Search Results (70)

Background: Paediatric hepatocellular carcinoma (HCC), including its fibrolamellar variant (FLC), is a rare malignancy with distinct biological behaviour and limited therapeutic options. While complete surgical resection is a key determinant of survival, many patients present with unresectable tumours at diagnosis. The role of neoadjuvant chemotherapy in improving resectability, particularly in histologically distinct subtypes, remains inconclusive. Methods: We retrospectively analysed 43 patients (<18 years) with histologically confirmed conventional HCC (cHCC, n = 27) or FLC (n = 16) enrolled in the German Pediatric Liver Tumour Registry. We assessed clinical characteristics, treatment response, surgical outcomes, and survival. Special focus was placed on the impact of neoadjuvant chemotherapy in initially unresectable tumours. Results: FLC and cHCC exhibited significant differences in clinical presentation, such as age of presentation, AFP elevation, or presence of underlying liver disease. Although overall survival did not significantly differ between groups, cHCC tumours showed a markedly higher response to chemotherapy (62.5% partial remission vs. 0% in FLC). Complete resection (R0) was achieved in 77% of all patients and was the strongest predictor of survival. Importantly, a subset of cHCC patients who initially had unresectable tumours became eligible for curative surgery following neoadjuvant chemotherapy. Notably, delayed resection after chemotherapy led to outcomes comparable to those with upfront surgery, whereas progression during chemotherapy was associated with a universally poor prognosis. Conclusions: This study supports upfront resection as the preferred strategy in paediatric HCC and FLC whenever feasible. In cHCC, neoadjuvant chemotherapy demonstrated a favourable response profile and contributed to secondary resectability in a subset of initially unresectable cases, supporting a potential role within a multimodal treatment approach. In contrast, FLC showed limited responsiveness to current systemic therapies. These findings emphasise the importance of histology-specific strategies and highlight the ongoing need for more effective systemic options, particularly for unresectable FLC. Full article

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), unlike pediatric acute-onset neuropsychiatric syndrome (PANS), is triggered by infections. This study aimed to assess the differences in low-grade endotoxemia and oxidative stress between these conditions. A cross-sectional study compared serum levels of soluble NOX2-dp (sNOX-2-dp), isoprostanes, lipopolysaccharide (LPS), and zonulin in 30 PANDAS, 21 PANS, and 30 control (CT) children matched for age and gender. Zonulin was used to assess gut permeability. Patients with PANDAS showed significantly higher serum levels of sNOX2-dp, isoprostanes, LPS, and zonulin than PANS and controls, while no significant differences were found between PANS and controls. sNOX2-dp correlated with isoprostanes (Rs = 0.708; p < 0.001), LPS (Rs = 0.584; p < 0.001), and zonulin (Rs = 0.662; p < 0.001). Multiple regression identified isoprostanes (β = 0.599; p < 0.001) and zonulin (β = 0.295; p = 0.01) as independent predictors of sNOX2-dp (R² = 81%). PANDAS and PANS showed distinct profiles of LPS, zonulin, NOX2, and isoprostanes. Future research should explore therapies targeting endotoxemia and oxidative stress for potential clinical benefits. Full article

Background: Disorders of Gut–Brain Interaction (DGBIs) are present in 23.0% of the paediatric population, according to Rome IV. Latin American (LA) prevalence of DGBIs in children with Autism Spectrum Disorder (ASD) is unknown. The aim of this study was to determine the prevalence of DGBIs and possible associations in schoolchildren and adolescents with ASD from LA. Methods: An observational analytical study was conducted in LA cities. Caregivers of children with ASD completed the Rome IV Questionnaire for Pediatric Gastrointestinal Symptoms to identify DGBIs. Sociodemographic, clinical, and family variables were included. Statistical analysis involved central tendency measures, univariate and bivariate analysis, calculation odds ratios (ORs), and 95% confidence intervals (95%CIs), with p < 0.05 significance. Results: The study included 353 children with ASD. Predominantly male (78.8%), white (56.1%), attending private schools (79.3%), altered nutritional status (43.9%), born by c-section (57.5%), firstborn (54.7%), level of autism not classified at the time of the study (49.0%). A total of 58.9% presented DGBI. Functional constipation (FC) was the most frequent (27.2%). Those from Central America (CA) had a higher likelihood of presenting a DGBI (OR = 1.98, 95% CI = 1.25–3.12, p = 0.0018). Conclusions: Over half of LA schoolchildren and adolescents with ASD presented DGBI, FC being the most common, and higher likelihood of DGBI in CA. Full article

