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Consequences of age-associated thymic atrophy include declining T-cell responsiveness to pathogens and vaccines and diminished T-cell self-tolerance. Cortical thymic epithelial cells (cTECs) are primary targets of thymic aging, and recent studies suggested that their maintenance requires mTOR signaling downstream of medullary TEC (mTEC)-derived growth factors. Here, to test this hypothesis, we generated a knock-in mouse model in which FGF21 and mCherry are expressed by most mTECs. We find that mTEC-derived FGF21 promotes temporally distinct patterns of mTORC1 and mTORC2 signaling in cTECs, promotes thymus and individual cTEC growth and maintenance, increases T-cell responsiveness to viral infection, and diminishes indicators of peripheral autoimmunity in older mice. The effects of FGF21 overexpression on thymus size and mTOR signaling were abrogated by treatment with the mTOR inhibitor rapamycin. These results reveal a mechanism by which paracrine FGF21 signaling regulates thymus size and function throughout the lifespan, as well as potential therapeutic targets for improving T-cell function and tolerance in aging., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Focal vibration therapy (FVT) is increasingly used in the treatment of spastic paresis. In adults, it has been shown to reduce spasticity and to increase torque production from the vibrated muscles by restoring reciprocal inhibition of antagonists, thereby improving overall gait. In children with spastic cerebral palsy (CP), FVT has also been suggested to reduce spasticity, increase torque production and improve gait function, but evidence is limited., Methods: We report the case of a child with unilateral spastic CP (USCP) and equinus gait (GFMCS II level) with (i) ankle dorsiflexor paresis, (ii) ankle plantar flexor overactivity, especially in gastrosoleus complex and peroneus longus, (iii) spastic myopathy, affecting gastrosoleus complex in particular, and (iv) calf pain seemingly related to muscle overactivity. The child was treated with a two-month program of alternating dorsiflexor and plantar flexor focal vibration therapy (FVT) and botulinum neurotoxin A (BoNT-A) injections into plantar flexors, alongside conventional physiotherapy., Results and Discussion: Clinical evaluations during the two-month program showed (i) improved walking speed (ii) decreased ankle dorsiflexor paresis and ankle plantar flexor overactivity, especially spastic co-contraction and spasticity, (iii) improved passive extensibility in plantar flexors, and (iv) reduced pain. This is the first report of the combination of FVT and BoNT-A injections having promising effects on equinus gait in USCP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2025 Boulay, Coq, Sangeux, Authier, Ulian, Pradines, Baude, Desnous, Jouve, Parratte, Peltier, Pesenti and Gracies.)

The importance of calcium (Ca2+) as a second messenger in T cell signaling is exemplified by genetic deficiencies of STIM1 and ORAI1, which abolish store-operated Ca2+ entry (SOCE) resulting in combined immunodeficiency (CID). We report five unrelated patients with de novo missense variants in ITPR3, encoding a subunit of the inositol 1,4,5-trisphosphate receptor (IP3R), which forms a Ca2+ channel in the endoplasmic reticulum (ER) membrane responsible for the release of ER Ca2+ required to trigger SOCE, and for Ca2+ transfer to other organelles. The patients presented with CID, abnormal T cell Ca2+ homeostasis, incompletely penetrant ectodermal dysplasia, and multisystem disease. Their predominant T cell immunodeficiency is characterized by significant T cell lymphopenia, defects in late stages of thymic T cell development, and impaired function of peripheral T cells, including inadequate NF-κB- and NFAT-mediated, proliferative, and metabolic responses to activation. Pathogenicity is not due to haploinsufficiency, rather ITPR3 protein variants interfere with IP3R channel function leading to depletion of ER Ca2+ stores and blunted SOCE in T cells., (© 2024 Blanco et al.)

Purpose: After vertical parasagittal hemispherotomy a restricted diffusion is often seen ipsilaterally and even distant from the adjacent resection margin. This retrospective cohort study analyses the anatomic site and the time course of the diffusion restriction after vertical parasagittal hemispherotomy., Methods: Fifty-nine patients were included into this study, all of them having had one pre-operative and at least one post-operative MRI, including diffusion imaging at b‑values of 0 and 1000 s/mm 2 with a calculated ADC., Results: Diffusion restriction occurred exclusively on the operated site in all patients. In the basal ganglia, diffusion restriction was present in 37 of 38 patients at the first postoperative day with a duration of 38 days. In the midbrain, the posterior limb of the internal capsule and the thalamus, a restricted diffusion became postoperatively prominent at day 9 in all three localizations, with a duration of 36, 34 and 36 days, respectively. The incidence of thalamic lesions was lower if a preoperative damage had occurred., Conclusion: The restricted diffusion in the basal ganglia resembles direct effects of the operation at its edges, whereas the later appearing diffusion restriction in the midbrain and the posterior limb of the internal capsule rather belong to a degeneration of the descending fibers being transected by the hemispherotomy in the sense of a Wallerian degeneration. The presence of preoperative hemispheric lesions influences the development of diffusion restriction at subacute fiber degeneration., Competing Interests: Conflict of interest M. Hittinger, T. Hartlieb, D.H. Heiland, P. Heiland, T. Pieper, M. Staudt, A. Berlis, M. Kudernatsch and I. Mader declare that they have no competing interests., (© 2024. The Author(s).)

