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Introduction: PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis) or Marshall syndrome is the most frequent cause of recurrent auto-inflammatory fever in children. Frequent episodes impair the child's quality of life and family life. Total tonsillectomy demonstrated efficacy in improving symptoms, but few studies assessed partial tonsillectomy in this indication. The aim of the present study was to assess postoperative course after partial tonsillectomy for PFAPA syndrome, with comparison to total tonsillectomy., Materials and Methods: This retrospective cohort study adhered to STROBE guidelines. It included children with PFAPA syndrome on EUROFEVER criteria, treated by partial or total tonsillectomy between January 1, 2011 and December 31, 2022 in our university hospital center. For comparisons, the significance threshold was set at P<0.005., Results: Thirty-six children were included: 16 with partial and 20 with total tonsillectomy. With partial tonsillectomy, the number of episodes decreased by 10 per year (range, 5-21) (P<0.005) over 6 years' follow-up. The decrease was 50% with partial tonsillectomy and 93% with total tonsillectomy (P=0.056). The decrease in number was statistically suggestive (P=0.028). There were no complications with partial tonsillectomy and 2 patients with complications (10%) with total tonsillectomy. Two of the 16 patients with partial tonsillectomy (12.5%) required totalization, achieving remission in both cases., Conclusion: Partial tonsillectomy significantly reduced the frequency, duration and intensity of postoperative episodes in PFAPA syndrome. It may be less effective than total tonsillectomy, but has a lower risk of complications awaiting remission in adolescence., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Bacterial infections (BIs) are widespread in ICUs. The aims of this study were to assess compliance with antibiotic recommendations and factors associated with non-compliance., Methods: We conducted an observational study in eight French Paediatric and Neonatal ICUs with an antimicrobial stewardship programme (ASP) organised once a week for the most part. All children receiving antibiotics for a suspected or proven BI were evaluated. Newborns < 72 h old, neonates < 37 weeks, age ≥ 18 years and children under surgical antimicrobial prophylaxis were excluded., Results: 139 suspected (or proven) BI episodes in 134 children were prospectively included during six separate time-periods over one year. The final diagnosis was 26.6% with no BI, 40.3% presumed (i.e., not documented) BI and 35.3% documented BI. Non-compliance with antibiotic recommendations occurred in 51.1%. The main reasons for non-compliance were inappropriate choice of antimicrobials (27.3%), duration of one or more antimicrobials (26.3%) and length of antibiotic therapy (18.0%). In multivariate analyses, the main independent risk factors for non-compliance were prescribing ≥ 2 antibiotics (OR 4.06, 95%CI 1.69-9.74, p = 0.0017), duration of broad-spectrum antibiotic therapy ≥ 4 days (OR 2.59, 95%CI 1.16-5.78, p = 0.0199), neurologic compromise at ICU admission (OR 3.41, 95%CI 1.04-11.20, p = 0.0431), suspected catheter-related bacteraemia (ORs 3.70 and 5.42, 95%CIs 1.32 to 15.07, p < 0.02), a BI site classified as "other" (ORs 3.29 and 15.88, 95%CIs 1.16 to 104.76, p < 0.03), sepsis with ≥ 2 organ dysfunctions (OR 4.21, 95%CI 1.42-12.55, p = 0.0098), late-onset ventilator-associated pneumonia (OR 6.30, 95%CI 1.15-34.44, p = 0.0338) and ≥ 1 risk factor for extended-spectrum β-lactamase-producing Enterobacteriaceae (OR 2.56, 95%CI 1.07-6.14, p = 0.0353). Main independent factors for compliance were using antibiotic therapy protocols (OR 0.42, 95%CI 0.19-0.92, p = 0.0313), respiratory failure at ICU admission (OR 0.36, 95%CI 0.14-0.90, p = 0.0281) and aspiration pneumonia (OR 0.37, 95%CI 0.14-0.99, p = 0.0486)., Conclusions: Half of antibiotic prescriptions remain non-compliant with guidelines. Intensivists should reassess on a day-to-day basis the benefit of using several antimicrobials or any broad-spectrum antibiotics and stop antibiotics that are no longer indicated. Developing consensus about treating specific illnesses and using department protocols seem necessary to reduce non-compliance. A daily ASP could also improve compliance in these situations., Trial Registration: ClinicalTrials.gov: number NCT04642560. The date of first trial registration was 24/11/2020., (© 2024. The Author(s).)

