Dec 21. Epub 2020 Dec 21.

INSERM U1163, Institut Imagine, Paris, France.

Graft artery stenosis can have a significant short- and long-term negative impact on renal graft function. From the beginning of the COVID-19 pandemic, we noticed an unusual number of graft arterial anomalies following kidney transplant (KTx) in children. Nine children received a KTx at our center between February and July 2020, eight boys and one girl, of median age of 10 years. Seven presented Doppler features suggesting arterial stenosis, with an unusual extensive pattern. For comparison, over the previous 5-year period, persistent spectral Doppler arterial anomalies (focal anastomotic stenoses) following KTx were seen in 5% of children at our center. We retrospectively evidenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in five of seven children with arterial stenosis. The remaining two patients had received a graft from a deceased adolescent donor with a positive serology at D0. These data led us to suspect immune postviral graft vasculitis, triggered by SARS-CoV-2. Because the diagnosis of COVID-19 is challenging in children, we recommend pretransplant monitoring of graft recipients and their parents by monthly RT-PCR and serology. We suggest balancing the risk of postviral graft vasculitis against the risk of prolonged dialysis when considering transplantation in a child during the pandemic.
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http://dx.doi.org/10.1111/ajt.16464DOI Listing
December 2020

Overview of STING-Associated Vasculopathy with Onset in Infancy (SAVI) Among 21 Patients.

J Allergy Clin Immunol Pract 2021 Feb 18;9(2):803-818.e11. Epub 2020 Nov 18.

Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP Centre Université de Paris, Paris, France; Université de Paris, Imagine Institute, Laboratory of Immunogenetics of Pediatric Autoimmunity, INSERM UMR 1163, Paris, France. Electronic address:

Background: Gain-of-function mutations in STING1 underlie a type I interferonopathy termed SAVI (STING-associated vasculopathy with onset in infancy). This severe disease is variably characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease (ILD).

Objective: To describe a cohort of patients with SAVI.

Methods: Assessment of clinical, radiological and immunological data from 21 patients (17 families) was carried out.

Results: Patients carried heterozygous substitutions in STING1 previously described in SAVI, mainly the p.V155M. Most were symptomatic from infancy, but late onset in adulthood occurred in 1 patient. Systemic inflammation, skin vasculopathy, and ILD were observed in 19, 18, and 21 patients, respectively. Extensive tissue loss occurred in 4 patients. Severity of ILD was highly variable with insidious progression up to end-stage respiratory failure reached at teenage in 6 patients. Lung imaging revealed early fibrotic lesions. Failure to thrive was almost constant, with severe growth failure seen in 4 patients. Seven patients presented polyarthritis, and the phenotype in 1 infant mimicked a combined immunodeficiency. Extended features reminiscent of other interferonopathies were also found, including intracranial calcification, glaucoma and glomerular nephropathy. Increased expression of interferon-stimulated genes and interferon α protein was constant. Autoantibodies were frequently found, in particular rheumatoid factor. Most patients presented with a T-cell defect, with low counts of memory CD8+ cells and impaired T-cell proliferation in response to antigens. Long-term follow-up described in 8 children confirmed the clinical benefit of ruxolitinib in SAVI where the treatment was started early in the disease course, underlying the need for early diagnosis. Tolerance was reasonably good.

Conclusion: The largest worldwide cohort of SAVI patients yet described, illustrates the core features of the disease and extends the clinical and immunological phenotype to include overlap with other monogenic interferonopathies.
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http://dx.doi.org/10.1016/j.jaip.2020.11.007DOI Listing
February 2021

Ultrasound detected prenatal hyperechoic lung lesions and concordance with postnatal findings: A common aspect for multiple diagnoses.

Prenat Diagn 2021 Feb 5;41(3):323-331. Epub 2020 Nov 5.

Department of Pediatric Surgery, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.

Objective: Hyperechoic lung lesions are largely detected prenatally but their underlying etiology is still poorly defined. The aim of the study was to determine the concordance between pre and postnatal diagnosis of hyperechoic lung lesions.

Methods: Prenatal ultrasound (US) evaluation was performed by a fetal medicine specialist. Postnatal diagnosis was based on CT-scan. Pre- and postnatal features were retrieved from medical charts.

