To evaluate the pooled surgical success rate, postoperative changes in intraocular pressure (IOP) and antiglaucoma medication burden following glaucoma drainage device (GDD) implantation in pediatric glaucoma, with subgroup analyses according to implant type. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Web of Science, PubMed, Scopus, and the Cochrane Library were searched on September 16, 2025. Eligible studies included at least 10 pediatric patients undergoing GDD implantation with a minimum follow-up of 3 months and reporting surgical success, IOP, or medication outcomes. Risk of bias in individual studies was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses using the DerSimonian-Laird method were performed for pooled surgical success, IOP reduction, and medication reduction. Subgroup analyses were conducted for Ahmed glaucoma valve (AGV), Ahmed ClearPath (ACP), Baerveldt glaucoma implant (BGI), Aurolab aqueous drainage implant (AADI), and Paul glaucoma implant (PGI). Twenty-three studies including 1082 pediatric patients (1233 eyes) were analyzed. The overall pooled surgical success rate was 76% (95% CI, 71.1%-80.3%; I2 = 73.6%). Subgroup success rates were 70.7% for AADI, 78.9% for ACP, 73.0% for AGV, 82.3% for BGI, and 80.0% for PGI. The pooled mean IOP reduction was -16.14 mmHg (95% CI, -17.06 to -15.21; I2 = 88.3%), and the mean reduction in glaucoma medications was -1.63 (95% CI, -1.76 to -1.51; I2 = 91.4%). Meta-regression analysis demonstrated that longer follow-up duration was associated with lower surgical success and a smaller reduction in medication use, suggesting that medication requirements increased over time. GDD implantation in pediatric glaucoma is associated with meaningful IOP reduction, decreased medication burden, and an overall favorable surgical success rate across diverse pediatric glaucoma subtypes. However, substantial heterogeneity, non-uniform success definitions, and declining success with longer follow-up suggest that long-term durability may be limited, and outcomes should be interpreted cautiously, particularly in inter-device comparisons.
Perioperative corticosteroids, particularly methylprednisolone, have been used for decades in pediatric cardiac surgery to attenuate the systemic inflammatory response associated with cardiopulmonary bypass. This systematic review and meta-analysis evaluated the efficacy and safety of perioperative methylprednisolone in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. This systematic review and meta-analysis followed PRISMA 2020 guidelines (PROSPERO CRD420251231338). We searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and CENTRAL from inception to November 2025 for randomized controlled trials comparing perioperative intravenous methylprednisolone with placebo or standard care in patients aged < 18 years undergoing cardiac surgery with cardiopulmonary bypass. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. The primary outcome was all-cause in-hospital or 30-day mortality. Secondary outcomes included mechanical ventilation duration, cardiac intensive care unit length of stay, postoperative infections, and hyperglycemia. Random-effects models with Paule-Mandel estimator and Hartung-Knapp confidence intervals were used to pool risk ratios and mean differences. We included eight randomized controlled trials (1,735 pediatric patients; 867 on methylprednisolone, 868 controls). Overall, methylprednisolone was not associated with reduced mortality compared with control (RR 0.66, 95% CI 0.35-1.25; I² = 0%; 6 trials, 1,586 patients). However, methylprednisolone reduced the duration of mechanical ventilation (MD - 0.27 days, 95% CI - 0.46 to - 0.09; I²=0%; 5 trials) but significantly increased the risk of hyperglycemia (RR 2.28, 95% CI 1.38-3.78; I²=45.0%; 6 trials). No differences were observed in infection rates (RR 1.06, 95% CI 0.68-1.66; I²=0%; 5 trials) or ICU length of stay (MD - 0.13 days, 95% CI - 0.51 to 0.25; I²=0%; 5 trials). Perioperative methylprednisolone was not associated with reduced overall mortality in pediatric cardiac surgery. Among secondary outcomes, methylprednisolone was associated with a modest reduction in mechanical ventilation duration but with a significantly increased risk of postoperative hyperglycemia. These findings indicate that any potential benefit in ventilatory outcomes should be weighed against the higher metabolic risk. Further research is required to determine whether any patient subgroups may derive net clinical benefit from its use.