Theoretical background: The study of psychological well-being in children and adolescents living with chronic illness is of particular relevance, as the physical and psychosocial aspects of the illness can have a significant impact on their quality of life. Previous research has highlighted that depression, nonproductive thoughts and various aspects of problematic internet use may be related to life satisfaction and ways of coping with illness. This study aims to examine how depression, nonproductive thoughts, and problematic internet use interact with illness perception and burden to affect psychological well-being and life satisfaction. Methods: A cross-sectional study was conducted with 207 chronically ill children aged 10–18 years. The children, aged between 10 and 18 years old, attended regular check-ups in different specialities (gastroenterology, pulmonology, onco-haematology, and paediatric rehabilitation). A cross-sectional study was carried out using psychological instruments to measure life satisfaction (SWLS), nonproductive thoughts (NPG-K), problematic internet use (PIU-Q), illness perception (PRISM) and illness burden (PRISM-D, IIRS), and depression (BDI-R). Spearman rank correlation analysis was used to explore the associations between variables. Results: Life satisfaction was negatively related to nonproductive thoughts (r = −0.28, p < 0.001), internet obsession (r = −0.20, p < 0.01), and internet neglect (r = −0.20, p = 0.004). Conversely, a positive correlation was found with the PRISM (r = 0.14, p = 0.042), suggesting that less dominance of illness detection is associated with higher life satisfaction. Depression and nonproductive thoughts showed a strong positive relationship (r = 0.49, p < 0.001), and depression and problematic internet use also showed significant correlations for the obsession, neglect and control subscales (r = 0.23–0.29, all p < 0.001). Cluster analysis identified three psychological profiles: ‘positive fighters’, ‘avoidant sufferers’, and ‘negative observers’, distinguished by differences in depression, nonproductive thoughts, illness burden, and well-being. Conclusions: The results suggest that the quality of life of children and adolescents with chronic illness is significantly affected by mental health factors, particularly depression, nonproductive thoughts and problematic internet use. Illness perception and illness-related distress also play a key role in shaping life satisfaction and overall psychosocial well-being. These findings underscore the need for targeted psychological interventions in pediatric chronic care to enhance well-being and promote adaptive coping and suggest that psychological interventions and targeted psychosocial support can significantly improve these children’s quality of life. Further research is needed to explore intervention options and to develop optimal support strategies. Full article

Background: The demand for children’s palliative care is increasingly urgent, with over 21 million children worldwide needing access, yet only 5–10% currently receiving it. Mapping the development of children’s palliative care is important in tracking progress and focusing priorities for future work. Methods: In 2023, a cross-sectional survey was conducted to assess the status of children’s palliative care globally, focusing on eight key indicators. Children’s palliative care experts and stakeholders were asked to evaluate the perceived levels of development in their countries across five defined levels, ranging from no known provision to broad integration into health care services. Efforts were made to engage non-responding countries. Regional palliative care associations were consulted to validate the results. Results: The survey was distributed to experts in 167/197 countries (85%), achieving data collection for 131 countries (78% of surveys sent). A total of 42% of countries (83) were at the lowest level of development (Level 1), while only 6% (11) of countries reached the highest level (Level 5), showing significant regional variation. An overall increase in children’s palliative care globally was seen, including significant movement between levels. Variations were seen between regions and across country income categories, providing insight to inform ongoing efforts in service development, advocacy, education, research and access to essential medicines. Conclusions: There has been global progress in children’s palliative care, although substantial gaps remain in access, particularly between high-income countries and low- and middle-income countries (LMICs). The study highlights the importance of a comprehensive approach to children’s palliative care, with advocacy and education and training programmes being crucial for sustainable development. Full article

