Publications by authors named "Etienne Merlin"

54 Publications

Retraction Note: Efficacy of vitamin C for the prevention and treatment of upper respiratory tract infection. A meta-analysis in children.

Eur J Clin Pharmacol 2021 May 14. Epub 2021 May 14.

Department of General Practice, Clermont Auvergne University, Faculty of Medicine, 28 Place Henri Dunant, 63000, Clermont-Ferrand, France.

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http://dx.doi.org/10.1007/s00228-021-03150-9DOI Listing
May 2021

Maximal Fat Oxidation During Exercise Is Already Impaired in Pre-pubescent Children With Type 1 Diabetes Mellitus.

Front Physiol 2021 9;12:664211. Epub 2021 Apr 9.

Laboratoire IAPS, Université de Toulon, Toulon, France.

We evaluated substrate utilization during submaximal exercise, together with glycemic responses and hormonal counter-regulation to exercise, in children with type 1 diabetes mellitus (T1DM). Twelve pre-pubescent children with T1DM and 12 healthy children were matched by sex and age. Participants completed a submaximal incremental exercise test to determine their fat and carbohydrate oxidation rates by indirect calorimetry. Levels of glycemia, glucagon, cortisol, growth hormone, noradrenaline, adrenaline, and insulin were monitored until 120 min post-exercise. Absolute peak oxygen uptake (VO peak) was significantly lower in the children with T1DM than in the healthy controls (1131.4 ± 102.5 vs. 1383.0 ± 316.6 ml.min, = 0.03). Overall carbohydrate and lipid oxidation rates were the same in the two groups, but for exercise intensities, higher than 50% of VO peak, fat oxidation rate was significantly lower in the children with T1DM. The absolute maximal lipid oxidation rate was significantly lower in the T1DM children (158.1 ± 31.6 vs. 205.4 ± 42.1 mg.min, = 0.005), and they reached a significantly lower exercise power than the healthy controls (26.4 ± 1.2 vs. 35.4 ± 3.3 W, = 0.03). Blood glucose responses to exercise were negatively correlated with pre-exercise blood glucose concentrations ( = -0.67; = 0.03). Metabolic and hormonal responses during sub-maximal exercise are impaired in young children with T1DM.
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http://dx.doi.org/10.3389/fphys.2021.664211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062964PMC
April 2021

Peripheral blood stem cell collection in children with extremely low body weight (≤8 kg). What have we learned over the past 25 years and where are the limits?

J Clin Apher 2020 Dec 31. Epub 2020 Dec 31.

CHU Clermont-Ferrand, Service Hématologie Oncologie Pédiatrique, Hôpital Estaing, Clermont-Ferrand, France.

Hematopoietic progenitor cells-apheresis (HPC-A) collection is now a routine procedure for autologous hematopoietic stem cell transplantation. Here we present our 25 years' experience of HPC-A collection in children weighing 8 kg or less, with a focus on the evolution of our standard operating procedures, and the safety limits for these young patients, in the Pediatric Apheresis Unit of Clermont-Ferrand University Hospital (France). Fifteen children weighing 8 kg or less underwent 26 HPC-A collections over 25 years. Median CD34+ cell yield by leukapheresis was 4.4 10 /kg. No procedure-related complications were encountered during or after the collection. No patient had profound thrombocytopenia or anemia that needed post-collection transfusions. Our experience in pediatric oncology patients who underwent HPC-A collections shows that this procedure can be performed even in the smallest of children with no increase in toxicity provided all precautions are taken to ensure that the procedure is carried out under the ideal conditions.
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http://dx.doi.org/10.1002/jca.21863DOI Listing
December 2020

Access to paediatric rheumatology care in juvenile idiopathic arthritis: what do we know? A systematic review.

Rheumatology (Oxford) 2020 Dec;59(12):3633-3644

HESPER Laboratory, Claude-Bernard University, Lyon, France.

Objective: This review examines time to access appropriate care for JIA patients and analyses the referral pathway before the first paediatric rheumatology (PR) visit. We also describe factors associated with a longer referral.

Methods: We performed a systematic literature review, screening electronic databases (PubMed, Web of Science, EMBASE, Cochrane library and Open Grey database) up to February 2020. Articles written before 1994 (i.e. before the introduction of the unifying term JIA) were excluded.

Results: From 595 nonduplicate citations found, 15 articles were finally included in the review. Most of the studies took place in Europe. The median time to first PR visit ranged from 3 to 10 months, with some disparities between referral pathway and patient characteristics. Patients with systemic-onset JIA had the shortest time to referral. Some clinical and biological factors such as swelling, fever, and elevated CRP and/or ESR were associated with a shorter time to first PR visit. Conversely, enthesitis, older age at symptom onset or pain were associated with a longer time. Whatever the country or world region, and despite disparities in healthcare system organization and healthcare practitioner availabilities, times to access PR were not wide-ranging.

