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1. A model of hemodialysis after acute kidney injury in rats

Author

J. Mallet, P.-A. Billiet, M. Scarton, N. Benichou, M. Bobot, K. Chaibi, A. Hertig, J. Hadchouel, D. Dreyfuss, S. Gaudry, and S. Placier

Subjects
Acute kidney injury, Intensive care unit, Renal replacement therapy, Hemodialysis, Adenine 0.75%, Animal model, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Acute kidney injury (AKI) is frequent among critically ill patients. Renal replacement therapy (RRT) is often required to deal with severe complications of AKI. This technique is however associated with side effects such as hemodynamic instability and delayed renal recovery. In this study, we aimed to describe a novel model of hemodialysis in rats with AKI and depict a dialysis membrane performance. Methods Eighteen Sprague–Dawley rats received 0.75% adenine-rich diet to induce AKI. After 2 weeks, nine underwent an arterio-venous extracorporeal circulation (ECC) (ECC group) for 2 h without a dialysis membrane on the circuit and nine received a hemodialysis session (HD group) for 2 h with an ECC circuit. All rats were hemodynamically monitored, and glomerular filtration rate (GFR) was measured by transcutaneous fluorescence after the injection of FITC-Sinistrin. Blood samples were collected at different time points to assess serum creatinine and serum urea concentrations and to determine the Kt/V. Sinistrin concentration was also quantified in both plasma and dialysis effluent. Results After 2 weeks of adenine-rich diet, rats exhibited a decrease in GFR. Both serum urea and serum creatinine concentrations increased in the ECC group but remained stable in the HD group. We found no significant difference in serum creatinine and serum urea concentrations between groups. At the end of experiments, mean serum urea was 36.7 mmol/l (95%CI 19.7–46.9 mmol/l) and 23.6 mmol/l (95%CI 15.2–33.5 mmol/l) in the ECC and HD groups, respectively (p = 0.15), and mean serum creatinine concentration was 158.0 µmol/l (95%CI 108.1–191.9 µmol/l) and 114.0 µmol/l (95%CI 90.2–140.9 µmol/l) in the ECC and HD groups, respectively (p = 0.11). The Kt/V of the model was estimated at 0.23. Sinistrin quantity in the ultrafiltrate raised steadily during the dialysis session. After 2 h, the median quantity was 149.2 µg (95% CI 99.7–250.3 µg). Conclusions This hemodialysis model is an acceptable compromise between the requirement of hemodynamic tolerance which implies reducing extracorporeal blood volume (using a small dialyzer) and the demonstration that diffusion of molecules through the membrane is achieved.

Published
2023
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2. Protective Role of the Podocyte IL-15 / STAT5 Pathway in Focal Segmental Glomerulosclerosis

Author

Niasse, Aïssata, Louis, Kevin, Lenoir, Olivia, Schwarz, Chloé, Xu, Xiaoli, Couturier, Aymeric, Dobosziewicz, Hélène, Corchia, Anthony, Placier, Sandrine, Vandermeersch, Sophie, Hennighausen, Lothar, Frère, Perrine, Galichon, Pierre, Surin, Brigitte, Ouchelouche, Souhila, Louedec, Liliane, Migeon, Tiffany, Verpont, Marie-Christine, Yousfi, Nadir, Buob, David, Xu-Dubois, Yi-Chun, François, Hélène, Rondeau, Eric, Mesnard, Laurent, Hadchouel, Juliette, and Luque, Yosu

Published
2024
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4. Pulmonary hypertension without heart failure causes cardiorenal syndrome in a porcine model

Author

Arthur Orieux, Chloé Samson, Laurence Pieroni, Sarah Drouin, Simon Dang Van, Tiffany Migeon, Perrine Frere, Dorothée Brunet, David Buob, Juliette Hadchouel, Julien Guihaire, Olaf Mercier, and Pierre Galichon

Subjects
Medicine, Science
Abstract

Abstract Cardiorenal syndromes type 1 and 2 are complex disorders in which cardiac dysfunction leads to kidney dysfunction. However, the mechanisms remain incompletely explained, during pulmonary hypertension in particular. The objective of this study is to develop an original preclinical model of cardiorenal syndrome secondary to a pulmonary hypertension in piglets. Twelve 2-month-old Large White piglets were randomized in two groups: (1) induction of pulmonary hypertension by ligation of the left pulmonary artery and iterative embolizations of the right lower pulmonary artery, or (2) Sham interventions. We evaluated the cardiac function using right heart catheterization, echocardiography and measurement of biochemistry markers). Kidney was characterized using laboratory blood and urine tests, histological evaluation, immunostainings for renal damage and repair, and a longitudinal weekly assessment of the glomerular filtration rate using creatinine-based estimation and intravenous injection of an exogenous tracer on one piglet. At the end of the protocol (6 weeks), the mean pulmonary artery pressure (32 ± 10 vs. 13 ± 2 mmHg; p = 0.001), pulmonary vascular resistance (9.3 ± 4.7 vs. 2.5 ± 0.4 WU; p = 0.004) and central venous pressure were significantly higher in the pulmonary hypertension group while the cardiac index was not different. Piglets with pulmonary hypertension had higher troponin I. We found significant tubular damage and an increase in albuminuria in the pulmonary hypertension group and negative correlation between pulmonary hypertension and renal function. We report here the first porcine model of cardiorenal syndrome secondary to pulmonary hypertension.

Published
2023
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5. Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child

Author

Lévy, Romain, Zhang, Peng, Bastard, Paul, Dorgham, Karim, Melki, Isabelle, Hadchouel, Alice, Hartoularos, George C., Neven, Bénédicte, Castelle, Martin, Roy, Charlotte, Toin, Tom, Berteloot, Laureline, Bizien, Lucy, Abid, Hanène, Burgard, Marianne, Houhou-Fidouh, Nadhira, Rozenberg, Flore, Jouanguy, Emmanuelle, Ye, Chun Jimmie, Gorochov, Guy, Zhang, Qian, and Casanova, Jean-Laurent

Published
2021

6. CD31 signaling promotes the detachment at the uropod of extravasating neutrophils allowing their migration to sites of inflammation

Author

Francesco Andreata, Marc Clément, Robert A Benson, Juliette Hadchouel, Emanuele Procopio, Guillaume Even, Julie Vorbe, Samira Benadda, Véronique Ollivier, Benoit Ho-Tin-Noe, Marie Le Borgne, Pasquale Maffia, Antonino Nicoletti, and Giuseppina Caligiuri

Subjects
CD31, neutrophils, transmigration, iigrins, ITIM, Medicine, Science, Biology (General), QH301-705.5
Abstract

Effective neutrophil migration to sites of inflammation is crucial for host immunity. A coordinated cascade of steps allows intravascular leukocytes to counteract the shear stress, transmigrate through the endothelial layer, and move toward the extravascular, static environment. Those events are tightly orchestrated by integrins, but, while the molecular mechanisms leading to their activation have been characterized, the regulatory pathways promoting their detachment remain elusive. In light of this, it has long been known that platelet-endothelial cell adhesion molecule (Pecam1, also known as CD31) deficiency blocks leukocyte transmigration at the level of the outer vessel wall, yet the associated cellular defects are controversial. In this study, we combined an unbiased proteomic study with in vitro and in vivo single-cell tracking in mice to study the dynamics and role of CD31 during neutrophil migration. We found that CD31 localizes to the uropod of migrating neutrophils along with closed β2-integrin and is required for essential neutrophil actin/integrin polarization. Accordingly, the uropod of Pecam1-/- neutrophils is unable to detach from the extracellular matrix, while antagonizing integrin binding to extracellular matrix components rescues this in vivo migratory defect. Conversely, we showed that sustaining CD31 co-signaling actively favors uropod detachment and effective migration of extravasated neutrophils to sites of inflammation in vivo. Altogether, our results suggest that CD31 acts as a molecular rheostat controlling integrin-mediated adhesion at the uropod of egressed neutrophils, thereby triggering their detachment from the outer vessel wall to reach the inflammatory sites.

Published
2023
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7. Digital Action Plan (Web App) for Managing Asthma Exacerbations: Randomized Controlled Trial

Author

Nicole Beydon, Camille Taillé, Harriet Corvol, Judith Valcke, Jean-Jacques Portal, Laurent Plantier, Gilles Mangiapan, Caroline Perisson, Guillaume Aubertin, Alice Hadchouel, Guillaume Briend, Laurent Guilleminault, Catherine Neukirch, Pierrick Cros, Corinne Appere de Vecchi, Bruno Mahut, Eric Vicaut, and Christophe Delclaux

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundA written action plan (WAP) for managing asthma exacerbations is recommended. ObjectiveWe aimed to compare the effect on unscheduled medical contacts (UMCs) of a digital action plan (DAP) accessed via a smartphone web app combined with a WAP on paper versus that of the same WAP alone. MethodsThis randomized, unblinded, multicenter (offline recruitment in private offices and public hospitals), and parallel-group trial included children (aged 6-12 years) or adults (aged 18-60 years) with asthma who had experienced at least 1 severe exacerbation in the previous year. They were randomized to a WAP or DAP+WAP group in a 1:1 ratio. The DAP (fully automated) provided treatment advice according to the severity and previous pharmacotherapy of the exacerbation. The DAP was an algorithm that recorded 3 to 9 clinical descriptors. In the app, the participant first assessed the severity of their current symptoms on a 10-point scale and then entered the symptom descriptors. Before the trial, the wordings and ordering of these descriptors were validated by 50 parents of children with asthma and 50 adults with asthma; the app was not modified during the trial. Participants were interviewed at 3, 6, 9, and 12 months to record exacerbations, UMCs, and WAP and DAP use, including the subjective evaluation (availability and usefulness) of the action plans, by a research nurse. ResultsOverall, 280 participants were randomized, of whom 33 (11.8%) were excluded because of the absence of follow-up data after randomization, leaving 247 (88.2%) participants (children: n=93, 37.7%; adults: n=154, 62.3%). The WAP group had 49.8% (123/247) of participants (children: n=45, 36.6%; mean age 8.3, SD 2.0 years; adults: n=78, 63.4%; mean age 36.3, SD 12.7 years), and the DAP+WAP group had 50.2% (124/247) of participants (children: n=48, 38.7%; mean age 9.0, SD 1.9 years; adults: n=76, 61.3%; mean age 34.5, SD 11.3 years). Overall, the annual severe exacerbation rate was 0.53 and not different between the 2 groups of participants. The mean number of UMCs per year was 0.31 (SD 0.62) in the WAP group and 0.37 (SD 0.82) in the DAP+WAP group (mean difference 0.06, 95% CI −0.12 to 0.24; P=.82). Use per patient with at least 1 moderate or severe exacerbation was higher for the WAP (33/65, 51% vs 15/63, 24% for the DAP; P=.002). Thus, participants were more likely to use the WAP than the DAP despite the nonsignificant difference between the action plans in the subjective evaluation. Median symptom severity of the self-evaluated exacerbation was 4 out of 10 and not significantly different from the symptom severity assessed by the app. ConclusionsThe DAP was used less often than the WAP and did not decrease the number of UMCs compared with the WAP alone. Trial RegistrationClinicalTrials.gov NCT02869958; https://clinicaltrials.gov/ct2/show/NCT02869958

Published
2023
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8. COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study

