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Summary: Background: Data on oral vancomycin for primary sclerosing cholangitis (PSC)‐associated inflammatory bowel disease (IBD) are limited. Aims: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. Methods: In this retrospective multi‐centre cohort study, we matched vancomycin‐treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. Results: 113 PSC‐IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin‐treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97–6.31; adjusted OR [aOR] 5.24, 95% CI 2.68–10.22). Benefit was maintained in sensitivity analyses restricted to non‐transplanted patients and those with baseline moderate–severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002–7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). Conclusion: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing. [ABSTRACT FROM AUTHOR]

Children commonly refuse induction of anesthesia. Anesthesia providers must then decide whether to honor the child's dissent or to proceed over objection. In some circumstances, a forced induction involves restraining the child, incurring both practical and ethical harms to the patient‐provider encounter. This educational review explores the practical dilemma encountered when a child dissents to induction of anesthesia. In the course of exploring this dilemma, dissent and associated terms are defined and compared, and the prominent ethical underpinnings regarding pediatric decision‐making are described to clarify dissent as an ethical and practical concept. Important legal and professional standards are summarized, and practice trends are discussed to depict the current state of practice, including novel approaches to honoring pediatric dissent for elective surgeries. This information is then used to invite providers to consider where they ethically situate themselves within a legally and professionally defined space of acceptable practice. Finally, these considerations are synthesized to discuss important nuances regarding pediatric refusal, and some key questions are presented for clinicians to ponder as they consider their practice of choosing whether to honor pediatric dissent at induction. [ABSTRACT FROM AUTHOR]

Background: In infants with complete atrioventricular canal (CAVC) defects, post‐operative left atrioventricular valve regurgitation (LAVVR) is a known major cause of morbidity and mortality and a common indication for re‐operation. However, there is scarce data to identify risk factors for poor outcomes. Our study aims to find echocardiographic characteristics that predict post‐operative LAVVR at discharge and 1‐year follow‐up. Methods: Retrospective cohort study of patients with initial CAVC repair at our hospital who were followed for 1 year between 2013 and 2022. Patients with major co‐morbid conditions were excluded. Serial echocardiograms were reviewed. Anatomic details, quantitative and qualitative measure of LAVVR including the number of regurgitant jets, regurgitant jet length and vena contracta width, and ventricular function were collected. The time points measured include pre‐operative transthoracic echocardiogram (TTE), post‐operative transesophageal echocardiogram (PO‐TEE), routine protocol based post‐operative day 1 (POD1) TTE, discharge TTE and 1‐year post‐operative (1yPO) TTE. Paired t‐tests, chi‐square analysis, and linear regression analysis were performed comparing measured variables to LAVVR outcomes. Results: Fifty‐two patients were included; 92% had Trisomy 21. The majority were classified as Rastelli A (71%), others Rastelli C (29%). Only two patients had moderate or greater LAVVR pre‐operatively. The mean age at repair was 125 ± 44 days. Pre‐operative LAVVR was the only significant predictor of LAVVR severity at 1 year after backward stepwise regression. Of those with < moderate LAVVR on PO‐TEE, 20% had worsening to ≥ moderate at discharge, but only 9% remained that way at 1 year. Of those with ≥ moderate LAVVR on PO‐TEE, 40% improved to < moderate by 1 year. Two patients who worsened at 1 year, both secondary to likely cleft suture dehiscence. Only one patient required reoperation in the immediate post‐operative period secondary to severe LAVVR due to suture dehiscence. Routine protocol‐based POD1 echo did not have any association with altered outcomes. Conclusion: Pre‐operative LAVVR was the only significant predictor of LAVVR severity at 1 year. A significant percentage (40%) of patient with ≥ moderate LAVVR on PO‐TEE improved to < moderate by 1 year. Furthermore, routine protocol‐based POD1 echo did not have any association with altered outcomes. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Cutis marmorata telangiectatica congenita (CMTC) presents as marbled erythema and may exhibit diverse associated anomalies. Thorough multidisciplinary evaluation is crucial. Treatment varies with inconclusive evidence, necessitating further research. Our case underscores CMTC's rarity and heterogeneous nature, advocating for comprehensive management approaches and ongoing research. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This current case series adds to the spectrum of Arthrogryposis renal dysfunction cholestasis (ARC)‐associated variants. Increased awareness and early genetic testing for ARC are suggested in cases with failure to thrive, renal tubular dysfunction, and rickets, even when the degree of cholestasis is mild. Prompt identification and intervention may improve the quality of life. [ABSTRACT FROM AUTHOR]

Antibiotic overprescription in China has long been considered a problem on the supply side, linked to the financial incentives of physicians. Based on the conversation analysis of 187 video‐recorded naturally occurring medical consultations in Chinese paediatric primary care settings, this study finds that the driving force behind the problem of antibiotic overprescription in China has changed. Physicians use a low‐authority communication style to recommend treatment, displaying a low level of medical authority and a willingness to accommodate caregivers' preferences in antibiotic prescribing decisions. The problem is now attributed to physician–caregiver interaction, doctor–patient relationship and the antibiotic‐saturated prescribing culture. Practice implications involve deepening the understanding of the evolving nature of the antibiotic overprescription problem in China, building trust between physicians and patients/caregivers in order to facilitate the physicians' role as the gatekeeper of antibiotics and providing training programmes to help physicians develop effective communication skills. [ABSTRACT FROM AUTHOR]

Marchetti and Sawrikar's (2024) systematic review of parent illness representations of their child's anorexia nervosa provides a valuable synthesis of 32 qualitative studies. The key themes that emerge paint a concerning picture of parents' perceptions of AN as: difficult to identify and understand; of chronic duration; uncontrollable; severe; and associated with serious consequences. A sense of hopelessness and low‐parental self‐efficacy was identified. This Commentary explores the key findings of this review in four areas: AN treatment and recovery (control/cure); emotional representations of the illness; parent understanding of the illness (coherence) and its causes; and consequences of the AN. These illness perceptions are discussed along with relevant quantitative investigations of parent experiences, with a view to suggesting how the toll on parents might be reduced and how reducing burdens on parents might also lead to improved timely treatment outcomes. It is proposed that two broad features are needed: improved help‐seeking experiences in the health care system; and, more parent‐focussed support. [ABSTRACT FROM AUTHOR]

Objective: Controlling molluscum contagiosum (MC) infections is critical in atopic dermatitis (AD) management. This post hoc analysis assessed the efficacy and safety of berdazimer gel, 10.3% (topical, antiviral, nitric oxide–releasing medication) versus vehicle in MC patients with or without AD. Methods: Three Phase 3, multicenter, randomized, double‐blind, vehicle‐controlled, parallel‐group trials (B‐SIMPLE[berdazimer sodium in molluscum patients with lesions]1, −2, −4) enrolled patients 6 months and older with 3–70 mollusca. Berdazimer or vehicle was applied once daily to all MC lesions for 12 weeks. Data from three Phase 3 studies were integrated for subgroup efficacy and safety assessments using several weighted meta‐analysis approaches. Patients with concurrent AD or a history of AD/eczema were categorized as AD+ subgroup (AD− when absent). Primary efficacy endpoint: complete lesion clearance at Week 12. Safety endpoints included adverse events (AEs) through Week 24 and local skin reactions through Week 12. Results: Of 1598 enrolled patients, 209 (13.1%) were AD+. Baseline mean lesion counts were greater in AD+ (26.4) than AD− (19.3). Complete clearance rates were higher at Week 12 for berdazimer compared with vehicle in AD+ (n = 209; 35.0% vs. 27.4%; odds ratio [OR], 1.3; 95% CI, 0.7–2.5) and AD− (n = 1389; 29.1% vs. 18.9%; OR 1.8; 95% CI 1.4–2.4) subgroups. AEs in AD+ were application‐site pain (21.6% with berdazimer vs. 11.9% with vehicle), dermatitis (12.8% vs. 2.4%), and erythema (9.6% vs. 7.1%). Conclusions: Berdazimer gel showed favorable efficacy regardless of AD status. Berdazimer‐induced erythema may be indistinguishable from AD symptoms or with inflammatory response upon resolution of molluscum. [ABSTRACT FROM AUTHOR]

Unwanted hair is a common concern among patients presenting to pediatric dermatology clinics, and parents and patients alike inquire about the safety of methods employed for elective removal. Various methods of hair removal exist with different levels of invasiveness and permanence, from simple mechanical depilation to light‐based therapies. All methods of hair removal appear to be safe and generally well tolerated in children, and there are no age restrictions to any modality. In this review, we aim to address the available literature on the safety and efficacy of hair removal modalities in pediatric patients and propose guidance on how to manage requests for at‐home and in‐office therapies within an ethical framework. [ABSTRACT FROM AUTHOR]