Background: Iatrogenic withdrawal syndrome (IWS) poses a significant clinical challenge in pediatric intensive care units (PICUs) within Japan. Despite the existing availability of tools to assess pain and delirium, a validated instrument specifically designed for IWS has been notably absent in Japanese clinical practice. The Sophia Observation withdrawal Symptoms-Paediatric Delirium (SOS-PD) scale is globally recognized as an effective tool for IWS evaluation. To bridge this gap, this study aimed to validate the Japanese version of the SOS-PD scale. Methods: A prospective, cohort, observational study was undertaken in a single-center PICU in Japan. Participants ranged from neonates to children aged 20 years, excluding those with pre-existing neurological conditions or coma. Criterion validity was evaluated by comparing Japanese SOS-PD scale scores between a Weaning Group (WEAN) undergoing sedative/opioid tapering and a Maintenance Group (MAIN) receiving stable medication. Correlation analysis was also conducted against pediatric intensivists’ observational NRS (NRSobs). Inter-rater reliability of the Japanese SOS-PD scale was assessed utilizing kappa statistics and intraclass correlation coefficient (ICC). Results: In support of criterion validity, the WEAN group demonstrated significantly higher scores in both NRSobs and the IWS component of the Japanese SOS-PD scale compared to the MAIN group (p < 0.001). A strong correlation was observed between the Japanese SOS-PD IWS component and NRSobs (r = 0.91, p < 0.001). Inter-rater reliability was also robust, with a kappa coefficient of 0.95 and an ICC of 0.98. Conclusions: The Japanese version of the SOS-PD scale exhibits strong validity and inter-rater reliability for IWS assessment within Japanese PICUs. This validated instrument can support the early detection and appropriate management of pediatric IWS in Japan, with the potential to enhance the quality of patient care. Full article

Monitoring infliximab (IFX) concentrations is crucial for optimizing IFX therapy in children with inflammatory bowel diseases (IBDs) who show low response rates due to inadequate drug exposure. Substantial variation occurs in IFX trough concentrations in paediatric patients. Objectives: This study aimed to investigate IFX pharmacokinetics (PK) in children with IBD during both the induction phase and maintenance phases and to identify covariates associated with IFX PK. Methods: This single-centre retrospective cohort study was conducted at an academic children’s hospital. Data was extracted from paediatric IBD patients receiving IFX between January 2018 and October 2023 and included demographic-, clinical- and laboratory parameters collected from electronic health records. Linear mixed model analysis was performed to investigate associations between these parameters and IFX trough concentrations. Target attainment [≥15 μg/mL in induction or 5–10 μg/mL in maintenance phase] of the IFX dosing regimens was evaluated. Results and Conclusions: A total of 115 children (417 unique IFX concentrations) were included. Multivariate analysis revealed significant positive associations between IFX and albumin concentrations (β = 0.388, p = 0.010) and IFX concentrations with dose (β = 6.534, p < 0.001), and an inversion association between IFX concentrations and treatment phase (β = −4.922, p < 0.001). During the induction and maintenance phases, 57.2% and 30.6% of IFX concentrations were subtherapeutic, respectively. A systematic search of studies investigating factors influencing IFX concentrations was concurrently performed. Our findings were critically compared against existing literature to assess relevant clinical and biochemical determinants of IFX PK in children with IBD. Our findings highlight the need for personalized dosing strategies in pediatric IBD patients, particularly during the induction phase. By implementing therapeutic drug monitoring (TDM) and considering clinical and biochemical factors, clinicians can implement more personalized strategies, potentially improving treatment efficacy and reducing the risk of treatment failure or adverse effects. This approach could lead to better target attainment, potentially enhancing clinical outcomes and minimizing premature switching to other therapies. Full article