Conclusion: This is the first systematic review to summarize research on access to PR for JIA patients. The pathway of care for JIA patients remains complex, and reasons for delayed referral depend on several factors. Standardized clinical guidelines and fast-track pathways to facilitate prompt referral to specialized teams have to allow for worldwide disparities in healthcare provision.
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http://dx.doi.org/10.1093/rheumatology/keaa438DOI Listing
December 2020

Randomized Double-Blind Controlled Trial on the Effect of Proteins with Different Tryptophan/Large Neutral Amino Acid Ratios on Sleep in Adolescents: The PROTMORPHEUS Study.

Nutrients 2020 Jun 24;12(6). Epub 2020 Jun 24.

Toulon University, Laboratory of the Impact of Physical Activity on Health (IAPS), 83000 Toulon, France.

Disturbed sleep is common in adolescents. Ingested nutrients help regulate the internal clock and influence sleep quality. The purpose of this clinical trial is to assess the effect of protein tryptophan (Trp)/large neutral amino acids (LNAAs) ratio on sleep and circadian rhythm. Ingested Trp is involved in the regulation of the sleep/wake cycle and improvement of sleep quality. Since Trp transport through the blood-brain barrier is competing with LNAAs, protein with higher Trp/LNAAs were expected to increase sleep efficiency. This randomized double-blind controlled trial will enroll two samples of male adolescents predisposed to sleep disturbances: elite rugby players (n = 24) and youths with obesity (n = 24). They will take part randomly in three sessions each held over a week. They will undergo a washout period, when dietary intake will be calibrated (three days), followed by an intervention period (three days), when their diet will be supplemented with three proteins with different Trp/LNAAs ratios. Physical, cognitive, dietary intake, appetite, and sleepiness evaluations will be made on the last day of each session. The primary outcome is sleep efficiency measured through in-home electroencephalogram recordings. Secondary outcomes include sleep staging, circadian phase, and sleep-, food intake-, metabolism-, and inflammation-related biochemical markers. A fuller understanding of the effect of protein Trp/LNAAs ratio on sleep could help in developing nutritional strategies addressing sleep disturbances.
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http://dx.doi.org/10.3390/nu12061885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353359PMC
June 2020

Muscle function and architecture in children with juvenile idiopathic arthritis.

Acta Paediatr 2021 01 18;110(1):280-287. Epub 2020 May 18.

Laboratoire AME2P, Université Clermont Auvergne, Clermont-Ferrand, France.

Aim: To assess muscle function and functional abilities in children with juvenile idiopathic arthritis (JIA).

Methods: Fourteen children with JIA and 14 healthy controls matched for age and sex were included. Muscle characteristics, both structural (thickness, cross-sectional area (CSA) and fascicle angle) and qualitative (intermuscular adipose tissue; IMAT), were assessed in thigh muscles using ultrasound and peripheral quantitative computed tomography (pQCT). Muscle function and functional abilities were determined from the assessment of maximal voluntary isometric contraction (MVIC) knee extensors force and vertical jump performance.

Results: No significant difference in MVIC force was observed between the two groups. However, squat jump height was significantly reduced in children with JIA (18.3 ± 5.4 vs 24.3 ± 7.9 cm, P < .05). No differences in structural parameters were observed, but IMAT/CSA (0.22 ± 0.02 vs 0.25 ± 0.03; P = .01) was significantly lower in children with JIA than in healthy children.

Conclusion: Knee extensor muscle architecture and force were comparable between children with and without JIA, but functional abilities (vertical jump performance) were poorer in JIA. The lower IMAT area in JIA could result from a lower physical activity level compared with healthy children.
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http://dx.doi.org/10.1111/apa.15335DOI Listing
January 2021

Body Mass Index and Calprotectin Blood Level Correlation in Healthy Children: An Individual Patient Data Meta-Analysis.

J Clin Med 2020 Mar 20;9(3). Epub 2020 Mar 20.

Department of Pediatrics, Clermont Ferrand University Hospital, F-63000 Clermont-Ferrand, France.

Background: Calprotectin (CP) is a protein complex involved in many inflammatory diseases. Obesity is characterized by low-grade inflammation and elevated circulating levels of calprotectin. However, associations between body mass index (BMI) and calprotectin levels have not been explored in otherwise healthy children.

Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and Cochrane Library database up to July 2019. Healthy children's blood calprotectin values were extracted, and potential correlations were explored.

Results: A total of six studies that included data on 593 healthy children were identified. Median calprotectin value was 900.0 (482.0; 1700) ng·mL. Multivariable analysis showed no significant associations with age, sample type (serum vs. plasma), or sex. In contrast, a significant effect of BMI z-score ( < 0.001) emerged. Indeed, a positive correlation between BMI z-score and CP, was detected in girls (R: 0.48; < 0.001) and boys (R: 0.39; < 0.001).

Conclusion: Calprotectin blood levels correlate with the degree of adiposity in healthy children, but are not affected by age, sex, or sample type (serum or plasma).
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http://dx.doi.org/10.3390/jcm9030857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141538PMC
March 2020

Validation of the new classification criteria for hereditary recurrent fever in an independent cohort: experience from the JIR Cohort Database.