Author

Spyros A. Papiris, Ilaria Campo, Francesca Mariani, Maria Kallieri, Lykourgos Kolilekas, Andriana I. Papaioannou, Efsun Gonca Chousein, Erdogan Cetinkaya, Francesco Bonella, Raphael Borie, Maria Kokosi, Thomas Pickworth, Maria Molina-Molina, Mercè Gasa, Elżbieta Radzikowska, Justyna Fijolek, Stéphane Jouneau, Emmanuel Gomez, Cormac McCarthy, Elisabeth Bendstrup, Wojciech J. Piotrowski, Rishi Pabary, Alice Hadchouel, Nathalie Coolen-Allou, Tiago Alfaro, Carlos Robalo Cordeiro, Elvira-Markela Antonogiannaki, Ioannis P. Tomos, Despoina Papakosta, Theodoros Kontakiotis, Panagiota Panagiotou, Konstantinos Douros, Andrea Schams, Sara Lettieri, Vassiliki Papaevangelou, Christina Kanaka-Gantenbein, Anna Karakatsani, Stelios Loukides, Ulrich Costabel, Bruno Crestani, Cliff Morgan, Ryushi Tazawa, Andrew Bush, Matthias Griese, and Effrosyni D. Manali

Subjects
Medicine
Published
2023
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10. Heterozygous expression of Cre recombinase in podocytes has no impact on the anti‐glomerular basement membrane glomerulonephritis model in C57BL/6J mice

Author

Cyril Mousseaux, Tiffany Migeon, Perrine Frère, Marie Christine Verpont, Elisabeth Lutete, Claire Navarro, Liliane Louedec, and Juliette Hadchouel

Subjects
crescentic glomerulonephritis, mouse models, NPHS2‐Cre, NTS, Physiology, QP1-981
Abstract

Abstract A recent article described a thickening of the glomerular basement membrane (GBM) along with changes in the expression of key components of the extracellular matrix in 6‐month‐old NPHS2‐Cre transgenic mice, which express the Cre recombinase specifically in podocytes. This transgenic line has been widely used to characterize the implication of candidate genes in glomerular diseases in younger mice. Using a different mouse strain (C57BL/6J) than the previous report (129S6/SvEvTac), we sought to characterize 3‐ and 6‐month‐old NPHS2‐Cre+/− mice in control and pathological conditions. At baseline, there was no difference in renal function and histology between control and NPHS2‐Cre+/− mice. Notably, GBM thickness evaluated by transmission electron microscopy was similar between the two groups. We then induced an immune‐mediated severe glomerular insult, the anti‐glomerular basement membrane glomerulonephritis model (anti‐GBM‐GN) in 3‐month‐old control and NPHS2‐Cre+/− mice. NPHS2‐Cre+/− mice exhibited the same alterations in renal function and structure as control mice. In summary, our study strongly suggests that NPHS2‐Cre+/− transgenic mice on a C57BL/6J background can be safely used for podocyte‐specific gene inactivation in control conditions and in the anti‐GBM‐GN model.

Published
2022
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11. Protective role of the podocyte IL-15 / STAT5 pathway in focal and segmental glomerulosclerosis

Author

Niasse, Aïssata, primary, Louis, Kevin, additional, Lenoir, Olivia, additional, Schwarz, Chloé, additional, Xu, Xiaoli, additional, Couturier, Aymeric, additional, Dobosziewicz, Hélène, additional, Corchia, Anthony, additional, Placier, Sandrine, additional, Vandermeersch, Sophie, additional, Hennighausen, Lothar, additional, Frère, Perrine, additional, Galichon, Pierre, additional, Surin, Brigitte, additional, Ouchelouche, Souhila, additional, Louedec, Liliane, additional, Migeon, Tiffany, additional, Verpont, Marie-Christine, additional, Yousfi, Nadir, additional, Buob, David, additional, Xu-Dubois, Yi-Chun, additional, François, Hélène, additional, Rondeau, Eric, additional, Mesnard, Laurent, additional, Hadchouel, Juliette, additional, and Luque, Yosu, additional

Published
2024
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12. Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach

Author

Guillaume Lezmi, Shamila Vibhushan, Claudia Bevilaqua, Nicolas Crapart, Nicolas Cagnard, Naziha Khen-Dunlop, Christine Boyle-Freyssaut, Alice Hadchouel, and Christophe Delacourt

Subjects
Congenital thoracic malformations, Cystic lung, Transcriptome, Transforming growth factor, Laser capture microdissection, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background The pathophysiology of congenital cystic adenomatoid malformations (CCAM) of the lung remains poorly understood. Aim This study aimed to identify more precisely the molecular mechanisms limited to a compartment of lung tissue, through a transcriptomic analysis of the epithelium of macrocystic forms. Methods Tissue fragments displaying CCAM were obtained during planned surgical resections. Epithelial mRNA was obtained from cystic and normal areas after laser capture microdissection (LCM). Transcriptomic analyses were performed and the results were confirmed by RT-PCR and immunohistochemistry in independent samples. Results After controlling for RNA quality, we analysed the transcriptomes of six cystic areas and five control areas. In total, 393 transcripts were differentially expressed in the epithelium, between CCAM and control areas. The most highly redundant genes involved in biological functions and signalling pathways differentially expressed between CCAM and control epithelium included TGFB2, TGFBR1, and MAP 2 K1. These genes were considered particularly relevant as they have been implicated in branching morphogenesis. RT-qPCR analysis confirmed in independent samples that TGFBR1 was more strongly expressed in CCAM than in control tissues (p

Published
2020
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13. Comparative therapeutic strategies for preventing aortic rupture in a mouse model of vascular Ehlers-Danlos syndrome.

Author

Anne Legrand, Charline Guery, Julie Faugeroux, Erika Fontaine, Carole Beugnon, Amélie Gianfermi, Irmine Loisel-Ferreira, Marie-Christine Verpont, Salma Adham, Tristan Mirault, Juliette Hadchouel, and Xavier Jeunemaitre

Subjects
Genetics, QH426-470
Abstract

Vascular Ehlers-Danlos syndrome is a rare inherited disorder caused by genetic variants in type III collagen. Its prognosis is especially hampered by unpredictable arterial ruptures and there is no therapeutic consensus. We created a knock-in Col3a1+/G182R mouse model and performed a complete genetic, molecular and biochemical characterization. Several therapeutic strategies were also tested. Col3a1+/G182R mice showed a spontaneous mortality caused by thoracic aortic rupture that recapitulates the vascular Ehlers-Danlos syndrome with a lower survival rate in males, thin non-inflammatory arteries and an altered arterial collagen. Transcriptomic analysis of aortas showed upregulation of genes related to inflammation and cell stress response. Compared to water, survival rate of Col3a1+/G182R mice was not affected by beta-blockers (propranolol or celiprolol). Two other vasodilating anti-hypertensive agents (hydralazine, amlodipine) gave opposite results on aortic rupture and mortality rate. There was a spectacular beneficial effect of losartan, reversed by the cessation of its administration, and a marked deleterious effect of exogenous angiotensin II. These results suggest that blockade of the renin angiotensin system should be tested as a first-line medical therapy in patients with vascular Ehlers-Danlos syndrome.

Published
2022
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14. Pharmaceutical Oral Formulation of Methionine as a Pediatric Treatment in Inherited Metabolic Disease

Author

Benjamin Querin, Arnaud Schweitzer-Chaput, Salvatore Cisternino, Sylvain Auvity, Anne-Sophie Fauqueur, Abdel Negbane, Alice Hadchouel, Joël Schlatter, and Camille Cotteret

Subjects
acceptability, methionine, nutrient, rare disease, stability indicating, Pharmacy and materia medica, RS1-441
Abstract

L-Methionine (Met) is an essential alpha-amino acid playing a key role in several metabolic pathways. Rare inherited metabolic diseases such as mutations affecting the MARS1 gene encoding methionine tRNA synthetase (MetRS) can cause severe lung and liver disease before the age of two years. Oral Met therapy has been shown to restore MetRS activity and improve clinical health in children. As a sulfur-containing compound, Met has a strongly unpleasant odor and taste. The objective of this study was to develop an optimized pediatric pharmaceutical formulation of Met powder, to be reconstituted with water, to obtain a stable oral suspension. Organoleptic characteristics and physicochemical stability of the powdered Met formulation and suspension were evaluated at three storage temperatures. Met quantification was assessed by a stability-indicating chromatographic method as well as microbial stability. The use of a specific fruit flavor (e.g., strawberry) with sweeteners (e.g., sucralose) was considered acceptable. No drug loss, pH changes, microbiological growth, or visual changes were observed at 23 ± 2 °C and 4 ± 2 °C with the powder formulation for 92 days, and the reconstituted suspension for at least 45 days. The developed formulation facilitates the preparation, administration, the dose adjustment and palatability of Met treatment in children.

Published
2023
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15. Mutation affecting the conserved acidic WNK1 motif causes inherited hyperkalemic hyperchloremic acidosis

Author

Louis-Dit-Picard, Helene, Kouranti, Ilektra, Rafael, Chloe, Loisel-Ferreira, Irmine, Chavez-Canales, Maria, Abdel-Khalek, Waed, Argaiz, Eduardo R., Baron, Stephanie, Vacle, Sarah, Migeon, Tiffany, Coleman, Richard, Do Cruzeiro, Marcio, Hureaux, Marguerite, Thurairajasingam, Nirubiah, Decramer, Stephane, Girerd, Xavier, O'Shaugnessy, Kevin, Mulatero, Paolo, Roussey, Gwenaelle, Tack, Ivan, Unwin, Robert, Vargas-Poussou, Rosa, Staub, Olivier, Grimm, Richard, Welling, Paul A., Gamba, Gerardo, Clauser, Eric, Hadchouel, Juliette, and Jeunemaitre, Xavier

Subjects
Gene mutations -- Health aspects, Protein kinases -- Genetic aspects -- Health aspects, Kidney tubules -- Physiological aspects -- Health aspects, Acidosis -- Genetic aspects -- Causes of -- Models, Health care industry
Abstract

Gain-of-function mutations in with no lysine (K)1 (WNK1) and WNK4genes are responsible for familial hyperkalemic hypertension (FHHt), a rare, inherited disorder characterized by arterial hypertension and hyperkalemia with metabolic acidosis. More recently, FHHt-causing mutations in the Kelch-like 3-Cullin 3 (KLHL3-CUL3) E3 ubiquitin ligase complex have shed light on the importance of WNK's cellular degradation on renal ion transport. Using full exome sequencing for a 4-generation family and then targeted sequencing in other suspected cases, we have identified new missense variants in the WNK1 gene clustering in the short conserved acidic motif known to interact with the KLHL3-CUL3 ubiquitin complex. Affected subjects had an early onset of a hyperkalemic hyperchloremic phenotype, but normal blood pressure values' Functional experiments in Xenopus laevis oocytes and HEK293T cells demonstrated that these mutations strongly decrease the ubiquitination of the kidney-specific isoform KS-WNK1 by the KLHL3-CUL3 complex rather than the long ubiquitous catalytically active L-WNK1 isoform. A corresponding CRISPR/Cas9 engineered mouse model recapitulated both the clinical and biological phenotypes. Renal investigations showed increased activation of the Ste20 proline alanine-rich kinase-[Na.sup.+]-[Cl.sup.-] cotransporter (SPAK-NCC) phosphorylation cascade, associated with impaired ROMK apical expression in the distal part of the renal tubule. Together, these new WNK1 genetic variants highlight the importance of the KS-WNK1 isoform abundance on potassium homeostasis., Introduction Familial hyperkalemic hypertension (FHHt), also known as Gordon syndrome and pseudohypoaldosteronism type 2, is a rare disease associated with net positive [Na.sup.+] balance and renal [K.sup.+] retention resulting in [...]