Results: Seventy five patients were included from January 2009 to December 2018. Main prenatal diagnoses were bronchopulmonary sequestrations (BPS) (n = 24%-32%), pulmonary cystic malformations (PCM) (n = 19%-25%), congenital lobar emphysemas (CLE) (n = 15%-20%). Mediastinal shift was observed in 18 cases (24%). The prenatal detection of a systemic arterial supply had a diagnostic accuracy of 90%, while the prenatal detection of a cystic component had a diagnostic accuracy of 76.5%. All 16 neonates with prenatal isolated mediastinal shift were asymptomatic at birth. Seven neonates showed respiratory distress that was not predicted prenatally.

Conclusions: Hyperechoic lung malformations reflect a heterogeneous group of lesions with a good concordance for bronchopulmonary sequestration, but not a satisfying prediction for cystic lesions.
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http://dx.doi.org/10.1002/pd.5854DOI Listing
February 2021

Safety and efficacy of brentuximab vedotin as a treatment for lymphoproliferative disorders in primary immunodeficiencies.

Haematologica 2020 09 1;105(9):e461-464. Epub 2020 Sep 1.

Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP, Paris; Paris University, Paris; INSERM UMR 1163, Institut Imagine, Paris.

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http://dx.doi.org/10.3324/haematol.2019.230276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556515PMC
September 2020

A diagnostic dilemma in a boy with lupus and dyspnea: Questions.

Pediatr Nephrol 2021 Apr 17;36(4):849-851. Epub 2020 Jul 17.

AP-HP, Hôpital Universitaire Necker-Enfants Malades, Service de Néphrologie de Pédiatrique, Centre de référence MARHEA, Paris, France.

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http://dx.doi.org/10.1007/s00467-020-04691-4DOI Listing
April 2021

A diagnostic dilemma in a boy with lupus and dyspnea: Answers.

Pediatr Nephrol 2021 Apr 17;36(4):853-856. Epub 2020 Jul 17.

AP-HP, Hôpital Universitaire Necker-Enfants Malades, Service de Néphrologie Pédiatrique, Centre de référence MARHEA, Paris, France.

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http://dx.doi.org/10.1007/s00467-020-04698-xDOI Listing
April 2021

Effectiveness and safety of ruxolitinib for the treatment of refractory systemic idiopathic juvenile arthritis like associated with interstitial lung disease : a case report.

Ann Rheum Dis 2020 Feb 13. Epub 2020 Feb 13.

Pediatric Hematology-Immunology and Rheumatology Unit, Hôpital Necker-Enfants Malades, AP-HP Centre, Paris, France.

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http://dx.doi.org/10.1136/annrheumdis-2020-216983DOI Listing
February 2020

The "salt and pepper" pattern on renal ultrasound in a group of children with molecular-proven diagnosis of ciliopathy-related renal diseases.

Pediatr Nephrol 2020 06 10;35(6):1033-1040. Epub 2020 Feb 10.

Pediatric Radiology Department, Hospital Necker-Enfants Malades, AP-HP, Paris, France.

Background: While typical ultrasound patterns of ciliopathy-related cystic kidney diseases have been described in children, ultrasound findings can overlap between different diseases and atypical patterns exist. In this study, we assessed the presence of the "salt and pepper" pattern in different renal ciliopathies and looked for additional ultrasound features.

Methods: This single-center, retrospective study included all patients with a molecular-proven diagnosis of renal ciliopathy, referred to our center between 2007 and 2017. Images from the first and follow-up ultrasound exams were reviewed. Basic ultrasound features were grouped into patterns and compared to genetic diagnoses. The "salt and pepper" aspect was described as enlarged kidneys with heterogeneous, increased parenchymal echogenicity.

Results: A total of 41 children with 5 different renal ciliopathies were included (61% male; median age, 6 years [range, 3 days to 17 years]). The "salt and pepper" pattern was present in 14/15 patients with an autosomal recessive polycystic kidney disease (ARPKD). A similar pattern was found in 1/4 patients with an autosomal dominant polycystic kidney disease and in 1/11 patients with HNF1B mutation. Additional signs found were areas of cortical sparing, comet-tail artifacts, and color comet-tail artifacts.