Rheumatology (Oxford) 2020 Oct;59(10):2947-2952

National Referral Centre of Auto-Inflammatory Diseases and Inflammatory Amyloidosis, - CEREMAIA, Department of Pediatrics, Versailles Hospital, Le Chesnay.

Objective: The new classification criteria for the hereditary recurrent fever (HRF) syndrome [cryopyrin-associated periodic syndrome (CAPS), TNF-α receptor-associated periodic syndrome (TRAPS), FMF and mevalonate kinase deficiency] have been published recently. These criteria define two core sets of criteria for each HRF: mixed criteria, including genetic and clinical variables, and clinical criteria, relying on clinical variables only. Our aim was to validate the criteria for HRF in an independent cohort, the JIR Cohort database, an international repository of systemic inflammatory diseases.

Methods: We enrolled patients with HRF, periodic fever, adenitis, pharyngitis and aphthous stomatitis syndrome (PFAPA) and syndrome of undefined recurrent fever (SURF). A score ranging from zero to two was attributed to their respective genotypes: zero (no mutation), one (non-confirmatory genotype) or two (confirmatory genotype). The criteria were applied to all patients based on genotype scoring. The treating physician's diagnosis served as the gold standard for the determination of specificity.

Results: We included 455 patients. The classification criteria showed excellent specificity for CAPS and TRAPS (98% specificity each), fair specificity for FMF (88%), but poor specificity for mevalonate kinase deficiency (58%). Sub-analysis showed excellent accuracy of the mixed criteria for all four HRFs. Misclassification was mainly attributable to clinical criteria sets, with false-positive patients in all four HRF clinical criteria sets.

Conclusion: This study represents the final validation step of the HRF classification criteria as recommended by the ACR. Genetic data appear to be necessary to classify patients with HRF correctly.
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http://dx.doi.org/10.1093/rheumatology/keaa031DOI Listing
October 2020

Childhood Leukemia Survivors and Metabolic Response to Exercise: A Pilot Controlled Study.

J Clin Med 2020 Feb 19;9(2). Epub 2020 Feb 19.

Université de Toulon, Laboratoire IAPS, F-83041 Toulon, France.

Background: Leukemia is the most common cancer in pediatrics, with many late effects such as higher risk of dyslipidemia, insulin resistance, obesity, and metabolic syndrome. The objective of this work was to investigate substrate oxidation during submaximal exercise in survivors of childhood acute leukemia.

Methods: A total of 20 leukemia survivors and 20 healthy children were matched by sex, age, and Tanner stage. They all took a submaximal incremental exercise test to determine fat and carbohydrate oxidation rates.

Results: Cardiorespiratory fitness was significantly lower in leukemia survivors, with lower relative VO peaks ( < 0.001), lower heart rate values ( = 0.02), and lower exercise power ( = 0.012), whereas rest metabolism and body mass index did not differ between the two groups. During exercise, upward of heart rate relative to VO peak was significantly higher ( < 0.001) in childhood leukemia survivors. We found lower carbohydrate and fat oxidation rates ( = 0.07) in leukemia survivors compared with healthy children, and also a significantly lower relative maximal fat oxidation rate ( = 0.014).

Conclusion: Despite impaired physical fitness and metabolic response to exercise, childhood leukemia survivors remained sensitive to physical activity interventions, and could readily adapt to submaximal exercise intensity.
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http://dx.doi.org/10.3390/jcm9020562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073622PMC
February 2020

Acute intense exercise improves sleep and decreases next morning consumption of energy-dense food in adolescent girls with obesity and evening chronotype.

Pediatr Obes 2020 06 4;15(6):e12613. Epub 2020 Feb 4.

Laboratoire Impact de l'Activité Physique sur la Santé (IAPS), Université de Toulon, Toulon, France.

Background: Although adolescence and obesity are related to impaired sleep duration and quality, exercise was admitted as a nonpharmacological treatment for sleep and better control of energy balance.

Objectives: To investigate the acute effects of intense exercise on sleep and subsequent dietary intake.

Methods: Sixteen adolescent girls with obesity (age 13.7 ± 1.1 years, weight 82.7 ± 10.2 kg, body mass index (BMI) 30.5 ± 3.4 kg/m , fat mass (FM) 39.2 ± 3.1%, Pittsburgh Sleep Quality Index (PSQI) 8.6 ± 2.8, paediatric daytime sleepiness scale (PDSS) 19.6 ± 5.9) took part in two experimental sessions in a random order: Control (CTL) and Exercise (EX). The two sessions were identical except for a continuous ergocycle exercise bout lasting 40 minutes and performed at 70% VO at the end of the morning of EX. Energy expenditure and sleep were measured by accelerometry and next-morning dietary intake in an ad libitum meal.