N, N‐diethyl‐meta‐toluamide (DEET) has been considered the 'gold standard' for insect repellent use since the 1950s and constitutes most insect repellents on the market. However, conflicting data in the scientific literature and confusing information in the media are at the core of debates about the safety of DEET insect repellents for the protection of children against arthropod bites. The few fatal occurrences involving DEET insect repellents and complications of their use in the pediatric population are typically the result of accidental overdoses or misuse of insect repellents that disregard warnings on product labels. With appropriate application, the safety record of DEET insect repellents continues to be excellent with few side effects. The purpose of this review is to provide a summary of the literature on safety outcomes of DEET insect repellent use in children; outline the pediatric recommendations relating to DEET insect repellents; and provide an overview of EPA‐approved and naturally derived alternatives to DEET that possess low toxicity while providing a similar level of protection to synthetic insect repellents. [ABSTRACT FROM AUTHOR]

Dupilumab is an interleukin‐4 receptor antagonist important in the treatment of refractory atopic dermatitis (AD), particularly among pediatric patients. Two boys with a history of AD and cardiac transplant who developed psoriasiform dermatitis in response to dupilumab therapy are reported. These patients paradoxically developed an immune‐mediated adverse drug reaction despite taking systemic immunosuppressive agents. While the literature suggests possible pathomechanisms for psoriasiform dermatitis despite immunosuppression, further research is necessary to better characterize this unique and unexpected phenomenon. [ABSTRACT FROM AUTHOR]

Summary: Kabuki syndrome (KS) is now listed in the Human Inborn Errors of Immunity (IEI) Classification. It is a rare disease caused by KMT2D and KDM6A variants, dominated by intellectual disability and characteristic facial features. Recurrently, pathogenic variants are identified in those genes in patients examined for autoimmune cytopenia (AIC), but interpretation remains challenging. This study aims to describe the genetic diagnosis and the clinical management of patients with paediatric‐onset AIC and KS. Among 11 patients with AIC and KS, all had chronic immune thrombocytopenic purpura, and seven had Evans syndrome. All had other associated immunopathological manifestations, mainly symptomatic hypogammaglobinaemia. They had a median of 8 (5–10) KS‐associated manifestations. Pathogenic variants were detected in KMT2D gene without clustering, during the immunological work‐up of AIC in three cases, and the clinical strategy to validate them is emphasized. Eight patients received second‐line treatments, mainly rituximab and mycophenolate mofetil. With a median follow‐up of 17 (2–31) years, 8/10 alive patients still needed treatment for AIC. First‐line paediatricians should be able to recognize and confirm KS in children with ITP or multiple AIC, to provide early appropriate clinical management and specific long‐term follow‐up. The epigenetic immune dysregulation in KS opens exciting new perspectives. [ABSTRACT FROM AUTHOR]

Summary: Killer immunoglobulin‐like receptor (KIR) and KIR‐ligand (KIRL) interactions play an important role in natural killer cell‐mediated effects after haematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR–KIRL interactions may identify donors with optimal NK cell‐mediated alloreactivity in the adult transplant setting. Paediatric acute leukaemia patients were retrospectively analysed, and KIR‐KIRL combinations and maximal inhibitory KIR ligand (IM‐KIR) scores were determined. Clinical outcomes were examined using a series of graphs depicting clinical events and endpoints. The graph methodology demonstrated that prognostic variables significant in the occurrence of specific clinical endpoints remained significant for relevant downstream events. KIR‐KIRL combinations were significantly predictive for reduced grade 3–4 aGVHD likelihood, in patients transplanted with increased inhibitory KIR gene content and IM‐KIR = 5 scores. Improvements were also observed in associated outcomes for both ALL and AML patients, including relapse‐free survival, GRFS and overall survival. This study demonstrates that NK cell KIR HLA interactions may be relevant to the paediatric acute leukaemia transplant setting. Reduction in aGVHD suggests KIR effects may extend beyond NK cells. Moving forward clinical trials utilizing donors with a higher iKIR should be considered for URD HCT in paediatric recipients with acute leukaemia to optimize clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Telehealth for paediatric speech and language therapy became one of the most salient modes of service delivery during the COVID‐19 pandemic. Evidence for speech and language therapy services via telehealth in comparison to face‐to‐face delivery demonstrates promising outcomes, and studies have begun to explore practitioner and client experiences. However, across the literature, many critical elements of services are overlooked, and there is a need to frame the evidence base within a theoretical model that can draw out practical implications that consider the range of factors having an impact on clinical implementation in real‐world contexts. The APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side‐effects, and Equity) criteria offer such a model. The current study explored practising UK speech and language therapists' (SLTs) clinical experience of telehealth through the lens of the APEASE criteria and aimed to identify recommendations for future service provision from the practitioner perspective. Methods: An online survey structured using the APEASE criteria was developed in collaboration with the UK Royal College of Speech and Language Therapists. Quantitative data were analysed using descriptive statistics and qualitative data were analysed using reflexive thematic analysis. Results: Four hundred and thirty‐eight qualified and practicing UK paediatric SLTs completed the survey. Telehealth was broadly acceptable and practicable to SLTs yet there remains some uncertainty about its efficacy and cost‐effectiveness compared to face‐to‐face interventions and how equitable it is for different population groups. SLTs reported that effective implementation of telehealth services was dependent upon several contextual factors; affordability was a perceived barrier to clients having access to telehealth resources, intervention via telehealth was perceived as more acceptable than assessment, and whilst many SLTs welcomed aspects of telehealth, there were concerns about the physical and mental health consequences for practitioners. Six themes for the future development of telehealth in paediatric speech and language therapy were identified: (1) balanced and tailored services; (2) technology and equipment; (3) information and communication; (4) capacity building; (5) monitoring and evaluation; and (6) leadership and governance. Conclusions: Outcomes highlight promising, concerning and uncertain aspects of telehealth in paediatric speech and language therapy. SLTs value a flexible and tailored approach to service delivery and recommend that effective leadership, clear communication, ongoing policy and guidance development, upskilling of users and careful evaluation of impact are required to ensure optimal implementation. The APEASE criteria offer a valuable opportunity to enhance and streamline practice and research to ensure sustainable implementation of telehealth in the paediatric speech and language therapy services of tomorrow. WHAT THIS PAPER ADDS: What is already known on this subject: The COVID‐19 pandemic led to the increased use of telehealth as a main mode of service delivery in paediatric speech and language therapy. Pre‐COVID‐19, evidence for the use of telehealth in this field included small‐scale experimental studies that reported on children with particular disorders and explored telehealth outcomes in comparison to face‐to‐face delivery. The realities of at‐scale clinical practice were not well‐represented, and critical elements of service such as cost‐effectiveness were often overlooked in the paediatric literature. Furthermore, despite emerging global evidence for temporary telehealth responses to the crisis in speech and language therapy, the long‐term and future use of telehealth remains unclear. What this paper adds to existing knowledge: The current study applied the lens of the APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side‐effects, and Equity) criteria, which were used in this case to consider socioeconomic, ecological and cultural factors to capture an overarching understanding of the use of telehealth in paediatric speech and language therapy, and to inform the role of telehealth in future, longer‐term and at‐scale service development. Results indicated emerging trends in UK paediatric speech and language therapists' (SLTs') perceptions of telehealth and SLTs perceived a hybrid approach to service delivery, combining mostly face‐to‐face services with some telehealth, was likely to continue in the future. We identified six themes to guide the future development of telehealth in paediatric speech and language therapy services: (1) balanced and tailored services; (2) technology and equipment; (3) information and communication; (4) capacity building; (5) monitoring and evaluation; and (6) leadership and governance. What are the potential or actual clinical implications of this work?: UK SLTs believe that speech and language therapy services using telehealth should be reflective, tailored and flexible to meet the requirements and circumstances of the children, young people and families served, as well as the physical and emotional needs of practitioners. SLTs recommend that this service development is clearly communicated to all stakeholders and suggested that those using telehealth should be supported through appropriate training, and ongoing effectiveness should be monitored. Telehealth is here to stay and the APEASE criteria offer a unique opportunity to ensure sustainable models of service delivery; to support co‐ordinated leadership at the local, national and international levels and the development of policy and clinical guidance. [ABSTRACT FROM AUTHOR]