Conclusion: Although the "salt and pepper" ultrasound pattern is predominantly found in ARPKD, it may be detected in other ciliopathies. The color comet-tail artifact is an interesting sign when suspecting a renal ciliopathy in case of enlarged hyperechoic kidneys with no detectable microcysts on B-mode grayscale ultrasound.
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http://dx.doi.org/10.1007/s00467-020-04480-zDOI Listing
June 2020

Severe Abdominal Manifestations in Juvenile Dermatomyositis.

J Pediatr Gastroenterol Nutr 2020 02;70(2):247-251

Laboratoire d'Immunogénétique des maladies auto-immunes de l'enfant, Institut Imagine, INSERM U 1163.

Juvenile dermatomyositis (JDM) is a rare and heterogeneous pediatric-onset idiopathic inflammatory myopathy. Gastrointestinal (GI) involvement occurs in 22% to 37% of JDM patients but has only been described in case reports. In this retrospective, single-center, observational study, we aimed to assess the causes and management of severe GI manifestations in JDM patients. We studied a cohort of 9 patients among 110 JDM patients followed during the study period (8.3%). The GI complications were related to JDM in most cases (17/19), with digestive tract involvement (n = 10), acute pancreatitis (n = 4), and hepatitis (n = 3). Three patients died from refractory JDM 2.9 years (2-3.6) after the JDM diagnosis. We highlight the need to consider pancreatitis as a main diagnostic factor in JDM patients with severe GI manifestations and the requirement of early aggressive treatment for these patients.
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http://dx.doi.org/10.1097/MPG.0000000000002575DOI Listing
February 2020

A Treatment-Decision Score for HIV-Infected Children With Suspected Tuberculosis.

Pediatrics 2019 09;144(3)

Service de Pneumologie et d'Allergologie Pédiatriques, and.

Background: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis.

Methods: HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony.

Results: A total of 438 children were enrolled in the study; 251 (57.3%) had tuberculosis, including 55 (12.6%) with culture- or Xpert-confirmed tuberculosis. The final 4 models included Xpert, fever lasting >2 weeks, unremitting cough, hemoptysis and weight loss in the past 4 weeks, contact with a patient with smear-positive tuberculosis, tachycardia, miliary tuberculosis, alveolar opacities, and lymph nodes on the chest radiograph, together with abdominal lymph nodes on the ultrasound and QFT results. The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score developed on model 2 had a sensitivity of 88.6% and a specificity of 61.2% for a tuberculosis diagnosis.

Conclusions: Our score had a good diagnostic performance. Used in an algorithm, it should enable prompt treatment decision in children with suspected tuberculosis and a high mortality risk, thus contributing to significant public health benefits.
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http://dx.doi.org/10.1542/peds.2018-2065DOI Listing
September 2019

Comprehensive Review of 3D Segmentation Software Tools for MRI Usable for Pelvic Surgery Planning.

J Digit Imaging 2020 02;33(1):99-110

LTCI, Télécom Paris, Institut Polytechnique de Paris, Paris, France.

Patient-specific 3D modeling is the first step towards image-guided surgery, the actual revolution in surgical care. Pediatric and adolescent patients with rare tumors and malformations should highly benefit from these latest technological innovations, allowing personalized tailored surgery. This study focused on the pelvic region, located at the crossroads of the urinary, digestive, and genital channels with important vascular and nervous structures. The aim of this study was to evaluate the performances of different software tools to obtain patient-specific 3D models, through segmentation of magnetic resonance images (MRI), the reference for pediatric pelvis examination. Twelve software tools freely available on the Internet and two commercial software tools were evaluated using T2-w MRI and diffusion-weighted MRI images. The software tools were rated according to eight criteria, evaluated by three different users: automatization degree, segmentation time, usability, 3D visualization, presence of image registration tools, tractography tools, supported OS, and potential extension (i.e., plugins). A ranking of software tools for 3D modeling of MRI medical images, according to the set of predefined criteria, was given. This ranking allowed us to elaborate guidelines for the choice of software tools for pelvic surgical planning in pediatric patients. The best-ranked software tools were Myrian Studio, ITK-SNAP, and 3D Slicer, the latter being especially appropriate if nerve fibers should be included in the 3D patient model. To conclude, this study proposed a comprehensive review of software tools for 3D modeling of the pelvis according to a set of eight criteria and delivered specific conclusions for pediatric and adolescent patients that can be directly applied to clinical practice.
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http://dx.doi.org/10.1007/s10278-019-00239-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064712PMC
February 2020

Idiopathic, heritable and veno-occlusive pulmonary arterial hypertension in childhood: computed tomography angiography features in the initial assessment of the disease.

