Immunosuppression in two cases of indeterminate hepatitis.

Background: Pediatric acute liver failure (PALF) is a potentially lethal and rapidly progressive clinical syndrome, with a large proportion of cases remaining indeterminate despite extensive investigations. Patients and Results: In this case report, we describe two male children with indeterminate PALF and a family history of autoimmune disease, both of whom were lymphopenic with necrosis, inflammation, and lymphocytic infiltrates on their liver biopsies. One of these patients subsequently developed hepatitis-associated aplastic anemia. Notably, in addition to receiving standard liver failure care, both patients were successfully treated off-label with anti-thymocyte globulin (ATG), as well as a more prolonged course of cyclosporine and corticosteroids. Conclusions: The fact that these medications all suppress T lymphocytes further supports the theory that T-cell activation plays a prominent role in the pathophysiology of indeterminate hepatitis. Further research should examine the short-term and long-term effects of ATG in this population, as well as the necessary duration of treatment with immune-suppressing agents.

A Prospective Study of Parental Experience with Thickening Feeds for Children with Oropharyngeal Dysphagia and Gastroesophageal Reflux.

Thickening is efficacious and commonly recommended for oropharyngeal dysphagia and gastroesophageal reflux. Little is known about parental experience with this practice. Results of this cross-sectional questionnaire study suggest attitudes are positive, but parents frequently adjust recipes/nipple sizes, which might increase aspiration risk. Clinical follow-up is essential to ensure safe feeding.

Characterization of Eosinophilic Esophagitis in Infants and Toddlers.

OBJECTIVES: The objective of this study is to determine demographic and clinical characteristics of infants and toddlers <2 years with eosinophilic esophagitis (EoE) and to assess treatment response in this rarely studied pediatric age group. METHODS: Retrospective study of children <2 years diagnosed with EoE at a single center from 2016 to 2018. EoE was defined by ≥15 eosinophils per high power field (eos/hpf) on at least 1 esophageal biopsy. Demographics, symptoms, and endoscopic findings were collected via chart review. EoE treatment [proton pump inhibitor (PPI), swallowed steroids, dietary restriction, or a combination] and treatment responses on all follow-up endoscopies were reviewed, with remission defined as <15 eos/hpf. RESULTS: Forty-two children ages 1.3 ± 0.4 years underwent 3.8 ± 2.3 endoscopies over 3.6 ± 1.7 years of follow-up. Thirty-six children (86%) were male, and comorbidities included atopy (86%), reflux (74%), and a history of cow's milk protein allergy (40%). Common symptoms were feeding difficulties in 67% of patients (with gagging or coughing with feeding in 60% and difficulty with progression to pureed or solid foods in 43%), vomiting (57%), and coughing/wheezing (52%). Of the 37 patients with follow-up endoscopies, 25 (68%) had histologic remission. There was an effect of therapy type on histologic response ( P = 0.004) with the best responses seen on combinations of diet/steroids or diet/PPI and the worst response seen on PPIs alone. All patients showed improvement in ≥1 symptom at the time of first follow-up endoscopy. CONCLUSIONS: EoE should be considered in young children with feeding difficulties, vomiting, or respiratory symptoms. All patients improved clinically with standard medical or dietary interventions, however there is dissociation between clinical and histologic response with only 2 of 3 patients achieving histologic remission.

Uncertain threat is associated with greater impulsive actions and neural dissimilarity to Black versus White faces.

Race is a social construct that contributes to group membership and heightens emotional arousal in intergroup contexts. Little is known about how emotional arousal, specifically uncertain threat, influences behavior and brain processes in response to race information. We investigated the effects of experimentally manipulated uncertain threat on impulsive actions to Black versus White faces in a community sample (n = 106) of Black and White adults. While undergoing fMRI, participants performed an emotional go/no-go task under three conditions of uncertainty: 1) anticipation of an uncertain threat (i.e., unpredictable loud aversive sound); 2) anticipation of an uncertain reward (i.e., unpredictable receipt of money); and 3) no anticipation of an uncertain event. Representational similarity analysis was used to examine the neural representations of race information across functional brain networks between conditions of uncertainty. Participants-regardless of their own race-showed greater impulsivity and neural dissimilarity in response to Black versus White faces across all functional brain networks in conditions of uncertain threat relative to other conditions. This pattern of greater neural dissimilarity under threat was enhanced in individuals with high implicit racial bias. Our results illustrate the distinct and important influence of uncertain threat on global differentiation in how race information is represented in the brain, which may contribute to racially biased behavior.