Results: Higher sleep duration (P < 0.03) and quality (decreased WASO: P < 0.02; increased SE%: P < 0.02) were observed in EX compared with CTL. This was associated with a nonsignificant decrease in caloric intake (-78 kcal) and a significant decrease in food energy density (P < 0.04), fat, and sugar consumption (respectively, P < 0.02 and P < 0.05) the following morning.

Conclusions: Acute exercise efficaciously increased sleep duration and quality, resulting in a decrease in subsequent energy-dense food consumption in adolescent girls with obesity.
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http://dx.doi.org/10.1111/ijpo.12613DOI Listing
June 2020

Metabolic response to exercise in childhood brain tumor survivors: A pilot controlled study.

Pediatr Blood Cancer 2020 02 18;67(2):e28053. Epub 2019 Oct 18.

Laboratoire IAPS, Université de Toulon, Toulon, France.

Background/objectives: Survival rates in children diagnosed with malignant brain tumors exceed 70%. A higher risk of dyslipidemia, central obesity, and insulin resistance has been reported among these children. We investigated substrate utilization during submaximal exercise.

Design/methods: Ten brain tumor survivors and 10 healthy children were matched by sex, age, and Tanner stage. Participants completed a submaximal incremental exercise test to determine their fat and carbohydrate oxidation rates.

Results: The relative oxygen volume (VO ) peak was significantly higher in the control group than in the survivors of childhood brain tumors (43.3 ± 11.9 and 32.4 ± 10.2 mL/kg /min, P = .04). At the same relative exercise intensity, there was no difference in the carbohydrate or lipid oxidation rate between the two groups, or in the maximal fat oxidation (MFO) rate, or in the heart rate or percentage of VO peak to reach MFO. Healthy children achieved MFO at significantly higher muscular power than did brain tumor survivors (47.9 ± 20.8 and 21.8 ± 9.6 W, P = .003).

Conclusion: Because child brain tumor survivors are less physically fit than healthy children, and substrate utilization during submaximal exercise is not different, physical activity should be promoted for child brain tumor survivors.
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http://dx.doi.org/10.1002/pbc.28053DOI Listing
February 2020

Authors' response to letter to the editor: "Meta-analysis on vitamin C and the common cold in children may be misleading".

Eur J Clin Pharmacol 2019 12 28;75(12):1749-1750. Epub 2019 Aug 28.

Department of General Practice, Faculty of Medicine, Clermont Auvergne University, 28 place Henri Dunant, 63000, Clermont-Ferrand, France.

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http://dx.doi.org/10.1007/s00228-019-02734-wDOI Listing
December 2019

A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

J Clin Immunol 2019 10 10;39(7):702-712. Epub 2019 Aug 10.

Service de Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker Pasteur, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France.

Purpose: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles.

Methods: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included.

Results: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04).

Conclusion: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode.
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http://dx.doi.org/10.1007/s10875-019-00658-9DOI Listing
October 2019

Extracorporeal photopheresis for the treatment of graft rejection in 33 adult kidney transplant recipients.

Transfus Apher Sci 2019 Aug 22;58(4):515-524. Epub 2019 Jul 22.

Service de Néphrologie, CHU Clermont-Ferrand, Clermont-Ferrand, France; Université Clermont Auvergne, Clermont-Ferrand, France.

Background - Extracorporeal photopheresis (ECP) has shown encouraging results in the prevention of allograft rejection in heart transplantation. However, the role of ECP in kidney transplant (KT) rejection needs to be determined. Methods - This multicentre retrospective study included 33 KT recipients who were treated with ECP for allograft rejection (23 acute antibody-mediated rejections (AMRs), 2 chronic AMRs and 8 acute cellular rejections (ACRs)). The ECP indications were KT rejection in patients who were resistant to standard therapies (n = 18) or in patients for whom standard therapies were contraindicated because of concomitant infections or cancers (n = 15). Results - At 12 months (M12) post-ECP, 11 patients (33%) had a stabilization of kidney function with a graft survival rate of 61%. The Banff AMR score (g + ptc + v) was a risk factor for graft loss at M12 (HR 1.44 [1.01-2.05], p < 0.05). The factorial mixed data analysis identified 2 clusters. Patients with a functional graft at M12 tended to have cellular and/or chronic rejections. Patients with graft loss at M12 tended to have acute rejections and/or AMR; higher serum creatinine levels; DSA levels and histologic scores of AMR; and a longer delay between the rejection and ECP start than those of patients with functional grafts. Conclusions - ECP may be helpful to control ACR or moderate AMR in KT recipients presenting concomitant opportunistic infections or malignancies when it is initiated early.
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http://dx.doi.org/10.1016/j.transci.2019.06.031DOI Listing
August 2019

TNF blockade contributes to restore lipid oxidation during exercise in children with juvenile idiopathic arthritis.

Pediatr Rheumatol Online J 2019 Jul 22;17(1):47. Epub 2019 Jul 22.

CHU Clermont-Ferrand, Pédiatrie, Hôpital Estaing, F-63000, Clermont-Ferrand, France.