Pediatr Radiol 2019 05 16;49(5):575-585. Epub 2019 Jan 16.

M3C-Necker, Congenital and Pediatric Cardiology, Hôpital Universitaire Necker-Enfants malades, Paris, France.

Background: In children, idiopathic and heritable pulmonary arterial hypertension present echocardiographic and heart catheterization findings similar to findings in pulmonary veno-occlusive disease.

Objective: To provide a systematic analysis of CT angiography anomalies in children with idiopathic or heritable pulmonary arterial hypertension, or pulmonary veno-occlusive disease. We also sought to identify correlations between CT findings and patients' baseline characteristics.

Materials And Methods: We retrospectively analyzed CT features of children with idiopathic and heritable pulmonary arterial hypertension or pulmonary veno-occlusive disease and 30 age-matched controls between 2008 and 2014. We compared CT findings and patient characteristics, including gene mutation type, and disease outcome until 2017.

Results: The pulmonary arterial hypertension group included idiopathic (n=15) and heritable pulmonary arterial hypertension (n=11) and pulmonary veno-occlusive disease (n=4). Median age was 6.5 years. Children with pulmonary arterial hypertension showed enlargement of pulmonary artery and right cardiac chambers. A threshold for the ratio between the pulmonary artery and the ascending aorta of ≥1.2 had a sensitivity of 90% and a specificity of 100% for pulmonary arterial hypertension. All children with pulmonary veno-occlusive disease had thickened interlobular septa, centrilobular ground-glass opacities, and lymphadenopathy. In children with idiopathic and heritable pulmonary arterial hypertension, presence of intrapulmonary neovessels and enlargement of the right atrium were correlated with higher mean pulmonary artery pressure (P=0.011) and pulmonary vascular resistance (P=0.038), respectively. Mediastinal lymphadenopathy was associated with disease worsening within the first 2 years of follow-up (P=0.024).

Conclusion: CT angiography could contribute to early diagnosis and prediction of severity in children with pulmonary arterial hypertension.
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http://dx.doi.org/10.1007/s00247-018-04331-yDOI Listing
May 2019

Targeted therapy in patients with PIK3CA-related overgrowth syndrome.

Nature 2018 06 13;558(7711):540-546. Epub 2018 Jun 13.

INSERM U1151, Institut Necker Enfants Malades, Paris, France.

CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.
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http://dx.doi.org/10.1038/s41586-018-0217-9DOI Listing
June 2018

Hemodynamic Shock Caused by Tension Pneumoperitoneum in a 5-Year-Old Girl.

Pediatr Emerg Care 2018 Jun;34(6):e102-e103

From the Departments of Pediatric Emergency.

Tension pneumoperitoneum is a relatively rare occurrence in the pediatric population. However, tension pneumoperitoneum is associated with significant morbidity and mortality if it is not promptly diagnosed and treated. A 5-year-old girl was admitted to emergency department with abdominal pain. She was in shock, and the radiograph film of the abdomen revealed a voluminous tension pneumoperitoneum. Aggressive fluid challenges were performed in intensive care followed by urgent laparotomy. Primary abdominal compartment due to trapped gas caused a decreased venous return and visceral perfusion. In the absence of hemodynamic improvement after vascular filling, needle decompression was performed before surgery.
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http://dx.doi.org/10.1097/PEC.0000000000001471DOI Listing
June 2018

Bronchopulmonary sequestrations in a paediatric centre: ongoing practices and debated management.

Eur J Cardiothorac Surg 2018 08;54(2):246-251

Deparmtent of Pediatric Surgery, AP-HP, Hopital Necker-Enfants malades, Paris, France.

Objectives: Bronchopulmonary sequestration (BPS) is the second most common congenital lung malformation, with an estimated incidence ranging from 0.15% to 1.8%. Surgical treatment is elective in patients with symptoms, but the management of asymptomatic patients remains controversial.

