European Journal of Pediatrics最新文献

Effective pain control in infants and toddlers is challenging, with limited data on topical anaesthetic safety. This study evaluates the safety and feasibility of a single S-Caine patch, a eutectic 70 mg lidocaine/70 mg tetracaine mixture with heat-assisted delivery, in children under 3 years. In this nonrandomised clinical trial (2019-2024) at a single tertiary paediatric centre, 67 of 106 eligible children under 3 years (median 0.55 years [IQR, 0.13-1.09]; range 3 days-3 years; 58% male) with arterial or central venous catheters received a single S-Caine patch applied for 30 min. Primary outcomes were safety, measured by plasma lidocaine concentrations (Cmax) versus a 0.100 mg/L safety threshold, adverse events monitoring, and feasibility assessed by Likert scales. Secondary outcomes included subgroup analyses by demographic and procedural factors. Median plasma lidocaine concentrations at - 15, 15, 30, 60, 120, and 240 min were < 0.010, < 0.010, 0.018, 0.020, 0.016, and 0.013 mg/L, respectively. Median Cmax was 0.025 [0.014-0.038] mg/L, remaining well below the predefined safety threshold across all subgroups (p < 0.001). Two patients exceeded the threshold (0.270 and 0.110 mg/L) without clinical effects. Minor adverse events occurred in 49 patients (73%): exclusively transient local erythema; resolving or decreasing within 30 min. Feasibility was excellent (≥ 4/5) in 87% at application and 82% at removal.

Conclusion:  In this clinical trial including 67 children, the S-Caine patch was safe and feasible for use in patients under three, with plasma lidocaine concentrations well below strict clinically relevant thresholds and adverse events only occurring locally, supporting its role as a non-invasive analgesic for procedural pain. Future studies are needed to confirm safety in larger paediatric populations.

Clinical trial registration: EU Clinical Trials Register, EudraCT Number 2019-002094-55, https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-002094-55/BE .

What is known: • Procedural pain management in young children is challenging, as current options are often invasive, distressing, or carry systemic side effects. Safe, effective, and non-invasive analgesic strategies are limited, particularly for infants and toddlers undergoing common procedures.

What is new: • The S-Caine patch provides a safe, non-invasive analgesic option for children under three, with plasma lidocaine levels well below strict safety thresholds and only minor transient local reactions, improving procedural comfort and reducing reliance on systemic pain interventions.

The recent surge in unaccompanied minor asylum seekers (UMAS) arriving in Switzerland presents significant public health challenges, particularly regarding immunization. Many of these adolescents lack vaccination documentation, requiring catch-up vaccination strategies. This study aimed to evaluate immunity against tetanus, hepatitis B, measles, mumps, rubella and varicella among UMAS upon arrival in Switzerland, to optimize vaccination strategies, and provide protection. This retrospective observational study included 100 UMAS patients followed at Geneva University Hospitals in 2023. Patients received a booster of diphtheria-tetanus-pertussis-inactivated poliovirus vaccine (dTPa-IPV) at the first visit at HUG, followed by serology testing one month later during the second visit. Immunity was defined based on established antibody thresholds. Data on demographics, vaccination history since arrival in Switzerland, and serology for tetanus, hepatitis B, measles, rubella, mumps, and varicella were collected from medical records. Among the 100 UMAS included, 83% originated from Afghanistan, 6% from Burundi, 4% from Somalia, 2% from Eritrea, and the remainder from other countries. The median age was 16 years, and 94% were male. Serological testing on arrival showed that 83% were immune to varicella, whereas immunity to measles was lower at 66%. Immunity rates were higher for mumps (90%) and rubella (89%). Only 22% had protective anti-HBs levels. After administration of a single dTPa-IPV booster, 89% achieved protective tetanus IgG concentrations at one-month follow-up.Conclusion: A substantial proportion of UMAS lacked immunity to measles, hepatitis B, and, to a lesser extent, tetanus and varicella, underscoring the need for systematic catch-up vaccination. Based on these findings, a pragmatic two-visit strategy appears optimal: Visit 1: administer MMR (or MMRV), Tdap-IPV, and hepatitis B vaccines to all UMAS; Visit 2 (after 1 month): repeat MMR (or MMRV) and perform tetanus and hepatitis B serology to guide additional doses. This streamlined approach maximizes early protection while remaining feasible within high-income healthcare settings.