Published
2020
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17. Deletion of Yy1 in mouse lung epithelium unveils molecular mechanisms governing pleuropulmonary blastoma pathogenesis

Author

Kim Landry-Truchon, Nicolas Houde, Mickaël Lhuillier, Louis Charron, Alice Hadchouel, Christophe Delacourt, William D. Foulkes, Louise Galmiche-Rolland, and Lucie Jeannotte

Subjects
yy1, pleuropulmonary blastoma, congenital pulmonary airway malformation, mir-125a-3p, emt, lung development, Medicine, Pathology, RB1-214
Abstract

Pleuropulmonary blastoma (PPB) is a very rare pediatric lung disease. It can progress from abnormal epithelial cysts to an aggressive sarcoma with poor survival. PPB is difficult to diagnose as it can be confounded with other cystic lung disorders, such as congenital pulmonary airway malformation (CPAM). PPB is associated with mutations in DICER1 that perturb the microRNA (miRNA) profile in lung. How DICER1 and miRNAs act during PPB pathogenesis remains unsolved. Lung epithelial deletion of the Yin Yang1 (Yy1) gene in mice causes a phenotype mimicking the cystic form of PPB and affects the expression of key regulators of lung development. Similar changes in expression were observed in PPB but not in CPAM lung biopsies, revealing a distinctive PPB molecular signature. Deregulation of molecules promoting epithelial–mesenchymal transition (EMT) was detected in PPB specimens, suggesting that EMT might participate in tumor progression. Changes in miRNA expression also occurred in PPB lung biopsies. miR-125a-3p, a candidate to regulate YY1 expression and lung branching, was abnormally highly expressed in PPB samples. Together, these findings support the concept that reduced expression of YY1, due to the abnormal miRNA profile resulting from DICER1 mutations, contributes to PPB development via its impact on the expression of key lung developmental genes. This article has an associated First Person interview with the joint first authors of the paper.

Published
2020
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18. Simulation Game Versus Multiple Choice Questionnaire to Assess the Clinical Competence of Medical Students: Prospective Sequential Trial

Author

Fonteneau, Tristan, Billion, Elodie, Abdoul, Cindy, Le, Sebastien, Hadchouel, Alice, and Drummond, David

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundThe use of simulation games (SG) to assess the clinical competence of medical students has been poorly studied. ObjectiveThe objective of this study was to assess whether an SG better reflects the clinical competence of medical students than a multiple choice questionnaire (MCQ). MethodsFifth-year medical students in Paris (France) were included and individually evaluated on a case of pediatric asthma exacerbation using three successive modalities: high-fidelity simulation (HFS), considered the gold standard for the evaluation of clinical competence, the SG Effic’Asthme, and an MCQ designed for the study. The primary endpoint was the median kappa coefficient evaluating the correlation of the actions performed by the students between the SG and HFS modalities and the MCQ and HFS modalities. Student satisfaction was also evaluated. ResultsForty-two students were included. The actions performed by the students were more reproducible between the SG and HFS modalities than between the MCQ and HFS modalities (P=.04). Students reported significantly higher satisfaction with the SG (P

Published
2020
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19. Alveolar proteinosis of genetic origins

Author

Alice Hadchouel, David Drummond, Rola Abou Taam, Muriel Lebourgeois, Christophe Delacourt, and Jacques de Blic

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Pulmonary alveolar proteinosis (PAP) is a rare form of chronic interstitial lung disease, characterised by the intra-alveolar accumulation of lipoproteinaceous material. Numerous conditions can lead to its development. Whereas the autoimmune type is the main cause in adults, genetic defects account for a large part of cases in infants and children. Even if associated extra-respiratory signs may guide the clinician during diagnostic work-up, next-generation sequencing panels represent an efficient diagnostic tool. Exome sequencing also allowed the discovery of new variants and genes involved in PAP. The aim of this article is to summarise our current knowledge of genetic causes of PAP.

Published
2020
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20. CD31 signaling promotes the detachment at the uropod of extravasating neutrophils allowing their migration to sites of inflammation

Author

Andreata, Francesco, primary, Clément, Marc, additional, Benson, Robert A, additional, Hadchouel, Juliette, additional, Procopio, Emanuele, additional, Even, Guillaume, additional, Vorbe, Julie, additional, Benadda, Samira, additional, Ollivier, Véronique, additional, Ho-Tin-Noe, Benoit, additional, Le Borgne, Marie, additional, Maffia, Pasquale, additional, Nicoletti, Antonino, additional, and Caligiuri, Giuseppina, additional

Published
2023
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22. Energy depletion by cell proliferation sensitizes the kidney epithelial cells to injury.

Author

Galichon, Pierre, Lannoy, Morgane, Li Li, Serre, Justine, Vandermeersch, Sophie, Legouis, David, Valerius, M. Todd, Hadchouel, Juliette, and Bonventre, Joseph V.

Abstract

Acute kidney injury activates both proliferative and antiproliferative pathways, the consequences of which are not fully elucidated. If an initial proliferation of the renal epithelium is necessary for the successful repair, the persistence of proliferation markers is associated with the occurrence of chronic kidney disease. We hypothesized that proliferation in stress conditions impacts cell viability and renal outcomes. We found that proliferation is associated with cell death after various stresses in kidney cells. In vitro, the ATP/ADP ratio oscillates reproducibly throughout the cell cycle, and cell proliferation is associated with a decreased intracellular ATP/ADP ratio. In vivo, transcriptomic data from transplanted kidneys revealed that proliferation was strongly associated with a decrease in the expression of the mitochondria-encoded genes of the oxidative phosphorylation pathway, but not of the nucleus-encoded ones. These observations suggest that mitochondrial function is a limiting factor for energy production in proliferative kidney cells after injury. The association of increased proliferation and decreased mitochondrial function was indeed associated with poor renal outcomes. In summary, proliferation is an energy-demanding process impairing the cellular ability to cope with an injury, highlighting proliferative repair and metabolic recovery as indispensable and interdependent features for successful kidney repair. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Proceedings of the 23rd Annual Meeting of the Society in Europe for Simulation Applied to Medicine

Author

Anna Klimenko, Zhanna Tigai, Arnaud Desvergez, Arnaud Winer, Jean-Bernard Gouyon, Médéric Descoins, Bragard Isabelle, Gillet Aline, Servotte Jean-Christophe, Van Cauwenberge Isabelle, Donneau Anne-Françoise, Etienne Anne-Marie, Guillaume Michèle, Ghuysen Alexandre, Carla Sá-Couto, Pedro Vieira-Marques, Abel Nicolau, Diana Almeida, Ana Margarida Ferreira, Claudio Perretta, Diego Enriquez, Silvina Brizuela, Santiago Di Sipio, Angel Scapin, Sebastian Figueroa, Edgardo Szyld, David Drummond, Jennifer Truchot, Eleonora Fabbro, Pierre-François Ceccaldi, Patrick Plaisance, Antoine Tesnière, Alice Hadchouel, David Greaney, Mags Bourke, Crina Burlacu, Sinead Harte, Andrew Blackmore, Sanjay Gupta, Jade Zhao, Ranjev Kainth, Thomas Simpson, Gabriel Reedy, Amir Darakhshsan, Jerome Planchon, Anthony Vacher, Jeremy Comblet, Alexandre Mignon, Pierre Pasquier, Kassio Silva Temperly, Cecilia Hissai Yaegashi, Ana Maria de Lara, Bruno Bonat Cardoso, Nicole Karina Nicolaiko Temperly, Eduardo Murilo Novak, Libera Fresiello, Gianfranco Ferrari, Steven Jacobs, Bart Meyns, Marie Serge, Soraya Aiouaz, Cyril Astrugue, Vincent Deroissard, Pierre Parneix, Caroline Bervas, Anne-Gaëlle Venier, Michelet Daphné, Truchot Jennifer, Tesnière Antoine, Pippa Letchworth, Shane Duffy, Dan Phillips, Saana Korva, Hanna Vuojärvi, Secheresse Thierry, Pansu Pascal, Lima Laurent, Verhaeghe Caroline, Gonzalves Antoine, Bouet Pierre-Emmanuel, Gillard Philippe, Descamps Philippe, Legendre Guillaume, Paul Delval, and Sonia Abdenouri

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Published
2017
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25. COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study

Author

Spyros A. Papiris, Ilaria Campo, Francesca Mariani, Maria Kallieri, Lykourgos Kolilekas, Andriana I. Papaioannou, Efsun Gonca Chousein, Erdogan Cetinkaya, Francesco Bonella, Raphael Borie, Maria Kokosi, Thomas Pickworth, Maria Molina-Molina, Mercè Gasa, Elżbieta Radzikowska, Justyna Fijolek, Stéphane Jouneau, Emmanuel Gomez, Cormac McCarthy, Elisabeth Bendstrup, Wojciech J. Piotrowski, Rishi Pabary, Alice Hadchouel, Nathalie Coolen-Allou, Tiago Alfaro, Carlos Robalo Cordeiro, Elvira-Markela Antonogiannaki, Ioannis P. Tomos, Despoina Papakosta, Theodoros Kontakiotis, Panagiota Panagiotou, Konstantinos Douros, Andrea Schams, Sara Lettieri, Vassiliki Papaevangelou, Christina Kanaka-Gantenbein, Anna Karakatsani, Stelios Loukides, Ulrich Costabel, Bruno Crestani, Cliff Morgan, Ryushi Tazawa, Andrew Bush, Matthias Griese, Effrosyni D. Manali, National and Kapodistrian University of Athens (NKUA), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Centre Hospitalier Universitaire de La Réunion (CHU La Réunion)

Subjects
Pulmonary and Respiratory Medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medizin
Abstract

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

Published
2022
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26. Digital Action Plan (Web App) for Managing Asthma Exacerbations: Randomized Controlled Trial

Author

Beydon, Nicole, primary, Taillé, Camille, additional, Corvol, Harriet, additional, Valcke, Judith, additional, Portal, Jean-Jacques, additional, Plantier, Laurent, additional, Mangiapan, Gilles, additional, Perisson, Caroline, additional, Aubertin, Guillaume, additional, Hadchouel, Alice, additional, Briend, Guillaume, additional, Guilleminault, Laurent, additional, Neukirch, Catherine, additional, Cros, Pierrick, additional, Appere de Vecchi, Corinne, additional, Mahut, Bruno, additional, Vicaut, Eric, additional, and Delclaux, Christophe, additional

Published
2023
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29. Educational and health outcomes associated with bronchopulmonary dysplasia in 15-year-olds born preterm.

Author

David Drummond, Alice Hadchouel, Heloise Torchin, Jean-Christophe Rozé, Catherine Arnaud, Adèle Bellino, Laure Couderc, Stéphane Marret, Marie Mittaine, Didier Pinquier, Marie Vestraete, Jessica Rousseau, Pierre-Yves Ancel, Christophe Delacourt, and EPIPAGEADO study group

Subjects
Medicine, Science
Abstract

IntroductionTo evaluate the consequences of bronchopulmonary dysplasia (BPD) on academic outcomes and healthcare use in adolescents born very preterm.MethodsThis cohort study included 15-year-old adolescents born very preterm (< 32 weeks) between 2011 and 2013, with and without BPD, and controls born full term. Data regarding academic performance, current medical follow-up, and family characteristics were collected. Multivariate logistic regression was used to quantify relationships between academic outcomes and BPD.ResultsFrom the 1341 children included in the initial cohort, 985 adolescents were eligible and 351 included (55 preterms with a history of BPD, 249 without, and 47 controls). Among adolescents born very preterm, a history of BPD was associated with a higher risk to attend a school for children with special needs (p < 0.05) and to have repeated a grade (p = 0.01). It was also associated with an increased number of medical and paramedical consultations. A history of BPD was not associated with the parents' employment status, family structure, or the presence of younger siblings.ConclusionThis study highlights that a history of BPD is associated with poorer academic outcomes and high healthcare use in adolescence.