Methods: We retrospectively reviewed the medical records of 99 patients treated for BPS in our institution from January 2000 to December 2015. BPS was diagnosed prenatally in 86 (87%) cases. Management throughout this 16-year period was based on 3 interventions: resection by open surgery, resection by thoracoscopy and embolization.

Results: Among the 86 patients with a prenatal diagnosis of BPS, 14% had symptoms at birth and 10% had delayed symptoms at a median delay of 8 months (4.5-42 months). For the other 13 patients, symptoms occurred at a median age of 34 months (range 3-96 months). Embolization of the feeding vessel was performed in 46 patients with 6 secondary surgical resections (13%). A total of 59 patients were operated on: 23 cases by open surgery and 36 cases by thoracoscopy. The mean hospitalization stay was significantly longer for open surgery: 4.8 ± 1.3 days vs 4.1 ±1.5 days, respectively (P = 0.03). Differences in hospitalization stay were also found between asymptomatic and symptomatic patients: 3.5 ± 1.2 vs 5.1 ±1.6 days, respectively (P = 0.002). Two of the operated patients died.

Conclusions: When surgery is chosen, thoracoscopy appears to be a valuable procedure. A better understanding of the natural history of BPS is still needed to define the optimal management and the respective roles of surgery, embolization or non-interventional follow-up.
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http://dx.doi.org/10.1093/ejcts/ezy049DOI Listing
August 2018

Associations Among Mucosal and Transmural Healing and Fecal Level of Calprotectin in Children With Crohn's Disease.

Clin Gastroenterol Hepatol 2018 07 2;16(7):1089-1097.e4. Epub 2018 Mar 2.

The Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address:

Background & Aims: Bowel healing is an important goal of therapy for patients with Crohn's disease (CD). Although there have been many studies of mucosal healing, transmural healing (ie, in the bowel wall) has not been investigated in children. We analyzed data from the ImageKids study to determine associations among mucosal, transmural healing and levels of calprotectin and C-reactive protein in children with CD.

Methods: We collected data from a multi-center study designed to develop 2 magnetic resonance enterography (MRE)-based measures for children with CD (6-18 years old). In our analysis of 151 children (mean age, 14.2 ± 2.4 years), all patients underwent MRE and a complete ileocolonoscopic evaluation; fecal levels of calprotectin and blood levels of C-reactive protein were measured. Mucosal healing was defined as simple endoscopic severity index in CD score below 3, transmural healing as an MRE visual analogue score below 20 mm, and deep healing as a combination of transmural and mucosal healing.

Results: We identified mucosal healing with transmural inflammation in 9 children (6%), transmural healing with mucosal inflammation in 38 children (25%), deep healing in 21 children (14%), and mucosal and transmural inflammation in 83 children (55%). The median level of calprotectin was lowest in children with deep healing (mean level, 10 μg/g; interquartile range, 10-190 μg/g), followed by children with either transmural or mucosal inflammation, and highest in children with mucosal and transmural inflammation (810 μg/g; interquartile range, 539-1737 μg/g) (P < .001). Fecal level of calprotectin identified children with deep healing with an area under the receiver operating characteristic curve value of 0.93 (95% CI, 0.89-0.98); level of C-reactive protein identified children with deep healing with an area under the receiver operating characteristic curve value of 0.81 (95% CI, 0.71-0.9). A calprotectin cutoff value of 100 μg/g identified children with deep healing with 71% sensitivity and 92% specificity; a cutoff value of 300 μg/g identified children with mucosal healing with 80% sensitivity and 81% specificity.

Conclusions: In a prospective study of children with CD, we found that one-third have healing in only the mucosa or the bowel wall (not both). Levels of fecal calprotectin below 300 μg/identify children with mucosal healing, but a lower cutoff value (below 100 μg/g) is needed to identify children with deep healing. Clinicaltrials.gov no: NCT01881490.
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http://dx.doi.org/10.1016/j.cgh.2018.01.024DOI Listing
July 2018

Successful haematopoietic stem cell transplantation in a case of pulmonary alveolar proteinosis due to GM-CSF receptor deficiency.

Thorax 2018 06 20;73(6):590-592. Epub 2017 Dec 20.