Background: Even with increasing access to rapid HIV diagnosis and early antiretroviral therapy (ART) initiation, infants living with HIV seem to have adverse outcomes. We assessed the probability of death, viral suppression, and other HIV-related events in the first three years of life among early-treated children with perinatally-acquired HIV in South Africa, Mozambique, and Mali., Methods: We enrolled a cohort of infants who initiated ART within the initial 6 months of life and within 3 months of diagnosis. These children were monitored 2, 6, 12 and 24 weeks after enrolment, followed by biannual check-ups up to 4 years after enrolment. We assessed the probability of death, viral load (VL) suppression, severe immunosuppression (according to WHO guidelines), and engagement in care using Kaplan-Meier plots, and hazard ratios for these outcomes using multivariable Cox regression models., Findings: Two hundred and fifteen infants were enrolled and monitored for a median of 34 months [IQR, 16.3; 44.1]. ART initiation occurred at a median of 34 days of age [IQR, 26.0; 73.0]. The probability of death at 1 year of ART was 10% (95% CI, 6-14), increased to 12% (95% CI, 8-17) at 2 and remained in 12% at 3 years. The main risk factor for HIV/AIDS-related mortality was baseline viral load [HR: 2.98 (95% CI, 1.25-7.12)]. Sixty-one of 146 (42%) children achieved sustained virological control below lower limit of detection for any ≥1 year period between enrolment and 4 years after enrolment. Viral suppression during follow-up was inversely associated with baseline viral load [Hazard Ratio (HR): 0.72 (95% CI, 0.58-0.89] and adverse maternal social events [HR: 0.26 (95% CI, 0.15-0.45)]. Adherence to ART was assessed as optimal in 81% of the visits. Female sex at birth, lower age at diagnosis and maternal adverse social life events were risk factors for low adherence [Odds ratio, OR 1.25 (95% CI, 1.00-1.56); 1.12 (95% CI, 1.01-1.27) and 2.52 (95% CI, 2.16-12.37), respectively]., Interpretation: Despite early ART, mortality remains high in infants. High baseline VL and adverse maternal social environment increased the risk of poor outcomes. Sustained supportive strategies are essential during and after pregnancy, to achieve better survival., Funding: Early Treated Perinatally HIV Infected Individuals: Improving Children's Actual Life (EPIICAL) is a research consortium funded by ViiV Healthcare and led by Penta Foundation. The funder was not involved in the analysis and interpretation of data, writing of the report, or the decision to submit the paper for publication. The corresponding authors had access to all data and take final responsibility for the decision to submit., Competing Interests: The following institutions, to which the author-researchers belong, received funding from the sponsor (Penta Foundation) to carry out this research, who in turn received a non-competitive grant from ViiV named Early Treated Perinatally HIV Infected Individuals: Improving Children's Actual Life (EPIICAL): Fundación de Investigación Biomédica Hospital 12 de Octubre, Stellenbosch University, University of the Witwatersrand, Africa Health Research Institute, Fundação Ariel Glaser contra o SIDA Pediátrico, Centro de Investigaçao em Saude de Manhiça, Instituto Nacional de Saúde, Bambino Gesù Children's Hospital, Ragon Institute of MGH, MIT, and Harvard, University College of London, Gianni Benzi Pharmacological Research Foundation, University of Miami, Centre Hospitalier Universitaire Gabriel Touré, ISGlobal, Columbia University Irving Medical Center, University of Rome “Tor Vergata”, Penta Foundation. The authors reported no other relationships/conditions/circumstances that present a potential conflict of interest for this research. Elisa López reported being a full employee of ViiV Healthcare since April 2023. Outside the submitted work, Tacilta Nhampossa reported a grant from EDCTP Career Development Fellowships. Proposal: TMA2017CDF-1927 (2019–2022). Sheila Fernández-Luis reported a grant from Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and cofounded by European Social Fund. Paolo Palma reported a grant from NIH from 2020 to 2025 named PAVE, grant from NIH-NIAID (Targting HIV reservoirs in children with HIVIS-DNA and MVA-CMDR vaccines, and reported being the founder of Promiomics, a spin-off company of University Tor Vergata. Nicola Cotugno reported being the CRO and founder of Promiomics, a spin-off company of University Tor Vergata. Helena Rabie reported personal fees from ViiV community engagement meeting, personal fees from MSD Community engagement meeting., (© 2024 The Author(s).)