Background/Objectives: Artificial intelligence (AI) and machine learning (ML) are transforming healthcare by enabling predictive, diagnostic, and therapeutic advancements. Pediatric healthcare presents unique challenges, including limited data availability, developmental variability, and ethical considerations. This narrative review explores the current trends, applications, challenges, and future directions of ML in pediatric healthcare. Methods: A systematic search of the PubMed database was conducted using the query: (“artificial intelligence” OR “machine learning”) AND (“pediatric” OR “paediatric”). Studies were reviewed to identify key themes, methodologies, applications, and challenges. Gaps in the research and ethical considerations were also analyzed to propose future research directions. Results: ML has demonstrated promise in diagnostic support, prognostic modeling, and therapeutic planning for pediatric patients. Applications include the early detection of conditions like sepsis, improved diagnostic imaging, and personalized treatment strategies for chronic conditions such as epilepsy and Crohn’s disease. However, challenges such as data limitations, ethical concerns, and lack of model generalizability remain significant barriers. Emerging techniques, including federated learning and explainable AI (XAI), offer potential solutions. Despite these advancements, research gaps persist in data diversity, model interpretability, and ethical frameworks. Conclusions: ML offers transformative potential in pediatric healthcare by addressing diagnostic, prognostic, and therapeutic challenges. While advancements highlight its promise, overcoming barriers such as data limitations, ethical concerns, and model trustworthiness is essential for its broader adoption. Future efforts should focus on enhancing data diversity, developing standardized ethical guidelines, and improving model transparency to ensure equitable and effective implementation in pediatric care. Full article

Background/Objectives: Non-invasive ventilation (NIV) has emerged as a possible first-step treatment to avoid invasive intubation in pediatric intensive care units (PICUs) due to its advantages in reducing intubation-associated risks. However, the timely identification of NIV failure is crucial to prevent adverse outcomes. This study aims to identify predictors of first-attempt NIV failure in PICU patients by testing various machine learning techniques and comparing their predictive abilities. Methods: Data were sourced from the TIPNet registry, which comprised patients admitted to 23 Italian Paediatric Intensive Care Units (PICUs). We selected patients between January 2010 and January 2024 who received non-invasive ventilation (NIV) as their initial approach to respiratory support. The study aimed to develop a predictive model for NIV failure, selecting the best Machine Learning technique, including Generalized Linear Models, Random Forest, Extreme Gradient Boosting, and Neural Networks. Additionally, an ensemble approach was implemented. Model performances were measured using sensitivity, specificity, AUROC, and predictive values. Moreover, the model calibration was evaluated. Results: Out of 43,794 records, 1861 admissions met the inclusion criteria, with 678 complete cases and 97 NIV failures. The RF model demonstrated the highest AUROC and sensitivity equal to 0.83 (0.64, 0.94). Base excess, weight, age, systolic blood pressure, and fraction of inspired oxygen were identified as the most predictive features. A check for model calibration ensured the model’s reliability in predicting NIV failure probabilities. Conclusions: This study identified highly sensitive models for predicting NIV failure in PICU patients, with RF as a robust option. Full article