Paediatric Haematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

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http://dx.doi.org/10.1136/thoraxjnl-2017-211076DOI Listing
June 2018

Mortality and its determinants in antiretroviral treatment-naive HIV-infected children with suspected tuberculosis: an observational cohort study.

Lancet HIV 2018 02 23;5(2):e87-e95. Epub 2017 Nov 23.

Unité d'Immunologie Hématologie Rhumatologie Pédiatrique, Hôpital Necker Enfants Malades, AP-HP, Paris, France.

Background: Tuberculosis is a major cause of morbidity and mortality in HIV-infected children, but is difficult to diagnose. We studied mortality and its determinants in antiretroviral treatment (ART)-naive HIV-infected children presenting with suspected tuberculosis.

Methods: In this observational cohort study, HIV-infected children aged 13 years or younger with suspected tuberculosis were followed up for 6 months as part of the ANRS 12229 PAANTHER 01 cohort in eight hospitals in four countries (Burkina Faso, Cambodia, Cameroon, and Vietnam). Children started ART and antituberculosis treatment at the clinician's discretion and were retrospectively classified into one of three groups by tuberculosis documentation: confirmed by culture or Xpert MTB/RIF, unconfirmed, and unlikely. We assessed mortality and associated factors using Kaplan-Meier methods and Cox proportional hazard models. The ANRS 12229 PAANTHER 01 study is registered at ClinicalTrials.gov, number NCT01331811.

Findings: 266 (61%) of 438 children enrolled in the study between April 27, 2011, and May 31, 2014, were ART-naive and included in the analysis (40 had confirmed tuberculosis, 119 unconfirmed tuberculosis, and 107 unlikely tuberculosis). 112·5 person-years of follow-up were available. 154 children (58%) started antituberculosis treatment and 212 (80%) started ART. 50 children (19%) died. Mortality by 6 months was higher in children with confirmed tuberculosis (14 deaths; 2 month survival probability 65·0% [95% CI 50·2-79·8]) compared with unconfirmed tuberculosis (19 deaths; 83·5% [76·8-90·3]) and unlikely tuberculosis (17 deaths; 83·5% [76·3-90·7]; log-rank p=0·0141) and was lower in children with confirmed or unconfirmed tuberculosis who started antituberculosis treatment (p<0·0001 for both). In a multivariate analysis, ART started during the first month of follow-up (hazard ratio 0·08; 95% CI 0·01-0·67), confirmed tuberculosis (6·33; 2·15-18·64), young age (5·90; 2·02-17·19), CD4 less than 10% (2·63; 1·25-5·53), miliary features (4·08; 1·56-10·66), and elevated serum transaminases (4·40; 1·82-10·65) were all independently associated with mortality.

Interpretation: In our cohort, mortality was high in the first 6 months after suspicion of tuberculosis in ART-naive children. ART should be started early, particularly in children with factors associated with high mortality. Documented or empirical tuberculosis treatment decision should be accelerated to reduce mortality and allow early ART initiation.

Funding: ANRS and Fondation Total.
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http://dx.doi.org/10.1016/S2352-3018(17)30206-0DOI Listing
February 2018

Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children.

J Allergy Clin Immunol 2016 12 20;138(6):1752-1755. Epub 2016 Aug 20.

Pediatric Hematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, Paris, France; Paris Descartes University, Sorbonne-Paris-Cité, Institut Imagine, Paris, France; INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric Autoimmunity, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2016.07.015DOI Listing
December 2016

Anything that Looks Like a Neuroendocrine Cell Hyperplasia of Infancy Is Not Necessarily a Neuroendocrine Cell Hyperplasia of Infancy.

Chest 2016 06;149(6):1578-9

Pediatric Pulmonology and Allergy, Hôpital Universitaire Necker-Enfants Malades, Paris, France.

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http://dx.doi.org/10.1016/j.chest.2016.02.683DOI Listing
June 2016

Lung involvement in children with lysinuric protein intolerance.

J Inherit Metab Dis 2015 Mar 22;38(2):257-63. Epub 2014 Oct 22.