Background: The published experience concerning autologous peripheral blood stem cell collection in children is very limited. Methods: The data of pediatric patients who underwent autologous stem cell mobilization and apheresis between January 2011 and April 2020 were analyzed retrospectively. Results: We studied retrospectively 64 mobilization and apheresis procedures in 48 pediatric patients (34 males, 14 females), mean age of 7.31 ± 5.38 (range, 1.5–19.7) years, the underlying disease was mostly neuroblastoma (NBL). The body weight of 21 patients (43.75%) was 15 kg or less. The targeted autologous peripheral stem cell apheresis (APSCA) was successfully achieved in 98% of patients. Neuroblastoma patients were younger than the rest of the patients and underwent apheresis after receiving fewer chemotherapy cycles than others and all of them mobilized within the first session successfully. Plerixafor was added to mobilization in nine heavily pretreated patients (18.7%), median two doses (range, 1–4 doses). 11 patients (22.9%) underwent radiotherapy (RT) before mobilization with doses of median 24 Gy (range, 10.8–54.0 Gy). Patients with RT were older at the time of apheresis and had received more chemotherapy courses than patients without RT. As a result, patients with a history of RT had significantly lower peripheral CD34+ cells and CD34+ yields than those without RT. In 17 patients (35.4%), 22 different complications were noted. The most common complications were catheter‐related infections (n:10, 20.8%), followed by catheter‐related thrombosis in eight patients (16.7%). Conclusions: Patients who had far less therapy before apheresis were more likely to mobilize successfully. Our study provides a detailed practice approach including complications during APSCA aiming to increase the success rates of apheresis in transplantation centers. [ABSTRACT FROM AUTHOR]

Background: Pediatric allogeneic hematopoietic cell transplant (allo‐HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. Methods: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo‐HCT recipients with at least one HAdV‐positive PCR. Results: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo‐HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. Conclusions: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease. [ABSTRACT FROM AUTHOR]

Background: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post‐transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. Methods: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. Results: Twenty‐six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1–10.3). EBV DNA load monitoring by qPCR was performed at 1–3 month intervals. EBV DNAemia onset occurred at a median of 73 days post‐transplant (IQR 52–307), followed by DNAemia peak at a median of 268 days (IQR 112–536). Rituximab was administered at a median of 9 days post peak (IQR 0–118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375–439) weekly for 1–4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow‐up (median 2094 days post‐transplant [IQR 1538–3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. Conclusions: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short‐term reduction in DNA load; however, recurrent DNAemia is common. [ABSTRACT FROM AUTHOR]

Introduction: Acute‐on‐chronic liver failure (ACLF) is associated with increased mortality and morbidity in patients with biliary atresia (BA). Data on impact of ACLF on postoperative outcomes, however, are sparse. Method: We performed a retrospective analysis of patients with BA aged <18 years who underwent LT between 2011 and 2021 at our institution. ACLF was defined using the pediatric ACLF criteria: ≥1 extra‐hepatic organ failure in children with decompensated cirrhosis. Results: Of 107 patients (65% female; median age 14 [9–31] months) who received a LT, 13 (12%) had ACLF during the index admission prior to LT. Two (15%) had Grade 1; 4 (30%) had Grade 2; and 7 (55%) had Grade ≥3 ACLF. ACLF cohort was younger at time of listing (5 [4–8] vs. 9 [6–24] months; p <.001) and at LT (8 [8–11] vs. 16 [10–40] months, p <.001) compared to no‐ACLF group. Intraoperatively, ACLF patients had higher blood loss (40 [20–53] vs. 10 [6–19] mL/kg; p <.001) and blood transfusion requirements (33 [21–69] vs. 18 [7–25] mL/kg; p =.004). Postoperatively, they needed higher vasopressor support (31% vs. 10.6%; p =.04) and had higher total hospital length of stay (106 [45–151] vs. 13 [7–30] days; p =.023). Rate of return to the operating room, hospital readmission rates, and 1‐year post‐LT survival rates were comparable between the groups. Conclusion: Despite higher perioperative complications, survival outcomes for ACLF in BA after LT are favorable and comparable to those without ACLF. These encouraging data reiterate prioritization during organ allocation of these critically ill children for LT. [ABSTRACT FROM AUTHOR]

Background: Antibody‐mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large‐scale pediatric‐specific data regarding AMR treatment outcomes. Methods: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1–18 years at transplant with biopsy‐proven AMR between 2009 and 2019 and at least 12 months of follow‐up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. Results: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post‐transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m2 at AMR diagnosis was associated with a 5.6‐fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. Conclusions: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one‐third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure. [ABSTRACT FROM AUTHOR]

Background: Although neurotoxicity is a major adverse event associated with busulfan, little information is available regarding the association between drug interactions and neurological symptoms during busulfan‐based regimens. This study evaluated the association between prophylactic echinocandins and neurological complications in patients receiving busulfan‐containing conditioning regimens for stem cell transplantation. Methods: We retrospectively included consecutive patients who administered intravenous busulfan as a conditioning regimen at our facility between 2007 and 2022. Prophylactic echinocandin use was defined as the use of an echinocandin antifungal drug to prevent invasive fungal disease in SCT recipients. The primary outcome was the incidence of neurological complications within 7 days of busulfan initiation and was compared between the echinocandin group (patients received prophylactic echinocandin) and nonechinocandin group (patients received prophylactic antifungal drugs other than echinocandin and those without antifungal prophylaxis). Results: Among the 59 patients included in this study, the incidence of neurological complications in the echinocandin (n = 26) and nonechinocandin groups (n = 33) was 30.8% and 63.6%, respectively. We observed a negative association between prophylactic echinocandin use and the development of neurological complications after adjusting for the propensity score for receiving prophylactic echinocandins (adjusted odds ratio 0.294, 95% confidence interval 0.090 to 0.959). We observed a lower incidence of neurological complications in the echinocandin group than in the nonechinocandin group. Conclusion: Our results suggested that the choice of antifungal prophylaxis is associated with busulfan neurotoxicity. [ABSTRACT FROM AUTHOR]

Introduction: Most kidneys from small pediatric donors are transplanted to adult recipients because of the perceived risk of surgical complications and graft thrombosis. In this study, we aim to demonstrate our favorable outcomes in transplanting pediatric kidneys from donors <15 k into pediatric recipients. Methods: This study retrospectively analyzes the outcomes of seven pediatric recipients of en block kidney transplants from pediatric donors weighing <15 kg performed at King Fahad Specialist Hospital‐Dammam from December 2014 to January 2018. Baseline characteristics of donors and recipients were collected. The incidences of surgical complication, immediate, and intermediate graft function were the primary outcomes. Results: The study included seven recipients monitored for a mean duration of 6.86 ± 1.35. Donors' and recipients' mean weights were 7.4 ± 3.2 kg and 20.7 ± 9.2 kg, respectively. Ureteric stricture occurred in one patient. There was a substantial improvement of 1‐year estimated glomerular filtration rate (eGFR) compared to the 1‐week mark (106.7 ± 26.38 mL/min. 1.73 m2 vs. 63.7 ± 22.92 mL/min/1.73 m2, p =.0069). The observed improvement in renal function persisted at the 5‐year mark and during the last follow‐up, with eGFR of 70.3 ± 40.7 mL/min/1.73 m2, and 79.8 ± 30.8 mL/min/1.73 m2, respectively. There was also increase of 27.9% in the size of the en bloc kidney observed at the 6 months. Conclusion: In a specialized transplant center with highly skilled surgeons, the utilization of en bloc kidney transplant from donors weighing less than 15 kg is an effective strategy for expanding the donor pool and ensuring favorable graft outcomes. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusion Tonsillectomy procedures are commonly performed worldwide. At our academic tertiary care facility, we perform approximately 1000 tonsillectomy procedures annually. We have found inconsistent pain management strategies in pediatric tonsillectomy patients have contributed to variability in postoperative complications and the number and types of postoperative pain medications required in the Post Anesthesia Care Unit (PACU). This project aimed to assess the impact of implementing a standardized perioperative pain management protocol on reducing postoperative complications in pediatric patients who underwent a tonsillectomy procedure.A pre‐post‐intervention design was utilized, comparing characteristics and outcomes of pediatric patients for whom a standardized perioperative pain management protocol was implemented over a 12‐week period compared to those who did not. The standardized perioperative pain management protocol was utilized intraoperatively by the anesthesiologists, nurse anesthetists, and residents. A Qualtrics survey was used by the Post Anesthesia Care Unit (PACU) nurses to gather data as they cared for patients who underwent tonsillectomy. Four outcomes were measured: (1) postoperative pain medication administration, (2) rate of postoperative respiratory complications, (3) rate of adherence, and (4) usability of a standardized pain management protocol. Data were compared between pre and post‐implementation groups.During the quality improvement project, 180 children underwent tonsillectomy, with 81 in the control group and 99 in the intervention group. The median age did not differ between groups. The control group had higher postoperative opioid medication usage (93.8% vs. 54.5%) and a higher number of opioids administered in the recovery room. Postoperative IV fentanyl was reduced in the intervention group (49.4% vs. 28.3% in the intervention, p = .004). Respiratory interventions were more frequent in the control group (24.7% vs. 7.1%), with increased respiratory team activation. Respiratory team activation in the Post Anesthesia Care Unit (PACU) includes a 511 page for anesthesia provider assistance. Respiratory interventions included bag‐mask ventilation, lidocaine, propofol or succinylcholine administration, and reintubation. The intervention group had 100% adherence to the pain management protocol, and providers found it easy to use.The quality improvement project highlighted notable improvements in the intervention group for whom a standardized perioperative pain management protocol was used, including reduced opioid medication administration, lower incidence of respiratory interventions, and high adherence to the pain management protocol. These findings underscore the effectiveness and feasibility of standardized protocols in enhancing patient outcomes. [ABSTRACT FROM AUTHOR]