Published
2019
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30. Medical students’ learning processes the first time they role-play in psychiatry: A grounded theory study

Author

C. Loubières, Cédric Lemogne, Bruno Falissard, C. Layat Burn, Marie Koenig, Daphné Michelet, J.-S. Cadwallader, Antoine Tesniere, M.-A. Piot, Jan-Joost Rethans, A. Hadchouel, RS: SHE - R1 - Research (OvO), and Skillslab

Subjects
Formation par simulation, medicine.medical_specialty, Students, Medical, Process (engineering), media_common.quotation_subject, education, EMPATHY, Role-playing, ?tudiants en m?decine, SIMULATED PATIENTS, Affect (psychology), Grounded theory, Constructivist grounded theory, Arts and Humanities (miscellaneous), Perception, Simulation training, medicine, Humans, Student learning, Role Playing, Students, Psychiatry, Jeux de r?le, media_common, Medicap Apprentissage, Education, Medical, Debriefing, WORLDS, EDUCATION, Apprentissage, Psychiatry and Mental health, Grounded Theory, Triangulation (psychology), Psychology, Psychiatrie
Abstract

BACKGROUND: Recent changes in psychiatric care and teaching that limit patient contact for medical students can be overcome in part by simulation-based education. Understanding the learning processes of medical students involved in psychiatric simulation-based programmes could usefully inform efforts to improve this teaching. This study explored the learning processes of medical students the first time they role-play in psychiatry.METHODS: We used constructivist grounded theory to analyse semi-structured interviews of 13 purposively sampled medical students and the six psychiatrists who trained them. To improve the triangulation process, the results of this analysis were compared with those of the analyses of the role-play video and the debriefing audio-tapes.RESULTS: Five organising themes emerged: improving the students' immediate perception of patients with mental disorders; cultivating clinical reasoning; managing affect; enhancing skills and attitudes and fostering involvement in learning psychiatry.CONCLUSION: Results suggest that psychiatric role-playing can improve students' progressive understanding of psychiatry through the development of intuition and by allaying affects. Emotional elaboration and student involvement appear to be key features.

Published
2022
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32. Systemic inflammatory syndrome in children with <scp> FARSA </scp> deficiency

Author

Fabienne Charbit‐Henrion, Roman Goguyer‐Deschaumes, Keren Borensztajn, Marc Mirande, Jérémy Berthelet, Fernando Rodrigues‐Lima, Anis Khiat, Marie‐Louise Frémond, Brigitte Bader‐Meunier, Marco M. Rodari, Luis Seabra, Gillian I. Rice, Marie Legendre, David Drummond, Laureline Berteloot, Charles‐Joris Roux, Nathalie Boddaert, Philippe Drabent, Thierry Jo Molina, Florence Lacaille, Manoelle Kossorotoff, Nadine Cerf‐Bensussan, Marianna Parlato, Alice Hadchouel, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Manchester [Manchester], UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], and Couvet, Sandrine

Subjects
Amino Acyl-tRNA Synthetases/genetics, ARSopathy, [SDV]Life Sciences [q-bio], Syndrome, autoinflammation, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Amino Acyl-tRNA Synthetases, [SDV] Life Sciences [q-bio], Consanguinity, Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Charcot-Marie-Tooth Disease, Genetics, Charcot-Marie-Tooth Disease/genetics, Humans, FARSA, Lung Diseases, Interstitial/genetics, Lung Diseases, Interstitial, Genetics (clinical)
Abstract

International audience; Variants in aminoacyl-tRNA synthetases (ARSs) genes are associated to a broad spectrum of human inherited diseases. Patients with defective PheRS, encoded by FARSA and FARSB, display brain abnormalities, interstitial lung disease and facial dys-morphism. We investigated four children from two unrelated consanguineous families carrying two missense homozygous variants in FARSA with significantly reduced PheRS-mediated aminoacylation activity. In addition to the core ARS-phenotype, patients showed an inflammatory profile associated with autoimmunity and interferon score, a clinical feature not ascribed to PheRS-deficient patients to date. JAK inhibition improved lung disease in one patient. Our findings expand the genetic and clinical spectrum of FARSA-related disease

Published
2022
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33. Proceedings of Réanimation 2017, the French Intensive Care Society International Congress