Background: Craniopharyngioma is a rare condition in children, but it is the most frequent tumor that occurs in the hypothalamic pituitary region. Chemical meningitis has been described as an uncommon postoperative complication, but no chemical meningitis due to a spontaneous rupture leading to craniopharyngioma diagnosis in children has been reported., Case Presentation: This is a case of a 13-year-old boy presenting with fever, vomiting and headache for two days. The CT scan revealed a suprasellar lesion, and lumbar puncture showed aseptic meningitis. The cerebral MRI suggested a craniopharyngioma and the cerebrospinal fluid cholesterol concentration was abnormally high. A thorough medical history indicated some visual disturbance, which improved at the onset of meningitis, and an inflection of the growth curve. The anatomopathological analysis of the tumor confirmed the diagnosis of craniopharyngioma., Conclusions: This case is the first to report the discovery of a craniopharyngioma with meningoencephalitis caused by the rupture of a craniopharyngioma cyst in a child. Diagnosis was facilitated by determining the cholesterol level in the cerebrospinal fluid, as well as fine anamnesis to identify visual and growth disturbances., (© 2023. The Author(s).)

Aim: To investigate the prevalence of infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses among children admitted to paediatric emergency departments (PEDs)., Methods: From April to July 2020, a prospective, multicentre cohort study was conducted in the PEDs of eight French university hospitals. Regardless of the reason for admission, a nasopharyngeal swab sample from each child was screened using reverse transcription polymerase chain reaction tests for SARS-CoV-2 and other respiratory viruses. We determined the prevalence of SARS-CoV-2 and other respiratory viruses and identified risk factors associated with a positive test., Results: Of the 924 included children (median [interquartile range] age: 4 years [1-9]; boys: 55%), 908 (98.3%) were tested for SARS-CoV-2. Only three samples were positive (0.3%; 95% confidence interval: 0.1-1) and none of these children had symptoms of coronavirus disease 2019. Of the 836 samples (90%) tested for other viruses, 129 (15.4%) were positive (primarily rhinovirus). Respiratory viruses were significantly more common in young children and in children with respiratory tract symptoms and fever., Conclusion: The prevalence of SARS-CoV-2 among children admitted to emergency departments was low. In contrast, and despite social distancing and other protective measures, the prevalence of other respiratory viruses detection was high., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background and Objectives: The incorporation of drugs in the hair of young children differs from that of adults and the metabolism of cannabis cannot be the same. Our primary objective was to analyze the distribution of the different cannabinoids in children's hair samples. The secondary objective was to correlate the intensity of toxic environmental exposure to cannabinoid metabolite levels., Methods: This was a prospective, single-center, observational pilot study of a pediatric cohort. Included subjects were all children less than 6 years of age admitted to a tertiary pediatric emergency unit for proven cannabis intoxication during the reference period. A hair strand was sampled within 12h of emergency admission., Results: Forty-one pediatric patients were consecutively enrolled. Hair analysis showed that 34 children were positive for Δ9-THC (range 0.06-284.4ng/mg); 41 % of them were also positive for THC-COOH (range 0.26-2.76pg/mg). Depending on the Δ9-THC concentration (>1ng/mg), 39 % of the children could be considered exposed to an intensely toxic environment. The rate of THC-COOH detection steadily increased from 2015 to 2018 (18 %, 40 %, 50 %, 58 % for each consecutive year). Children intensely exposed weighed less on admission (p=0.02), had more comatose presentations (p=0.02), and more previous social issues (75 % versus 12 %, OR 22.0, p=0.0002)., Conclusion: Hair testing in this context indirectly shows the intensity of children's toxic