The rapid growth in the use of pediatric physiologically based pharmacokinetic (PBPK) models, particularly for regulatory applications, has focused emphasis on model verification and ensuring system parameters are robust, including how these change with age. Uncertainty remains regarding the ontogeny of some enzymes and transporters, in this study 2 published ontogeny profiles for hepatic CYP3A4 were compared. Clinical pharmacokinetic data on 4 intravenously administered CYP3A4 substrates (alfentanil, fentanyl, midazolam, and sildenafil) used across the pediatric age range was collected from the literature. The PBPK models were verified in the adult population and then used to compare the Salem and a modified Upreti ontogeny profiles for CYP3A4 in terms of parent drug clearance and area under the curve from birth onward. Overall, the modified Upreti ontogeny profile resulted in 15 out of 17 age‐related predictions within 2‐fold and 12 out of 17 predictions within 1.5‐fold ranges of observed values, for the Salem ontogeny these values were 12 out of 17 and 8 out of 17, respectively. The Upreti ontogeny profile performed better than Salem, average fold error and absolute average fold error were 1.14 and 1.35 compared to 1.56 and 1.90, respectively.Identifying the optimal CYP3A4 ontogeny is important for regulatory use of PBPK especially given the number of drugs cleared by this enzyme. This study broadens the evidence from previous studies that Upreti is more favorable than Salem, but further work is needed especially in the neonatal and early infant age range. [ABSTRACT FROM AUTHOR]

Functional constipation (FC) is a common condition in childhood in the United Kingdom and worldwide. Various radiological approaches have been established for diagnostic purposes. The radiopaque marker study (ROMS) is universally accepted and used to assess colonic transit time (CTT) in children with FC. Despite being widely used, there is a lack of standardization with various technical protocols, reproducibility of different populations, the purpose for using investigation, variance in the number of markers used, the amount of study days and calculations, the need to empty the colon before performing the test, and whether to perform on medication or off, or the use of specific diets. As part of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) motility working group (MWG), we decided to explore further into the evidence, in order to provide guidance regarding the use of ROMS in dealing with FC in the pediatric population. [ABSTRACT FROM AUTHOR]

The current regulatory path for new drug registration in East Asian countries has led to significant delay of the new medicines in these countries. A unified regulatory path and allowance of mutual usage of clinical data in East Asian countries would lead to cost saving in drug development and expedite the new drug registration in these countries. The objectives of the present analysis are to compare the approval dates of a selection of products developed by Pfizer in the United States and East Asian countries (China, Japan, Korea) and compare the pharmacokinetics and recommended doses of these products in East Asian countries. Eighteen products (20 drugs, 2 products with 2 combination drugs) with exposure data available in at least 2 of the 3 East Asian countries across different therapeutic areas were included in the analyses. The results showed that most products had delayed approval in East Asian countries (up to 8 years) after US or EU approval. No distinct differences were observed in the drug exposure and recommended doses for the selected products in East Asian countries. These results together with literature data of genetic similarity of the East Asian populations support the mutual usage of the clinical data in the East Asian countries for expedited regulatory submission and approval. [ABSTRACT FROM AUTHOR]

Background: The stretching of the lead caused by somatic growth may lead to complications (dislodgement, fracture, failure) of transvenous leads implanted in pediatric patients. Atrial loop and absorbable ligatures may prevent it. Periodical lead advancement with lead pushing from the pocket may be an option to growth‐induced stretching. Our aim was to analyze retrospectively the outcome of periodical transvenous lead advancement in children with pacemaker (PM). Methods: A procedure of lead advancement was performed in patients with a single‐chamber PM implanted for isolated congenital complete atrioventricular block or sinus node dysfunction with growth‐induced lead straightening/stretching. The PM pocket was opened, the lead was released from subcutaneous adherences and was gently advanced to shape again a loop/semi‐loop in the atrium without dislodging the tip. Lead data (threshold, sensing, impedance) were compared before and after the procedure. Data are described as median (25th–75th centiles). Results: 14 patients with 13 VVIR and 1 AAIR PM implanted at 6.8 (5.9–8.0) years of age, 23 (19–26) kg, 118 (108–124) cm, underwent 30 advancement procedures, 1.5 (1.0–2.3) per patient, during follow‐up [45 (35–63) months]. Delta between procedures was: 18 (14–25) months, 11 (7–13) cm, 6 (4–9) kg; 90% of leads were successfully advanced without complications. Three unsuccessful procedures occurred with longer times [30 (14–37) months]. Electrical lead parameters did not show significant differences pre‐/post‐procedures. Conclusion: the advancement of transvenous leads in children seems safe and effective. This procedure may be another possible choice to preserve transvenous lead position and function until growth has completed. [ABSTRACT FROM AUTHOR]

Aims: We examined the longitudinal associations of sedentary time (ST), light physical activity (LPA), and moderate‐to‐vigorous PA (MVPA) from childhood with carotid‐femoral pulse wave velocity (cfPWV), a measure of arterial stiffness and carotid intima‐media thickness (cIMT). Methods: We studied 1339 children, aged 11 years from Avon Longitudinal Study of Parents and Children, UK, followed up for 13 years. Accelerometer‐based ST, LPA, and MVPA were assessed at ages 11, 15, and 24 years clinic visits. cfPWV and cIMT were measured with Vicorder and ultrasound, respectively, at ages 17 and 24 years. Results: Among 1339 [56.4% female] participants, mean ST increased from ages 11 through 24 years, while mean LPA and MVPA decreased. Persistently high ST tertile from childhood was associated with increased cfPWV progression, effect estimate 0.047 m/s; [(95% CI 0.005 to 0.090); p = 0.030], but not cIMT progression. Persistently high LPA tertile category was associated with decreased cfPWV progression in males −0.022 m/s; [(−0.028 to −0.017); p < 0.001] and females −0.027 m/s; [(−0.044 to −0.010); p < 0.001]. Cumulative LPA exposure decreased the odds of progressively worsening cfPWV [Odds ratio 0.994 (0.994–0.995); p < 0.0001] and cIMT. Persistent exposure to ≥60 min/day of MVPA was paradoxically associated with increased cfPWV progression in males 0.053 m/s; [(0.030 to 0.077); p < 0.001] and females 0.012 m/s; [(0.002 to 0.022); p = 0.016]. Persistent exposure to ≥60 min/day of MVPA was inversely associated with cIMT progression in females −0.017 mm; [(−0.026 to −0.009); p < 0.001]. Conclusion: LPA >3 h/day from childhood may attenuate progressively worsening vascular damage associated with increased ST in youth. [ABSTRACT FROM AUTHOR]

Aims: Paediatric diabetes care has become increasingly specialised due to the multidisciplinary approach and technological developments. Guidelines recommend sufficient experience of treatment teams. This study evaluates associations between hospital volume and resource use and hospital expenditure in Dutch children with diabetes. Methods: Retrospective cohort study using hospital claims data of 5082 children treated across 44 Dutch hospitals (2019–2020). Hospitals were categorised into three categories; small (≥20–100 patients), medium (≥100–200 patients) and large (≥200 patients). All‐cause hospitalisations, consultations, technology and hospital expenditure were analysed and adjusted for age, sex, socio‐economic status (SES) and hospital of treatment. Results: Fewer hospitalisations were observed in large hospitals compared to small hospitals (OR 0.48; [95% CI 0.32–0.72]; p < 0.001). Median number of yearly paediatrician visits was 7 in large and 6 in small hospitals, the significance of which was attenuated in multilevel analysis (OR ≥7 consultations: 1.89; [95%CI 0.74–4.83]; p = 0.18). Technology use varies between individual hospitals, whereas pump usage and real‐time continuous glucose monitoring showed no significant differences between hospital volumes. Mean overall expenditure was highest in medium‐sized centres with €6434 per patient (IQR €2555–7955); the difference in diabetes care costs was not significant between hospital patient volumes. Conclusions: Care provision patterns vary by hospital patient volume. Large hospitals had the lowest hospitalisation rates. The use of diabetes technology was not different between hospital patient volumes. Medium‐sized hospitals showed the highest overall expenditure, but diabetes care costs were similar across hospital volumes. [ABSTRACT FROM AUTHOR]