Background: Chronobiology has gained attention in the context of paediatric neurological and neuropsychiatric disorders, including migraine, epilepsy, autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD). Disruptions in circadian rhythms are associated with key symptoms such as sleep disturbances, mood dysregulation, and cognitive impairments, suggesting a potential for chronobiology-based therapeutic approaches. Methods: This narrative review employs a systematic approach to identify relevant studies through searches of three major scientific databases, NCBI/PubMed, ScienceDirect, and Scopus, up to July 2024. We used a combination of broad and condition-specific keywords, such as “chronobiology”, “biorhythm”, “pediatric”, “epilepsy”, “ADHD”, and “ASD”, among others. Articles in English that focused on clinical features, treatments, or outcomes related to circadian rhythms in paediatric populations were included, while non-peer-reviewed articles and studies lacking original data were excluded. Rayyan software was used for article screening, removing duplicates, and facilitating consensus among independent reviewers. Results: A total of 87 studies were included in the analysis. Findings reveal a consistent pattern of circadian rhythm disruptions across the disorders examined. Specifically, dysregulation of melatonin and cortisol secretion is observed in children with ASD, ADHD, and PTSD, with altered circadian timing contributing to sleep disturbances and mood swings. Alterations in core clock genes (CLOCK, BMAL1, PER, and CRY) were also noted in children with epilepsy, which was linked to seizure frequency and timing. Chronotherapy approaches showed promise in managing these disruptions: melatonin supplementation improved sleep quality and reduced ADHD symptoms in some children, while light therapy proved effective in stabilizing sleep–wake cycles in ASD and ADHD patients. Additionally, behaviour-based interventions, such as the Early Start Denver Model, showed success in improving circadian alignment in children with ASD. Conclusions: This review highlights the significant role of circadian rhythm disruptions in paediatric neurological and neuropsychiatric disorders, with direct implications for treatment. Chronobiology-based interventions, such as melatonin therapy, light exposure, and individualized behavioural therapies, offer potential for improving symptomatology and overall functioning. The integration of chronotherapy into clinical practice could provide a paradigm shift from symptom management to more targeted, rhythm-based treatments. Future research should focus on understanding the molecular mechanisms behind circadian disruptions in these disorders and exploring personalized chronotherapeutic approaches tailored to individual circadian patterns. Full article

Background: This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD). Methods: A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21). We analysed for clinical, biological, and endoscopic remission; treatment failure; hospitalisations; emergency visits; and adverse drug reactions. The IFX doses were adjusted to maintain trough concentrations ≥ 5 µg/mL, with specific targets for proactive TDM. Results: Of the 38 patients, 21 had Crohn’s disease (CD), 16 ulcerative colitis (UC), and 1 undetermined IBD. The mean (standard deviation) IFX trough concentrations were 6.83 (5.66) µg/mL (reactive) and 12.38 (9.24) µg/mL (proactive) (p = 0.08). No statistically significant differences between groups were found in remission rates or treatment failure. The proactive group had fewer hospitalisations (14.29% vs. 23.53%; p = 0.47) and shorter median hospitalisation days (6 vs. 19; p = 0.50), although the difference was not statistically significant. The number of patients with adverse reactions (infusion related reactions and infections) was higher in the proactive group (38.10% vs. 23.53%; p = 0.34) but the difference was not significantly different. Conclusions: Proactive TDM showed no significant differences in treatment outcomes compared to reactive TDM. However, the results in both the reactive and proactive TDM groups were not worse than those reported in other studies. Further studies with larger samples are needed to optimize the treatment strategies for pediatric IBD patients. Full article

Background and Objectives: There is an increasing use of fecal matter transplantation (FMT) worldwide as research into the impact of the gut microbiome in various disease states is growing. FMT is the transfer of stool from a healthy human donor to a patient for the purpose of restoring intestinal dysbiosis. This review will assess the efficacy and safety of FMT in the treatment of pediatric inflammatory bowel diseases (IBDs) and explore the future directions of the use of FMT in children. Materials and Methods: A systematic review was performed where a literature search of publications published prior to 15 September 2023 was performed. Efficacy outcomes and safety data as well as microbiome analysis were reviewed from the studies where applicable. Results: Nine studies on UC and two studies on CD satisfied eligibility criteria and individually analysed. Most of the studies provided microbiome analyses. Conclusions: FMT is a safe treatment for paediatric IBD, and is shown to be effective in inducing clinical response by some studies. However the lack of randomized controlled trials limited the results of our study. Full article