Background: The assessment of gait disorders in patients with neuromotor conditions, such as cerebral palsy (CP), has been a focus of clinical and research attention, with electromyography (EMG) offering a nuanced understanding of neurological and neuromuscular disorders. However, the interpretation of EMG data in the context of gait analysis remains challenging due to the complexity of neuromotor dynamics and variability in assessment methodologies., Research Question: To which consensus can we get in a group of experts in the fields of neurological and neuromuscular disorders, biomechanics, and clinical gait analysis to establish standardized protocols and a common language for the measurement and analysis of EMG data in gait disorders, particularly in people living with CP?, Methods: A three-round Delphi process was conducted from February to September 2023 to gather opinions of 53 experts on the use of surface EMG data during gait in the context of CP. The surveys were conducted using the tool 'SoSci Survey' with a focus on free-text answers., Results: The experts agreed on the usefulness of EMG data, but a consensus on specific clinical decisions involving EMG could not be reached. Additionally, the study provides a terminological framework for EMG evaluation during gait and a comprehensive list of practical problems and solutions, when evaluating EMG data. The study indicates that, despite a general community consensus on the ideal approaches to data processing and evaluation, these methods are not commonly implemented in a standardized manner. Both raw and enveloped data are widely used in clinical routines, however, the protocol for generating normative data lacks consistency across gait laboratories., Significance: The study suggests that while there may be differences in the way EMG data is analyzed, there is a shared understanding of the key features that are relevant for gait analysis., Competing Interests: Declaration of Competing Interest “Each of the authors has read and concurs with the content in the final manuscript. The material within has not been and will not be submitted for publication elsewhere except as an abstract." There is no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this randomized controlled trial, we assessed the non-inferiority of buddy taping to splinting after reduction of displaced extra-articular proximal and middle phalangeal finger fractures in children. The primary outcome was the rate of secondary fracture displacements; the secondary outcomes were patient comfort, analgesic efficacy and total range of active motion 6 months after injury. Eighty-one patients participated: 43 with taping and 38 with splinting. Secondary displacement occurred in eight patients: five in the splinting group and three in the taping group. Risk difference was below the predefined non-inferiority of 10%. Patient comfort was significantly higher in the taping group, with no group differences for other parameters. Our previous study recommended taping for undisplaced finger fractures in children. With the current data, we recommend taping these finger fractures irrespective of displacement or need for reduction. We are encouraged to propose taping as an alternative to splinting for increased patient comfort, lower cost, and shorter application time. Level of evidence: I., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Objective: Regarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might be improved., Design and Intervention: International online survey., Results: Replies were received from 560 NICUs in 24 countries between January and May 2023. LU uptake varied considerably (20%-98% of NICUs) between countries. In 428 units (76%), LU was used for clinical indications, while 34 units (6%) only used it for research purposes. One-third of units had <2 years of experience, and only 71 units (13%) had >5 years of experience. LU was mainly performed by neonatologists. LU was most frequently used to diagnose respiratory diseases (68%), to evaluate an infant experiencing acute clinical deterioration (53%) and to guide surfactant treatment (39%). The main pathologies diagnosed by LU were pleural effusion, pneumothorax, transient tachypnoea of the newborn and respiratory distress syndrome. The main barriers for implementation were lack of experience with technical aspects and/or image interpretation. Most units indicated that specific courses and an international guideline on neonatal LU could promote uptake of this technique., Conclusions: Although LU has been adopted in neonatal care in most European countries, the uptake is highly variable. The main indications are diagnosis of lung disease, evaluation of acute clinical deterioration and guidance of surfactant. Implementation may be improved by developing courses and publishing an international guideline., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: There is limited caregiver-reported evidence determining health care transition (HCT) outcomes for their adolescents/young adults with special health care needs (AYA-SHCN). A subcommittee of the International and Interdisciplinary Healthcare Transition Research Consortium aimed to identify multidimensional outcomes of a successful HCT among AYA-SHCN based on parents/caregivers' perspectives., Methods: After literature review and expert interviews, a three-stage Delphi process identified HCT outcomes based on parents/caregivers' perspectives. Participants were parents/caregivers of patients attending the Victory Junction Therapeutic Camp and a nationally representative sample from Cint Healthcare Digital Solutions Platform. The cumulative 272 responses collected on a Health Insurance Portability and Accountability Act-compliant web-based engine (Qualtrics) rated potential HCT outcomes by level of importance on a Likert scale from 1 (not important) to 9 (very important) and narrowed in subsequent iterations., Results: The Delphi process included 127 (Stage 1), 82 (Stage 2), and 63 (Stage 3) parents/caregivers. The initial 25 HCT outcomes were narrowed to 13, across four major domains: coping/satisfaction, behavioral, structural, and HCT/healthcare-focused outcomes. The top outcome was "My child takes their medications as prescribed." Several traditionally considered important outcomes for HCT were eliminated., Discussion: Thirteen HCT outcomes for AYA-SHCN were identified in four major domains: coping/satisfaction, behavioral, structural, and HCT/healthcare focused. Future research in larger samples would allow stratification to represent diverse patients and caregiver populations. Identifying international consensus-derived outcomes among parents/caregivers is imperative for the evaluation of HCT preparation strategies that ensure appropriate support for diverse AYA-SHCN and their families during this process and enable implementation of the most effective interventions., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To compare the predictive values of the General Movements Assessment (GMA) and the Standardized Infant NeuroDevelopmental Assessment (SINDA) neurological scale for atypical neurodevelopmental outcome in 3-month-old at-risk infants., Method: A total of 109 infants (gestational age 30 weeks; range: 24-41; 52 males) attending a non-academic outpatient clinic were assessed with the GMA and the SINDA at 3 (2-4) months corrected age. The GMA pays attention to the complexity of general movements and presence of fidgety movements. Atypical neurodevelopmental outcome at 24 months corrected age (and older) implied cerebral palsy (CP) or a Bayley Mental Development Index or Bayley Psychomotor Development Index lower than 70., Results: At 24 months corrected (and older) age, 16 children had an atypical outcome, including 14 children with CP. Regarding markedly reduced general movement complexity in combination with absent or sporadic fidgety movements, the GMA predicted an atypical outcome with specificity, positive, and negative predictive values greater than 0.900, and sensitivity of 0.687 (95% confidence interval [CI] = 0.460-0.915). SINDA predicted an atypical outcome with sensitivity, specificity, and negative predictive value greater than 0.900 and a positive predictive value of 0.652 (95% CI = 0.457-0.847). Regarding absent fidgety movements only or markedly reduced general movement complexity, the GMA predicted the outcome less well than both general movement criteria., Interpretation: The SINDA and GMA both predict neurodevelopmental outcome well, but SINDA is easier to learn than the GMA; being a non-video-based assessment, it allows caregiver feedback during the consultation whereas the GMA usually does not., What This Paper Adds: The General Movements Assessment (GMA) and Standardized Infant NeuroDevelopmental Assessment (SINDA) neurological scale predict atypical neurodevelopmental outcome equally well. The GMA and SINDA neurological scale predict CP and atypical neurodevelopmental outcome well. The GMA works best to predict neurodevelopmental outcome when based on both general movement complexity and fidgety movements., (© 2024 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Purpose: Up to 90% of nonambulatory patients with cerebral palsy (CP) experience hip displacement during their lifetime. Reconstructive surgery is recommended. Redisplacement rate is an outcome parameter., Methods: In a systematic literature review (MEDLINE, Embase and CENTRAL databases) until January 2023 we searched for reports with redisplacement rates after bony hip reconstructive surgery in nonambulatory patients. Quantitative data synthesis, subgroup analysis and meta-regression with moderators were carried out., Results: The pooled mean redisplacement rate was 16% (95% CI: 12-21%) with a prediction interval of 3-51% (Q: 149; df: 32; P < 0.001; I2: 78%; τ2: 0.67 and τ: 0.82) in 28 studies (1540 hips). Varus derotation osteotomy (VDRO) alone showed a higher redisplacement rate than VDRO + pelvic osteotomy (30% vs 12%, P < .0001). Mean age in the VDRO-alone subgroup was 7.1 years and in the combined group 9.5 years (P = .004). In meta-regression, lower redisplacement rates were observed with higher preoperative migration index (MI) (correlation coefficient: -0.0279; P = .0137), where comprehensive surgery was performed. Variance in true effects are explained by type of bone surgery (57%), preoperative MI (11%), age (5%) and MI for definition of failure (20%). No significant reduction in the redisplacement rate could be observed over the mid-years of studies (1977-2015)., Conclusion: Our pooled data support the more extensive surgical approach in patients with high preoperative MI and emphasize the superiority of combined surgery. Studies should report a coordinated set of parameters and outcome classifications according to internationally accepted gradings to reduce redisplacement in future.