Aim: There is a lack of studies on paediatric triage systems. This study aimed to evaluate patient safety of the Gothenburg‐developed paediatric triage system West Coast System for Triage—Paediatric (WEST‐P). Method: This study was performed at the paediatric emergency department in Gothenburg, Sweden, October 2020 to April 2021. Included patients were double‐triaged with the WEST‐P, and the established Rapid Emergency Triage and Treatment System—Paediatrics (RETTS‐p). We compared the level of urgency between both systems to identify potentially undertriaged patients. Also, we assessed the patient safety according to clinical assessment at presentation, and pre‐defined criteria. Results: This study included 2290 (23%) of triaged patients (44% girls, median age: 5.0 years) during the study period. A higher number of patients triaged to low urgency in WEST‐P compared to RETTS‐p (p < 0.0001) was observed, and 497 cases with low WEST‐P and high RETTS‐p urgencies identified. Of these, 29 had a clinical assessment indicating high urgency. After patient safety assessment, seven (0.4%) were determined undertriaged by the new triage system WEST‐P. Conclusion: Our findings demonstrate a low risk of undertriage in the new WEST‐P. Thus, the WEST‐P has a high degree of patient safety when used in a paediatric emergency department. [ABSTRACT FROM AUTHOR]

Aim: Given the multifaceted nature of paediatric palliative care (PPC), integrative medicine and mind–body therapies, in particular, are increasingly used in this setting. However, to our knowledge, their use in PPC has never been specifically reviewed. Therefore, this work aims to provide a comprehensive overview of the application and possible beneficial effects of mind–body therapies in the PPC setting. Methods: Papers about the use of meditation and mindfulness, biofeedback, hypnosis, yoga, tai chi and qi gong, imagery, creative outlets, and art therapy in PPC were identified by browsing PubMed and CINHAL. Results: We found that the harmless nature of mind–body therapies has been extensively described, and available studies consistently show some benefits on the anxiety, stress, and quality of life of parents/caregivers and healthcare providers. However, well‐grounded and robust evidence does not fully support the efficacy of mind–body therapies, especially in patients. Conclusion: Considering the peculiarity of the PPC setting, we suggest that mind–body therapies should be further considered and properly investigated through larger controlled studies and according to the different populations of PPC children, as well as for parents, caregivers, and healthcare professionals. [ABSTRACT FROM AUTHOR]

Background and objective: Even though children with complex problems frequently need psychosocial care, two thirds does not receive treatment. Various barriers, particularly expectations of barriers, can hinder effective access of care. Our aim was to assess the practical barriers expected by parents, and the child, family and need factors associated with these expected barriers. Methods: We sent web‐based questionnaires to parents of a random sample of children known to have or be at risk of having complex problems (response = 77%). We used backward regression analyses to examine which factors were associated with expected barriers for children using psychosocial care, or no care at all. Results: Seventy‐three percent of all parents expected practical barriers. Parents of children using psychosocial care expected more barriers than when using no care at all. For children who used no care, parents of girls expected more barriers (regression coefficient 0.54; 95%—confidence interval 0.16, 0.92) as did families having less social support (−0.30; −0.50, −0.11). When children used psychosocial care, parents expected more barriers when their child was of school‐age (0.38; 0.01, 0.75), of non‐western origin (vs. native) (0.52; 0.17, 0.88), when parents were older (i.e., 36+ years) (−0.77; −1.12, −0.42), experienced more adverse life events (0.29; 0.13, 0.45) or had less social support (−0.17; −0.34, 0.00). Conclusion: Even when their child is already receiving treatment, parents continue to expect practical barriers to psychosocial care. Psychosocial care services and their gatekeepers should address these concerns. Access to psychosocial care can be improved by removing practical barriers, especially if children already receive psychosocial care, or when parents have a limited network or belong to an ethnic minority. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine is a selective α2‐adrenergic agonist originally approved for sedation of adults in the intensive care unit and subsequently approved for procedural sedation in adults undergoing medical procedures. Dexmedetomidine is widely used off‐label for procedural sedation in children. Aims: To evaluate efficacy and safety of monotherapy dexmedetomidine for magnetic resonance imaging procedural sedation of children ≥1month–<17years across three ascending doses. Methods: Randomized, double‐blind, dose‐ranging study of procedural sedation recruited patients at USA and Japanese sites from February 2020 to November 2021. Patients were stratified into Cohort A (≥1month–<2years) or Cohort B (≥2–<17years). Cohort A loading doses/maintenance infusions: 0.5 mcg/kg/0.5 mcg/kg/h, 1.0 mcg/kg/1.0 mcg/kg/h, and 1.5 mcg/kg/1.5 mcg/kg/h. Cohort B loading doses/maintenance infusions: 0.5 mcg/kg/0.5 mcg/kg/h, 1.2 mcg/kg/1.0 mcg/kg/h, and 2.0 mcg/kg/1.5 mcg/kg/h. Primary endpoint was percentage of overall patients completing MRI without rescue propofol at the high versus low dose. Key secondary endpoint was percentage in each age cohort who did not require propofol at the high versus low dose. Results: One hundred twenty‐two patients received high‐ (n = 38), middle‐ (n = 42), or low‐dose (n = 42) dexmedetomidine. A greater percentage completed MRI without propofol rescue, while receiving high‐ versus low‐dose dexmedetomidine (24/38 [63.2%] vs. 6/42 [14.3%]) (odds ratio: 10.29, 95% confidence interval: 3.47–30.50, p <.001). Similar results were seen in both age cohorts. The most common adverse events were bradypnea, bradycardia, hypertension, and hypotension, and the majority were of mild‐to‐moderate severity. Conclusions: Dexmedetomidine was well tolerated. The high dose was associated with meaningfully greater efficacy compared with lower doses. Based on these results, the recommended starting dose for procedural sedation in children ≥1month–<2years is loading dose 1.5 mcg/kg/maintenance infusion 1.5 mcg/kg/h; children ≥2–<17years is loading dose 2.0 mcg/kg/maintenance infusion 1.5 mcg/kg/h. [ABSTRACT FROM AUTHOR]

The next‐generation sequencing technologies application discovers novel genetic alterations frequently in pediatric acute lymphoblastic leukemia (ALL). RAS signaling pathway mutations at the time of relapse ALL frequently appear as small subclones at the time of onset, which are considered as the drivers in ALL relapse. Whether subclones alterations in the RAS signaling pathway should be considered for risk group stratification of ALL treatment is not decided yet. In this work, we investigate the RAS signaling pathway mutation spectrum and the related prognosis in pediatric ALL. We employed an NGS panel comprising 220 genes. NGS results were collected from 202 pediatric ALL patients. 155 patients (76.7%) harbored at least one mutation. The incidences of RAS signaling pathway mutations are different significantly between T‐ALL and B‐ALL. In B‐ALL, the RAS pathway is mostly involved, and NRAS (17.6%), KRAS (22.7%), and PTPN11 (7.7%) were the three most frequently mutated genes. Co‐occurring mutations of CREBBP and NRAS, FLT3, or PTPN11 (p = 0.002, p = 0.009, and p = 0.003, respectively) were found in this cohort. The 3‐year RFS rates for the RAS signaling pathway mutation‐positive and negative cases was 76.5 % versus 89.7 % (p = 0.012). Four cases relapsed in the lately 3 years were RAS signaling pathway mutation‐positive. RAS signaling pathway mutation is an important biomarker for poorer relapse‐free survival in pediatric B‐ALL patients despite good early MRD levels. [ABSTRACT FROM AUTHOR]