Background: Children with juvenile idiopathic arthritis (JIA) have impaired physical abilities. TNF-α plays a crucial role in this pathogenesis, but it is also involved in the use of lipids and muscle health. Objective of this study was to explore substrate oxidation and impact of TNF blockade on energy metabolism in children with JIA as compared to healthy children.

Methods: Fifteen non-TNF-blockaded and 15 TNF-blockaded children with JIA and 15 healthy controls were matched by sex, age, and Tanner stage. Participants completed a submaximal incremental exercise test on ergocycle to determine fat and carbohydrate oxidation rates by indirect calorimetry.

Results: The maximal fat oxidation rate during exercise was lower in JIA children untreated by TNF blockade (134.3 ± 45.2 mg.min) when compared to the controls (225.3 ± 92.9 mg.min, p = 0.007); but was higher in JIA children under TNF blockade (163.2 ± 59.0 mg.min, p = 0.31) when compared to JIA children untreated by TNF blockade. At the same relative exercise intensities, there was no difference in carbohydrate oxidation rate between three groups.

Conclusions: Lipid metabolism during exercise was found to be impaired in children with JIA. However, TNF treatment seems to improve the fat oxidation rate in this population.

Trial Registration: In ClinicalTrials.gov, reference number NCT02977416 , registered on 30 November 2016.
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http://dx.doi.org/10.1186/s12969-019-0354-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647146PMC
July 2019

Questions Regarding the Relationship Between Serum S100A8/A9 and S100A12 Levels, and the Maintenance of Clinically Inactive Disease in Juvenile Idiopathic Arthritis: Comment on the Article by Hinze et al.

Arthritis Rheumatol 2019 11 20;71(11):1968-1969. Epub 2019 Sep 20.

Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.

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http://dx.doi.org/10.1002/art.41022DOI Listing
November 2019

Cold Vibration (Buzzy) Versus Anesthetic Patch (EMLA) for Pain Prevention During Cannulation in Children: A Randomized Trial.

Pediatr Emerg Care 2021 Feb;37(2):86-91

From the CHU Clermont-Ferrand, Urgences Pédiatriques, Hôpital Estaing.

Introduction: The purpose of this study was to assess differences in observed pain-related behaviors during cannulation between a device combining cold and vibration (Buzzy) and the standard care (EMLA patch).

Methods: Patients 18 months to 6 years old, requiring venous access in a pediatric emergency department, received either the Buzzy device or the EMLA patch. Predefined week randomization ensured equal allocation to the 2 intervention groups. Pain during cannulation was measured using the Children's Hospital of Eastern Ontario Pain Scale. Parent and nurse reports, cannulation success, and venous access times were also assessed.

Results: In total, 607 included patients were randomized into the Buzzy group (n = 302) or the EMLA group (n = 305). Observed pain-related behaviors scores, parent-assessed pain scores, and nurse-reported pain ratings were higher with Buzzy.

Conclusions: Pain relief by a combination of cold and vibration during cannulation is not as effective as the standard-care method in children 18 months to 6 years old.
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http://dx.doi.org/10.1097/PEC.0000000000001867DOI Listing
February 2021

Medical pathways of children with juvenile idiopathic arthritis before referral to pediatric rheumatology centers.

Joint Bone Spine 2019 11 20;86(6):739-745. Epub 2019 May 20.

Inserm CIC 1405, service de pédiatrie, CHU Estaing, 63003 Clermont-Ferrand, France.

Objective: A better understanding about the referral pathway of patients suffering from juvenile idiopathic arthritis (JIA) is required The aim of this study was to describe and analyze time from onset of symptoms to first pediatric rheumatology (PR) visit and the referral pathway of children with incident JIA in two French competence centers.

Methods: From October 2009 to October 2017, new JIA patients were registered in the "Auvergne-Loire cohort on JIA". We collected referral pathway, symptom onset, biological and clinical data at first assessment in PR department.

Results: In all, 111 children were included. Median time to first PR visit was 3.3 months [interquartile range (IQR) 1.3, 10.7] with a significant difference between JIA subtypes. After exclusion of systemic JIA, older age at onset of symptoms, and presence of enthesitis or joint pain were significantly associated with a longer time to first PR visit, while joint swelling or limping, abnormal ESR or CRP were associated with a shorter time. The median number of health care practitioners met was 3 [IQR 3, 4]. Orthopedists referred children to a PR center in 64% of cases, pediatricians in 50%, emergency care practitioners in 27% and general practitioners in 25%. Although non-systemic JIAs are not an emergency, 45% were referred to the emergency room.

Conclusion: Time to first PR visit is rather short compared to other countries but remains too long. Pediatric rheumatologists should offer primary care providers basic training on JIA and fast direct access to PR departments if JIA is suspected.
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http://dx.doi.org/10.1016/j.jbspin.2019.04.014DOI Listing
November 2019

Impaired Muscular Fat Metabolism in Juvenile Idiopathic Arthritis in Inactive Disease.

Front Physiol 2019 1;10:528. Epub 2019 May 1.