Gastrointestinal factors associated with risk of bronchiectasis in children.

OBJECTIVE: To evaluate gastrointestinal (GI) risk factors for bronchiectasis in children. We hypothesized that upper GI tract dysmotility would be associated with increased risk of bronchiectasis. STUDY DESIGN: Subjects in this retrospective cohort study included those evaluated for persistent pulmonary symptoms in the Aerodigestive Center at Boston Children's Hospital who underwent chest computed tomography (CT) between 2002 and 2019. To determine gastrointestinal predictors of bronchiectasis, baseline characteristics, comorbidities, enteral tube status, medications received, gastroesophageal reflux burden, adequacy of swallow function, esophageal dysmotility, gastric dysmotility, and neutrophil count on bronchoalveolar lavage (BAL) were compared between patients with and without bronchiectasis. Proportions were compared with Fisher's exact test and binary logistic regression with stepwise selection was used for multivariate analysis. ROC analyses were utilized to compare BAL neutrophils and bronchiectasis. RESULTS: Of 192 subjects, 24% were found to have evidence of bronchiectasis on chest CT at age 7.9 ± 0.5 years. Enteral tubes (OR 5.77, 95% CI 2.25-14.83, p < 0.001) and increased BAL neutrophil count (OR 5.79, 95% CI 1.87-17.94, p = 0.002) were associated with increased risk while neurologic comorbidities were associated with decreased risk (OR 0.24, 95% CI 0.09-0.66, p = 0.006). Gastroesophageal reflux was not found to be a significant risk factor. Neutrophil counts >10% had 72% sensitivity and 60% specificity for identifying bronchiectasis. CONCLUSIONS: Enteral tubes were associated with significantly increased risk of bronchiectasis but gastroesophageal reflux was not. Providers should consider obtaining chest CT to evaluate for bronchiectasis in children found to have unexplained elevated BAL neutrophil count.

Airway Impedance: A Novel Diagnostic Tool to Predict Extraesophageal Airway Inflammation.

OBJECTIVE: To validate a novel biomarker, airway impedance for extraesophageal disease. STUDY DESIGN: We prospectively recruited patients with respiratory symptoms undergoing combined endoscopy and direct laryngoscopy for the evaluation of symptoms. The direct laryngoscopy was performed and videotaped for blinded scoring by 3 otolaryngologists and an impedance catheter was placed onto the posterior larynx to obtain measurements. Following this, an endoscopy was performed and impedance measurements and biopsies were taken at 3 esophageal heights. Impedance values were compared within and between patients. RESULTS: Eighty-eight patients were recruited, of which 73 had complete airway and endoscopic exams. There was no significant correlation between airway impedance values and mean reflux finding scores (r2 = 0.45, P = .07). There was no significant positive correlation between airway impedance and esophageal impedance values (r2 = 0.097-0.138, P > .2). Patients taking proton pump inhibitors had significantly lower mean airway impedance values (706 ± 450 Ω) than patients not taking them (1069 ± 809 Ω, P = .06). Patients who had evidence of aspiration on video fluoroscopic swallow studies had lower airway impedance (871 ± 615 Ω) than patients without aspiration (1247 ± 360 Ω, P = .008). Inhaled steroids did not impact airway impedance levels (P = .7). CONCLUSIONS: Airway impedance may be an important diagnostic tool to diagnose gastroesophageal reflux or aspiration, eliminating the subjectivity of airway appearance alone.

Real-World Exploration Increases Across Adolescence and Relates to Affect, Risk Taking, and Social Connectivity.

Cross-species research suggests that exploratory behaviors increase during adolescence and relate to the social, affective, and risky behaviors characteristic of this developmental stage. However, how these typical adolescent behaviors manifest and relate in real-world settings remains unclear. Using geolocation tracking to quantify exploration-variability in daily movement patterns-over a 3-month period in 58 adolescents and adults (ages 13-27) in New York City, we investigated whether daily exploration varied with age and whether exploration related to social connectivity, risk taking, and momentary positive affect. In our cross-sectional sample, we found an association between daily exploration and age, with individuals near the transition to legal adulthood exhibiting the highest exploration levels. Days of higher exploration were associated with greater positive affect irrespective of age. Higher mean exploration was associated with greater social connectivity in all participants but was linked to higher risk taking selectively among adolescents. Our results highlight the interplay of exploration and socioemotional behaviors across development and suggest that societal norms may modulate their expression in naturalistic contexts.

Reward-motivated memories influence new learning across development.