Background: Severity of dyskinesia in children with cerebral palsy is often assessed using observation-based clinical tools. Instrumented methods to objectively measure dyskinesia have been proposed to improve assessment accuracy and reliability. Here, we investigated the technique and movement features that were most suitable to objectively measure the severity of dystonia in children with cerebral palsy., Methods: A prospective observational study was conducted with 12 participants with cerebral palsy with a predominant motor type of dyskinesia, spasticity, or mixed dyskinesia/spasticity who had upper limb involvement (mean age: 12.6 years, range: 6.7-18.2 years). Kinematic and electromyography data were collected bilaterally during three upper limb tasks. Spearman rank correlations of kinematic or electromyography features were calculated against dystonia severity, quantified by the Dyskinesia Impairment Scale., Findings: Kinematic features were more influential compared to electromyography features at grading the severity of dystonia in children with cerebral palsy. Kinematic measures quantifying jerkiness of volitional movement during an upper limb task with a reaching component performed best (|r s | = 0.78-0.9, p < 0.001)., Interpretation: This study provides guidance on the types of data, features of movement, and activity protocols that instrumented methods should focus on when objectively measuring the severity of dystonia in children with cerebral palsy., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Moral distress denotes a negative reaction to a morally challenging situation. It has been associated with adverse outcomes for healthcare professionals, patients and healthcare institutions. We argue that existing definitions, along with measures of moral distress, compromise the validity of empirical research. First, the definition and measurement of moral distress conflate moral events and psychological distress, even though they are distinct phenomena that should be assessed independently. Second, in many studies, there is a lack of clarity in distinguishing between moral and non-moral events. Finally, prior research on moral distress often overlooks the substantial body of evidence demonstrating the impact of diverse work-related factors, beyond moral events, on both distress and job retention. These challenges might undermine the effectiveness of interventions aimed at alleviating moral distress. We outline a comprehensive research agenda that encompasses conceptual clarifications, the refinement of data collection instruments, the design of studies and the application of appropriate statistical methods., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research., Methods: All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed., Results: The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with <5 % for almost all variables. A considerable number of missing source data occurred for CFTR variants. Availability of ICs varied largely between centers (10 centers had >5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved., Conclusions: Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kathleen Jahn, Andreas Jung, Philipp Latzin, Alexander Moeller, Christian Murer, Lutz Naehrlich, Alain Sauty and Jakob Usemann have received honoraria from Vertex Pharmaceuticals. Andreas Jung has received consulting fees and honoraria from EffRx Pharmaceuticals and Viatris. Philipp Latzin has received honoraria from CSL Vifor., (Copyright © 2023. Published by Elsevier B.V.)

Background: The most prevalent infections encountered in neonatal care are healthcare-associated infections. The majority of healthcare-associated infections are considered preventable with evidence-based infection prevention and control (IPC) practices. However, substantial knowledge gaps exist in IPC implementation in neonatal care. Furthermore, the knowledge of factors which facilitate or challenge the uptake and sustainment of IPC programmes in neonatal units is limited. The integration of implementation science approaches in IPC programmes in neonatal care aims to address these problems., Objectives: The aim of this narrative review was to identify determinants which have been reported to influence the implementation of IPC programmes and best practices in inpatient neonatal care settings., Sources: A literature search was conducted in PubMed, MEDLINE (Medical Literature Analysis and Retrieval System Online) and CINAHL (Cumulative Index to Nursing and Allied Health Literature) in May 2022. Primary study reports published in English, French, German, Spanish, Portuguese, Italian, Danish, Swedish or Norwegian since 2000 were eligible for inclusion. Included studies focused on IPC practices in inpatient neonatal care settings and reported determinants which influenced implementation processes., Content: The Consolidated Framework for Implementation Research was used to identify and cluster reported determinants to the implementation of IPC practices and programmes in neonatal care. Most studies reported challenges and facilitators at the organizational level as particularly relevant to implementation processes. The commonly reported determinants included staffing levels, work- and caseloads, as well as aspects of organizational culture such as communication and leadership., Implications: The presented knowledge about factors influencing neonatal IPC can support the design, implementation, and evaluation of IPC practices., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

While advancements in the treatment of diabetes continue to rapidly evolve, many of the newer technologies have financial barriers to care, opposing the egalitarian ethos of Banting who sold his patent on insulin for a nominal cost to allow it to be made widely available. Inequity in access to new therapies drives disparity in diabetes burden with potential for these gaps to widen in the future. The 2023 International Conference on Advanced Technologies and Treatments of Diabetes (ATTD) presented ground-breaking and current research in diabetes technology. Oral presentations of the ATTD conference 2023 were analyzed to describe what percentage of speakers discussed equity in their talks. Overall, less than a quarter of presenters discussed equity, though there was regional variation. To ensure that diabetes technologies reduce disparity and improve outcomes, we encourage future speakers at diabetes (technology) conferences to consider equity of diabetes care and incorporate this into their presentations., Competing Interests: MD declares receiving speaker fees from Medtronic, Dexcom, Boerhinger Ingelheim, research support from Dexcom, Medtronic, Novonordisk, Pfizer, SOOIL, and has served as advisory board membership for Dexcom. RL receives consulting fees from Abbott DIabetes Care, Gluroo, PhysioLogic Devices, Provention Bio and is chief medical advisor for Tidepool. He receives research support from NIDDK 1K23DK122017 and P30 DK116074, JDRF, Abbott, Insulet, Medtronic and Tandem. ED declares receiving speaker fees from Lilly, and being part of speaker’s bureau for Dexcom. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Leadley, Addala, Berkeley, Crocket, Davis, Hewapathirana, Hussain, Lal, Lomax, Wilkinson, de Bock and Burckhardt.)