Author

Bougouin, Wulfran, Marijon, Eloi, Planquette, Benjamin, Karam, Nicole, Dumas, Florence, Celermajer, David, Jost, Daniel, Lamhaut, Lionel, Beganton, Frankie, Cariou, Alain, Meyer, Guy, Jouven, Xavier, Bureau, Côme, Charpentier, Julien, Salem, Omar Ben Hadj, Guillemet, Lucie, Arnaout, Michel, Ferre, Alexis, Geri, Guillaume, Mongardon, Nicolas, Pène, Frédéric, Chiche, Jean-Daniel, Mira, Jean-Paul, Labro, Guylaine, Belon, François, Luu, Vinh-Phuc, Chenet, Julien, Besch, Guillaume, Puyraveau, Marc, Piton, Gaël, Capellier, Gilles, Martin, Maëlle, Lascarrou, Jean-Baptiste, Le Thuaut, Aurélie, Lacherade, Jean-Claude, Martin-Lefèvre, Laurent, Fiancette, Maud, Vinatier, Isabelle, Lebert, Christine, Bachoumas, Konstantinos, Yehia, Aihem, Henry-Laguarrigue, Matthieu, Colin, Gwenhaël, Reignier, Jean, Privat, Elodie, Escutnaire, Joséphine, Dumont, Cyrielle, Baert, Valentine, Vilhelm, Christian, Hubert, Hervé, Robert-Edan, Vincent, Lakhal, Karim, Quartin, Andrew, Hobbs, Brian, Cely, Cynthia, Bell, Cynthia, Pham, Tai, Schein, Roland, Geng, Yimin, Ng, Chaan, Ehrmann, Stephan, Gandonnière, Charlotte Salmon, Boisramé-Helms, Julie, Le Tilly, Olivier, De Bretagne, Isabelle Benz, Mercier, Emmanuelle, Mankikian, Julie, Bretagnol, Anne, Meziani, Ferhat, Halimi, Jean Michel, Le Guellec, Chantal Barin, Gaudry, Stéphane, Hajage, David, Tubach, Florence, Pons, Bertrand, Boulet, Eric, Boyer, Alexandre, Chevrel, Guillaume, Lerolle, Nicolas, Carpentier, Dorothée, de Prost, Nicolas, Lautrette, Alexandre, Mayaux, Julien, Nseir, Saad, Ricard, Jean-Damien, Dreyfuss, Didier, Robert, René, Garzotto, Franscesco, Kipnis, Eric, Tetta, Ciro, Ronco, Claudio, Schnell, David, Aurelie, Bourmaud, Reynaud, Marie, Clec’h, Christophe, Benyamina, Mourad, Vincent, François, Mariat, Christophe, Bornstain, Caroline, Rouleau, Stephane, Leroy, Christophe, Cohen, Yves, Morel, Jerome, Legrand, Matthieu, Terreaux, Jeremy, Darmon, Michaël, Cantier, Marie, Morisot, Adeline, Guérot, Emmanuel, Canet, Emmanuel, De Montmollin, Etienne, Voiriot, Guillaume, Neuville, Mathilde, Timsit, Jean-François, Sonneville, Romain, Fayssoil, Abdallah, Stojkovic, Tania, Behin, Anthony, Ogna, Adam, Lofaso, Frédéric, Laforet, Pascal, Wahbi, Karim, Prigent, Helene, Duboc, Denis, Orlikowski, David, Eymard, Bruno, Annane, Djillali, Le Guennec, Loic, Cholet, Clémentine, Bréchot, Nicolas, Hekimian, Guillaume, Besset, Sébastien, Lebreton, Guillaume, Nieszkowska, Ania, Trouillet, Jean Louis, Leprince, Pascal, Combes, Alain, Luyt, Charles-Edouard, Griton, Marion, Sesay, Musa, De Panthou, Nadia Sibaï, Bienvenu, Thomas, Biais, Matthieu, Nouette-Gaulain, Karine, Fossat, Guillaume, Baudin, Florian, Coulanges, Cécile, Bobet, Sabrine, Dupont, Arnaud, Courtes, Léa, Benzekri, Dalila, Kamel, Toufik, Muller, Grégoire, Bercault, Nicolas, Barbier, François, Runge, Isabelle, Skarzynski, Marie, Mathonnet, Armelle, Boulain, Thierry, Jouan, Youenn, Teixera, Noémie, Hassen-Khodja, Claire, Guillon, Antoine, Gaborit, Christophe, Grammatico-Guillon, Leslie, Rebière, Cécile, Azoulay, Elie, Misset, Benoit, Ruckly, Stephane, Garrouste-Orgeas, Maïté, Kentish-Barnes, Nancy, Duranteau, Jacques, Thuong, Marie, Joseph, Liliane, Renault, Anne, Lesieur, Olivier, Larbi, Anne-Gaelle Si, Viquesnel, Gérald, Zuber, Benjamin, Marque, Sophie, Kandelman, Stanislas, Pichon, Nicolas, Floccard, Bernard, Galon, Marion, Chevret, Sylvie, Kentish-Barnes, Nancy, Seegers, Valérie, Legriel, Stéphane, Jaber, Samir, Lefrant, Jean Yves, Reuter, Danielle, Guisset, Olivier, Cracco, Christophe, Seguin, Amélie, Durand-Gasselin, Jacques, Thirion, Marine, Cohen-Solal, Zoé, Foulgoc, Hélène, Rogier, Julien, Delobbe, Elsa, Schortgen, Frédérique, Asfar, Pierre, Julie, Boisramé-Helms, Grimaldi, David, Fabien, Grelon, Anguel, Nadia, Sigismond, Lasocki, Matthieu, Henry-Lagarrigue, Gonzalez, Frédéric, François, Legay, Guitton, Christophe, Schenck, Maleka, Jean-Marc, Doise, Radermacher, Peter, Kentish-Barnes, Nancy, Makunza, Joseph Nsiala, Nathalie, Mejeni Kamdem, Pierre, Akilimali, Adolphe, Kilembe Manzanza, Mahieu, Rafael, Reydel, Thomas, Jamet, Angéline, Chudeau, Nicolas, Huntzinger, Julien, Grange, Steven, Courte, Anne, Lemarie, Jérémie, Gibot, Sébastien, Champey, Julia, Dellamonica, Jean, Du Cheyron, Damien, Contou, Damien, Tadié, Jean-Marc, Cour, Martin, Beduneau, Gaetan, Marchalot, Antoine, Guérin, Laurent, Jochmans, Sebastien, Terzi, Nicolas, Preau, Sebastien, Brun-Buisson, Christian, Dessap, Armand Mekontso, Vedrenne-Cloquet, Meryl, Breinig, Sophie, Jung, Camille, Brussieux, Maxime, Marcoux, Marie-Odile, Durrmeyer, Xavier, Blondé, Renaud, Angoulvant, François, Grasset, Jérôme, Naudin, Jérôme, Dauger, Stéphane, Remy, Solenn, Kolev-Descamp, Karine, Demaret, Julie, Monneret, Guillaume, Javouhey, Etienne, Chomton, Maryline, Sauthier, Michaël, Vallieres, Emilie, Jouvet, Philippe, Geslain, Guillaume, Guellec, Isabelle, Rambaud, Jérôme, Schmidt, Matthieu, Schellongowski, Peter, Dorget, Amandine, Patroniti, Nicolo, Taccone, Fabio Silvio, Miranda, Dinis Reis, Reuter, Jean, Prodanovic, Hélène, Pierrot, Marc, Balik, Martin, Park, Sunghoon, Guérin, Claude, Papazian, Laurent, Jean, Reignier, Ayzac, Louis, Loundou, Anderson, Forel, Jean-Marie, Mezidi, Mehdi, Aublanc, Mylène, Perinel-Ragey, Sophie, Lissonde, Floriane, Louf-Durier, Aurore, Tapponnier, Romain, Yonis, Hodane, Coudroy, Remi, Frat, Jean-Pierre, Boissier, Florence, Thille, Arnaud W., Richard, Flore, Le Gullou-Guillemette, Hélène, Fahri, Jonathan, Kouatchet, Achille, Bodet-Contentin, Laetitia, Garot, Denis, Le Pennec, Déborah, Vecellio, Laurent, Tavernier, Elsa, Dequin, Pierre François, Messika, Jonathan, Martin, Yolaine, Maquigneau, Natacha, Puechberty, Christelle, Stoclin, Annabelle, Villard, Serge, Dechanet, Aline, De Jong, Audrey, Monnin, Marion, Girard, Mehdi, Chanques, Gérald, Molinari, Nicolas, Decavèle, Maxens, Campion, Sébastien, Ainsouya, Roukia, Niérat, Marie-Cécile, Raux, Mathieu, Similowski, Thomas, Demoule, Alexandre, Razazi, Keyvan, Tchir, Martial, May, Faten, Carteaux, Guillaume, Pauline, Rougevin-Baville, Marc, Andronikof, Bedos, Jean Pierre, Mehrsa, Koukabi, Mauger-Briche, Carole, Mijon, François, Trouiller, Pierre, Sztrymf, Benjamin, Cretallaz, Pierre, Mermillod-Blondin, Romain, Savary, Dominique, Sedghiani, Ines, Doghri, Hamdi, Jendoubi, Asma, Hamdi, Dhekra, Cherif, Mohamed Ali, Hechmi, Youssef Zied El, Zouheir, Jerbi, Persico, Nicolas, Maltese, Francois, Ferrigno, Cécile, Bablon, Amandine, Marmillot, Cécile, Roch, Antoine, Sedghiani, Ines, Papin, Grégory, Gainnier, Marc, Argaud, Laurent, Christophe, Adrie, Souweine, Bertrand, Goldgran-Toledano, Dany, Marcotte, Guillaume, Dumenil, Anne Sylvie, Carole, Schwebel, Cecchini, Jerôme, Tuffet, Samuel, Fartoukh, Muriel, Roux, Damien, Thyrault, Martial, Armand, Mekontso Dessap, Chauveau, Simon, Wesner, Nadège, Monnier-Cholley, Laurence, Bigé, Naïke, Ait-Oufella, Hafid, Guidet, Bertrand, Dubée, Vincent, Labroca, Pierre, Lemarié, Jérémie, Chiesa, Gérard, Laroyenne, Isabelle, Borrini, Léo, Klotz, Rémi, Sy, Quoc Phan, Cristina, Marie-Christine, Paysant, Jean, Fillâtre, Pierre, Gacouin, Arnaud, Revest, Matthieu, Tattevin, Pierre, Flecher, Erwan, Le Tulzo, Yves, Jamme, Matthieu, Daviaud, Fabrice, Marin, Nathalie, Thy, Michael, Duceau, Baptiste, Ardisson, Fanny, Sandrine, Valade, Venot, Marion, Schlemmer, Benoît, Zafrani, Lara, Pons, Stéphanie, Styfalova, Lenka, Bouadma, Lila, Radjou, Aguila, Lebut, Jordane, Mourvillier, Bruno, Dorent, Richard, Dilly, Marie-Pierre, Nataf, Patrick, Wolff, Michel, Le Gall, Aëlle, Bourcier, Simon, Tandjaoui-Lambiotte, Yacine, Das, Vincent, Alves, Mikael, Bigé, Naïke, Kamilia, Chtara, Rania, Ammar, Baccouch, Najeh, Turki, Olfa, Ben, Hmida Chokri, Bahloul, Mabrouk, Bouaziz, Mounir, Dupuis, Claire, Perozziello, Anne, Letheulle, Julien, Valette, Marc, Herrmann-Storck, Cécile, Crosby, Laura, Elkoun, Khalid, Madeux, Benjamin, Martino, Frédéric, Migueres, Hélène, Piednoir, Pascale, Posch, Matthias, Thiery, Guillaume, Huynh-Ky, Minh-Tu, Bouchard, Pierre Alexandre, Sarrazin, Jean-François, Lellouche, François, Nay, Mai-Anh, Lortat-Jacob, Brice, Rozec, Bertrand, Colnot, Marion, Belin, Nicolas, Barrot, Loïc, Navellou, Jean-Christophe, Patry, Cyrille, Chaignat, Claire, Claveau, Melanie, Claude, Frédéric, Aubron, Cécile, Mcquilten, Zoe, Bailey, Michael, Board, Jasmin, Buhr, Heidi, Cartwright, Bruce, Dennis, Mark, Forrest, Paul, Hodgson, Carol, Mcilroy, David, Murphy, Deirdre, Murray, Lynnette, Pellegrino, Vincent, Pilcher, David, Sheldrake, Jayne, Tran, Huyen, Vallance, Shirley, Cooper, Jamie, Bombled, Camille, Vidal, Charles, Margetis, Dimitri, Amour, Julien, Coart, Domien, Dubois, Jasperina, Van Herpe, Tom, Mesotten, Dieter, Bailly, Sébastien, Lucet, Jc, Lepape, Alain, L’hériteau, François, Aupée, Martine, Bervas, Caroline, Boussat, Sandrine, Berger-Carbonne, Anne, Machut, Anaïs, Savey, Anne, Tudesq, Jean-Jacques, Valade, Sandrine, Galicier, Lionel, De Bazelaire, Cédric, Munoz-Bongrand, Nicolas, Mignard, Xavier, Biard, Lucie, Mokart, Djamel, Nyunga, Martine, Bruneel, Fabrice, Rabbat, Antoine, Perez, Pierre, Meert, Anne Pascale, Benoit, Dominique, Mariotte, Eric, Ehooman, Franck, Hamidfar-Roy, Rebecca, Hourmant, Yannick, Mailloux, Arnaud, Beurton, Alexandra, Teboul, Jean-Louis, Girroto, Valentina, Laura, Galarza, Richard, Christian, Monnet, Xavier, Dubée, Vincent, Merdji, Hamid, Dang, Julien, Preda, Gabriel, Baudel, Jean-Luc, Desnos, Cyrielle, Zeitouni, Michel, Belaroussi, Ines, Parrot, Antoine, Blayau, Clarisse, Fulgencio, Jean-Pierre, Quesnel, Christophe, Labbe, Vincent, De Chambrun, Marc Pineton, Beloncle, François, Merceron, Sybille, Fedun, Yannick, Lecomte, Bernard, Devaquet, Jérôme, Puidupin, Marc, Verdière, Bruno, Amoura, Zahir, Vuillard, Constance, Xavier, Jais, Bourlier, Delphine, David, Amar, Caroline, Sattler, David, Montani, Gerald, Simmoneau, Olivier, Sitbon, Humbert, Marc, Laurent, Savale, Dujardin, Olivier, Bouglé, Adrien, Ait, Hamou Nora, Salem, Joe Elie, El-Helali, Najoua, Coppere, Zoé, Gibelin, Aude, Taconet, Clementine, Djibre, Michel, Maamar, Adel, Colobert, Elen, Fillatre, Pierre, Uhel, Fabrice, Camus, Christophe, Moraly, Josquin, Dahoumane, Redouane, Maury, Eric, Tan, Boun Kim, Emmanuel, Vivier, Pauline, Misslin, Laurence, Parmeland, Philippe, Poirié, Zahar, Jean-Ralph, Catherine, Haond, Christian, Pommier, Karim, Ait-Bouziad, Mounia, Hocine, Laura, Témime, Rasoldier, Vero Hanitra, Mager, Guy, Eraldi, Jean-Pierre, Gelinotte, Stéphanie, Bougerol, François, Dehay, Julien, Rigaud, Jean-Philippe, Declercq, Pierre Louis, Michel, Julien, Aissa, Nejla, Henard, Sandrine, Guerci, Philippe, Latar, Ichraq, Levy, Bruno, Girerd, Nicolas, Kimmoun, Antoine, Abdallah, Saousen Ben, Nakaa, Sabrine, Hraiech, Kmar, Braiek, Dhouha