The 2024 international pediatric sepsis consensus definition has undergone a paradigm shift from a systemic inflammatory response syndrome (SIRS)-based framework to the organ dysfunction-centered Phoenix Sepsis Criteria (PSC). We aimed to evaluate the diagnostic concordance, predictive performance for 28-day pediatric intensive care unit (PICU) mortality, and phenotypic overlap between these two pediatric sepsis definitions. This single-center retrospective cohort study included 1034 children aged > 1 month to < 18 years with confirmed or suspected infection who were directly admitted to the PICU of Children's Hospital of Chongqing Medical University between January 1, 2020, and November 21, 2023. All patients were independently evaluated for sepsis using both the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) SIRS criteria and the 2024 PSC. Diagnostic agreement was assessed using the Kappa coefficient. Binary logistic regression was employed to establish association models between factors and phenotypes, as well as between factors and PICU 28-day mortality. Predictive performance was compared using the C-statistic. Among 1034 patients, 613 (59.3%) met the Sepsis-SIRS criteria with a 28-day PICU mortality of 15.2% (93/613), 744 (72.0%) met the Sepsis-Phoenix criteria with a mortality of 16.3% (121/744), 489 (47.3%) met both criteria with a mortality of 18.6% (91/489), and 166 (16.1%) met neither criterion with a mortality of 2.4% (4/166). Agreement between the two criteria was poor (kappa = 0.202, 95% CI: 0.143-0.261). After adjusting for clinically relevant confounders, the PSC remained a strong independent predictor of 28-day mortality (adjusted OR = 5.123, 95% CI: 2.128-12.333, p < 0.001), whereas the SIRS criteria showed no independent predictive value (adjusted OR = 0.937, 95% CI: 0.523-1.678, p = 0.827). The PSC demonstrated significantly superior discriminatory ability compared with the SIRS criteria (C-statistic = 0.809 vs. 0.589, p < 0.001). Notably, 20.2% of SIRS-positive patients were not classified as sepsis by the Phoenix Criteria, and this subgroup had an extremely low mortality of 1.6%, reflecting higher specificity of the PSC. The SIRS and PSC identify partially overlapping populations with distinct risk stratification, showing poor diagnostic concordance. The PSC has superior independent predictive performance for PICU 28-day mortality and may be considered for prognostic assessment of infected children in the PICU setting. Importantly, historical study results based on the SIRS criteria should be extrapolated cautiously to PSC-defined populations.
The purpose of the study is to evaluate the demographic characteristics, clinical features, and management strategies of TNF inhibitor-related autoimmune disorders (TIRAIDs) in pediatric rheumatology practice. The medical records of 71 pediatric patients treated with a TNF inhibitor for a rheumatologic disease and who exhibited any TIRAIDs during a 10-year period were retrospectively evaluated. The prevalence of TIRAIDs was 2.8% among 2450 pediatric patients who needed to use any TNF inhibitor drugs due to a rheumatologic disease. There was a female predominance (n = 40, 56%). TIRAIDs were observed in 49 patients (69%) receiving etanercept, 16 patients (23%) receiving adalimumab, and 6 patients (8%) receiving infliximab. The median time to TIRAIDs was 21.6 months. Non-infectious uveitis (38%) was the most common TIRAID, followed by paradoxical psoriasis (PP) (25%), lupus-like disease (8%), multiple sclerosis (7%), episcleritis (7%), and hidradenitis suppurativa (1%). In 58% of patients, treatment was switched to another TNF inhibitor, while in 42%, it was switched to a non-TNF biological therapy and/or cDMARDs. Complete resolution of TIRAIDs was observed in 63% of the patients. C-reactive protein levels and Juvenile Arthritis Disease Activity Score-27 were significantly higher during the development of TIRAIDs in patients with juvenile idiopathic arthritis compared to the remission period (p < 0.001 and p = 0.041, respectively). Among TIRAIDs, non-infectious uveitis and PP were the most frequently observed manifestations, predominantly occurring during etanercept treatment. Disease activity tended to increase during the onset of TIRAIDs. Discontinuation of TNF inhibitor therapy and switching to another biological treatment may be effective in achieving clinical remission.