Background/Objectives: The prevalence of food allergy (FA) in children is increasing. Dysbiosis of the microbiome has been linked to FA but needs to be better understood. We aimed to characterize the gut and skin microbiome of young food-allergic children over time and within different types of immunoglobulin E (IgE)-mediated FA. Methods: We studied 23 patients, as a pilot study of an ongoing prospective multicenter cohort study including children < 2y with newly diagnosed IgE-mediated FA. Samples (feces/skin swabs) were collected at enrollment and at 1-year follow-up and sequenced for the bacterial 16S rRNA gene (hypervariable v1–v2 region). Results: Gut and skin bacterial diversity was significantly higher in patients compared with controls and increased over time (beta test, Shannon diversity, p < 0.01). Within different types of IgE-mediated FA, bacterial diversity was similar. Community composition differed significantly over time and within IgE-mediated FA types (PERMANOVA: p < 0.01). Several significantly different genus abundances were revealed. We observed a positive correlation between high total IgE and a high abundance of the genus Collinsella in patients with a higher number of allergies/sensitizations (≥3), and patients with tree nut and/or peanut allergy. Conclusions: This study revealed an increased bacterial diversity in children with FA compared with non-atopic children. Importantly, the gut and skin microbiome differed in their composition over time and within different types of IgE-mediated FA. These findings contribute to the understanding of microbiome changes in children with FA and indicate the potential of the genus Collinsella as a biomarker for tree nut and/or peanut allergy and possibly for allergy persistence. Full article

Background: Traumatic injury is a leading cause of death and disability in children and young adults. There is a lack of evidence-based literature and guidelines on supporting families after severe child injury. This study aimed to assess the family needs and factors associated with those needs. Methods: A prospective multicenter follow-up study conducted at two Norwegian trauma centers involving children (aged 0–18 years) who sustained a moderate or severe traumatic injury with a New Injury Severity Score > 9. Sociodemographic and injury variables were recorded at baseline. The Family Needs Questionnaire—Paediatric Version, ranging from one (not at all met) to five (completely met) was completed by parents to assess the family needs at the 6-month follow-up. Bivariate logistic regression analyses were conducted to identify the factors associated with the family needs at 6 months post-injury. Results: Of the 63 children included, 38 (68% boys) with a mean age of 9.9 years (SD = 5.8) were available for follow-up. At 6 months, 82% reported needs for health information with a mean score of 3.8 (SD = 1.0), and involvement with care with a mean of 3.7 (SD = 1.2). Additionally, 71% reported emotional support needs (mean score 2.6, SD = 1.3). A higher number of injuries and a lower age of the child were significantly associated with increased odds of having more family needs. Conclusions: After moderate to severe pediatric traumatic injury, families report a need for health information, involvement in care, and emotional support. Paying attention to the number of injuries and the child’s age could help to identify families in need of information and support. Full article

Background: The COVID-19 pandemic affected the health of millions of people, both directly through infection and indirectly through delayed diagnosis and treatment of non-COVID-19 illnesses. The aim of this study was to check the impact of the COVID-19 pandemic on the diagnosis and treatment of appendicitis in children. Methods: The study was carried out at the Department of Paediatric Surgery of the Marciniak Hospital (Wrocław, Poland) and covered two periods, the pre-pandemic one (P1, 01/03/2019–29/02/2020) and the pandemic one (P2, 01/03/2020–28/02/2021). Results: The number of admissions of patients with suspected appendicitis and observation-only patients decreased during the pandemic (400/289 and 226/160, respectively). Although the number of operated children was similar during both analyzed periods (P1: 174, P2: 160), the rate of surgical interventions was significantly higher during P2 (55.4%) than during P1 (43.5%) (χ² test: p = 0.00272). The values of the variables quantifying disease progression and severity of inflammation, selected inflammation-related parameters detected by laboratory blood tests, latencies from the onset of symptoms to the admission and from the admission to the operation, and total duration of hospitalization did not differ significantly between the pre-pandemic and pandemic periods. Conclusions: These results show that the COVID-19 pandemic led to more rigorous and careful triage of pediatric patients suspected of acute appendicitis that did not have a negative impact on patient outcomes. Full article