Laboratoire des Adaptations Métaboliques en Conditions Physiologiques et Physiopathologiques, Université Clermont Auvergne, Clermont-Ferrand, France.

The objective of this study was to evaluate muscular metabolic function in children with inactive juvenile idiopathic arthritis (JIA). Fifteen children with inactive JIA and fifteen healthy controls were matched by sex, biological age, and Tanner stage. Participants completed a submaximal incremental exercise test to determine their fat and carbohydrate oxidation rates. Between the two groups, heart rate values and carbohydrate oxidation rates were the same, regardless of the relative intensity of exercise. Lipid oxidation rates were lower in JIA patients, regardless of the percentage of VO peak ( < 0.05). Respiratory exchange ratios beyond 50% of VO peak were higher in patients with JIA ( < 0.05). Respective maximal fat oxidation rates (MFO) for controls and children with JIA were 218.7 ± 92.2 vs. 157.5 ± 65.9 mg ⋅ min ( = 0.03) and 4.9 ± 1.9 vs. 3.4 ± 1.2 mg ⋅ min ⋅ kg ( = 0.04). There was no difference between the two groups in heart rate, percentage of VO peak, or power of exercise to achieve MFO. Controls reached their MFO at an exercise power significantly higher than did JIA subjects (42.8 ± 16.8 and 31.9 ± 9.8 W, = 0.004). Children with JIA show metabolic disturbance during exercise, even when the disease is considered inactive. This disturbance is seen in a lower lipid oxidation rate during submaximal exercise.
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http://dx.doi.org/10.3389/fphys.2019.00528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506786PMC
May 2019

Physical activity and sedentary levels in children with juvenile idiopathic arthritis and inflammatory bowel disease. A systematic review and meta-analysis.

Pediatr Res 2019 08 27;86(2):149-156. Epub 2019 Apr 27.

Université de Toulon, Laboratoire IAPS, 83041, Toulon, France.

Background: Physical activity (PA) is essential for children throughout their growth and maturation. It improves physiological and psychological health and limits the risk of developing metabolic disorders. However, some chronic physiological and metabolic diseases may lead to decreased PA. The diversity of outcomes in the literature offers no consensus for physical activity and sedentary levels in children with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD).

Methods: A literature review and a meta-analysis were carried out with original studies from a Medline database search. Only high-quality studies (STROBE checklist) written in English comparing PA level or sedentary behavior (SB) between children with the disorders and their healthy peers were considered. The aim was to examine PA and SB in children with JIA or IBD compared to their healthy peers.

Results: The literature review and meta-analysis identified decreased PA and increased time spent in SB in these populations, which may exacerbate both their lower physical fitness and the symptoms of their health disorders.

Conclusion: Results nevertheless show discrepancies due to the different materials and methods used and the variables measured. Further studies are needed to establish a gold standard method for assessing PA level in these populations.
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http://dx.doi.org/10.1038/s41390-019-0409-5DOI Listing
August 2019

In vitro PUVA treatment triggers calreticulin exposition and HMGB1 release by dying T lymphocytes in GVHD: New insights in extracorporeal photopheresis.

J Clin Apher 2019 Aug 12;34(4):450-460. Epub 2019 Mar 12.

Institute for Advanced Biosciences, Université Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Grenoble, France.

Background: Extracorporeal photopheresis (ECP) is an effective therapy for graft vs host disease (GVHD), based on infusion of UVA-irradiated and 8 methoxy-psoralen (PUVA)-treated leukocytes. Reinfusion of these apoptosing cells affects the functionality of pathogenic T cells through poorly understood immunomodulatory mechanisms. Apoptosis is usually a silent, tolerance-associated process, but can also be immunogenic, depending on death-inducers and environmental context.

Methods: To understand ECP mechanisms of action, human alloreactive T cells generated in an in vitro model mimicking GVHD were used, as well as primary cells from GVHD patients. Cells were submitted to PUVA treatment and their phenotype and immunogenicity were analyzed, using cell culture and flow cytometry.

Results: In vitro PUVA treatment induced the expression of several damage-associated molecular patterns (DAMPs) by dying T cells (calreticulin, high-mobility group box-1, and to a lesser extent heat shock proteins 70 and 90), especially upon T cell activation, leading to their phagocytosis by macrophages and dendritic cells (DCs). Allogeneic DCs preincubated with PUVA treated T cells induced comparable naive T cell proliferation and polarization as control allogeneic DC.

Conclusion: Altogether, in our experimental settings, in vitro PUVA-treatment induces a partially immunogenic phenotype allowing phagocytosis of apoptotic cells by macrophages and DC, however not sufficient to induce dendritic cell maturation and T cell activation. These data refine current models of ECP-mediated immune modulation and emphasize the need to further analyze PUVA-treated cell interactions with immune cells.
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http://dx.doi.org/10.1002/jca.21698DOI Listing
August 2019

Efficacy of vitamin C for the prevention and treatment of upper respiratory tract infection. A meta-analysis in children.