To systematically evaluate the accuracy, reliability, and clinical applicability of artificial intelligence and large language models (LLMs) in pediatric orthopedics, comparing their performance against established clinical guidelines and assessing their utility for patient education and clinical decision support. A search of PubMed and ScienceDirect (2020-2025) identified 2624 articles using the keywords 'ChatGPT', 'Gemini', 'Claude' and 'orthopedic pediatrics'. After screening and refinement using Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, 15 studies met inclusion criteria. Studies evaluated ChatGPT, Google Gemini, Meta AI, Microsoft Copilot, and Claude across multiple pediatric orthopedic conditions across conditions like developmental dysplasia of the hip, slipped capital femoral epiphysis, and scoliosis. Heterogeneity was assessed using Cochran's Q and I2 statistics, and publication bias was evaluated using funnel plots and Egger's test. LLM accuracy ranged from 44.3 to 93% (pooled: 74.1%), with pooled accuracy of 74.1%. Reproducibility was moderate, with ChatGPT demonstrating a Spearman coefficient of 0.55 for complex queries. Regional expert consensus scores varied significantly (Europe: 80, North America: 65; P = 0.034; Fleiss\kappa = 0.113). Up to 33% of responses to guideline-based questions were rated neutral or inaccurate. Reading complexity was elevated (Flesch-Kincaid grade: 12.7), exceeding the recommended sixth-grade level. Parent surveys indicated 82% trust in artificial intelligence as supplementary tools with professional oversight. Minimal statistical heterogeneity was observed (I2 = 0.00%), though publication bias was detected (Egger's test P = 0.0001). LLMs show potential for education and triage but lack consistency in complex scenarios, elevated reading complexity, and significant regional variability in expert assessments. These tools should be used as educational supplements under professional medical supervision rather than for independent clinical decision-making. Broader clinical application requires domain-specific tuning, standardized evaluation, and readability optimization. Level V- systematic review.
Due to the limited data available among middle-income countries, we aimed to determine the characteristics, outcomes and associated factors with death or graft failure in pediatric liver transplantation (LT). Based on the Thai National Liver Transplantation Registry, we analyzed the data of patients under 18 years who underwent LT in Thailand from 2016 to 2024. The study included 324 liver transplants (five re-LT), mainly from living donors (246 donors, 75.9%). Among 319 recipients, the most prevalent underlying condition was cirrhosis (274 patients, 85.9%; mostly biliary atresia), followed by acute liver failure (30 patients, 9.4%). In comparison with deceased donor LT, patients who underwent living donor LT (LDLT) reported less waiting time (485 days vs. 146 days, P < 0.001) and a lower pediatric end-stage liver disease (PELD)/model for end-stage liver disease (MELD) score (20.9 vs. 18.1, P = 0.02). The registry revealed 1- and 5-year patient survival rates of 91.7% and 89.6%, respectively. Mortality was noted in 34 patients, with infection as the leading cause of death (19 patients, 55.9%). PELD/MELD score ≥ 20 was associated with death (HR: 2.95; 95% CI: 1.29-6.27) or graft failure (HR: 3.10; 95% CI: 1.37-7.06) in patients who underwent LT due to cirrhosis. Pediatric LT in Thailand, mainly LDLT, has a satisfactory outcome. Patients with severe ESLD or high PELD/MELD scores are at risk for death and graft failure after LT. Infection is the most common cause of death. Therefore, timely LT and early effective treatment of infection are crucial.
This study evaluated the relationship between image quality level (IQL), radiation dose, image noise, and signal-to-noise ratio (SNR) in pediatric head CT, comparing energy-integrating detector CT (EID-CT) and photon-counting CT (PCCT) across age-specific phantoms. Head CT scans of 1-, 5-, and 10-year-old anthropomorphic phantoms were performed across a range of IQLs on EID-CT and PCCT. For each IQL, radiation dose, image noise, and SNR were recorded and compared between the two systems. PCCT required lower CTDIvol across all phantoms (p < 0.05). In the clinically relevant IQL-range (IQL 200-300) the 10-year-old phantom showed the greatest relative radiation dose reduction using PCCT (9%), compared to 0.45% in the 1-year-old phantom. Organ doses were highest in the 1-year-old phantom for red bone marrow and skin with no significant differences between the two systems. PCCT offered significantly higher SNR than EID-CT for brain parenchyma (p < 0.03) and bone (p = 0.012). Image noise was significantly lower in PCCT for brain parenchyma in the 1- and 5-year-old phantoms (p < 0.03) and for bone in the 1-year-old phantom (p = 0.012). Over the full IQL-range (1-300) the average SNR was up to ~ 20% higher for brain parenchyma and ~ 50% higher for bone with PCCT than with EID-CT for all phantoms. PCCT offers superior SNR for brain and bone while reducing radiation dose, with the largest radiation dose benefit in older pediatric phantoms, supporting optimized pediatric neuroimaging.