Background: Health‐seeking behavior (HSB) is an individual's reaction to sickness, for which they seek medical attention, regardless of the form such care may take. Poor HSB is frequently associated with lower health outcomes and greater mortality and disease rates in a nation. Sociodemographic factors, including age, gender, family structure, occupation, ethnicity, and rates of literacy and poverty, can influence a person's HSB. This study would benefit Pakistani parents of the paediatric population to make more informed health choices for their children. Aim: This study aims to determine the influence of sociodemographic factors on parental HSB for illnesses among the pediatric age group in Karachi. Materials and Methods: A cross‐sectional study was conducted in which 214 parents were interviewed about their choices for health‐seeking healthcare for their pediatric children of the pediatric age group (birth–18 years), who were attending the pediatric OPD and wards at Dr. Ruth Pfau Civil Hospital, Karachi in May 2023. Only parents or guardians with sick children were included. Their sociodemographic characteristics and health‐seeking choices were asked. Informed consent was obtained, and all data were recorded. SPSS version 25 was used for analysis. Results: For the first choice, the majority of parents (82.7%) preferred to seek healthcare for their children from medical doctors, followed by spiritual healers (10.7%), traditional healers (5.6%), and homoeopathic doctors (0.9%). For the second choice, the highest percentage was for a doctor (76.2%), followed by a spiritual healer (18.7%), a homoeopathic doctor (3.3%), and a traditional healer (1.9%). A significant correlation was found between the first visit and the decision makers (p = 0.019), the father's education level of the father (p = 0.001), the mother's occupation of the mother (p = 0.019), and the mother's education level of the mother (p = 0.001). Conclusion: Sociodemographic characteristics greatly influence parents' HSBs of parents for their children. Despite having low‐paying jobs and being uneducated, most people choose to refer to a doctor for their child due to awareness. Key points: Allopathy is the most popular choice among parents of children aged birth to 18 years in Karachi, Pakistan.People opt for allopathy (going to hospitals to consult licensed medical doctors), but in case of not getting satisfactory results, people opt for other forms of healing.Health‐seeking behaviors have been shown to depend on several factors, including sociodemographic factors, literacy, occupation, decision‐makers, beliefs, etc. However, the literacy and occupation of both parents have shown to have the greatest impact. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles in human milk are critical in supporting newborn growth and development. Bioavailability of dietary extracellular vesicles may depend on the composition of membrane lipids. Single‐nucleotide polymorphisms (SNPs) in the fatty acid desaturase gene cluster impact the content of long‐chain polyunsaturated fatty acids in human milk phospholipids. This study investigated the relation between variation in FADS1 and FADS2 with the content of polyunsaturated fatty acids in extracellular vesicles from human milk. Methods: Milk was obtained from a cohort of mothers (N = 70) at 2–4 weeks of lactation. SNPs in the FADS gene locus were determined using pyrosequencing for rs174546 in FADS1 and rs174575 in FADS2. Quantitative lipidomic analysis of polyunsaturated fatty acids in human milk and extracellular vesicles from human milk was completed by gas chromatography–mass spectrometry. Results: The rs174546 and rs174575 genotypes were independent predictors of the arachidonic acid content in extracellular vesicles. The rs174546 genotype also predicted eicosapentaenoic acid and docosahexaenoic acid in extracellular vesicles. The reduced content of long‐chain polyunsaturated fatty acids in extracellular vesicles in human milk may be due to lower fatty acid desaturase activity in mothers who are carriers of the A allele in rs174546 or the G allele in rs174575. Conclusion: The polyunsaturated fatty acid composition of milk extracellular vesicles is predicted by the FADS genotype. These findings yield novel insights regarding extracellular vesicle content and composition that can inform the design of future research to explore how lipid metabolites impact the bioavailability of human milk extracellular vesicles. [ABSTRACT FROM AUTHOR]

Background: Poor weight gain has been identified as an independent risk factor for increased surgical morbidity and mortality for patients with single‐ventricle physiology undergoing staged surgical palliation. Conversely, excessive weight gain has also emerged as an independent risk factor predicting increased morbidity and mortality in a single‐center study. Given this novel single‐center concept, we investigated the impact of excessive weight on patients with single‐ventricle physiology undergoing bidirectional Glenn palliation in a multicenter study model. Methods: Patients from the Pediatric Heart Network Single Ventricle Reconstruction Trial (n = 387) were analyzed in a retrospective cohort study examining the independent effect of weight percentile on intensive care unit (ICU) length of stay (LOS) and ventilator days. Locally estimated scatterplot smoothing (LOESS) regression was used to plot weight‐for‐length (WFL) percentiles by ICU LOS and ventilator days. Unadjusted and adjusted ordinal regression was used to model ICU LOS and ventilator days. Results: Scatterplots and LOESS regression curves demonstrated increasing ICU LOS and ventilator days for increasing WFL percentiles. Unadjusted ordinal regression analysis of ICU LOS demonstrated a trend of increasing ICU LOS for increasing WFL percentiles that was not statistically significant (P = 0.11). A similar trend was demonstrated in adjusted ordinal regression that was not statistically significant (P = 0.48). Unadjusted and adjusted ordinal regression analysis of ventilator days did not reach statistical significance (P = 0.07). Conclusion: Excessive weight gain has a clinically relevant but not statistically significant association with increased ICU LOS and ventilator days for those patients in the >90th WFL percentile for age. [ABSTRACT FROM AUTHOR]

Background: Central line–associated bloodstream infections are a major concern for children with intestinal failure and in animal research using parenteral nutrition (PN). In neonatal piglets receiving PN, we compared sepsis, line occlusions, line replacements, mortality, and costs with and without the use of a 4%‐tetrasodium ethylenediaminetetraacetic acid (T‐EDTA) locking solution. Methods: We performed a retrospective review of piglets with a central venous jugular catheter enrolled in 14‐day exclusive PN (TPN) trials or in 7‐day short bowel syndrome (SBS) trials, before and after initiation of T‐EDTA. Lines were locked with a 1‐ml solution for 2 h daily (T‐EDTATPN, n = 17; T‐EDTASBS, n = 48) and compared with our prior standard of care using 1.5‐ml heparin flushes twice daily (CONTPN, n = 34; CONSBS, n = 48). Line patency and signs of sepsis were checked twice daily. Jugular catheters were replaced for occlusions whenever possible. Humane end points were used for sepsis not responding to antibiotic treatment or unresolved catheter occlusions. Results: Compared with CON, sepsis was reduced using T‐EDTA, significantly for TPN (P = 0.006) and with a trend for SBS piglets (P = 0.059). Line occlusions necessitating line changes were reduced 15% in TPN studies (P = 0.16), and no line occlusions occurred for T‐EDTA SBS piglets. Conclusion: In our neonatal piglet research, use of T‐EDTA locking solution decreased sepsis and, although not statistically significant, reduced occlusions requiring line replacements. Given the expense of animal research, adding a locking solution must be cost‐effective, and we were able to show that T‐EDTA significantly reduced total research costs and improved animal welfare. [ABSTRACT FROM AUTHOR]

Objective: Patient education is central to Enhanced Recovery After Surgery protocols, but child‐focused materials are lacking. We developed and piloted a mobile application to support accessible, interactive patient and caregiver education about pediatric tonsillectomy. Methods: Thirty children ages 5–12 who were preparing for tonsillectomy, their caregivers, and six attending otolaryngologists participated in a user‐testing trial of a web‐based prototype. The trial measured feasibility, fidelity, and patient‐centered outcomes. Patients and caregivers rated usability/likeability on the mHealth App Usability Questionnaire. Otolaryngologists rated quality on the Mobile App Rating Scale. The full mobile application, "Ready for Tonsillectomy," was then developed for iOS and Android. Results: Enrollment was 88.2%, retention was 90.0%, and use was 96.3%. Mean (SD) patient ratings for usability/likeability were 6.3 (1.1) out of 7; caregiver ratings were 6.5 (1.1). In common themes from open‐ended feedback, patients described the application as helpful and appealing, and caregivers described it as informative, easy to understand, calming, and easy to use. Among caregivers who used the application during recovery, 92.3% reported that it helped them manage their child's pain. Providers would recommend the application to many or all of their patients (mean [SD]: 4.7 [0.5] out of 5). Mean provider ratings for domains of engagement, functionality, aesthetics, information quality, subjective quality, and app‐specific value ranged from 4.1 to 4.8 out of 5. Conclusion: Feasibility and fidelity were high. Families and otolaryngologists endorsed the resource as an engaging, informative tool that supports positive coping. Our mobile application offers a patient‐centered solution readily scalable to other surgeries. Level of Evidence: NA Laryngoscope, 134:2455–2463, 2024 [ABSTRACT FROM AUTHOR]