Eur J Clin Pharmacol 2019 Mar 21;75(3):303-311. Epub 2018 Nov 21.

Department of General Practice, Clermont Auvergne University, Faculty of Medicine, 28 place Henri Dunant, 63000, Clermont-Ferrand, France.

Purpose: Upper respiratory tract infection (URTI) is a common infection in children, generally caused by viral respiratory infection. Vitamin C is currently proposed as prophylaxis for URTI. The purpose of this study was to assess the effectiveness of vitamin C administration in children for the prevention and reduced duration of URTI through a systematic literature review.

Methods: Review of the literature conducted between October 2017 and January 2018 in the main medical databases (CENTRAL, Medline and Embase) and by a gray literature approach. The selection criteria were: double-blind randomized controlled trials (RCTs) comparing vitamin C use to placebo in children aged 3 months to 18 years without chronic infection. Efficacy was assessed in terms of incidence, duration and severity of symptoms of URTI. A meta-analysis was conducted where possible.

Results: Eight RCTs, including 3135 children aged 3 months to 18 years, were selected. Quantitative analysis showed no difference between vitamin C administration and placebo (odds ratio = 0.75, 95% CI [0.54-1.03], p = 0.07, I = 74%). Vitamin C administration was found to decrease the duration of URTI by 1.6 days (standardized mean differences = -0.30 [-0.53; -0.08], p = 0.009, I = 70%). Children under 6 years of age benefit from more effective vitamin C supplementation associated with echinacea. No serious adverse events were reported.

Conclusions: Although no preventive effects were found, vitamin C intake reduced the duration of URTI. Considering the frequency of URTI, the inappropriate prescription of antibiotics, and the safe nature of vitamin C, its supplementation is justified, especially in children under 6 years of age and those who present a high frequency of URTI. There is a sound rationale for further trials with greater statistical power among children of this age.
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http://dx.doi.org/10.1007/s00228-018-2601-7DOI Listing
March 2019

Corrigendum to "Single Bout Exercise in Children with Juvenile Idiopathic Arthritis: Impact on Inflammatory Markers".

Mediators Inflamm 2018 6;2018:2074269. Epub 2018 Sep 6.

Pédiatrie Générale Multidisciplinaire, Hôpital Estaing, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.

[This corrects the article DOI: 10.1155/2018/9365745.].
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http://dx.doi.org/10.1155/2018/2074269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146626PMC
September 2018

Inflammatory Response 24 h Post-Exercise in Youth with Juvenile Idiopathic Arthritis.

Int J Sports Med 2018 Oct 17;39(11):867-874. Epub 2018 Aug 17.

Universite Clermont Auvergne, AME2P, Clermont-Ferrand, France.

The aim of this study was to measure the impact, at 24 h post-exercise, of a single exercise bout on plasma inflammatory markers such as calprotectin, IL-6, sIL-6 R, sgp130 and the hypothalamic-pituitary-adrenal (HPA) axis in children with juvenile idiopathic arthritis (JIA).Twelve children with JIA attended the laboratory on three consecutive days (control day, exercise day and 24 h post-exercise), including a 20-min exercise bout on a cycle-ergometer at 70% of max. HR at 8:30 a.m. on day 2. Plasma concentrations of calprotectin, IL-6, sIL-6 R, sgp130, cortisol, ACTH and DHEA were measured on venous blood samples taken every day.at rest and at 8:30, 8:50, 9:30, 10:30 a.m. and 12:00, 3:00, 5:30 p.m.A single exercise bout increased plasma calprotectin 1.7-fold (p<0.001) but did not increase IL-6 and soluble IL-6 receptors in short-term post-exercise recovery. However, at 24 h post-exercise, calprotectin, IL-6 and its receptors had decreased compared to control-day levels. There was a transient 2-fold increase in post-exercise self-evaluated pain (p=0.03) that disappeared in the evening without repercussions the following day.Physical activity in children with JIA results in a slight transient systemic inflammation but seems to be followed by counter-regulation at 24 h post-exercise with a decrease in proinflammatory markers.
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http://dx.doi.org/10.1055/a-0640-9063DOI Listing
October 2018

Childhood- versus Adult-Onset Polyarteritis Nodosa Results from the French Vasculitis Study Group Registry.

Autoimmun Rev 2018 Oct 14;17(10):984-989. Epub 2018 Aug 14.

National Referral Center for Rare Systemic Autoimmune Diseases, Department of Internal Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (APHP), Université Paris Descartes, Paris, France. Electronic address:

Objective: To investigate differences between childhood (cPAN)- and adult-onset polyarteritis nodosa (aPAN) patients.

Methods: cPAN patients' clinical findings at onset and outcomes were compared to those of aPAN patients from the French Vasculitis Study Group registry matched for year of enrollment and initial systemic versus cutaneous disease. Their information on medications, disease activity and damage were collected. Kaplan-Meier relapse-free survival curves and the log-rank test were used to analyze cPAN versus aPAN differences for predefined outcomes.