Alazami syndrome is a neurodevelopmental disorder characterized by postnatal growth retardation, moderate to severe intellectual disability, and facial dysmorphology. It is caused by biallelic variants in the transcriptional regulator La ribonucleoprotein 7 (LARP7), where frameshift variants accounted for the majority of cases. The current study presents 7 new patients, including 3 males and 4 females from 3 unrelated families. Careful and thorough clinical examination identified novel oro-dental disease abnormalities, including a prominent premaxilla and enamel defects. The detected variants (c.1113_1116del, c.997 + 2T > C and c.518T > C) were not reported in the previous studies. The substitution c.518T > C represented the second missense variant to be identified in patients with Alazami syndrome. Male patients from the three families fulfilled ≥ 2 clinical warning signs of primary immunodeficiency. Lymphocyte subset counts and immunoglobulin levels were estimated in patients from two families. The values were within reference ranges, with only minor non-significant alterations in cytotoxic T-cell counts. A functional assay of B lymphocyte response was performed in one family, demonstrating impaired Streptococcus pneumoniae IgG antibody production following Pneumovax vaccination in the male patient, while his female sibling mounted an adequate response. In conclusion, the disease has a wide range of symptoms, which vary greatly among the affected patients. Our study expanded the clinical and molecular spectrum of the disorder and highlighted immunodeficiency as an underrecognized disease feature, potentially with a male sex predilection.

This work aims to study the changes in disease control during the transition to adult healthcare and the associations of disease control and psychiatric comorbidity with health-related quality of life (HRQoL) and experiences of care. Participants were adolescents and young adults (AYAs) with various chronic conditions, recruited from the New Children's Hospital in Helsinki, Finland. Data were collected before and 1 and 2 years after the transfer of care. Disease control was measured by predefined criteria and categorized as good, moderate, or poor. Psychiatric diagnoses were obtained from medical records. HRQoL was assessed using the Pediatric Quality of Life Inventory and the 16D instruments, while experiences of care were evaluated with questions from the Adolescent Friendly Hospital Survey. Of the 253 AYAs, 199 (79%) and 172 (68%) completed surveys 1 and 2 years after the transfer of care. The mean ages were 17.2, 18.3, and 19.8 years, respectively. Disease control was determined for 251 (99%) AYAs before transfer, 206 (81%) 1 year after, and 208 (82%) 2 years after the transfer of care. Disease control remained stable in most AYAs after transfer (good disease control: n = 70 (28%) before transfer, n = 94 (46%) 1 year, and n = 87 (42%) 2 years after the transfer of care) and showed no association with HRQoL or experiences of care. AYAs without psychiatric comorbidity had better disease control and HRQoL compared to those with a psychiatric diagnosis.

Conclusion:  Disease control in AYAs with chronic conditions remained stable throughout the transition to adult healthcare. Psychiatric comorbidity is an important contributor to inferior disease control and HRQoL across the transfer of care. Trial registration: Registration name, "The Bridge"; registration number, NCT04631965 ( https://clinicaltrials.gov/ct2/show/NCT04631965 ).

What is known: • The transfer of care from pediatric to adult healthcare has been associated with declines in health outcomes among adolescents and young adults with chronic conditions. • Psychiatric comorbidity may complicate the transition to adult healthcare.

What is new: • Disease control, health-related quality of life, and experiences of care are good in most AYAs after the transfer of care to adult healthcare. • Mental well-being likely plays a more crucial and complex role in the transition to adult care than currently understood.