Ben, Adhieb, Ali, M’ghirbi, Abdelwaheb, Ousji, Ali, Hammouda, Zeineb, Abroug, Fekri, Sellami, Walid, Hajjej, Zied, Samoud, Walid, Labbene, Iheb, Ferjani, Mustapha, Medhioub, Fatma Kaaniche, Allela, Rania, Algia, Najla Ben, Cherif, Samar, Attia, Delphine, Herinjatovo, Andrianjafy, Francois, Xavier Laborne, Bouhouri, Med Aziz, Slaoui, Mohamed Taoufik, Soufi, A., Khaleq, K., Hamoudi, D., Nsiri, A., Harrar, R., Maury, Eric, Goursaud, Suzanne, Gauberti, Maxime, Labeyrie, Paul-Emile, Gaberel, Thomas, Agin, Véronique, Maubert, Eric, Vivien, Denis, Gakuba, Clément, Armel, Anwar, Abdou, Rchi, Kalouch, Samira, Yaqini, Khalid, Chlilek, Aziz, Sellami, Walid, Yedder, Soumaya Ben, Tonnelier, Alexandre, Hervé, Fabien, Halley, Guillaume, Frances, Jean-Luc, Moriconi, Mickael, Saoli, Mathieu, Garnero, Aude, Demory, Didier, Arnal, Jean Michel, Canoville, Bertrand, Daubin, Cédric, Brunet, Jennifer, Ghezala, Hassen Ben, Snouda, Salah, Ben, Chiekh Imen, Kaddour, Moez, Ouanes, Islem, Marzouk, Mahdi, Haniez, Françoise, Jaillet, Hélène, Maas, Henri, Andrivet, Pierre, Darné, Christian, Viau, François, Ghezala, Hassen Ben, Ouanes, Islem, Dangers, Laurence, Montlahuc, Claire, Perbet, Sébastien, Ouanes, Islem, Hamouda, Zeineb, Nakee, Sabrine, Ouanes-Besbes, Lamia, Meddeb, Khaoula, Khedher, Ahmed, Sma, Nesrine, Ayachi, Jihene, Khelfa, Messaouda, Fraj, Nesrine, Lakhal, Hend Ben, Hammed, Hedia, Boukadida, Raja, Hafsa, Hajer, Chouchene, Imed, Boussarsar, Mohamed, Ben, Braiek Dhouha, Ouanes-Besbes, Lamia, Benatti, Kaoutar, Dafir, A., Aissaoui, W., Elallame, W., Haddad, W., Cherkab, R., Elkettani, C., Barrou, L., Hamou, Zakaria Ait, Repessé, Xavier, Charron, Cyril, Aubry, Alix, Paternot, Alexis, Maizel, Julien, Slama, Michel, Vieillard-Baron, Antoine, Trifi, Ahlem, Abdellatif, Sami, Fatnassi, Meriem, Daly, Foued, Nasri, Rochdi, Ismail, Khaoula Ben, Lakhal, Salah Ben, Bazalgette, Florian, Daurat, Aurelien, Roger, Claire, Muller, Laurent, Doyen, Denis, Plattier, Rémi, Robert, Alexandre, Hyvernat, Hervé, Bernardin, Gilles, Jozwiak, Mathieu, Gimenez, Julia, Mercado, Pablo, Depret, François, Tilouch, Najla, Mater, Houda, Habiba, Ben Sik Ali, Jaoued, Oussama, Gharbi, Rim, Hassen, Mohamed Fekih, Elatrous, Souheil, Pasquier, Pierre, Vuillemin, Quentin, Schaal, Jean-Vivien, Martinez, Thibault, Duron, Sandrine, Trousselard, Marion, Schwartzbrod, Pierre-Eric, Baugnon, Thomas, Dupic, Laurent, Gout, Caroline Duracher, De Saint Blanquat, Laure, Séguret, Sylvie, Le Ficher, Gaelle, Orliaguet, Gilles, Hubert, Philippe, Bigé, Naïke, Leblanc, Guillaume, Briand, Raphael, Brousse, Lucas, Brunet, Valentine, Chatelain, Léonard, Prat, Dominique, Jacobs, Frédéric, Demars, Nadège, Hamzaoui, Olfa, Moneger, Guy, Sztrymf, Benjamin, Duburcq-Gury, Emilie, Satre-Buisson, Léa, Duburcq, Thibault, Poissy, Julien, Robriquet, Laurent, Jourdain, Merce, Sécheresse, Thierry, Miquet, Mattéo, Simond, Alexis, Usseglio, Pascal, Hamdaoui, Yamina, Boussarsar, Mohamed, Desailly, Victoire, Brun, Patrick, Iglesias, Pauline, Huet, Jérémie, Masseran, Clémence, Claudon, Antoine, Ebeyer, Clément, Truong, Thomas, Tesnière, Antoine, Mignon, Alexandre, Gaudry, Stéphane, Resiere, Dabor, Valentino, Ruddy, Fabre, Julien, Roze, Benoit, Ferge, Jean-Louis, Charbatier, Cyrille, Marie, Sabia, Scholsser, Michel, Aitsatou, Signate, Raad, Mathieu, Cabie, Andre, Mehdaoui, Hossein, Cousin, Clement, Rousseau, Christophe, Llitjos, Jean-François, Alby-Laurent, Fanny, Toubiana, Julie, Belaidouni, Nadia, Cherruault, Marlène, Tamburini, Jérome, Bouscary, Didier, Fert, Sarah, Delile, Eugénie, Besnier, Emmanuel, Coquerel, David, Nevière, Rémi, Richard, Vincent, Tamion, Fabienne, Wei, Chaojie, Louis, Huguette, Margaux, Schmitt, Eliane, Albuisson, Sophie, Orlowski, Kimmoun, Antoine, Riad, Zakaria, Coroir, Marine, Rémy, Bernard, Camille, Bombled, Joffre, Jeremie, Aegerter, Philippe, Ilic, Dejan, Ginet, Marc, Pignard, Caroline, Nguyen, Philippe, Mourey, Guillaume, Samain, Emmanuel, Pili-Floury, Sebastien, Jouffroy, Romain, Nicolas, Caill, Alvarez, Jean-Claude, Tomasso, Maraffi, Philippe, Pascal, Raphalen, Jean-Herlé, Frédéric, J. Baud, Vivien, Benoit, Pierre, Carli, Baud, Frederic, Fredj, Hana, Blel, Youssef, Brahmi, Nozha, Ghezala, Hassen Ben, Hanak, Anne-Sophie, Malissin, Isabelle, Poupon, Joel, Risede, Patricia, Chevillard, Lucie, Megarbane, Bruno, Barghouth, Manel, M’rad, Aymen, Hmida, Marwa Ben, Thabet, Hafedh, Liang, Hao, Callebert, Jacques, Lagard, Camille, Megarbane, Bruno, Habacha, Sahar, Chatbri, Bassem, Camillerapp, Christophe, Labat, Laurence, Soichot, Marion, Garçon, Pierre, Goury, Antoine, Kerdjana, Lamia, Voicu, Sebastian, Deye, Nicolas, Megarbane, Bruno, Armel, Anwar, Anas, Benqqa, Othman, Mezgui, Moumine, S., Kalouch, S., Yakini, K. K., Chlilek, A., Hajji, Ahmed, Louati, Assaad, Khaldi, Ammar, Borgi, Aida, Ghali, Nargess, Bouziri, Asma, Menif, Khaled, Ben, Jaballah Najla, Armel, Anwar, Brochon, Jeanne, Dumitrescu, Mihaela, Thévenot, Sarah, Saulnier, Jean-Pascal, Husseini, Khaled, Laland, Catherine, Cremniter, Julie, Bousseau, Anne, Castel, Olivier, Brémaud-Csizmadia, Cassandra, Diss, Margot, Portefaix, Aurélie, Berthiller, Julien, Gillet, Yves, Aoul, Nabil Tabet, Douah, Ali, Addou, Zakaria, Youbi, Houari, Moussati, Mohamed, Belhabiche, Kamel, Mir, Souad, Abada, Sanaa, Amel, Zerhouni, Aouffen, Nabil, Bouzit, Zina, Grati, Ahmed H., Dhonneur, Gilles F., Boussarsar, Mohamed, Lau, Nicolas, Mezhari, Ilham, Roucaud, Nicolas, Le Meur, Matthieu, Paulet, Rémi, Coudray, Jean-Michel, Ghomari, Wahiba Imène, Boumlik, Reda, Peigne, Vincent, Daban, Jean-Louis, Boutonnet, Mathieu, Lenoir, Bernard, Yassine, Hafiani, Mohamed, Cheikh Chaigar, Khalid, Allali, Ihssan, Moussaid, Said, Elyoussoufi, Said, Salmi, Jazia, Amira Ben, Fatima, Jaziri, Wafa, Skouri, Maha, Bennasr, Khaoula, Ben Abdelghni, Sami, Turki, Abdallah Taeib, B., Medhioub, Fatma Kaaniche, Rollet-Cohen, Virginie, Sachs, Philippe, Merchaoui, Zied, Renolleau, Sylvain, Oualha, Mehdi, Eloi, Maxime, Jean, Sandrine, Demoulin, Maryne, Valentin, Cécile, Guilbert, Julia, Walti, Hervé, Carbajal, Ricardo, Leger, Pierre-Louis, Karaca-Altintas, Yasemin, Botte, Astrid, Labreuche, Julien, Drumez, Elodie, Devos, Patrick, Bour, Franck, Leclerc, Francis, Ahmed, Ayari, khaled, Menif, Louati, Assaad, Aida, Borgi, Ammar, Khaldi, Narjess, Ghali, Ahmed, Hajji, Asma, Bouziri, Jaballah, Nejla Ben, Leger, Pierre-Louis, Pansiot, Julien, Besson, Valérie, Palmier, Bruno, Baud, Olivier, Cauli, Bruno, Charriaut-Marlangue, Christiane, Mansuy, Amélie, Michel, Fabrice, Le Bel, Stéphane, Boubnova, Julia, Ughetto, Fabrice, Ovaert, Caroline, Fouilloux, Virginie, Paut, Olivier, Jacquet-Lagrèze, Matthias, Tiebergien, Nicolas, Hanna, Najib, Evain, Jean-Noël, Baudin, Florent, Courtil-Teyssedre, Sonia, Bompard, Dominique, Lilot, Marc, Chardonal, Laurent, Fellahi, Jean-Luc, Claverie, Claire, Pouessel, Guillaume, Dorkenoo, Aimée, Renaudin, Jean-Marie, Eb, Mireille, Deschildre, Antoine, Leteurtre, Stéphane, Yassine, Hafiani, Kamal, Belkadi, Adil, Oboukhlik, Ouafa, Aalalam, Mouhamed, Moussaoui, Rachid, Charkab, Lahoucine, Barrou, Dachraoui, Fahmi, Nakkaa, Sabrine, Zaineb, Hammouda, Mlika, Dorra, Gloulou, Olfa, Boussarsar, Mohamed, Zelmat, Setti-Aouicha, Batouche, Djamila-Djahida, Chaffi, Belkacem, Mazour, Fatima, Benatta, Nadia, Fathallah, Ines, Aloui, Rafaa, Zoubli, Aymen, Kouraichi, Nadia, Fathallah, Ines, Kouraichi, N., Salem, Shireen, Vicaut, Eric, Megarbane, Bruno, Ambroise, David, Loriot, Anne-Marie, Bourgogne, Emmanuel, Megarbane, Bruno, Ghadhoune, Hatem, Jihene, Guissouma, Trabelsi, Insaf, Allouche, Hend, Brahmi, Habib, Samet, Mohamed, Ghord, Hatem El, Lebeau, Rodolphe, Laplanche, Jean-Louis, Benturquia, Nadia, Megarbane, Bruno, Blel, Youssef, M’rad, A., Essafi, Fatma, Benabderrahim, A., Jouffroy, Romain, Resiere, Dabor, Sanchez, Bruno, Inamo, Jocelyn, Megarbane, Bruno, Batouche, Djamila-Djahida, Zerhouni, Amel, Tabeliouna, Kheira, Negadi, Amine, Mentouri, Zahia, Le Gall, Fanny, Hanouz, Jean-Luc, Normand, Hervé, Khoury, Abdo, Sall, Fatimata Seydou, De Luca, Alban, Pugin, Aurore, Pazart, Lionel, Vidal, Chrystelle, Leroux, Franck, Khoury, Abdo, L’Her, Erwan, Marjanovic, Nicolas, Khoury, Abdo, Desmettre, Thibault, Lambert, Christophe, Ragey, Sophie Perinel, Baboi, Loredana, Bazin, Jean-Etienne, Koffel, Catherine, Dhonneur, Gilles, Bouzit, Zina, Bradai, Larbi, Ayed, Issam Ben, Aissa, Fethi, Haouache, Hakim, Marechal, Yoann, Biston, Patrick, Piagnerelli, Michael, Bortolotti, Perrine, Colling, Delphine, Colas, Vincent, Voisin, Benoit, Dewavrin, Florent, Onimus, Thierry, Girardie, Patrick, Saulnier, Fabienne, Urbina, Tomas, Nguyen, Yann, Druoton, Anne-Lise, Soudant, Marc, Barraud, Damien, Conrad, Marie, Cravoisy-Popovic, Aurélie, Nace, Lionel, Bollaert, Pierre-Edouard, Martin, Ruste, Bitker, Laurent, Richard, Jean-Christophe, Brossier, David, Goyer, Isabelle, Marquis, Christopher, Lampin, Marie, Duhamel, Alain, Béhal, Hélène, Dhaoui, Tahar, Godeffroy, Véronique, Devouge, Eve, Evrard, Dominique, Delepoulle, Florence, Racoussot, Sylvie, Grandbastien, Bruno, Lampin, Marie, Heilbronner, Claire, Roy, Emeline, Masson, Alexandra, Hadchouel-Duvergé, Alice, Rigourd, Virginie, Delacroix, Elise, Wroblewski, Isabelle, Pin, Isabelle, Ego, Anne, Payen, Valerie, Debillon, Thierry, Millet, Anne, Denot, Julien, Berthelot, Véronique, Thueux, Emilie, Reymond, Marie, De Larrard, Alexandra, Amblard, Alain, Leger, Pierre-Louis, Aoul, Nabil Tabet, Lemiale, Virginie, Oziel, Johanna, Brule, Noelle, Moreau, Anne-Sophie, Marhbène, Takoua, Sellami, Salma, Jamoussi, Amira, Ayed, Samia, Mhiri, Emna, Slim, Leila, Khelil, Jalila Ben, Besbes, Mohamed, Chawki, Sylvain, Hamdi, Aicha, Ciroldi, Magali, Cottereau, Alice, Obadia, Edouard, Zerbib, Yoann, Andrejak, Claire, Ricome, Sylvie, Dupont, Hervé, Baudin, François, Dureau, Pauline, Tanguy, Audrey, Arbelot, Charlotte, Ben, Hassen Kais, Charfeddine, Ahmed, Granger, Benjamin, Laporte, Lucile, Hermetet, Coralie, Regaieg, Kais, Khemakhem, Rim, Chelly, Hedi, Cheikh, Chaigar Mohammed, Mountij, Hamid, Rghioui, Kawtar, Haddad, Wafae, Cherkab, Rachid, Barrou, Houcine, Naima, Aitmouden, bennani, Othmani M., Regaieg, Kais, Douib, Ahmed, Samet, Amal, Cungi, Pierre-Julien, Nguyen, Cédric, Cotte, Jean, D’aranda, Erwan, Meaudre, Eric, Avaro, Jean-Phillipe, Slaoui, Mohamed Taoufik, Mokline, Amel, Rahmani, Imene, Laajili, Achraf, Amri, Helmi, Gharsallah, Lazheri, Gasri, Bahija, Tlaili, Sofiene, Hammouda, Rym, Messadi, Amen Allah, Sudden Death Expertise Center, AKIKI Study Group, DO-RE-MI-FA Group, ENCEPHALITICA Study Group, for the HYPER2S Investigators and REVA Research Network, for the Purpura Fulminans Study Group, GFRUP RMEF, REVA ECMOnet, REA-RAISIN Study Group, for the EurêClark Study Group, and Groupe Communication et Simulation en Pédiatrie