Most studies confirm the effectiveness of virtual reality (VR) in alleviating pain and fear during pediatric venipuncture, with limited evidence regarding physiological stress markers and dynamic assessment. This study aims to investigate the effects of VR technology on pain, fear, and physiological responses in children, as well as family satisfaction during intravenous cannulation. This single-blind randomized controlled trial was conducted in the Pediatrics Department of Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China. A total of 188 children requiring intravenous cannulation procedures and their families were allocated into: the control group (n = 96), which received the conventional verbal comfort; and the experimental group (n = 92), which wore VR headsets. The primary outcomes were dynamic fear/pain scores assessed by nurses and self-reported by patients, which were surveyed using the Children's Emotional Manifestation Scale (CEMS) and the Children's Fear Scale (CFS)/the Face, Legs, Activity, Crying, and Consolability scale (FLACC) and the Wong-Baker FACES Pain Rating Scale (Wong-Baker), respectively. The secondary outcomes were dynamic heart rate (HR) and peripheral oxygen saturation (SpO2) measurement, and family satisfaction levels. The pre-specified time points were pre-intervention, immediately post-intervention, at tourniquet application, at venipuncture, and one minute after venipuncture. Results were reported following the Consolidated Standards of Reporting Trials 2025 guidelines. VR significantly reduced children's fear at two pre-venipuncture time points (nurse-assessed CEMS and child-reported CFS; partial η2 = 0.072 and 0.053, both p < 0.05). There were no significant group effects in nurse-assessed FLACC and child-reported Wong-Baker pain scores across three venipuncture time points. However, a significant time-by-group interaction was observed for nurse-assessed FLACC scores (partial η2 = 0.028, p = 0.006). Notably, nurse-assessed FLACC scores were lower than child-reported Wong-Baker scores in both control and experimental groups (Mean Diff.=-1.04 to -2.10, all p < 0.001). The dynamic changes in HR and SpO2 across five time points were lower within the experimental group (partial η2 = 0.106 and 0.045, both p < 0.01). Partial correlation analysis revealed that family satisfaction responded to children's pain, fear, and physiological stress in a "process-sensitive" pattern in the control group but an "outcome-oriented" pattern in the experimental group. In this trial, VR distraction effectively reduced procedural fear (but not pain) during venipuncture. However, the nurse assessment appears to suggest that the effects of VR distraction and conventional intervention on pain experience may vary over time. These findings underscore the importance of multidimensional pain/fear assessment in pediatrics. Our study confirms that VR distraction can significantly reduce fear in children undergoing intravenous cannulation, though pain scores were not significantly lowered. Multidimensional assessment (including subjective fear measures) is therefore important. VR may improve the patient and family experience of painful procedures. We recommend further trials with larger samples to confirm these findings and refine VR interventions. Chinese Clinical Trial Registry, ChiCTR2500113849 (Registration Date: Dec. 3, 2025; Retrospectively registered).
Anaphylaxis is a potentially life-threatening systemic hypersensitivity reaction. While triggers, clinical manifestations, and severity are influenced by age and sociocultural factors, most evidence regarding the impact of comorbidities and cofactors comes from adult studies. This study aimed to characterize the triggers, clinical features, and outcomes of pediatric anaphylaxis in a tertiary care center, with a particular emphasis on risk factors for severity. We retrospectively reviewed records from August 2023-August 2024 at the European Allergy Academy and Clinical Immunology Center of Excellence in Istanbul. Children aged 0-18 years (n = 100) with anaphylaxis as defined by the 2020 World Allergy Organization (WAO) criteria were included. Demographic, clinical, and follow-up data were collected. The updated 2024 (WAO) grading system was used to classify severity. Of the 3,959 records, 100 children fulfilled the inclusion criteria. A female predominance was noted in those ≤ 4 years, with males predominating thereafter. Medications were the leading trigger, followed by food, venom, and idiopathic causes. Foods were more prevalent among outpatients, and drugs were more prevalent among inpatients. Comorbidities were more common in hospital-onset anaphylaxis. Atopy was more common in food-induced anaphylaxis, whereas infections and polypharmacy were more common in drug-induced cases. Food-related reactions with endogenous factors were typically milder, whereas drug-related reactions-especially in older patients with polypharmacy or hospital-onset-tended to be more severe. Biphasic reactions were associated with delayed presentation, elevated WBC/ANC, and older age. Intramuscular adrenaline was administered in 95% of the patients, but prehospital autoinjector use was rare. Our findings underscore the need for early recognition and management, systematic evaluation of contributing factors, risk-adapted monitoring, and individualized follow-up in pediatric anaphylaxis patients.
