Dayton Children's Hospital

Few approved treatments exist for children with Crohn's disease (CD). The REALITI study retrospectively assessed the effectiveness and safety of ustekinumab in real-world clinical settings for children with CD. Data were collected from the prospective ImproveCareNow (ICN) registry for pediatric patients (≥ 2 to <18 years old) and young adult patients (≥ 18 to <26 years old), regardless of baseline CD severity. Additional analyses were conducted for a subset of patients who had moderately-to-severely active CD (short pediatric CD activity index [sPCDAI] ≥30). Key Week-52 endpoints included clinical remission (sPCDAI ≤10) and corticosteroid-free (CF) clinical remission. Safety events of interest were assessed at Week 52. Overall, 479 patients with CD were treated with ustekinumab, 348 pediatric patients and 131 young adults; most were biologic-exposed (pediatric, 98.9%; young adult, 95.4%). At Week 52 (observed case; excluding patients without Week 52 data), clinical remission was achieved by 47.3% (125/264) of pediatric patients and 44.8% (39/87) of young adults, and CF clinical remission by 41.3% (109/264) and 39.1% (34/87), respectively. At Week 52 (observed case), among patients with moderately-to-severely active CD, clinical remission was achieved by 36.9% (41/111) of pediatric patients and 34.3% (12/35) of young adults, and CF clinical remission by 31.5% (35/111) and 28.6% (10/35), respectively. Ustekinumab was well tolerated, with no new safety signals identified. In the REALITI study of real-world data from the ICN registry, the effectiveness and safety of ustekinumab treatment through 52 weeks were similar in pediatric and young adult patients with CD. ClinicalTrials.gov identifier: NCT05242458; https://clinicaltrials.gov/study/NCT05242458.

This open-label phase 1/2 clinical study uses a novel recombinant vector, rAAV-Olig001, with selective tropism for oligodendrocytes, to deliver gene therapy for Canavan disease (CD), a rare leukodystrophy characterized by defective aspartoacylase and elevated N-acetyl-aspartic acid (NAA) concentrations. A total of 8 participants received intracranial doses of 3.7 × 1013 vector genomes (vg) of rAAV-Olig001-ASPA (MYR-101), with an interim analysis at 12 months. The primary objective was to assess the safety of intracranial dosing of MYR-101 in children with typical CD. Efficacy measures included Mullen Scales of Early Learning (MSEL), Gross Motor Function Measure (GMFM) and analysis of NAA, myelination, white matter and extracellular water content in the brain. The participants were White; 5 (62.5%) were male. Of the participants, 7 (87.5%) experienced ≥1 serious adverse event, none of which were considered MYR-101 related. All participants experienced ≥1 adverse event. All adverse events and serious adverse events resolved fully. Treatment reduced NAA concentrations in cerebrospinal fluid (P = 0.0008), increased myelination (P = 0.0137) and improved MSEL developmental outcomes (P = 0.0171). Thus, interim results suggest that gene therapy with MYR-101 is well tolerated and shows early effects in CD. While these findings are preliminary, reductions in NAA concentrations indicate ASPA expression and increases in myelination and imply successful targeting of oligodendrocytes. These results may support the development of similar gene therapy strategies for other demyelinating and metabolic brain disorders. ClinicalTrials.gov registration: NCT04833907 .

Craniopagus deformity is a rare congenital anomaly occurring in 1 of 1 700 000 live births and represents 2%-6% of all conjoined twins. Staged surgical separation, with a focus on disconnecting shared venous anatomy, has become the mainstay of treatment for most patients in the modern era. The aim of this report was to classify the shared venous anatomy of these twins and determine implications on surgical separation. Cases from Dr James Goodrich's library were classified and rendered according to their venous anatomy into virtual models. Data from 16 sets of twins were studied. Two were O'Connell type I, 4 were type II, and 10 were type III twins. Two patterns of venous anatomical communication and sharing emerged with twins showing a more acute angle of rotation demonstrated a common circumferential sinus pattern, and twins with a greater rotational angle (type II) demonstrated a helical sinus orientation of their sagittal sinuses. This is the largest anatomical study of craniopagus twins, focused on shared venous anatomy. A better understanding of the anatomical patterns of these patients may result in safer surgical disconnection in the future. We observed that as axial rotation approaches 90°, the organization around a circumferential sinus slowly transitions into a continuous helical sinus, connecting the anterior superior sagittal sinus of each twin. In the future, as our understanding of the vascular anatomy matures, a vessel-specific plan for separation within these two patterns, taking into account blood flow and perfusion, will be possible before ever stepping foot into the operating room.