environmental exposure by the cannabinoid metabolite threshold. This was very helpful during the collegial examination of the toddlers' environment and led to a full investigation and to appropriate decisions concerning social measures., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interests to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Necrotizing enterocolitis (NEC) is a devastating condition in preterm infants due to multiple factors, including gut microbiota dysbiosis. NEC development is poorly understood, due to the focus on severe NEC (NEC-2/3)., Methods: We studied the gut microbiota, microbiome and metabolome of children with suspected NEC (NEC-1)., Results: NEC-1 gut microbiota had a higher abundance of the Streptococcus (second 10-days of life) and Staphylococcus (third 10-days of life) species. NEC-1 children showed a microbiome evolution in the third 10-days of life being the most divergent, and were associated with a different metabolomic signature than in healthy children. The NEC-1 microbiome had increased glycosaminoglycan degradation and lysosome activity by the first 10-days of life, and was more sensitive to childbirth, low birth weight and gestational age, than healthy microbiome. NEC-1 fecal metabolome was more divergent by the second month of life., Conclusions: NEC-1 gut microbiota and microbiome modifications appear more distinguishable by the third 10-days of life, compared to healthy children. These data identify a precise window of time (i.e., the third 10-days of life) and provide microbial targets to fight/blunt NEC-1 progression.

Objectives: Nontuberculous mycobacterial (NTM) lymphadenitis is a rare disease of children under 5 years. Its treatment is not standardized, even a "wait-and-see" approach is shown to be effective in the literature. Here, we discuss the diagnostic and therapeutic strategies employed in our departments., Methods: Records of pediatric patients treated for NTM cervical lymphadenitis from 2010 to 2015 in our tertiary center were retrospectively reviewed. Patients underwent cervical echotomography and/or CT scan. Every patient but one had microbiological explorations (NTM polymerase chain reaction [PCR] and culture) on fine needle aspiration of pus and/or adenitis biopsy. Differential diagnoses (tuberculosis, cat scratch disease) were excluded with serologies, chest X-Ray, and PCR on adenitis samples. Patients were classified as "proven diagnosis" (NTM detected), "highly probable" (suggestive clinical and anatomopathological aspect) or "possible" infection (suggestive adenitis alone). Treatments, follow-up and adverse events were reviewed., Results: Thirty-one patients were treated for NTM, median age 2.40 years (Interquartile Range IQR = [1.85-3.16]). Twenty-nine patients (96.77%) had an isolated cervico-facial localization. Median follow-up was 8.00 months (IQR = [4.20-13.43]). We found 17 "proven diagnosis" (58.62%), 5 "highly probable" (17.24%) and 7 "possible" infections (24.14%). "Proven" infections were due to: Mycobacterium avium (n = 12, 66.67%) and M. intracellulare (n = 5, 27.78%). All 29 patients received antibiotics, which were effective for 10 (34.48%, group 1); 10 underwent surgical excision for a poor outcome with antibiotics (34.48%, group 2); spontaneous or surgical drainage occurred in 9 on antibiotics (31.03%, group 3). The median times to resolution for group 1, 2 and 3 were respectively 6.33 months, 6.22 months and 9.53 months. Antibiotics treatment was mostly clarithromycin (n = 27, 93.10%) and/or rifampicin (n = 19, 65.52%); 18 patients (62.07%) received both. Median antibiotics duration was 6.23 months (IQR = [5.17-7.46]), with good compliance (79.31%). The observed adverse effects were 3 (13.04%) isolated transient transaminase elevations, 1 case (4.35%) of minor creatinine elevation, and 1 case (4.35%) of transient diarrhea. Surgical drainage caused 1 transient marginal mandibular nerve palsy, resolutive after 1 month., Conclusion: Antibiotics in NTM adenitis lead to resolution in 7 months, with good tolerance and compliance. The efficacy of "wait-and-see" attitude in the literature make excision surgery a second line treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The intestinal microbiota exerts vital biological processes throughout the human lifetime, and imbalances in its composition have been implicated in both health and disease status. Upon birth, the neonatal gut moves from a barely sterile to a massively colonized environment. The development of the intestinal microbiota during the first year of life is characterized by rapid and important changes in microbial composition, diversity, and magnitude. The pioneer bacteria colonizing the postnatal intestinal tract profoundly contribute to the establishment of the host-microbe symbiosis, which is essential for health throughout life. Escherichia coli is one of the first colonizers of the gut after birth. E. coli is a versatile population including harmless commensal, probiotic strains as well as frequently deadly pathogens. The prevalence of the specific phylogenetic B2 group, which encompasses both commensal and extra- or intraintestinal pathogenic E. coli strains, is increasing among E. coli strains colonizing infants quickly after birth. Fifty percent of the B2 group strains carry in their genome the pks gene cluster encoding the synthesis of a nonribosomal peptide-polyketide hybrid genotoxin named colibactin. In this review, we summarize both clinical and experimental evidence associating the recently emerging neonatal B2 E. coli population with several pathology and discuss how the expression of colibactin by both normal inhabitants of intestinal microflora and virulent strains may darken the borderline between commensalism and pathogenicity., (Copyright © 2016 the American Physiological Society.)

The intestinal barrier controls the balance between tolerance and immunity to luminal antigens. When this finely tuned equilibrium is deregulated, inflammatory disorders can occur. There is a concomitant increase, in urban populations of developed countries, of immune-mediated diseases along with a shift in Escherichia coli population from the declining phylogenetic group A to the newly dominant group B2, including commensal strains producing a genotoxin called colibactin that massively colonized the gut of neonates. Here, we showed that mother-to-offspring early gut colonization by colibactin-producing E. coli impairs intestinal permeability and enhances the transepithelial passage of luminal antigen, leading to an increased immune activation. Functionally, this was accompanied by a dramatic increase in local and systemic immune responses against a fed antigen, decreased regulatory T cell population, tolerogenic dendritic cells, and enhanced mucosal delayed-type hypersensitivity response. Conversely, the abolition of colibactin expression by mutagenesis abrogates the alteration of oral tolerance induced by neonatal colonization by E. coli. In conclusion, the vertical colonization by E. coli producing the genotoxin colibactin enhances intestinal translocation and subsequently alters oral tolerance. Thus, early colonization by E. coli from the newly dominant phylogenetic group B2, which produces colibactin, may represent a risk factor for the development of immune-mediated diseases., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

The neonatal gut is rapidly colonized by a newly dominant group of commensal Escherichia coli strains among which a large proportion produces a genotoxin called colibactin. In order to analyze the short- and long-term effects resulting from such evolution, we developed a rat model mimicking the natural transmission of E. coli from mothers to neonates. Genotoxic and non-genotoxic E. coli strains were equally transmitted to the offspring and stably colonized the gut across generations. DNA damage was only detected in neonates colonized with genotoxic E. coli strains. Signs of genotoxic stress such as anaphase bridges, higher occurrence of crypt fission and accelerated renewal of the mature epithelium were detected at adulthood. In addition, we observed alterations of secretory cell populations and gut epithelial barrier. Our findings illustrate how critical is the genotype of E. coli strains acquired at birth for gut homeostasis at adulthood.