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The overall survival of children with newly diagnosed acute myeloid leukemia (AML) in high-income countries has increased to 80% over the past decades. Nevertheless, a significant subset of patients experiences relapse and treatment is associated with both short- and long-term toxicities. The CHIP-AML22 protocol includes an updated standard-of-care treatment for children with AML within the NOPHO-DB-SHIP consortium. Targeted therapies are offered to specific subsets of patients and measures to reduce toxicity are being investigated. CHIP-AML22 is a multinational complex clinical trial in newly diagnosed de novo AML patients up to and including 18 years of age, sponsored by the Princess Máxima Center. The primary aim is to improve event-free survival. To achieve this, (1) FLT3-ITD+/NPM1wt patients can participate in a linked-trial assessing safety and efficacy of quizartinib, in addition to conventional chemotherapy during induction and consolidation therapy and as continuation monotherapy after allogeneic hematopoietic stem cell transplantation; (2) a randomization study is incorporated on the use of two doses of 3 mg/m2 gemtuzumab ozogamicin during induction therapy in CD33-positive patients; and (3) updated criteria are used for the identification of high-risk patients, based both on flow measurable residual disease (MRD) and (cyto)genetic profiling. The design allows for introduction of new treatment options in the future. Furthermore, a randomization is included aiming to demonstrate non-inferiority in disease-free survival after two versus three consolidation courses in standard-risk patients. Additionally, the use of the cardioprotective drug dexrazoxane is recommended in all patients. Interim analyses will be conducted to assess safety and efficacy in the linked trial and randomization studies. Based on power calculations, we aim to recruit a total of 905 patients in the Master protocol and 60 patients in the linked Quizartinib trial. The risk-based approach and use of targeted therapies in CHIP-AML22 illustrate a shift toward more personalized treatment. Besides improving event-free survival, this study aims to contribute to the international consensus on strategies to reduce toxicity for all patients. The design of this study provides a dynamic framework, allowing for the potential introduction of emerging therapeutic options in the future. CHIP-AML22 Master protocol: EU CT 2023-504999-25-00, Clinicaltrials.gov NCT05994690. Registered on 16-08-2023 Quizartinib linked-trial: EU CT 2023-505000-27-01, Clinicaltrials.gov NCT06262438. Registered on 16-02-2024.
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Food insecurity (FI) is associated with poorer physical and mental health outcomes, exacerbation of chronic diseases, and decreased access to healthcare. Children experiencing FI face additional risks, including lower psychosocial functioning and reduced academic achievement. Although national initiatives call for integrating nutrition support services into healthcare, clinical workflows for FI screening and referral remain inconsistently implemented and difficult to sustain. The goal of this study is to refine, adapt, and optimize a comprehensive FI screening and referral program, and identify effective implementation strategies for pediatric healthcare systems. We will use a RollOut Implementation and Optimization (ROIO) trial design to iteratively implement and refine the implementation strategies for our FI screening and referral program (I-FRESH: Implementing Food Referrals for Equity and Sustained Health) across 4 pediatric clinics. I-FRESH includes: (1) FI screening; (2) assessment of family needs and readiness to access services; (3) referral and navigation support to community nutrition programs; and (4) follow-up to assess fit, utilization, and ongoing needs. The Pragmatic, Robust Implementation and Sustainability Model (PRISM) will guide adaptation and evaluation of contextual determinants, while RE-AIM will guide assessment of outcomes (implementation feasibility and acceptability, fidelity, adoption, reach, effectiveness, and maintenance). We will identify several implementation strategies to increase the likelihood that I-FRESH can be successfully implemented and sustained in a pediatric healthcare system. We will enroll 240 participants and assess preliminary effectiveness on family‑level food security and pediatric nutrition‑related health outcomes (e.g. weight status, blood pressure, lipids, HbA1c, liver function tests). The information gathered in this trial will be utilized in the development of a fully powered Type 2 Hybrid Effectiveness-Implementation Trial that will test the effectiveness of the identified implementation strategies and impact of the FI program on clinical outcomes. By integrating PRISM and RE-AIM within an iterative ROIO design, this study will generate a scalable, contextresponsive implementation model for addressing FI in pediatric healthcare settings. Findings will inform sustainable strategies that link families to highquality nutrition support programs and improve nutritionrelated health outcomes for lowincome children. NCT06661538.