Background: Currently, over 4000 bariatric procedures are performed annually in Switzerland. To improve outcomes, patients need to have good knowledge regarding postoperative nutrition. To potentially provide them with knowledge between dietetic consultations, a health bot (HB) was created. The HB can answer bariatric nutrition questions in writing based on artificial intelligence., Objective: This study aims to evaluate the usability and perception of the HB among patients receiving bariatric care., Methods: Patients before or after bariatric surgery tested the HB. A mixed methods approach was used, which consisted of a questionnaire and qualitative interviews before and after testing the HB. The dimensions usability of, usefulness of, satisfaction with, and ease of use of the HB, among others, were measured. Data were analyzed using R Studio (R Studio Inc) and Excel (Microsoft Corp). The interviews were transcribed and a summary inductive content analysis was performed., Results: A total of 12 patients (female: n=8, 67%; male: n=4, 33%) were included. The results showed excellent usability with a mean usability score of 87 (SD 12.5; range 57.5-100) out of 100. Other dimensions of acceptability included usefulness (mean 5.28, SD 2.02 out of 7), satisfaction (mean 5.75, SD 1.68 out of 7), and learnability (mean 6.26, SD 1.5 out of 7). The concept of the HB and availability of reliable nutrition information were perceived as desirable (mean 5.5, SD 1.64 out of 7). Weaknesses were identified in the response accuracy, limited knowledge, and design of the HB., Conclusions: The HB's ease of use and usability were evaluated to be positive; response accuracy, topic selection, and design should be optimized in a next step. The perceptions of nutrition professionals and the impact on patient care and the nutrition knowledge of participants need to be examined in further studies., (©Marina Beyeler, Corinne Légeret, Fabian Kiwitz, Klazine van der Horst. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 08.11.2023.)

There is a lack of knowledge about the accuracy of the Conventional Gait Model (CGM), compared to the true bone motion. Accuracy is hindered by both marker misplacement and soft-tissue artefact (STA). The effect of the lateral knee marker (KNE) misplacement and STA was determined from a secondary analysis of 13 subjects equipped with a total knee prothesis for which simultaneous dual-plane fluoroscopy and marker-based motion capture was available. In average, STA alone led to 3.3°, 2.9° and 6.7° errors for knee flexion, knee abduction, and the absolute hip rotation respectively. In comparison, marker misplacement led to 0.9°, 4.0° and 12.3° errors for the same kinematics. We showed that STA alone may lead to knee flexion-adduction cross-talk. This finding has clinical repercussions for the use of knee cross talk as a qualitative indicator of knee axis alignment. Our study showed that cumulative effects of marker misplacement and STA affect the transverse plane angles, making challenging to track internal/external rotation with less than 5° of errors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Iatrogenic viscus perforation in pediatric gastrointestinal endoscopy (GIE) is a very rare, yet potentially life-threatening event. There are no evidence-based recommendations relating to immediate post-procedure follow-up to identify perforations and allow for timely management. This study aims to characterize the presentation of children with post-GIE perforation to better rationalize post-procedure recommendations., Methods: Retrospective study based on unrestricted pooled data from centers throughout Europe, North America, and the Middle East affiliated with the Endoscopy Special Interest Groups of European Society for Paediatric Gastroenterology Hepatology and Nutrition and North American Society for Pediatric Gastroenterology Hepatology and Nutrition. Procedural and patient data relating to clinical presentation of the perforation were recorded on standardized REDCap case-report forms., Results: Fifty-nine cases of viscus perforation were recorded [median age 6 years (interquartile range 3-13)]; 29 of 59 (49%) occurred following esophagogastroduodenoscopy, 26 of 59 (44%) following ileocolonoscopy, with 2 of 59 (3%) cases each following balloon enteroscopy and endoscopic retrograde cholangiopancreatography; 28 of 59 (48%) of perforations were identified during the procedure [26/28 (93%) endoscopically, 2/28 (7%) by fluoroscopy], and a further 5 of 59 (9%) identified within 4 hours. Overall 80% of perforations were identified within 12 hours. Among perforations identified subsequent to the procedure 19 of 31 (61%) presented with pain, 16 of 31 (52%) presented with fever, and 10 of 31 (32%) presented with abdominal rigidity or dyspnea; 30 of 59 (51%) were managed surgically, 17 of 59 (29%) managed conservatively, and 9 of 59 (15%) endoscopically; 4 of 59 (7%) patients died, all following esophageal perforation., Conclusions: Iatrogenic perforation was identified immediately in over half of cases and in 80% of cases within 12 hours. This novel data can be utilized to generate guiding principles of post-procedural follow-up and monitoring., Plain Language Summary: Bowel perforation following pediatric gastrointestinal endoscopy is very rare with no evidence to base post-procedure follow-up for high-risk procedures. We found that half were identified immediately with the large majority identified within 12 hours, mostly due to pain and fever., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Hip involvement remains a predictor of severe juvenile idiopathic arthritis (JIA) course and carries a high risk of disability. This study aims to determine the factors of poor prognosis of hip involvement in patients with JIA and to assess the treatment response., Methods: This is a multicenter observational cohort study. Patients were selected from the JIR Cohort database. Hip involvement was defined as clinically suspected and confirmed by an imaging tool. Follow-up data were collected during 5 years., Results: Among the 2223 patients with JIA, 341(15%) patients had hip arthritis. Male gender, enthesitis-related arthritis, and North African origin were factors associated with hip arthritis. Hip inflammation was associated with disease activity parameters during the first year, particularly Physician Global Assessment, joint count, and inflammatory marks. Structural hip progression was associated with early onset of the disease, a longer time to diagnosis, geographic origin, and JIA subtypes. Anti-TNF therapy was found to be the only treatment able to effectively reduce structural damage progression., Conclusion: The early onset diagnostic delay, origin, and systemic subtype of JIA predict a poor prognosis of hip arthritis in children with JIA. The use of anti-TNF was associated with a better structural prognosis., (© 2023 John Wiley & Sons Ltd.)