The glymphatic system, which facilitates cerebrospinal fluid (CSF) flow through the brain parenchyma, is important for brain development and waste clearance. Advances in imaging techniques, particularly magnetic resonance imaging, have make it possible to evaluate glymphatic structures and functions in vivo. Recently, several studies have focused on the development and alterations of the glymphatic system in pediatric disorders. This review discusses the development of the glymphatic system, advances of imaging techniques and their applications in pediatric disorders. First, the results of the reviewed studies indicate that the development of the glymphatic system is a long‐lasting process that continues into adulthood. Second, there is a need for improved glymphatic imaging techniques that are non‐invasive and fast to improve suitability for pediatric applications, as some of existing methods use contrast injection and are susceptible to motion artifacts from long scanning times. Several novel techniques are potentially feasible for pediatric patients and may be used in the future. Third, the glymphatic dysfunction is associated with a large number of pediatric disorders, although only a few have recently been investigated. In conclusion, research on the pediatric glymphatic system remains an emerging field. The preliminary applications of glymphatic imaging techniques have provided unique insight into the pathological mechanism of pediatric diseases, but mainly limited in visualization of enlarged perivascular spaces and morphological measurements on CSF volumes. More in‐depth studies on glymphatic functions are required to improve our understanding of the mechanisms underlying brain development and pediatric diseases. Level of Evidence: 5 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Background: Cardiac MRI feature‐tracking (FT) with breath‐holding (BH) cine balanced steady state free precession (bSSFP) imaging is well established. It is unclear whether FT‐strain measurements can be reliably derived from free‐breathing (FB) compressed sensing (CS) bSSFP imaging. Purpose: To compare left ventricular (LV) strain analysis and image quality of an FB CS bSSFP cine sequence with that of a conventional BH bSSFP sequence in children. Study Type: Prospective. Subjects: 40 children able to perform BHs (cohort 1 [12.1 ± 2.2 years]) and 17 children unable to perform BHs (cohort 2 [5.2 ± 1.8 years]). Field Strength/Sequence: 3T, bSSFP sequence with and without CS. Assessment: Acquisition times and image quality were assessed. LV myocardial deformation parameters were compared between BH cine and FB CS cine studies in cohort 1. Strain indices and image quality of FB CS cine studies were also assessed in cohort 2. Intraobserver and interobserver variability of strain parameters was determined. Statistical Tests: Paired t‐test, Wilcoxon signed‐rank test, intraclass correlation coefficient (ICC), and Bland–Altman analysis. A P‐value <0.05 was considered statistically significant. Results: In cohort 1, the mean acquisition time of the FB CS cine study was significantly lower than for conventional BH cine study (15.6 s vs. 209.4 s). No significant difference were found in global circumferential strain rate (P = 0.089), global longitudinal strain rate (P = 0.366) and EuroCMR image quality scores (P = 0.128) between BH and FB sequences in cohort 1. The overall image quality score of FB CS cine in cohort 2 was 3.5 ± 0.5 with acquisition time of 14.7 ± 2.1 s. Interobserver and intraobserver variabilities were good to excellent (ICC = 0.810 to 0.943). Data Conclusion: FB CS cine imaging may be a promising alternative technique for strain assessment in pediatric patients with poor BH ability. Level of Evidence: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The diagnosis of disorders of gut–brain interaction (DGBI) in children is exclusively based on clinical criteria called the Rome criteria. The inter‐rater reliability (IRR) measures how well two raters agree with a diagnosis using the same diagnostic tool. Previous versions of the Rome criteria showed only fair to moderate IRR. There have been no studies assessing the IRR of the current edition of the pediatric Rome criteria (Rome IV). This study sought to investigate the IRR of the pediatric Rome IV criteria and compare its reliability with the previous versions of the Rome criteria. We hypothesized that changes made to Rome IV would result in higher IRR than previous versions.This study used the same methodology as the previous studies on Rome II and III, including identical clinical vignettes, number of raters, and levels of expertise. Participants included 10 pediatric gastroenterology fellows and 10 pediatric gastroenterology specialists. IRR was assessed using the percentage of agreement and Cohen's kappa coefficient to account for possible agreement by chance.The average IRR percentage of agreement using the Rome IV criteria was 55% for pediatric gastroenterologists and 48.5% for fellows, indicating moderate agreement (k = 0.54 for specialists, k = 0.47 for fellows). The results demonstrated higher percentages of agreement and kappa coefficients compared to the Rome II and III criteria.The findings demonstrate improved reliability in Rome IV compared to Rome II and III, suggesting that the changes incorporated into the Rome IV criteria have enhanced diagnostic consistency. Despite the advancements, the reliability is still moderate, indicating the need for further refinement of future versions of the Rome criteria. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion The evidence in the effectiveness of deep brain stimulation in children with medication‐refractory non‐degenerative monogenic dystonia is heterogeneous and long‐term results are sparse.The objective is to describe long‐term outcomes in a single‐center cohort and compare our results with a meta‐analysis cohort form literature.We performed a retrospective single‐center cohort study including consecutive pediatric patients with non‐degenerative genetic or idiopathic dystonia treated with globus pallidus internus deep brain stimulation at our center and a systematic review and individual‐patient data meta‐analysis with the same inclusion criteria. The primary outcome was the change from baseline in the Burke‐Fahn‐Marsden Dystonia Rating Scale‐movement (BFMDRS‐M) score.The clinical cohort included 25 patients with a mean study follow‐up of 11.4 years. The meta‐analysis cohort included 224 patients with a mean follow‐up of 3 years. Overall, the BFMDRS‐M mean improvements at 1 year and at last follow‐up were 41% and 33% in the clinical cohort and 58.9% and 57.2% in the meta‐analysis cohort, respectively. TOR1A‐dystonia showed the greatest and most stable BFMDRS‐M improvement in both cohorts at 1 year and at last follow‐up (76.3% and 74.3% in the clinical cohort; 69.6% and 67.3% in the meta‐analysis cohort), followed by SGCE‐dystonia (63% and 63.9% in the meta‐analysis cohort). THAP1‐dystonia (70.1% and 29.8% in the clinical cohort; 52.3% and 42.0% in the meta‐analysis cohort) and KMT2B‐dystonia (33.3% and 41.3% in the clinical cohort; 38.0% and 26.7% in the meta‐analysis cohort) showed a less pronounced or sustained response.Globus pallidus deep brain stimulation long‐term treatment seems effective with a possible gene‐specific differential effect. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background and Purpose: Sepsis‐surviving adult individuals commonly develop immunosuppression and increased susceptibility to secondary infections, an outcome mediated by the axis IL‐33/ILC2s/M2 macrophages/Tregs. Nonetheless, the long‐term immune consequences of paediatric sepsis are indeterminate. We sought to investigate the role of age in the genesis of immunosuppression following sepsis. Experimental Approach: Here, we compared the frequency of Tregs, the activation of the IL‐33/ILC2s axis in M2 macrophages and the DNA methylation of epithelial lung cells from post‐septic infant and adult mice. Likewise, sepsis‐surviving mice were inoculated intranasally with Pseudomonas aeruginosa or by subcutaneous inoculation of the B16 melanoma cell line. Finally, blood samples from sepsis‐surviving patients were collected and the concentration of IL‐33 and Tregs frequency were assessed. Key Results: In contrast to 6‐week‐old mice, 2‐week‐old mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL‐33 levels, Tregs expansion, and activation of ILC2s and M2‐macrophages were observed in 6‐week‐old but not 2‐week‐old post‐septic mice. Moreover, impaired IL‐33 production in 2‐week‐old post‐septic mice was associated with increased DNA methylation in lung epithelial cells. Notably, IL‐33 treatment boosted the expansion of Tregs and induced immunosuppression in 2‐week‐old mice. Clinically, adults but not paediatric post‐septic patients exhibited higher counts of Tregs and seral IL‐33 levels. Conclusion and Implications: These findings demonstrate a crucial and age‐dependent role for IL‐33 in post‐sepsis immunosuppression. Thus, a better understanding of this process may lead to differential treatments for adult and paediatric sepsis. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is characterized by preventable morbidity, cost, and inequity. We sought to build an Asthma Learning Health System (ALHS) to coordinate regional pediatric asthma improvement activities. Methods: We generated quantitative and qualitative insights pertinent to a better, more equitable care delivery system. We used electronic health record data to calculate asthma hospitalization rates for youth in our region. We completed an "environmental scan" to catalog the breadth of asthma-related efforts occurring in our children's hospital and across the region. We supplemented the scan with grouplevel assessments and focus groups with parents, clinicians, and community partners. We used insights from this descriptive epidemiology to inform the definition of shared aims, drivers, measures, and prototype interventions. Results: Greater Cincinnati's youth are hospitalized for asthma at a rate three times greater than the U.S. average. Black youth are hospitalized at a rate five times greater than non-Black youth. Certain neighborhoods bear the disproportionate burden of asthma morbidity. Across Cincinnati, there are many asthma-relevant activities that seek to confront this morbidity; however, efforts are largely disconnected. Qualitative insights highlighted the importance of cross-sector coordination, evidence-based acute and preventive care, healthy homes and neighborhoods, and accountability. These insights also led to a shared, regional aim: to equitably reduce asthma-related hospitalizations. Early interventions have included population-level pattern recognition, multidisciplinary asthma action huddles, and enhanced social needs screening and response. Conclusion: Learning health system methods are uniquely suited to asthma's complexity. Our nascent ALHS provides a scaffold atop which we can pursue better, more equitable regional asthma outcomes. [ABSTRACT FROM AUTHOR]