The increasing prevalence of autism has led to considerable system challenges as specialist-driven approaches have struggled to keep pace. Recent research has challenged status quo models by demonstrating that community-based pediatric clinicians can accurately diagnose autism in young children. This research provides an opportunity to further expand capacity of community systems to conduct developmentally relevant, context-specific assessments of autistic people over their lifespan. In this Commentary, we propose a personalized lifespan approach to autism assessment as a precision care and system organization framework that considers the ongoing and evolving needs of autistic people and aligns the necessary expertise and resources to provide focused assessment when it is most informative. This framework consists of three key principles: (1) assessment is not a one-time, one-size-fits-all event; instead, assessment continues across the lifespan; (2) assessments should generate information that is relevant to the individual's current needs and life stage; and (3) wherever possible, community-based expertise should be engaged to promote the right assessment at the right time in the right place. Adopting this framework can reduce system access challenges, while also addressing the ongoing assessment needs of an autistic person across their life course. Historical models of autism care have not kept up with the demand for autism diagnostic evaluations, leading to lengthy wait times. Recent research has shown that community‐based pediatric clinicians can diagnose autism with high accuracy. In this paper, we suggest expanding these findings into a personalized lifespan approach to autism assessment that takes a broader view of assessment as occurring across many points over a person's lifetime and in a person's community whenever possible. This model can help to ensure that autistic people have ongoing access to learn more about themselves, and that they can get these answers when they need them and closer to home.
Biallelic pathogenic variants in progressive familial intrahepatic cholestasis (PFIC)-related genes cause severe pediatric cholestasis. However, the clinical significance of heterozygous variants in adult intrahepatic cholestasis remains unclear. We investigated the prevalence of heterozygous PFIC-related gene variants in Japanese adults with intrahepatic cholestasis. Whole-exome sequencing was performed in 19 adults diagnosed with intrahepatic cholestasis. Rare variants (allele frequency ≤ 0.01 in the Japanese population) predicted to be functionally damaging by in silico tools were extracted and classified according to ACMG/AMP guidelines. Allele frequencies were compared with the GEM Japan whole genome aggregation database. Four heterozygous variants in PFIC-related genes were identified in four patients (21%), and all variant carriers were diagnosed with drug-induced liver injury. One patient carried a known pathogenic ABCB11 splice-site variant (c.908+1G>A), which was extremely rare in the Japanese reference population. The remaining variants were predicted to be functionally damaging by in silico analyses but were classified as variants of uncertain significance by ACMG criteria. Rare variants in PFIC-related genes were identified in a subset of adults with intrahepatic cholestasis. Although all variant carriers were diagnosed with drug-induced liver injury, the clinical significance of these variants remains uncertain, particularly because most were classified as variants of uncertain significance. These findings should be considered exploratory and hypothesis-generating.