Background: The neutrophil-to-lymphocyte-ratio (NLR), neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) and monocyte-to-lymphocyte-ratio (MLR) may have diagnostic potential for tuberculosis (TB)., Methods: Data of two prospective multicenter studies in Switzerland were used, which included children <18 years with TB exposure, infection or disease or with febrile non-TB lower-respiratory-tract infection (nTB-LRTI)., Results: Of the 389 children included 25 (6.4%) had TB disease, 12 (3.1%) TB infection, 28 (7.2%) were healthy TB exposed and 324 (83.3%) nTB-LRTI. Median (IQR) NLR was highest with 2.0 (1.2, 2.2) in children with TB disease compared to TB exposed [0.8 (0.6, 1.3); P = 0.002] and nTB-LRTI [0.3 (0.1, 1.0); P < 0.001]. Median (IQR) NMLR was highest with 1.4 (1.2, 1.7) in children with TB disease compared to healthy exposed [0.7 (0.6, 1.1); P = 0.003] and children with nTB-LRTI [0.2 (0.1, 0.6); P < 0.001). Receiver operating characteristic curves to detect TB disease compared to nTB-LRTI for NLR and NMLR had an area under the curve of 0.82 and 0.86, the sensitivity of 88% and 88%, and specificity of 71% and 76%, respectively., Conclusion: NLR and NMLR are promising, easy-to-obtain diagnostic biomarkers to differentiate children with TB disease from other lower respiratory tract infections. These results require validation in a larger study and in settings with high and low TB endemicity., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Low rates of postnatal retention in HIV care and viral suppression have been reported in women living with HIV (WLWH) despite viral suppression at delivery. At the same time, postpartum follow-up is of crucial importance in light of the increasing support offered in many resource-rich countries including Switzerland to WLWH choosing to breastfeed their infant, if optimal scenario criteria are met., Methods: We longitudinally investigated retention in HIV care, viral suppression, and infant follow-up in a prospective multicentre HIV cohort study of WLWH in the optimal scenario who had a live birth between January 2000 and December 2018. Risk factors for adverse outcomes in the first year postpartum were assessed using logistic and proportional hazard models., Findings: Overall, WLWH were retained in HIV care for at least six months after 94.2% of the deliveries (694/737). Late start of combination antiretroviral therapy (cART) during the third trimester was found to be the main risk factor for failure of retention in HIV care (crude odds ratio [OR] 3.91; 95% confidence interval [CI], 1.50-10.22; p = 0.005). Among mothers on cART until at least one year after delivery, 4.4% (26/591) experienced viral failure, with illicit drugs use being the most important risk factor (hazard ratio [HR], 13.2; 95% CI, 2.35-73.6; p = 0.003). The main risk factors for not following the recommendations regarding infant follow-up was maternal depression (OR, 3.52; 95% CI, 1.18-10.52; p = 0.024)., Interpretation: Although the results are reassuring, several modifiable risk factors for adverse postpartum outcome, such as late treatment initiation and depression, were identified. These factors should be addressed in HIV care of all WLWH, especially those opting to breastfeed in resource-rich countries., Funding: This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project 850 and by the SHCS research foundation., Competing Interests: BMT received payments from Effik AG, and Pierre-Favre Pharma for her participation to advisory boards. The institution of EB received honoraria from Gilead Sciences, ViiV Healthcare, MSD, Pfizer AG, Ely Lilly, and Astra Zeneca for his participation to advisory boards, and travel grants from Gilead Sciences, ViiV Healthcare, MSD, and Pfizer AG. DLB received honoraria from Gilead Sciences, ViiV Healthcare, and Merck for his participation to advisory boards and for lectures, payments from Abbvie for lectures, and travel grants from Gilead Sciences. RK received research grants from Gilead Sciences, the Swiss National Science Foundation (SNSF) and the National Institutes of Health (NIH) unrelated to this work. CP received honoraria from Effik AG for his participation to advisory boards. The authors have no other conflicts of interest to disclose., (© 2023 The Author(s).)

Introduction: Very preterm birth and attention-deficit hyperactivity disorder (ADHD) are associated with impairments in response inhibition that often persist beyond childhood. Athletes skilled in martial arts show a neurocognitive profile that is associated with an improved inhibition processing stream, suggesting that engagement in this kind of sport has the potential to reduce impairments in this cognitive function. We investigated the behavioral and neurocognitive effects of judo training on response inhibition in children born very preterm and children with ADHD by a combined analysis of two randomized controlled trials., Methods: In both the CHIPMANC ( n = 65) and JETPAC ( n = 63) studies, participants were randomly allocated to a waitlist or a 12-wk judo training program in a 1:1 ratio. At pretest and posttest, participants completed a Go/NoGo task, the Movement Assessment Battery for Children-2 and a physical work capacity test on a bicycle ergometer. During the cognitive task, event-related potentials (N2, P3a, P3b) were recorded via electroencephalography., Results: The effects of the judo training were moderated by the study group. In contrast to children with ADHD (JETPAC), judo training reduced the commission error rate on the Go/NoGo task and increased the P3a amplitude in children born very preterm (CHIPMANC). No treatment effects were found for N2, P3b and physical fitness outcomes., Conclusions: The neurodevelopmental condition influences the cognitive benefits of judo training. Whereas judo may be ineffective in children with ADHD, children born very preterm can expect improved response inhibition due to a more effective engagement of focal attention to resolve the task-related response conflict., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Background: The conventional gait model (CGM1) is extensively used for 3D clinical gait analysis. It uses lateral wand-mounted markers for the thigh and shank segments to avoid colinearity of the tracking markers. However, gait analysts may be tempted to use skin-mounted markers instead., Research Question: Does it matter if the lateral markers for the thigh and shank segments are mounted on wands or directly taped to the skin when using the CGM1?, Methods: Gait sessions from 147 and 73 patients equipped with wand-mounted and skin-mounted markers, respectively, were extracted from the database of a single clinical gait laboratory. The marker trajectories were reprocessed with the CGM1. The risk of marker colinearity was assessed from the planar angle constructed from the proximal joint center, the lateral joint marker and the lateral segmental marker (i.e. skin or wand). We assessed the effect of marker misplacement and soft-tissue artefact on kinematics., Results: The averaged planar angles calculated from static ranged from 10° to 30° and 7° to 21° for the skin-mounted thigh and shank markers respectively, while planar angles were always larger than 25° with wand-mounted markers. One cm misplacement of the thigh marker altered hip rotation by 10° if skin-mounted against 5° if wand-mounted. Soft tissue artefact led to 7.6° or 4.3° depending if it was skin- or wand-mounted, respectively., Significance: Our analysis showed moderate risk of collinearity, increased effect of STA, and larger potential effect of marker misplacement with the use of