Background: This narrative review considers implications for the increasing prevalence of diagnosed autism spectrum disorder (ASD) in clinical settings. Clinicians and researchers can be guided through an improved understanding of associated factors increasing the risk for suicidality and suicide in individuals manifesting symptoms of ASD and high ASD traits (ASDTs). Methods: A systematic literature review is supplemented with reverse citations to ensure updated information. By title and abstract, 456 articles were identified. Of those, 50 were used initially, and 15 were later added manually or through reverse citations. Results: Higher suicidal thoughts and behaviors (STBs) and suicide rates exist across the age spectrum in individuals with ASD/high ASDTs compared to matched comparison groups from the general population. Associated, poorly understood factors include comorbid psychiatric conditions and suicide risk factors that overlap with ASD symptoms. Increased risk of STB in higher functioning ASD is emphasized. Interpersonal conflict and depression are significant risk factors, as are comorbid borderline personality, bipolar disorder, anxiety, and obsessive-compulsive disorders. Conclusion: Multiple diagnostic challenges are considered that affect appropriate care to address the increasing incidence of STB and suicide in ASD. This overview integrates extant knowledge for case formulation and treatment planning. It provides support for more focused research to improve ASD-related screening instruments and to address the unique features of ASD-related psychopathology. Improved training is needed for clinicians in screening and preventive efforts and to enhance their competence and comfort for addressing and treating STBs in those with ASDTs and ASD. (N=248).

Abstract Introduction Hypoglossal nerve stimulation (HGNS) has emerged as an alternative treatment for obstructive sleep apnea (OSA) patients in patients who cannot tolerate continuous positive airway pressure therapy. While clinical trials of HGNS have demonstrated reductions in the Apnea-Hypopnea Index (AHI), treatment efficacy remains variable. Current assessment methods like polysomnography and drug-induced sleep endoscopy have limitations in quantifying the complex interaction between upper airway anatomy and airflow. Novel methods are needed to understand how HGNS treats OSA by counterbalancing inspiratory upper airway collapse. Methods Three male participants underwent four-dimensional computed tomography (4DCT) scanning during natural non-REM stage 2 (N2) sleep, both with and without HGNS. The 4DCT images had an in-plane resolution of 0.445x0.445 mm, slice thickness of 0.25 mm, and field of view of 210x210x160 mm, extending from the superior nasal cavity to the glottis. Simultaneous electroencephalographic monitoring and airflow measurements were recorded. Computational fluid dynamics (CFD) simulations were performed using anatomical data and airway dynamics from 4DCT imaging combined with measured airflow patterns. We assessed: 1) changes in airway cross-sectional area (CSA), 2) the mechanical work performed by muscles and air pressure in airway dilation and collapse, and 3) airway flow resistance. Results HGNS led to substantial increases in neuromuscular work for airway dilation (reaching 490%) and airway CSA (up to 300%). The most pronounced effects were observed in the oropharyngeal region, while responses in the nasopharynx and hypopharynx showed inter-subject variability. All participants exhibited increased minute ventilation (15-36%), alongside marked reductions in airway resistance (73-97%). Conclusion The quantitative parameters established in this study may provide insights into the variable therapeutic responses to HGNS in OSA treatment. These analytical methods hold potential for identifying non-responders, understanding treatment limitations, and optimizing device settings in clinical practice. This novel approach combines dynamic imaging with CFD simulation to reveal the underlying balance between neuromuscular control and air pressure, offering additional insights of HGNS efficacy in addition to traditional methods. Support (if any)

To compare the perceptions about the future of telehealth utilization in a cohort of pediatric epilepsy providers.

To review risk factors for the development of medical device-related and immobility-related pressure injuries in hospitalized pediatric patients. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. After participating in this educational activity, the participant will be better able to:1. Describe trends in pressure injuries (PIs) for hospitalized pediatric patients as summarized in current literature.2. Identify risk factors predictive of medical device-related and immobility-related PIs in hospitalized pediatric patients.3. Summarize the methodology used to understand risk factors for developing PIs in the hospitalized pediatric patient population.