Emerging research suggests a link between attention deficit hyperactivity disorder (ADHD) and central sensitization (CS), a condition characterized by heightened sensitivity to pain and sensory stimuli. This study aimed to measure the severity of CS symptoms in children with ADHD and in their parents; compare results with those of a neurotypical group; and explore associations between CS symptoms and pain intensity as well as potential familial patterns. Participants included 37 children with ADHD (mean age = 11.54 years; 62.2% male) and 29 neurotypical children (mean age = 13.07 years; 58.6% male). Children completed the Central Sensitization Inventory (CSI) - Child and Adolescent Version and rated their pain intensity at the time of assessment and over the past week. One parent per child completed the adult version of the CSI. Children with ADHD reported significantly higher CSI-indexed CS symptom scores than those in the comparison group (p < 0.001). In categorical analyses, neurotypical children were significantly more likely to fall into the subclinical (lowest symptom) CS range (adjusted p < 0.005). Children with ADHD also reported significantly greater pain intensity both currently (p = 0.016) and over the past week (p = 0.003). Stronger correlations between CSI-indexed CS and self-reported pain were observed in the ADHD group, particularly for current pain (ρ = 0.66, p = 0.002). Parents of children with ADHD also had elevated CS scores (p = 0.003), with the majority falling in the severe range. A moderate correlation between parent and child CSI-indexed CS scores was observed across the entire sample (ρ = 0.47, p = 0.002), while a strong correlation between parents' CS scores and their own medical conditions was found only in the ADHD group (ρ = 0.66, p = 0.002). Children with ADHD, and their parents, reported elevated CSI-indexed CS symptoms and pain intensity, suggesting that CS symptoms may represent a clinically relevant feature in some ADHD presentations. These findings support the value of considering sensory and pain-related assessments in ADHD evaluations and highlight the need for further research into potential mechanisms and integrative interventions that may improve outcomes and reduce functional impairment in pediatric neuropsychiatric conditions. Not applicable.
An intramural course in an anomalous aortic origin of a coronary artery (AAOCA) is a high-risk feature for sudden cardiac death (SCD). One of the proposed mechanisms for this association involves a "flap valve" effect in the intramural segment. The (patho-)histological characteristics of this segment may contribute to risk stratification, however, current data are scarce. The aim of this study was to identify the histological features of the intramural segment and their potential relevance to vascular wall properties and the aortic valve commissure, thereby providing insights into possible functional implications of AAOCA. This prospective multicenter study included consecutive pediatric and adult AAOCA patients who underwent surgical unroofing between 2021 and 2024. The excised arterial vascular wall tissue (i.e. the intramural segment), was immunohistochemically examined for vascular wall components. Two independent observers reviewed the data, correlating findings with preoperative CTA to assess spatial relationships with surrounding aortic and AAOCA tissues. Results were also compared with a post-mortem AAOCA specimen and control tissues. Fifteen patients (mean age 42.9 ± 14.0 years, age range 11-66 years, 60% female) undergoing surgery for AAOCA were included. Fourteen patients (93%) had an anomalous aortic origin of a right coronary artery (AAORCA) and one patient (7%) had an anomalous aortic origin of a left coronary artery (AAOLCA). The mean intramural segment length was 7.8 ± 3.6 mm in AAORCA and 16.0 mm in the AAOLCA. Histologically, a two-layered tunica media without interposing tunica adventitia was identified in all intramural segments. Pre-operative CTA showed a close spatial relationship of the aortic side of the intramural segment with the aortic valve commissure. In line with this, extensive fibrous tissue was observed histologically on the aortic side of the intramural segment, consistent with commissure. In contrast, the vascular wall on the coronary arterial side of the intramural segment showed overall medial degeneration, characterized by mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, elastic fiber thinning, loss of smooth muscle cell nuclei, and collagen alterations. These abnormalities were more prevalent with increasing age. Histology of the intramural segment revealed structural alterations which may be consistent with reduced vascular compliance. Further studies, including post-SCD specimens, are needed to refine risk stratification.
The Extravascular Implantable Cardioverter-Defibrillator (EV-ICD) utilizes a substernal lead to provide defibrillation and anti-tachycardia pacing (ATP) while avoiding transvenous complications. General anesthesia (GA) was applied for implantation procedures in the EV-ICD pivotal trial and is currently recommended by the manufacturer. However, GA carries specific risks and consumes significant resources. This study evaluates the feasibility, safety, and procedural efficiency of EV-ICD implantation performed under cardiologist-administered deep sedation with noninvasive ventilation (DS-NIV) compared to standard GA. We retrospectively analyzed 24 consecutive patients undergoing EV-ICD implantation in our center. Patients received either GA (n = 14) or DS-NIV (n = 10) using a propofol-ketamine protocol delivered by cardiologists. Analyses focused on peri-procedural feasibility and safety, procedural workflow and anesthesia characteristics, and early device electrical performance. No anesthesia-related complications occurred in either group. The DS-NIV group demonstrated significantly shorter wheels-to-incision times (median: 45 vs. 70 min, p = 0.022), whereas the procedural duration did not differ significantly from the GA group. Patients receiving DS-NIV required fewer vasopressors (60% vs. 100%, p = 0.024) despite higher propofol infusion rates (800 vs. 350 mg/h, P<0.001). Defibrillation testing success and electrical parameters were comparable. In a median follow-up of 182 days two patients received appropriate EV-ICD therapies and no inappropriate ATP or shocks were delivered. EV-ICD implantation under cardiologist-administered DS-NIV appears to be feasible and safe, offering improved workflow efficiency compared to GA. These findings support deep sedation as a practical alternative in experienced centers, potentially expanding access to EV-ICD therapy.