skin- rather than wand-mounted markers., Competing Interests: Conflict of interest statement We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We further confirm that any aspect of the work covered in this manuscript that has involved humans has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Estimates of the total cumulative exposure to antibiotics of children in low-resource settings, and the source of these treatments, are limited., Methods: We estimated the average number of antibiotic treatments children received in the first 5 years of life in 45 low- and middle-income countries (LMICs) using Demographic and Health Survey data. The 2-week point prevalence of fever, diarrhea, or cough and antibiotic treatment for these illnesses were estimated for ages 0-59 months and aggregated to estimate cumulative illness and antibiotic treatment for each country. We estimated treatment rates and contribution to total antibiotic use attributable to medical care, informal care, and self-medication., Results: Forty-five countries contributed 438 140 child-observations. The proportion of illness episodes treated with antibiotics ranged from 10% (95% confidence interval [CI], 9%-12%]) in Niger to 72% (95% CI, 69%-75%) in Jordan. A mean of 42.7% (95% CI, 42.1%-43.3%) of febrile and 32.9% of nonfebrile (95% CI, 32.4%-33.5%) illness episodes received antibiotics. In their first 5 years, we estimate children received 18.5 antibiotic treatments on average (interquartile range [IQR], 11.6-24.6) in LMICs. Cumulative antibiotic exposure ranged from 3.7 treatments in Niger (95% CI, 2.8%-4.6%) to 38.6 treatments in the Democratic Republic of Congo (95% CI, 34.7%-42.4%). A median of 9.0% of antibiotic treatments was attributable to informal care (IQR, 5.9%-21.2%), and 16.9% to self-medication (IQR, 9.5%-26.2%)., Conclusions: Childhood antibiotic exposure is high in some LMICs, with considerable variability. While access to antibiotics for children is still not universal, important opportunities for reducing excess use also exist, particularly with respect to the informal care sector and self-medication., Competing Interests: Potential conflicts of interest. J. B. reports contracts or grants with the European and Developing Countries Clinical Trials Partnership (institution, Impact of duration of antibiotic therapy and of oral step-down to amoxicillin or co-amoxiclav on effectiveness, safety and selection of antimicrobial resistance in severe and very severe childhood community-acquired pneumonia (CAP): a randomised controlled trial (PediCAP Trial), project number, RIA2017MC-2023), Horizon 2020 (institution, Establishing Innovative Optimal Approaches for Infection Prevention of Resistant Bacteria in NICUs by Integrating Research, Implementation Science and Surveillance in a Sustainable Global Platform (Neo-IPC), grant number 965328), Swiss National Science Foundation (institution, A randomised controlled trial of adjunct corticosteroid therapy in hospitalised children with community acquired pneumonia (KIDS-STEP), grant number 173532), National Institute for Health Research (institution, project number 13/88/11), and Wellcome Trust (institution, Antimicrobial Resistance, Prescribing, and Consumption Data to Inform Country Antibiotic Guidance and Local Action [ADILA], award number 13573-10); consulting fees paid to institution from Pfizer and Sandoz; participation on data and safety monitoring boards or advisory boards (Phase Ib, Placebo-controlled Randomized Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of INO-4201 Followed by Electroporation as a Booster Vaccination in Healthy Volunteers Who Have Previously Received the VSV-ZEBOV Vaccine (Boost-EBOV) Chair, unfunded; Avenir trial, member, expenses; Lakana trial, member, unfunded) and Trial Steering Committee (Finding the right dose of posaconazole for children & young people with Cystic Fibrosis and Aspergillus infection [cASPerCF] Chair, unfunded); and unpaid board membership for SwissPedNet. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and study aims  The ability to perform endoscopy procedures safely and effectively is a key aspect of quality clinical care in Pediatric Gastroenterology, Hepatology and Nutrition (PGHN). The aim of this survey, which was part of a global survey on PGHN training in Europe, was to assess endoscopy training opportunities provided across Europe. Methods  Responses to standardized questions related to endoscopy training were collected from training centers across Europe through the presidents/representatives of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition National Societies from June 2016 to December 2019. Results  A total of 100 training centers from 19 countries participated in the survey. In 57 centers, the endoscopy suit was attached to the PGHN center, while in 23, pediatric endoscopies were performed in adult endoscopy facilities. Ninety percent of centers reported the availability of specialized endoscopy nurses and 96 % of pediatric anesthetists. Pediatric endoscopies were performed by PGHN specialists in 55 centers, while 31 centers reported the involvement of an adult endoscopist and 14 of a pediatric surgeon. Dividing the number of procedures performed at the training center by the number of trainees, ≤ 20 upper, lower, or therapeutic endoscopies per trainee per year were reported by 0 %, 23 %, and 56 % of centers, respectively, whereas ≤ 5 wireless capsule endoscopies per trainee per year by 75 %. Only one country (United Kingdom) required separate certification of competency in endoscopy. Conclusions  Differences and deficiencies in infrastructure, staffing, and procedural volume, as well as in endoscopy competency assessment and certification, were identified among European PGHN training centers limiting training opportunities in pediatric endoscopy., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Children with spastic cerebral palsy gradually lose muscle extensibility but the interplay between the muscular and neurological components of the condition is unclear especially in the pathophysiology of equinovalgus gait., Aim: This study aimed to quantify the muscular and neurological disorders in young children with unilateral cerebral palsy, and to investigate the role of the peroneus longus (PL) in equinovalgus gait., Design, Setting and Population: This was an observational study with prospective assessments of 31 children (median age: 2.9 years, range: 2-6) from outpatient clinic in a tertiary teaching hospital., Methods: Clinical measures of plantar flexor extensibility (X V1 ), stretch response (X V3 ), and active ankle dorsiflexion angle (X A ) were obtained as well as walking velocity and electromyography of tibialis anterior (TA), gastrocnemius medialis (GM) and PL during walking., Results: We found reduced extensibility of the triceps surae on the paretic side (effect size r = 0.73, p < 0.001 for soleus and r = 0.68, p < 0.001 for gastrocnemius) and a correlation between reduced triceps surae extensibility and earlier stretch response (ρ = 0.5, p = 0.004). During the swing phase, there was major co-contraction between TA and GM/PL, and significantly larger activation of PL compared to GM (r = 0.46, p = 0.011). Both GM and PL activation decreased with age., Conclusions: Our results suggest gradual deterioration of the muscular disorder and a link between the muscular and neurological disorders, although plantar flexor co-contraction improved with age. The PL was more activated than the GM and may be considered an intervention target to treat equinovalgus gait., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Chronic