Service de Pneumologie pédiatrique, Hôpital Jeanne de Flandre, CHRU de Lille, Paris, France,

Background And Objectives: Lysinuric protein intolerance (LPI) is a rare multisystemic metabolic disease. The objective of the study was to describe presentation and course of lung involvement in a cohort of ten children.

Patients And Methods: Retrospective review of patients followed at Necker-Enfants Malades University Hospital between 1980 and 2012 for a LPI. In patients with lung involvement, clinical data, chest radiographs, pulmonary function tests, bronchoalveolar lavages, and lung biopsies were analyzed. The first and last high-resolution computed tomography (HRCT) were also reviewed.

Results: Lung involvement was observed in ten of 14 patients (71 %). Five patients had an acute onset of respiratory symptoms, three had a progressive onset and two were free of symptoms. During the period studied, six patients (60 %) died, all in a context of respiratory failure. Clinical presentation and course were highly variable, even in the same family. HRCT were performed in seven cases, showing in all cases an interstitial pattern and fibrosis in four. All ten patients had pulmonary alveolar proteinosis (PAP) confirmed by histopathological analysis. Five patients had pulmonary fibrosis (at biopsy and/or HRCT scan). Two patients underwent whole lung lavages, without efficiency.

Conclusion: PAP is a constant feature in children with LPI and lung involvement. Pulmonary fibrosis is frequent and these two pathologies may develop independently. This study shows the heterogeneity of presentation and outcome. Lung injury could be secondary to impaired phagocytic function and abnormal inflammatory and immune responses intrinsic to the SLC7A7 mutant phenotype. HRCT is recommended to detect lung involvement.
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http://dx.doi.org/10.1007/s10545-014-9777-5DOI Listing
March 2015

Pulmonary alveolar proteinosis in children on La Réunion Island: a new inherited disorder?

Orphanet J Rare Dis 2014 Jun 14;9:85. Epub 2014 Jun 14.

Service de Pneumologie Pédiatrique, AP-HP, Hôpital Necker-Enfants Malades, service de Pneumologie Pédiatrique, Centre de Référence pour les Maladies Respiratoires Rares de l'Enfant, 149-161 rue de Sèvres, 75015 Paris, France.

Background: Pulmonary alveolar proteinosis (PAP) is very rare in children. Only a few small series have been published, with little information about long-term progression. The objective of our study was to describe the clinical, radiological and pathological features, and the long-term course of PAP in a cohort of 34 children from La Réunion Island.

Methods: Data were retrospectively collected from medical files. Radiological and pathological elements were reviewed by two pediatric radiologists and three pathologists, respectively.

Results: Thirteen cases were familial and 32/34 (94%) cases were family connected. Disease onset occurred in the first six months of life in 82% of the patients. Thoracic computed tomography scans showed the typical "crazy-paving" pattern in 94% of cases. Respiratory disease was associated with a liver disorder, with the detection of liver enlargement at diagnosis in 56% of cases. The course of the disease was characterized by frequent progression to chronic respiratory insufficiency, accompanied by the appearance of cholesterol granulomas and pulmonary fibrosis. Overall prognosis was poor, with a mortality of 59% and an overall five-year survival rate from birth of 64%. Whole-lung lavages were performed in 21 patients, with no significant effect on survival. Liver disease progressed to cirrhosis in 18% of children, with no severe complication.

Conclusions: PAP in children from la Réunion Island is characterized by an early onset, associated liver involvement, poor prognosis and frequent progression to lung fibrosis, despite whole-lung lavages treatment. The geographic clustering of patients and the detection of many familial links between most of the cases strongly suggest a genetic etiology, with an autosomal recessive mode of inheritance.
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http://dx.doi.org/10.1186/1750-1172-9-85DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062771PMC
June 2014

Primary pulmonary alveolar proteinosis: computed tomography features at diagnosis.

Pediatr Radiol 2014 Jul 6;44(7):795-802. Epub 2014 Mar 6.

Department of Pediatric Radiology, Hôpital Necker Enfants-Malades, Assistance Publique des Hôpitaux de Paris, 149 rue de Sèvres, 75743, Paris Cedex 15, France,

Background: Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of periodic acid-schiff-positive lipoproteinaceous material in the alveoli. Early diagnosis allows setting up of therapeutic lung lavages, which reduces the need for oxygen supplementation and weight gain.