A clear distinction between viral, bacterial, or non-infectious tonsillopharyngitis is not always possible due to overlapping clinical symptoms. Patient near point-of-care diagnostics may contribute to supporting clinical assessment and, in turn, guide antibiotic treatment. We performed a prospective cluster-randomized multi-center study with cross-over design in 25 pediatric offices located in and around the city of Berlin, Germany, from December 2023 to May 2024. The primary objective was to determine whether using a rapid molecular point of care test (mPOC) reduces antibiotic prescription rates in children 3 to <18 years of age with febrile tonsillopharyngitis. As a secondary objective, sick days, re-assessments, and hospitalizations were evaluated. A total of 1111 patients were included in the final analysis. A positive test result in the mPOC group was observed in 67.1% (n = 471/702) and 65.8% (n = 194/295) in the standard care (SC) control group (which had optional rapid antigen testing). Interestingly, only 27.9% (n = 114/409) of children in the SC group were managed exclusively on a clinical diagnosis. Overall, two-thirds of all patients received a prescription for antibiotics (67.2%; n = 747/1111), with no significant difference between the study groups. In 95.5% (n = 635/665) of children with a positive test, an antibiotic was prescribed, as well as in 10.8% (n = 36/332) of test-negative cases. The probability of prescribing antibiotics was significantly higher when the McIsaac score was ≥3 (OR =4.67 (CI 95% 3.22-6.79, p < 0.0001)). In patients <5 years, the number of sick leave days was 37% higher than in older ones (IRR = 1.37 (95% CI 1.18-1.59, p<0.0001)).

Conclusion:  A McIsaac score ≥ 3 and a positive streptococcal test result were strong drivers for antibiotic prescription. No difference in antibiotic prescription rates between study groups was observed. Antibiotic usage was high in our patient cohort and requires further efforts regarding diagnostic and antibiotic stewardship. Tonsillopharyngitis also utilized substantial resources during follow-up.

What is known: • A clear distinction between viral, bacterial, or non-infectious pharyngitis is not always possible due to the overlapping clinical symptoms. • Rapid antigen tests (RADT) or molecular diagnostic tests (mPOC) as part of point-of-care testing may contribute to antibiotic treatment guidance.

What is new: • In children with febrile tonsillopharyngitis, we could not observe a reduction in antibiotic prescription rates using mPOC compared to routine care, including RADT. • Further efforts regarding diagnostic and antibiotic stewardship are warranted. Trial registration number (DRKS-ID): DRKS00034362.

Upper gastrointestinal endoscopy (UGIE) with duodenal biopsies remains the gold standard for diagnosing celiac disease (CD) in children and adolescents. Despite clear guidelines, clinical practices may vary across centers. This self-reported survey study assessed adherence to European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines for pediatric CD in endoscopic practice, focusing on pitfalls and the use of novel technologies. A web-based, multicenter survey was distributed to pediatric gastroenterology centers that are members of the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (SIGENP). Thirty-eight responses from 34 SIGENP centers were analyzed. Overall, 31/34 (91%) respondents reported taking ≥ 5 duodenal biopsies for suspected CD, all including samples from both the duodenal bulb and distal duodenum. However, 9/31 (29%) endoscopists reported not correctly orienting the biopsy specimens. Among patients with persistently elevated anti-transglutaminase IgA (TGA-IgA) despite adherence to a gluten-free diet (GFD), 16 of 33 respondents (48%) performed a second UGIE at a time point other than the recommended 2 years after GFD initiation. Only 8/36 (22%) reported using novel endoscopic technologies, and 10/37 (27%) occasionally employed wireless capsule endoscopy. Artificial intelligence had not yet been incorporated into clinical practice.

Conclusions:  This study demonstrates overall compliance with ESPGHAN guidelines, although gaps persist in biopsy orientation and follow-up timing for patients with persistent TGA-IgA positivity. The use of novel endoscopic technologies is still limited, indicating the need for further studies and dedicated training programs to support their implementation in clinical practice.

What is known: • Diagnostic pitfalls in celiac disease remain a major challenge in endoscopy practice. • New endoscopic tools proved to be useful to decrease the number of misdiagnoses and related healthcare costs of celiac disease.

What is new: • Major gaps remain regarding proper orientation of biopsies, and the timing of follow-up endoscopy in patients with persistent TGA-IgA positivity. • Further studies and dedicated training programs are required to facilitate the effective integration of advanced endoscopic technologies into the diagnostic workflow.