pain is a frequent complaint in children and adolescents, with great international variation in prevalence. Paediatricians are usually the first-line contact for pain problems in children and might refer patients to other specialists or pain clinics where available. Prevalence estimates of paediatric chronic pain and paediatricians' care experiences in Switzerland are currently lacking., Objectives: The aim of this study was to assess the prevalence of paediatric chronic pain in Swiss paediatrician practices and paediatricians' professional experience and confidence with, and care provision for patients with paediatric chronic pain., Methods: Data were collected in 2019 using a cross-sectional online questionnaire among Swiss paediatricians. Ordinary least square regression analyses and Monte Carlo simulations were applied to estimate the prevalence rate of paediatric chronic pain. Explorative multivariate logistic regression analyses investigated whether sociodemographic and professional factors were associated with paediatricians' confidence in treating and experience with paediatric chronic pain., Results: We included 337 paediatricians in our anonymised analyses. The prevalence rate of paediatric chronic pain in our sample was estimated to be between 2.54% and 3.89%. Twenty percent of paediatricians reported feeling confident in treating paediatric chronic pain, 77.2% had referred patients with paediatric chronic pain to another specialist and more than half had at least some experience with paediatric chronic pain. Experience and confidence with treating paediatric chronic pain were associated with male gender., Conclusion: Our study is the first to estimate the prevalence of paediatric chronic pain by means of a sample of Swiss paediatricians. The prevalence rate was considerably lower than other estimates. Given the lack of training and confidence with treating paediatric chronic pain reported by paediatricians, absence of awareness and resulting under-diagnosis is possible.

Objectives/background: Disease-related malnutrition is common in patients with chronic diseases and has detrimental effects, therefore, skills in nutrition care are essential core competencies for paediatric digestive medicine. The aim of this survey, conducted as part of a global survey of paediatric gastroenterology, hepatology and nutrition (PGHN) training in Europe, was to assess nutrition care-related infrastructure, staff, and patient volumes in European PGHN training centres., Methods: Standardized questionnaires related to clinical nutrition (CN) care were completed by representatives of European PGHN training centres between June 2016 and December 2019., Results: One hundred training centres from 17 European countries, Turkey, and Israel participated in the survey. Dedicated CN clinics exist in 66% of the centres, with fulltime and part-time CN specialists in 66% and 42%, respectively. Home tube feeding (HTF) andhome parenteral nutrition (HPN) programmes are in place in 95% and 77% of centres, respectively. Twenty-four percent of centres do not have a dedicated dietitian and 55% do not have a dedicated pharmacist attached to the training centre. Even the largest centres with >5000 outpatients reported that 25% and 50%, respectively do not have a dedicated dietitian or pharmacist. Low patient numbers on HTF and HPN of <5 annually are reported by 13% and 43% of centres, respectively., Conclusions: The survey shows clear differences and deficits in Clinical Nutrition training infrastructure, including staff and patient volumes, in European PGHN training centres, leading to large differences and limitations in training opportunities in Clinical Nutrition., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: This survey evaluated the effects of the recognition of pediatric gastroenterology, hepatology and nutrition (PGHN) on European PGHN training centers., Method: Standardized questionnaires were collected from training centers via the presidents/representatives of the National Societies Network of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, from June 2016 to December 2019., Results: A total of 100 training centers from 19 countries participated in the survey: 55 from 12 countries where PGHN is formally recognized (Group 1) and 45 from 7 countries where it is not (Group 2). Training centers in Group 2 were less likely to have an integrated endoscopy suite, a written training curriculum and a training lead (P=0.059, P<0.001 and P=0.012, respectively). Trainees in Group 2 were less likely to be exposed to an adequate number of diagnostic endoscopies, while no differences were found in relation to liver biopsies. Half of the training centers in both Groups do not have dedicated beds for PGHN patients, while in 64% and 58%, respectively, trainees do not participate in on-call programs for PGHN emergencies. Research training is mandatory in 26% of the centers. The duration of training, as well as the assessment and accreditation policies, vary between countries., Conclusions: This study has revealed significant discrepancies and gaps in infrastructure and training programs, training leadership, and assessment of training and certification across European training centers in PGHN. Strategies to support the recognition of PGHN and to standardize and improve training conditions should be developed and implemented.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic&#95;AG-6496.pdf., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Pediatric gastrointestinal motility disorders present significant challenges for diagnosis and management, emphasizing the need for appropriate training in Pediatric Neurogastroenterology and Motility (PNGM). The aim of this survey, part of a comprehensive survey on training in pediatric gastroenterology, hepatology and nutrition, was to evaluate training related to PNGM across European training centers., Method: Standardized questionnaires were collected from training centers through the National Societies Network of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), from June 2016 to December 2019., Results: In total, 100 training centers from 19 countries participated in the survey. Dedicated PNGM clinics were available in 22 centers; pH-monitoring in 60; pH/impedance in 66; standard manometry in 37; and high-resolution manometry in 33. If all motility studies were performed partially or fully by the trainees, the median (range) annual numbers/per trainee were as follows: pH-monitoring 30 (1-500); pH/impedance 17 (1-131); standard manometries 10 (1-150); and high-resolution manometries 8 (1-75). The motility assessment was performed by pediatric gastroenterologists (43 centers); adult gastroenterologists (10 centers); pediatric surgeons (5 centers); and both pediatric gastroenterologists and pediatric surgeons (9 centers). Annual numbers ≤10 for pH-monitoring, pH/impedance, standard manometries and high-resolution manometries were reported by 7 (12%), 15 (23%), 11 (30%) and 14 (42%) centers, respectively., Conclusions: Significant differences exist in PNGM-related infrastructure, staff and procedural volumes at training centers across Europe. ESPGHAN and the National Societies should take initiatives to ensure the acquisition of competence in PNGM-related knowledge and skills, and develop strategies for assessment and accreditation.