Results: Twenty-one children with systemic and 13 with cutaneous PAN were compared with 84 systemic- and 27 cutaneous-matched aPAN patients. Median follow-up exceeded 5 years for both groups. At study entry, mononeuritis multiplex was less frequent in systemic cPAN than systemic aPAN (P = 0.04), and purpura and myalgias were less frequent in cutaneous cPAN than cutaneous aPAN (P < 0.03). During follow-up, systemic cPAN relapsed more often than matched systemic aPAN (P < 0.0001), while relapse rates were similar for cutaneous disease (P > 0.05). Mostly minor relapses, predominantly involving the skin, occurred in all 4 groups. At last visit, damage accrual was comparable for cPAN and aPAN patients, but fewer systemic cPAN patients were treatment-free (15% versus 42%; P = 0.03). Two (6%) cPAN and 8 (7%) aPAN patients died.

Conclusion: Systemic PAN is equally severe in children and adults and carries a higher risk of relapse. The main cutaneous PAN features seem not to be influenced by age at disease onset.
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http://dx.doi.org/10.1016/j.autrev.2018.08.001DOI Listing
October 2018

Single Bout Exercise in Children with Juvenile Idiopathic Arthritis: Impact on Inflammatory Markers.

Mediators Inflamm 2018 13;2018:9365745. Epub 2018 Jun 13.

Pédiatrie Générale Multidisciplinaire, Hôpital Estaing, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.

Objective: In a context of inflammatory disease such as juvenile idiopathic arthritis (JIA), we do not know what impact physical activity may have on a deregulated immune system. The objective is to measure the impact of a single bout of exercise on plasma inflammatory markers such as calprotectin, IL-6, sIL-6R, sgp130, and the hypothalamic-pituitary-adrenal axis in children with juvenile idiopathic arthritis.

Methods: Twelve children with JIA performed a nonexercise control day and a consecutive day that included a 20 min exercise bout at 70% of max-HR at 08:30 am. Venous blood samples were taken at 08:30, 08:50, 09:30, 10:30 am, and 12:00 pm to measure plasma concentrations of calprotectin, IL-6, sIL-6R, sgp130, cortisol, and ACTH. Pain was evaluated at 08:30, 08:50 am, and 06:00 pm.

Results: There was a transient twofold increase in postexercise self-evaluated pain ( = 0.03) that disappeared in the evening. A single bout of exercise resulted in a 1.7-fold increase in plasma calprotectin ( < 0.001) but not IL-6 and its soluble receptors. Calprotectin levels returned to baseline within 3 hours after cessation of exercise.

Conclusion: Acute exercise in children with JIA induced slightly musculoskeletal leg pain and transient increased plasma calprotectin levels but not IL-6 levels. Trial registration in ClinicalTrials.gov, reference number NCT 02502539, registered on 29 May 2015.
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http://dx.doi.org/10.1155/2018/9365745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020487PMC
December 2018

Ara h 2 basophil activation test does not predict clinical reactivity to peanut.

J Allergy Clin Immunol Pract 2018 Sep - Oct;6(5):1772-1774.e1. Epub 2018 Feb 2.

CHU de Clermont-Ferrand, Service d'Immunologie biologique, Pôle de Biologie et d'anatomopathologie, Clermont-Ferrand, France; UMR 1240, INSERM/IMoST UCA, Clermont-Ferrand, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2018.01.021DOI Listing
November 2019

Fibrous Arthropathy Associated With Morphea: A New Cause of Diffuse Acquired Joint Contractures.

Pediatrics 2017 Oct;140(4)

Unité d'Immuno-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker Enfants Malades, Institut IMAGINE, Assistance Publique - Hopitaux de Paris, Paris, France

Etiologies for childhood-onset diffuse joint contractures encompass a large group of inherited disorders and acquired diseases, in particular a subtype of juvenile idiopathic arthritis called "dry polyarthritis," dermatomyositis, and systemic sclerosis. We report on 2 boys, aged 5 and 8 years, who developed acquired symmetric painless joint contractures preceding the development of superficial plaques of morphea by 7 to 13 months. There was no other clinical involvement, biological inflammation, or autoantibodies. No urinary mucopolysaccharidosis was seen. In both patients, wrist MRI showed no joint effusion, no bone erosion, and no or mild synovial thickening with slight enhancement after gadolinium infusion. One patient underwent a synovial biopsy, which showed dense fibrosis with a sparse inflammatory infiltrate, similar to the pathologic pattern observed in the skin biopsy. With methotrexate and systemic steroids, joint contractures slowly improved in the first patient and remained stable in the second. These 2 cases suggest that fibrous synovitis should be considered in children with acquired diffuse, symmetric, painless contractures and without elevation of acute-phase reactants, even in the absence of cutaneous manifestations. Articular MRI with gadolinium and careful cutaneous examination at onset and during follow-up should provide clues for diagnosing this entity.
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http://dx.doi.org/10.1542/peds.2016-1899DOI Listing
October 2017