Long-term antithyroid drug (ATD) therapy is often required in pediatric Graves' disease, yet adherence can be challenging. Therefore, identifying reliable predictors of remission and relapse is crucial for optimizing disease management. This study aimed to evaluate the role of the baseline FT3/FT4 ratio in predicting remission and relapse, alongside other potential markers, including TRAb levels, thyroid volume, and body mass index (BMI). This retrospective, single-center study included pediatric patients diagnosed with Graves' disease and treated with ATDs. Age, sex, BMI, thyroid volume, TRAb, FT3, and FT4 levels were recorded at diagnosis, and the FT3/FT4 ratio was calculated. Remission was defined as maintaining euthyroidism for at least 12 months after discontinuation of ATD therapy, whereas relapse was defined as the recurrence of hyperthyroidism following remission. A total of 55 patients were evaluated. The remission rate was 43.6%, and among those who achieved remission, the relapse rate was 8.3%. No significant association was found between remission and age, sex, BMI, ATD duration, or the FT3/FT4 ratio. However, remission was significantly more likely in patients with TRAb levels < 10 IU/L (p < 0.05). Additionally, an inverse relationship was observed between thyroid volume and the likelihood of remission. Although the baseline FT3/FT4 ratio did not predict remission, it was significantly higher in patients who experienced relapse. An FT3/FT4 ratio > 0.54 pmol/pmol predicted relapse with 75% sensitivity and 98% specificity (AUC = 0.842; p = 0.048).

Conclusion: The baseline FT3/FT4 ratio demonstrated limited value in predicting remission but proved to be a strong indicator of relapse risk in pediatric Graves' disease. Additionally, lower TRAb levels (< 10 IU/L) and smaller thyroid volumes were associated with higher remission rates. Together, these findings suggest that incorporating the FT3/FT4 ratio, TRAb levels, and thyroid volume into routine assessment may enhance risk stratification and support more personalized treatment approaches for pediatric Graves' disease.

What is known: • Pediatric Graves' disease often requires long-term antithyroid drug therapy, and remission rates are variable; TRAb levels and thyroid volume are recognized predictors of remission.

What is new: • The baseline FT3/FT4 ratio has limited value in predicting remission but may serve as a strong predictor of relapse, with a ratio 0.54 pmol/pmol showing high specifi city for relapse in pediatric Graves' disease.

Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disorder caused by MEFV variants. Exon 10 variants, particularly M694V, are strongly associated with severe disease, but the impact of non-exon 10 variants in children remains less defined. To evaluate genotype-phenotype correlations in pediatric FMF by comparing patients with homozygous exon 10, compound heterozygous exon 10, and exon 10 combined with non-exon 10 variants. This single-center retrospective cohort study included 477 children fulfilling Eurofever/PRINTO criteria between 2018 and 2025. Patients were stratified into four genotype groups. Clinical features, laboratory parameters, and treatments were compared. Disease severity was assessed with the International Severity Scoring System for FMF (ISSF). Homozygous exon 10 variants were associated with an earlier disease onset, shorter diagnostic delay, higher ISSF scores, and a markedly greater requirement for anti-IL-1 therapy compared with other genotypic categories. Patients with compound exon 10 variants and those with combined exon 10-non-exon 10 variants exhibited broadly comparable overall disease severity, although differences were observed in selected clinical manifestations. In contrast, individuals with combined exon 10-non-exon 10 variants demonstrated higher attack frequency, increased inflammatory marker levels, and higher ISSF scores when compared with patients with a single exon 10 allele, supporting a modifier effect of non-exon 10 variants on disease expression.

Conclusion: Pediatric FMF patients homozygous for exon 10, especially M694V, show a more severe clinical course with higher disease activity and greater biologic treatment requirements. Exon 10-non-exon 10 variants present with attenuated but clinically relevant phenotypes, resembling compound exon 10 carriers. These findings emphasize the prognostic importance of comprehensive MEFV genotyping in risk stratification and individualized management.

What is known: • Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disorder, caused by MEFV gene mutations. • Exon 10 mutations, particularly M694V homozygosity, are associated with more severe disease, higher attack frequency, colchicine resistance, and increased risk of complications such as amyloidosis.

What is new: • This is one of the largest pediatric FMF cohorts systematically stratified into homozygous exon 10, compound heterozygous exon 10, exon 10-non-exon 10 groups, and single exon 10 allele • Exon 10-non-exon 10 variant combinations were associated with a clinically relevant inflammatory phenotype resembling compound exon 10 genotypes, suggesting a potential modifier role of non-exon 10 variants.