Programa Criança Feliz (PCF) is Brazil's home visitation program aimed at enhancing early childhood development. Evaluations of the program have found significant program challenges and implementation barriers, including the lack of a structured curriculum, insufficient training, and little supervisory support. This study tests the revised content of the home visits and new implementation strategies aimed at addressing these barriers and enhancing the quality of PCF home visits. The implementation strategies were piloted across 8 diverse municipalities in an implementation feasibility trial. The strategy bundle included a 40-hour initial training for home visitors using demonstration and simulation-based methods (based on the Reach Up methodology), an 8-hour supervision-focused training module for supervisors, and standardized home visit guidelines and an activities compendium. The new strategies were assessed using a one group pre-post analysis along with mixed methods to assess the extent to which they were acceptable, feasible, and associated with a change in home visit quality. A paired t-test and an independent t-test analysis were used to assess the change in home visit quality. The implementation outcomes were assessed with qualitative analysis and the Framework Method approach. The proposed home visitation guidelines, material, training, and supervision process were determined to be highly acceptable, feasible, and associated with improved quality of home visits. The home visit quality scores significantly increased by 14.68 points (SD = 14.89, CI 95%: 7.27-22.08, p = 0.0006), according to the paired t-test. The study participants provide insightful suggestions for adaptations that can occur before testing the strategies more broadly. Key suggested adaptations included adjusting activity difficulty to individual developmental levels rather than age alone, shortening training duration to improve staff access, and incorporating guidance for culturally diverse and traditional communities. The findings suggest three transferable design principles for home visitation and paraprofessional-delivered public health programs: reducing excessive discretion through structured, age-appropriate visit guidance; externalizing quality through experiential training methods such as demonstration and role-play; and embedding feedback loops through structured supervision and monitoring. These principles may generalize to programs facing heterogeneous staff preparation, high turnover, and limited supervisory capacity.
HSCR is caused by disruption of complex signaling pathways within the gene regulatory network (GRN) during enteric nervous system (ENS) development, including glial cell line-derived neurotrophic factor (GDNF) and GDNF family receptor alpha-1 (GFRα1). However, pathogenic variants in all GRN genes account for only ~ 80% cases; therefore, the epigenetic role remains to be elucidated. We compared GDNF and GFRα1 expression between HSCR patients and controls. qPCR revealed an upregulated GDNF expression in both ganglionic (206.37-fold) and aganglionic (126.35-fold) HSCR compared to control colons (ΔCT 7.65 ± 2.19 vs. 15.34 ± 1.34; p = 0.0001; and ΔCT 8.35 ± 2.57 vs. 15.34 ± 1.34; p = 0.0001). qPCR also showed an upregulated GFRα1 expression in both ganglionic (29.66-fold) and aganglionic (18.44-fold) HSCR compared to control colons (ΔCT 8.44 ± 1.98 vs. 13.33 ± 1.36; p = 0.0001; and ΔCT 9.13 ± 1.46 vs. 13.33 ± 1.36; p = 0.0001). In addition, no significant differences were observed between ganglionic and aganglionic segments for either GDNF or GFRα1 (ΔCT 7.65 ± 2.19 vs. 8.35 ± 2.57; p = 0.43; and ΔCT 8.44 ± 1.98 vs. 9.13 ± 1.46; p = 0.29). Our study demonstrates global aberrant expression of GDNF and GFRα1 in HSCR patients. These findings underscore the complexity of HSCR as a multifactorial disorder and highlight the importance of integrated signaling networks in ENS development, providing a rationale for further mechanistic and translational studies.