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic-AG6486.pdf., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background and Objectives: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder of the nervous system that classically presents with a combination of characteristic eye movement disorder and myoclonus, in addition to ataxia, irritability, and sleep disturbance. There is good evidence that OMAS is an immune-mediated condition that may be paraneoplastic in the context of neuroblastoma. This syndrome may be associated with long-term cognitive impairment, yet it remains unclear how this is influenced by disease course and treatment. Treatment is largely predicated on immune suppression, but there is limited evidence to indicate an optimal regimen., Methods: Following an international multiprofessional workshop in 2004, a body of clinicians and scientists comprising the International OMS Study group continued to meet biennially in a joint professionals and family workshop focusing on pediatric OMAS. Seventeen years after publication of the first report, a writing group was convened to provide a clinical update on the definitions and clinical presentation of OMAS, biomarkers and the role of investigations in a child presenting with OMAS, treatment and management strategies including identification and support of long-term sequelae., Results: The clinical criteria for diagnosis were reviewed, with a proposed approach to laboratory and radiologic investigation of a child presenting with possible OMAS. The evidence for an upfront vs escalating treatment regimen was reviewed, and a treatment algorithm proposed to recognize both these approaches. Importantly, recommendations on monitoring of immunotherapy response and longer-term follow-up based on an expert consensus are provided., Discussion: OMAS is a rare neurologic condition that can be associated with poor cognitive outcomes. This report proposes an approach to investigation and treatment of children presenting with OMAS, based on expert international opinion recognizing the limited data available., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: The widely recognized burden of liver diseases makes training in pediatric hepatology (PH) imperative. The aim of this survey, which was part of a global survey on training in pediatric gastroenterology, hepatology and nutrition (PGHN) across Europe, was to assess the PH and liver transplantation (LT) infrastructure, staff and training programs in PGHN training centers., Method: Standardized questionnaires were collected from training centers via the presidents/representatives of the National Societies Network of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) from June 2016 to December 2019., Results: A total of 100 PGHN training centers participated in the survey (14/100 were national referral centers in PH and/or LT). Dedicated PH clinics were available in 75%, but LT clinics in only 11%. Dedicated beds for PGHN inpatients were available in 47/95 (49%) centers. Full-time or part-time specialists for PH care were available in 31/45 (69%) and 11/36 (31%) centers, respectively. Liver biopsies (LB) were performed in 93% of centers by: a PGHN specialist (35%); an interventional radiologist (26%); a pediatric surgeon (4%); or a combination of them (35%). Dividing the annual number of LBs in the centers performing LBs by the number of trainees gave a median (range) of 10 (1-125) per trainee. Transient elastography was available in 60/92 (65%) of centers., Conclusions: The survey highlighted the differences and shortcomings in PH training across Europe. ESPGHAN should take initiatives together with National Societies to ensure the acquisition of PH knowledge and skills according to the ESPGHAN curriculum.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic-Hepatology-training-paper.pdf., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: About half of all children with rheumatic diseases need continuous medical care during adolescence and adulthood. A good transition into adult rheumatology is essential. Guidelines for a structured transition process have therefore been recommended by the European League Against Rheumatism (EULAR) and the Paediatric Rheumatology European Society (PReS). However, implementation of these guidelines requires resources often not available in a busy clinical practice., Aims: To assess the current practice of transitional care in Switzerland in relation to EULAR/PReS recommendations and to describe gaps and challenges in following the recommendations., Methods: All paediatric Swiss rheumatology centres and their collaborating adult centres offering a transition service to adult care were invited to participate in this survey. The responsible paediatric and adult rheumatologist of each centre was interviewed separately using a structured manual addressing the EULAR/PReS transitional care recommendations., Results: All 10 paediatric and 9 out of 10 adult rheumatologists agreed to participate. Centres varied in the number of patients in transition, from n = 0 to n = 111. The following EULAR/PReS recommendations were implemented and applied in most centres: continuity in the healthcare team, consultations focused on adolescents and young adults, joint consultations between the paediatric and adult rheumatologist, and access to the EULAR website. Only rarely did a centre have a written transition policy or evaluate their transitional care programme. The vast majority of the interviewees had no specific training in adolescent health. Most centres rated their transitional care performance as very good., Conclusion: Transition in Switzerland is not uniform and consequently the implementation of the EULAR/PReS recommendations is variable in Swiss rheumatology centres. Skills of healthcare professionals, continuity between clinical settings, size of the centres, and hospital focus on the needs of adolescents and young adults may represent key predictors of successful transitional care for patients with chronic rheumatic diseases. Future studies should examine these variables.

Transfusions are the mainstay of supportive therapy in patients with aplastic anemia (AA) and may lead to anti- HLA alloimmunization, thereby also increasing the risk for donor-specific antibodies in the setting of HLA-mismatched transplantation. Historically, AA patients were thought to be at particularly high risk for HLA alloimmunization. In past decades, blood product manufacturing (leukoreduction) and HLA antibody testing have improved significantly by single antigen bead (SAB) technology. It is currently unknown how those developments have impacted HLA alloimmunization and treatment outcome in patients with AA. We retrospectively investigated 54 AA patients treated by immunosuppressive therapy or allogeneic hematopoietic cell transplantation after the introduction of the SAB assay at our center. We compared the HLA antibody results to a historical AA cohort (n = 26), treated before introduction of leukoreduced blood products from 1975 to 1995. HLA alloimmunization was detected in 43 of 54 (80%) recently treated patients. Past pregnancy, female gender, disease severity, age, and a history of other transfusions were significantly associated with a larger number or higher intensity (mean fluorescence intensity) of HLA antibodies. Treatment outcome including bleeding episodes, response to treatment, engraftment, graft-versus-host disease, and overall survival was not associated with HLA alloimmunization. In the historical cohort a significantly higher number of HLA antibodies (P < .01) with a higher mean fluorescent intensity (P < .01) was observed. HLA alloimmunization remains frequent in AA tested by current techniques, but it has significantly decreased since prior decades and does not affect treatment outcome. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)