Background: Currently, the Accreditation Council of Graduate Medical Education requires time‐based pediatric experiences for emergency medicine (EM) residents in both pediatric emergency medicine (PEM) and critical care settings. The American Board of Emergency Medicine has published the Model of the Clinical Practice of Emergency Medicine, which is a list of content an EM resident should learn. However, this list is large and without prioritization and therefore can be difficult to incorporate into time‐limited curricula. Objectives: The primary objective of this study was to develop comprehensive categorization of PEM content using an EM lens. The second objective was to suggest a prioritization for the EM learner of the enumerated PEM elements. Methods: We first assembled a comprehensive list of PEM concepts, diagnoses, and procedures that might be taught to EM residents. We then convened focus groups composed of key stakeholders to help formulate content and concept themes important for EM resident training. Once the themes were identified, we divided the list of PEM topics into appropriate themes and then carried out a second round of focus groups expanded to include more diverse expert input for prioritizing the elements of the comprehensive list within each theme. Results: We prioritized 168 important PEM concepts from previous standards and emerging PEM literature among 10 identified themes: the pediatric normal, the bottom‐line boil‐it‐down approach, common presentations, high‐acuity pediatric cases and procedures, differences between children and adults, same between children and adults, red flags, infrequency of caring for a child compared with an adult, keep breadth but promote self‐directed depth, and triage and disposition. Conclusions: Based on input from stakeholders in EM resident education, we identified key themes within PEM education and created a framework for the hierarchical categorization of PEM content for within an EM residency. [ABSTRACT FROM AUTHOR]

Introduction: There is a growing consensus that children and young people (CYP) should be involved in matters that concern them. Progress is made in involving CYP in developing pediatric research agendas (PRAs), although the impact of their involvement remains unknown. We aimed to evaluate the impact of involving CYP in developing PRAs and assess the extent to which postpatient and public involvement (post‐PPI) activities were planned. Methods: We conducted a qualitative study using in‐depth interviews to identify and gain an in‐depth understanding of the impact of involving CYP in developing PRAs. The transcripts were uploaded to Atlas.ti to be coded and organised. Dutch‐language interviews were analysed and interpreted together with vocational education and training (VET) students. These students were aged between 14 and 18 years and were training to become nurses. Results: Three CYP and 15 researchers decided to participate. We focused on three categories of impact: agenda‐setting impact, individual impact and academic impact. Involving CYP creates a more enriched and clarified agenda. It ensured that both CYP and researchers underwent personal or professional growth and development, it created a connection between the people involved, awareness about the importance of involving CYP and it ensured that the people involved had a positive experience. The participants were unable to indicate the academic impact of their PRAs, but they did understand the key factors for creating it. In addition, the need to measure impact was highlighted, with a particular focus on assessing individual impact. Discussion: Our study outlines the diverse subthemes of impact that arise from involving CYP in developing PRAs. Despite the potential of research agendas to amplify CYP voices, only a minority of researchers strategized post‐PPI activities ensuring impactful outcomes, prompting the need for thorough evaluation of various impact forms and consistent alignment with the overarching goal of transforming the research field. Patient or Public Contribution: We involved VET students in the data analysis and interpretation phase by forming a young person advisory group. The data analysis of the interviews analysed by the VET students revealed four distinct themes: 1. Learnt new knowledge. 2. Learnt to collaborate. 3. Learnt to listen. 4. Assessment of the individual impact. [ABSTRACT FROM AUTHOR]

Introduction: The optimal dosing and monitoring of vancomycin in pediatrics is still unknown but has evolved to emphasize area under the curve over 24 h (AUC0–24) over minimum concentration (Cmin) monitoring. Real‐world data supporting the feasibility of two‐concentration kinetics with first‐order equations for the estimation of vancomycin AUC0–24 in pediatric patients are lacking. Objectives: To describe the interplay of vancomycin dose, AUC0–24, and Cmin using first‐order equations within four pediatric age groups. Methods: This is a single‐center, retrospective cohort study analyzing pediatric patients (<18 years) receiving intravenous vancomycin between 2020 and 2022. Included patients received at least 24 h of intravenous vancomycin with two concentrations obtained within 96 h of therapy initiation. Patients with baseline renal dysfunction were excluded. Patients were divided into four age categories: neonates (≤28 days), infants (29 days to <1 year), children (1–12 years), and adolescents (13–17 years). First‐order equations were utilized to estimate pharmacokinetic parameters and AUC0–24. Results: Overall, 219 patients (median age of 6 years [IQR 1–12]) met inclusion criteria. The median vancomycin daily dose was 30 mg/kg in neonates, 70 mg/kg in infants and children, and 52 mg/kg in adolescents. Median Cmin and AUC0–24 values among all age groups were 8.68 mg/L and 505 mg * h/L, respectively. For AUC0–24 values outside of the therapeutic range (400–600 mg * h/L), more values were SUPRAtherapeutic (>600 mg * h/L) than SUBtherapeutic (<400 mg * h/L). The overall trend within our data showed suboptimal correlation between Cmin and AUC0–24. However, 71% of patients with Cmin values of 5–10 mg/L had an AUC0–24 within the therapeutic range of 400–600 mg * h/L, whereas 23 patients (92%) with a SUPRAtherapeutic AUC0–24 had a Cmin value ≥15 mg/L. Approximately 10% of patients experienced acute kidney injury. Conclusions: Our data describe the relationship between vancomycin dose, Cmin, and AUC0–24 in pediatric patients. We demonstrated the feasibility of using first‐order equations to estimate AUC0–24, using two concentrations obtained at steady state to monitor efficacy and safety in pediatric patients receiving intravenous vancomycin. Our data showed suboptimal correlation between AUC0–24 and Cmin, which indicates that Cmin should not be used as a surrogate marker for a therapeutic AUC0–24 in pediatric patients. In alignment with the 2020 vancomycin consensus guidelines, we suggest utilizing AUC0–24 for efficacy and safety monitoring. [ABSTRACT FROM AUTHOR]

Background: Intraoperative Continuous Renal Replacement Therapy (iCRRT) can prevent life‐threatening complications, facilitate fluid management, and maintain metabolic homeostasis during liver transplantation (LT) in adults. There is a paucity of data in pediatric LT. We evaluated the safety, efficacy, and impact on survival of iCRRT in pediatric LT. Methods: We conducted a retrospective cohort study of all children requiring CRRT pre‐OLT at a quaternary children's hospital from 2014 to 2022. Demographic characteristics, intraoperative events, and post‐LT outcomes were compared between those who received iCRRT and those who did not. Results: Out of 306 patients who received LT, 30 (10%) were supported with CRRT at least 24 h prior to LT, of which 11 (36%) received iCRRT. The two cohorts were similar in demographics, diagnosis of liver disease, and severity of illness. The iCRRT patients experienced massive blood loss and increased transfusion requirements. There was no difference in intraoperative metabolic balance. One‐year post‐LT mortality rates were similar. Conclusion: ICRRT is safe in critically ill children with pre‐LT renal dysfunction. It optimizes fluid and blood product resuscitation while maintaining metabolic homeostasis. Candidates need to be carefully chosen for this highly resource‐intensive therapy to benefit this fragile population. [ABSTRACT FROM AUTHOR]

The study discusses a new approach to parental agency in pediatric palliative care based on an active form of caregiving. It also explores the possibility of a positive conceptualization of parental agency in its relational context. The paper begins with an illustrative case study based on a clinical situation. This is followed by an analysis of various aspects of parental agency based on empirical studies that disclose the insufficiencies of the traditional approach to parental agency. In the next step, parental agency is analyzed from a reality‐based perspective as an activity focused on relationships and the cognitive capacity of parents vis‐a‐vis their seriously ill children. The paper also considers the importance of the cultural and social contexts in which parental agency and decision‐making take place. This agency is addressed not as individualistic in form, and nor is it exercised in terms of fixed choices. Rather, the focus is on its dynamic and future‐oriented aspects. Consequently, parental agency should be comprehended not only as a form of proxy agency representing the child's best interests but also as a complex decision‐making process in which the parents learn from their child how to become good, compassionate caregivers and at the same time good parents. [ABSTRACT FROM AUTHOR]