Published
2017
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35. COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study

Author

Papiris, Spyros A., primary, Campo, Ilaria, additional, Mariani, Francesca, additional, Kallieri, Maria, additional, Kolilekas, Lykourgos, additional, Papaioannou, Andriana I., additional, Gonca Chousein, Efsun, additional, Cetinkaya, Erdogan, additional, Bonella, Francesco, additional, Borie, Raphael, additional, Kokosi, Maria, additional, Pickworth, Thomas, additional, Molina-Molina, Maria, additional, Gasa, Mercè, additional, Radzikowska, Elżbieta, additional, Fijolek, Justyna, additional, Jouneau, Stéphane, additional, Gomez, Emmanuel, additional, McCarthy, Cormac, additional, Bendstrup, Elisabeth, additional, Piotrowski, Wojciech J., additional, Pabary, Rishi, additional, Hadchouel, Alice, additional, Coolen-Allou, Nathalie, additional, Alfaro, Tiago, additional, Robalo Cordeiro, Carlos, additional, Antonogiannaki, Elvira-Markela, additional, Tomos, Ioannis P., additional, Papakosta, Despoina, additional, Kontakiotis, Theodoros, additional, Panagiotou, Panagiota, additional, Douros, Konstantinos, additional, Schams, Andrea, additional, Lettieri, Sara, additional, Papaevangelou, Vassiliki, additional, Kanaka-Gantenbein, Christina, additional, Karakatsani, Anna, additional, Loukides, Stelios, additional, Costabel, Ulrich, additional, Crestani, Bruno, additional, Morgan, Cliff, additional, Tazawa, Ryushi, additional, Bush, Andrew, additional, Griese, Matthias, additional, and Manali, Effrosyni D., additional

Published
2022
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36. Reclassifying inconclusive diagnosis for cystic fibrosis with new generation sweat test

Author

Nguyen-Khoa, Thao, primary, Hatton, Aurélie, additional, Drummond, David, additional, Aoust, Laura, additional, Schlatter, Joël, additional, Martin, Clémence, additional, Ramel, Sophie, additional, Kiefer, Sébastien, additional, Gachelin, Elsa, additional, Stremler, Nathalie, additional, Cosson, Laure, additional, Gabsi, Asma, additional, Remus, Natascha, additional, Benhamida, Myriam, additional, Hadchouel, Alice, additional, Fajac, Isabelle, additional, Munck, Anne, additional, Girodon, Emmanuelle, additional, and Sermet-Gaudelus, Isabelle, additional

Published
2022
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37. Simple actions to support breastfeeding can avoid unwanted weaning in infants younger than 6 months hospitalized for bronchiolitis: A before/after study (Bronchilact II)

Author

K. Ben Gueriba, Sylvain Renolleau, C. de Barbeyrac, V. Rigourd, Claire Heilbronner, M. Murmu, Alice Hadchouel, Marion Grimaud, E. Roy, and T. Hachem

Subjects
Male, Pediatrics, medicine.medical_specialty, Population, Psychological intervention, Breastfeeding, Health Promotion, Weaning, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Intervention (counseling), Outcome Assessment, Health Care, medicine, Humans, education, Before after study, education.field_of_study, business.industry, Infant, Newborn, Infant, medicine.disease, Hospitalization, Breast Feeding, Cross-Sectional Studies, Health promotion, Bronchiolitis, Acute Disease, Pediatrics, Perinatology and Child Health, Female, business, Program Evaluation
Abstract

Background Admission to hospital with bronchiolitis may adversely affect breastfeeding. Correct advice and support have been pointed out as a determining factor. Objectives We conducted a telephone survey to evaluate a set of actions to promote breastfeeding during hospitalization for acute bronchiolitis. Methods Population: All patients 6 months of age or younger hospitalized with acute bronchiolitis and receiving at least partial breastfeeding were eligible for the study. Patients discharged home whose parents accepted to be contacted by phone were also included. Intervention We established a set of actions to promote breastfeeding (posters, flyers, staff training, and equipment) in all pediatric wards attending to these patients. Comparison This was a cross-sectional study conducted during two epidemic seasons of bronchiolitis in a tertiary care hospital. Data on continued breastfeeding at 3 months (0.5–6; median, range) postdischarge were collected by telephone and compared with the same set of data collected from patients with bronchiolitis in the same setting the year before the intervention. Outcome We conducted a telephone survey to evaluate whether some actions regarding breastfeeding might diminish the risk of unwanted weaning during hospitalization for bronchiolitis. The primary outcome was the proportion of stopped or reduced breastfeeding at discharge. Secondary objectives were to evaluate whether there were factors associated with breastfeeding modification. Results The results of the evaluation before intervention (phase 1) are published by Heilbronner et al. In Phase 1 of our study, 84 patients were included and 43 mothers (51%) reported that breastfeeding was modified by hospitalization of their child: 20.4% stopped, 14% switched to partial breastfeeding, and 16.6% reduced breastfeeding. These mothers stated that causes of breastfeeding disturbances were lack of support and advice (63%), followed by severity of the child's respiratory disease (32%), logistical hospital difficulties (30%), and personal organizational issues (9.3%). The intervention took place in September. After the intervention, 50 patients could be included in the study between October 1and December 31, 2016. Among them, 40 (80%) mothers kept breastfeeding as before, four (8%) stopped, four (8%) switched to partial breastfeeding, and two (4%) reduced breastfeeding without stopping. Bronchiolitis was more severe among patients with altered breastfeeding in terms of ventilatory support. Conclusion Bronchiolitis is a high-risk event for breastfeeding disruption but interventions to promote breastfeeding might help to prevent the risk of unwanted weaning. More severe bronchiolitis probably poses the highest risk of weaning and the need for supplementary nutrition.

Published
2021
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39. Pulmonary hypertension without heart failure causes cardiorenal syndrome in a porcine model.

Author

Orieux, Arthur, Samson, Chloé, Pieroni, Laurence, Drouin, Sarah, Dang Van, Simon, Migeon, Tiffany, Frere, Perrine, Brunet, Dorothée, Buob, David, Hadchouel, Juliette, Guihaire, Julien, Mercier, Olaf, and Galichon, Pierre

Subjects
CARDIO-renal syndrome, PULMONARY hypertension, PULMONARY artery, PERSISTENT fetal circulation syndrome, KIDNEYS, CENTRAL venous pressure, HEART failure, HEART diseases
Abstract

Cardiorenal syndromes type 1 and 2 are complex disorders in which cardiac dysfunction leads to kidney dysfunction. However, the mechanisms remain incompletely explained, during pulmonary hypertension in particular. The objective of this study is to develop an original preclinical model of cardiorenal syndrome secondary to a pulmonary hypertension in piglets. Twelve 2-month-old Large White piglets were randomized in two groups: (1) induction of pulmonary hypertension by ligation of the left pulmonary artery and iterative embolizations of the right lower pulmonary artery, or (2) Sham interventions. We evaluated the cardiac function using right heart catheterization, echocardiography and measurement of biochemistry markers). Kidney was characterized using laboratory blood and urine tests, histological evaluation, immunostainings for renal damage and repair, and a longitudinal weekly assessment of the glomerular filtration rate using creatinine-based estimation and intravenous injection of an exogenous tracer on one piglet. At the end of the protocol (6 weeks), the mean pulmonary artery pressure (32 ± 10 vs. 13 ± 2 mmHg; p = 0.001), pulmonary vascular resistance (9.3 ± 4.7 vs. 2.5 ± 0.4 WU; p = 0.004) and central venous pressure were significantly higher in the pulmonary hypertension group while the cardiac index was not different. Piglets with pulmonary hypertension had higher troponin I. We found significant tubular damage and an increase in albuminuria in the pulmonary hypertension group and negative correlation between pulmonary hypertension and renal function. We report here the first porcine model of cardiorenal syndrome secondary to pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Published
2023
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40. Reclassifying inconclusive diagnosis for cystic fibrosis with new generation sweat test

Author

Thao Nguyen-Khoa, Aurélie Hatton, David Drummond, Laura Aoust, Joël Schlatter, Clémence Martin, Sophie Ramel, Sébastien Kiefer, Elsa Gachelin, Nathalie Stremler, Laure Cosson, Asma Gabsi, Natascha Remus, Myriam Benhamida, Alice Hadchouel, Isabelle Fajac, Anne Munck, Emmanuelle Girodon, Isabelle Sermet-Gaudelus, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), 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 (UPCité)-École Pratique des Hautes Études (EPHE), CHU Necker - Enfants Malades [AP-HP], Hôpital Cochin [AP-HP], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Fondation ILDYS (ILDYS), Université de Lorraine (UL), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Intercommunal de Créteil (CHIC), and Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Pulmonary and Respiratory Medicine, Chlorides, Cystic Fibrosis, [SDV]Life Sciences [q-bio], Cystic Fibrosis Transmembrane Conductance Regulator, Humans, Sweat
Abstract

International audience

Published
2022
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42. Comparative therapeutic strategies for preventing aortic rupture in a mouse model of vascular Ehlers-Danlos syndrome

Author

Legrand, Anne, primary, Guery, Charline, additional, Faugeroux, Julie, additional, Fontaine, Erika, additional, Beugnon, Carole, additional, Gianfermi, Amélie, additional, Loisel-Ferreira, Irmine, additional, Verpont, Marie-Christine, additional, Adham, Salma, additional, Mirault, Tristan, additional, Hadchouel, Juliette, additional, and Jeunemaitre, Xavier, additional

Published
2022
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43. Systemic inflammatory syndrome in children with FARSA deficiency

Author

Charbit‐Henrion, Fabienne, primary, Goguyer‐Deschaumes, Roman, additional, Borensztajn, Keren, additional, Mirande, Marc, additional, Berthelet, Jérémy, additional, Rodrigues‐Lima, Fernando, additional, Khiat, Anis, additional, Frémond, Marie‐Louise, additional, Bader‐Meunier, Brigitte, additional, Rodari, Marco M., additional, Seabra, Luis, additional, Rice, Gillian I., additional, Legendre, Marie, additional, Drummond, David, additional, Berteloot, Laureline, additional, Roux, Charles‐Joris, additional, Boddaert, Nathalie, additional, Drabent, Philippe, additional, Molina, Thierry Jo, additional, Lacaille, Florence, additional, Kossorotoff, Manoelle, additional, Cerf‐Bensussan, Nadine, additional, Parlato, Marianna, additional, and Hadchouel, Alice, additional

Published
2022
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44. Elexacaftor/Tezacaftor/Ivacaftor alters branching morphogenesis of the mouse embryonic lung

Author

Marie-Laure Franco-Montoya, Lucie Jeannotte, Alice Hadchouel, Kim Landry-Truchon, Mickaël Lhuillier, Alexandre Hinzpeter, Laura Aoust, Elise Dreano, Nicolas Houde, Christophe Delacourt, Stéphanie Chhun, Isabelle Sermet-Gaudelus, and Aleksander Edelman

Subjects
Fetus, Lung, FGF10, Forskolin, Embryo, Biology, Organ culture, Ivacaftor, Andrology, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, medicine, Ex vivo, medicine.drug
Abstract

IntroductionCFTR modulators triple combo-therapy Elexacaftor/Tezacaftor/Ivacaftor (ETI) has proven to clinically benefit homozygous and heterozygous F508del patients. As a result, an increasing number of pregnancies is expected. Studies of the potential impact of these modulators on the development of the foetus are mandatory.MaterialsWe used the early mouse embryonic lung organ culture model to analyse ex vivo the lung branching process and the relative expression of Fgf10, Fgfr2IIIb, Shh, and Hhip development regulator genes in different conditions: standard culture medium, treatment with ETI or with Forskolin ± Inh172. Development of lung branching and distal bud caliber were evaluated in lung explants from heterozygous F508del Cftrtm1Eur/+ and control Cftrtm1Eur+/+ (WT) mouse embryos at E12.5 during pseudo-glandular stage.ResultsExposure to ETI of the Cftrtm1Eur/+ and WT lung explants induced a significant decrease in lung branching after 48h culture and the percentage of terminal bud dilations was significantly increased. These results were recapitulated by cAMP-dependent CFTR continuous activation by Forskolin and reversed by addition of Inh172.ETI induced a significant decrease in Fgf10, Fgfr2IIIb, Shh and Hhip expression in lung explants of both E12.5 Cftrtm1Eur/+ and WT embryos treated with ETI for 72h.ConclusionOur results provide evidence that the triple association Elexacaftor/Tezacaftor/Ivacaftor alters lung branching morphogenesis of WT and heterozygous F508del mouse embryos during the pseudo-glandular stage. Those results argue for a close monitoring of pregnancies in patients treated with these drugs.Plain LanguageIntroductionThe triple combo-therapy Elexacaftor/Tezacaftor/Ivacaftor (ETI) improves homozygous and heterozygous F508del patients. As a result, an increasing number of pregnancies is expected. Studies of this treatment on the development of the foetus are lacking. We incubated lungs of murine foetus not carrying CFTR mutation or F508del heterozygous. We show that ETI induces significant defect of lung development and the formation of cysts. These results are at least partly due to CFTR activation. Those results argue for a close monitoring of pregnancies in patients treated with these drugs.