Objective: To provide a description of radiological features by CT at the onset of primary PAP in children.

Materials And Methods: The clinical and radiological data of 24 patients, including 16 boys and 8 girls (median age: 12 months), diagnosed with a primary form of PAP between April 1992 and May 2012 in a tertiary referral hospital, were retrospectively reviewed. CT images were examined for the presence of alveolar and interstitial elementary lesions. Correlation between clinical and radiological findings was assessed.

Results: The types of elementary lesions detected were: ground-glass opacities (n = 24), intralobular lines (n = 24), thickened interlobular septa (n = 22), thickened fissures (n = 21), airspace consolidation (n = 16), hyperinflation (n = 16), cystic lesions (n = 2) and micronodules (n = 1). A crazy-paving pattern was found in 92% of cases. Consolidation and hyperinflation were especially detected in younger children (median age, 8 months, P < 0.01). A density dependent gradient was found. The distribution of the lesions was symmetrical. There was no correlation between radiological and clinical data of severity of the disease.

Conclusion: CT findings are suggestive of diagnosis of PAP in immunocompetent children with chronic respiratory failure.
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http://dx.doi.org/10.1007/s00247-014-2888-1DOI Listing
July 2014

Extralobar pulmonary sequestration with combined gastric and intradiaphragmatic locations.

Pediatr Pulmonol 2014 May 10;49(5):512-4. Epub 2013 Sep 10.

AP-HP, Pediatric Surgery Department, Necker-Enfants Malades Hospital, Paris, France.

Extralobar pulmonary sequestration is a congenital lung malformation characterized by a non-functional lung segment with systemic feeding vessel. Over 90% of sequestrations are found in the thorax with less than 10% located in the abdomen. We present an unusual case of intra abdominal pulmonary sequestration, located suprarenally, adherent to both the stomach and the diaphragm. The malformation was surgically excised via laparoscopy in the second year of life, when no evidence of regression was found on follow up imaging. On the occasion of this description, the spectrum of bronchopulmonary foregut malformation is discussed.
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http://dx.doi.org/10.1002/ppul.22891DOI Listing
May 2014

Model-based iterative reconstruction in pediatric chest CT: assessment of image quality in a prospective study of children with cystic fibrosis.

Pediatr Radiol 2013 Mar 7;43(5):558-67. Epub 2012 Dec 7.

Institute of Radiation Physics, Lausanne University Hospital, Grand-Pré 1 , 1007, Lausanne, Switzerland.

Background: The potential effects of ionizing radiation are of particular concern in children. The model-based iterative reconstruction VEO(TM) is a technique commercialized to improve image quality and reduce noise compared with the filtered back-projection (FBP) method.

Objective: To evaluate the potential of VEO(TM) on diagnostic image quality and dose reduction in pediatric chest CT examinations.

Materials And Methods: Twenty children (mean 11.4 years) with cystic fibrosis underwent either a standard CT or a moderately reduced-dose CT plus a minimum-dose CT performed at 100 kVp. Reduced-dose CT examinations consisted of two consecutive acquisitions: one moderately reduced-dose CT with increased noise index (NI = 70) and one minimum-dose CT at CTDIvol 0.14 mGy. Standard CTs were reconstructed using the FBP method while low-dose CTs were reconstructed using FBP and VEO. Two senior radiologists evaluated diagnostic image quality independently by scoring anatomical structures using a four-point scale (1 = excellent, 2 = clear, 3 = diminished, 4 = non-diagnostic). Standard deviation (SD) and signal-to-noise ratio (SNR) were also computed.

Results: At moderately reduced doses, VEO images had significantly lower SD (P < 0.001) and higher SNR (P < 0.05) in comparison to filtered back-projection images. Further improvements were obtained at minimum-dose CT. The best diagnostic image quality was obtained with VEO at minimum-dose CT for the small structures (subpleural vessels and lung fissures) (P < 0.001). The potential for dose reduction was dependent on the diagnostic task because of the modification of the image texture produced by this reconstruction.

Conclusions: At minimum-dose CT, VEO enables important dose reduction depending on the clinical indication and makes visible certain small structures that were not perceptible with filtered back-projection.
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http://dx.doi.org/10.1007/s00247-012-2554-4DOI Listing
March 2013