Published
2021
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45. Deep phenotyping of MARS1 (interstitial lung and liver disease) and LARS1 (infantile liver failure syndrome 1) recessive multisystemic disease using Human Phenotype Ontology annotation: Overlap and differences. Case report and review of literature

Author

Charlotte La Fay, Pauline Heux, Anne Spraul, Marine Juzaud, Alice Hadchouel, Alexandre Fabre, Jean-Christophe Dubus, Celia Hoebeke, Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Bicêtre Hospital, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and COMBE, Isabelle

Subjects
Male, medicine.disease_cause, Bioinformatics, Liver disease, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MARS1, Hypoalbuminemia, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, Mutation, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Liver Diseases, 030305 genetics & heredity, LARS1, General Medicine, Syndrome, Phenotype, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Failure to thrive, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.symptom, Pulmonary alveolar proteinosis, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Methionine-tRNA Ligase, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Human Phenotype Ontology, Genetics, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Gene, 030304 developmental biology, business.industry, Infant, Infantile liver failure syndrome type 1, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Failure to Thrive, tRNA synthetase deficiency, Leucine-tRNA Ligase, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Lung Diseases, Interstitial
Abstract

Introduction Aminoacyl transfer RNA (tRNA) synthetases are associated with diseases when mutations occur in their encoding genes. Pulmonary alveolar proteinosis can be caused by mutation in the methionyl-tRNA synthetase (MARS) gene while mutations in the leucine-tRNA synthetase (LARS) gene lead to infantile liver failure syndrome type 1. We report the case of a patient with LARS1 pathogenics variants and two patients with MARS1 pathogenics variants. The aim of this study was to analyze the phenotypes of our three patients in detail and classify cases in the literature using Human Phenotype Ontology (HPO) terms. Results The first patient has two previously undescribed heterozygous variants in LARS1 (c.1818dup and c.463A>G). The other two patients' MARS1 variants (c.1177G>A and c.1700C>T) have already been described in the literature. All three patients had anemia, hepatomegaly, feeding difficulties, failure to thrive and hypoalbuminemia. Including ours, 65 patients are described in total, for whom 117 phenotypic abnormalities have been described at least once, 41.9% of which both in patients with LARS1 and MARS1 mutations. Conclusion Patients with LARS1 and MARS1 mutations seem to share a common phenotype but further deep phenotyping studies are required to clarify the details of these complex pathologies.

Published
2021
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46. Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child

Author

Marianne Burgard, George C. Hartoularos, Martin Castelle, Alice Hadchouel, Laureline Berteloot, Romain Lévy, Bénédicte Neven, Jean-Laurent Casanova, Qian Zhang, Karim Dorgham, Lucy Bizien, Chun Jimmie Ye, Hanène Abid, Tom Toin, Isabelle Melki, Peng Zhang, Nadhira Houhou-Fidouh, Paul Bastard, Emmanuelle Jouanguy, Charlotte Roy, Flore Rozenberg, Guy Gorochov, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de Pneumologie Allergologie [CHU Necker], University of California (UC), CHU Necker - Enfants Malades [AP-HP], MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [CHU Necker], Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de Génétique Médicale [CHU Necker], Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), Gestionnaire, HAL Sorbonne Université 5, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères - - GENVIR2020 - ANR-20-CE93-0003 - AAPG2020 - VALID, Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19. - - AABIFNCOV2020 - ANR-20-CO11-0001 - COVID-19 - VALID, Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant. - - GenMIS-C2021 - ANR-21-COVR-0039 - COVID-19 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of California, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
medicine.drug_class, Viremia, Monoclonal antibody, Antibodies, Monoclonal, Humanized, Virus, Neutralization, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Interferon, medicine, Genetics, Humans, 030304 developmental biology, Blood type, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Multidisciplinary, business.industry, SARS-CoV-2, COVID-19, interferon, Viral Load, Biological Sciences, medicine.disease, Antibodies, Neutralizing, Interferon-Stimulated Gene Factor 3, gamma Subunit, 3. Good health, Upper respiratory tract infection, Child, Preschool, inherited primary immunodeficiency, Immunology, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, RNA-seq, business, Viral load, 030215 immunology, medicine.drug
Abstract

Significance Life-threatening COVID-19 pneumonia can be caused by rare inborn errors of type I interferon (IFN) immunity, or by autoantibodies neutralizing IFN-α2 or IFN-ω. In 2018, we reported a girl with critical influenza pneumonia due to inherited IRF9 deficiency, a component of the ISGF-3 transcription factor. We report the course of COVID-19 in the same patient. She was admitted on day 1 of upper respiratory tract infection with viremia. Administration of SARS-CoV-2–specific neutralizing monoclonal antibodies on day 2 prevented the development of pneumonia. SARS-CoV-2–specific monoclonal antibodies were sufficient to overcome a lack of ISGF-3– and IRF9-dependent type I and type III IFN immunity to the virus. They should be considered in selected children at high risk of life-threatening COVID-19., We describe an unvaccinated child at risk for life-threatening COVID-19 due to an inherited deficiency of IRF9, which governs ISGF-3–dependent responses to type I and III interferons (IFN). She was admitted, with a high nasal SARS-CoV-2 load on day 1 of upper respiratory tract infection. She was viremic on day 2 and received casirivimab and imdevimab. Her clinical manifestations and viremia disappeared on days 3 and 4, respectively. Circulating SARS-CoV-2 virus induced the expression of IFN-stimulated genes in leukocytes on day 1, whereas the secretion of blood type I IFNs, which peaked on day 4, did not. Antibody-mediated SARS-CoV-2 neutralization is, therefore, sufficient to overcome a deficiency of antiviral IFNs.

Published
2021
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48. Salivary Telomere Length and Lung Function in Adolescents Born Very Preterm: A Prospective Multicenter Study.

Author

Alice Hadchouel, Laetitia Marchand-Martin, Marie-Laure Franco-Montoya, Laetitia Peaudecerf, Pierre-Yves Ancel, Christophe Delacourt, and EPIPAGEADO study group

Subjects
Medicine, Science
Abstract

Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full-term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p

Published
2015
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49. Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC

Author

Gerardo Gamba, Jesús García-Valdés, Eduardo R. Argaiz, Juliette Hadchouel, María Chávez-Canales, Norma Vázquez, David H. Ellison, Mauricio Ostrosky-Frid, Alejandro Rodríguez-Gama, Xochiquetzal Gonzalez-Rodriguez, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée (CoRaKID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Oregon Health and Science University [Portland] (OHSU), and Hadchouel, Juliette

Subjects
0301 basic medicine, Gene isoform, medicine.medical_specialty, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Physiology, Protein Serine-Threonine Kinases, Xenopus Proteins, Kidney, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Xenopus laevis, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Chlorides, WNK Lysine-Deficient Protein Kinase 1, Internal medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Animals, Humans, Solute Carrier Family 12, Member 3, Distal convoluted tubule, Phosphorylation, urogenital system, Chemistry, Activator (genetics), Sodium, WNK1, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Rats, WNK4, Enzyme Activation, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, FAMILIAL HYPERKALEMIC HYPERTENSION, Oocytes, Female, Cotransporter, Research Article
Abstract

Familial hyperkalemic hypertension (FHHt) can be mainly attributed to increased activity of the renal Na+:Cl−cotransporter (NCC), which is caused by altered expression and regulation of the with-no-lysine (K) 1 (WNK1) or WNK4 kinases. The WNK1 gene gives rise to a kidney-specific isoform that lacks the kinase domain (KS-WNK1), the expression of which occurs primarily in the distal convoluted tubule. The role played by KS-WNK1 in the modulation of the WNK/STE20-proline-alanine rich kinase (SPAK)/NCC pathway remains elusive. In the present study, we assessed the effect of human KS-WNK1 on NCC activity and on the WNK4-SPAK pathway. Microinjection of oocytes with human KS-WNK1 cRNA induces remarkable activation and phosphorylation of SPAK and NCC. The effect of KS-WNK1 was abrogated by eliminating a WNK-WNK-interacting domain and by a specific WNK inhibitor, WNK463, indicating that the activation of SPAK/NCC by KS-WNK1 is due to interaction with another WNK kinase. Under control conditions in oocytes, the activating serine 335 of the WNK4 T loop is not phosphorylated. In contrast, this serine becomes phosphorylated when the intracellular chloride concentration ([Cl−]i) is reduced or when KS-WNK1 is coexpressed with WNK4. KS-WNK1-mediated activation of WNK4 is not due to a decrease of the [Cl−]i. Coimmunoprecipitation analysis revealed that KS-WNK1 and WNK4 interact with each other and that WNK4 becomes autophosphorylated at serine 335 when it is associated with KS-WNK1. Together, these observations suggest that WNK4 becomes active in the presence of KS-WNK1, despite a constant [Cl−]i.

Published
2018
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50. Anaesthesia-Induced Transcriptomic Changes in the Context of Renal Ischemia Uncovered by the Use of a Novel Clamping Device

Author

Charles Verney, David Legouis, Sandrine Placier, Tiffany Migeon, Philippe Bonnin, David Buob, Juliette Hadchouel, Pierre Galichon, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Genève = University of Geneva (UNIGE), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Anatomopathologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Université de Genève (UNIGE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Xylazine, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, QH301-705.5, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, anaesthesia, Kidney, Article, animal models, Chemistry, Disease Models, Animal, Mice, acute kidney injury, Reperfusion Injury, Animals, Anesthesia, Ketamine, Kidney Diseases, Biology (General), Transcriptome, renal ischemia, QD1-999, surgical clamp
Abstract

International audience; Ischemia is a common cause of acute kidney injury worldwide, frequently occurring in patients undergoing cardiac surgery or admitted to the intensive care unit (ICU). Thus, ischemia-reperfusion injury (IRI) remains one of the main experimental models for the study of kidney diseases. However, the classical technique, based on non-traumatic surgical clamps, suffers from several limitations. It does not allow the induction of multiple episodes of acute kidney injury (AKI) in the same animal, which would be relevant from a human perspective. It also requires a deep and long sedation, raising the question of potential anaesthesia-related biases. We designed a vascular occluding device that can be activated remotely in conscious mice. We first assessed the intensity and the reproducibility of the acute kidney injury induced by this new device. We finally investigated the role played by the anaesthesia in the IRI models at the histological, functional and transcriptomic levels. We showed that this technique allows the rapid induction of renal ischemia in a repeatable and reproducible manner, breaking several classical limitations. In addition, we used its unique specificities to highlight the renal protective effect conferred by the anaesthesia, related to the mitigation of the IRI transcriptomic program.

Published
2021
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