Previously rewarding experiences can influence choices in new situations. Past work has demonstrated that existing reward associations can either help or hinder future behaviors and that there is substantial individual variability in the transfer of value across contexts. Developmental changes in reward sensitivity may also modulate the impact of prior reward associations on later goal-directed behavior. The current study aimed to characterize how reward associations formed in the past affected learning in the present from childhood to adulthood. Participants completed a reinforcement learning paradigm using high- and low-reward stimuli from a task completed 24 h earlier, as well as novel stimuli, as choice options. We found that prior high-reward associations impeded learning across all ages. We then assessed how individual differences in the prioritization of high- versus low-reward associations in memory impacted new learning. Greater high-reward memory prioritization was associated with worse learning performance for previously high-reward relative to low-reward stimuli across age. Adolescents also showed impeded early learning regardless of individual differences in high-reward memory prioritization. Detrimental effects of previous reward on choice behavior did not persist beyond learning. These findings indicate that prior reward associations proactively interfere with future learning from childhood to adulthood and that individual differences in reward-related memory prioritization influence new learning across age.

Adolescent-specific memory effects: evidence from working memory, immediate and long-term recognition memory performance in 8-30 yr olds.

Working memory and recognition memory develop across adolescence, but the relationship between them is not fully understood. We investigated associations between n-back task performance and subsequent recognition memory in a community sample (8-30 yr, n = 150) using tasks from the Adolescent Brain Cognitive Development Study (ABCD Study) to cross-sectionally assess memory in an age range that will be sampled longitudinally. We added a 24-h delay condition to assess long-term recognition. Overall working memory, immediate and long-term recognition performance peaked in adolescence. Age effects in recognition memory varied by items (old targets, old distractors, and new items) and delay (0 and 24 h). For immediate recognition, accuracy was higher for targets and new items than for distractors, with accuracy for targets peaking in adulthood and accuracy for new items peaking during adolescence. For long-term recognition, adolescents' accuracy was higher for targets than distractors, while adults showed similarly high accuracy for targets and distractors and children showed low accuracy for both. This pattern appeared to be specific to recognition of items from the high working memory load condition. The results suggest that working memory may facilitate long-term recognition of task-relevant over irrelevant items and may benefit the detection of new information during adolescence.

Reward Enhances Memory via Age-Varying Online and Offline Neural Mechanisms across Development.

Reward motivation enhances memory through interactions between mesolimbic, hippocampal, and cortical systems, both during and after encoding. Developmental changes in these distributed neural circuits may lead to age-related differences in reward-motivated memory and the underlying neural mechanisms. Converging evidence from cross-species studies suggests that subcortical dopamine signaling is increased during adolescence, which may lead to stronger memory representations of rewarding, relative to mundane, events and changes in the contributions of underlying subcortical and cortical brain mechanisms across age. Here, we used fMRI to examine how reward motivation influences the "online" encoding and "offline" postencoding brain mechanisms that support long-term associative memory from childhood to adulthood in human participants of both sexes. We found that reward motivation led to both age-invariant enhancements and nonlinear age-related differences in associative memory after 24 h. Furthermore, reward-related memory benefits were linked to age-varying neural mechanisms. During encoding, interactions between the prefrontal cortex (PFC) and ventral tegmental area (VTA) were associated with better high-reward memory to a greater degree with increasing age. Preencoding to postencoding changes in functional connectivity between the anterior hippocampus and VTA were also associated with better high-reward memory, but more so at younger ages. Our findings suggest that there may be developmental differences in the contributions of offline subcortical and online cortical brain mechanisms supporting reward-motivated memory.SIGNIFICANCE STATEMENT A substantial body of research has examined the neural mechanisms through which reward influences memory formation in adults. However, despite extensive evidence that both reward processing and associative memory undergo dynamic change across development, few studies have examined age-related changes in these processes. We found both age-invariant and nonlinear age-related differences in reward-motivated memory. Moreover, our findings point to developmental differences in the processes through which reward modulates the prioritization of information in long-term memory, with greater early reliance on offline subcortical consolidation mechanisms and increased contribution of systems-level online encoding circuitry with increasing age. These results highlight dynamic developmental changes in the cognitive and neural mechanisms through which motivationally salient information is prioritized in memory from childhood to adulthood.

Candida albicans evades NK cell elimination via binding of Agglutinin-Like Sequence proteins to the checkpoint receptor TIGIT.

Candida albicans is the most common fungal pathogen and a prevalent cause of deadly bloodstream infections. Better understanding of the immune response against it, and the ways by which it evades immunity, are crucial for developing new therapeutics against it. Natural Killer (NK) cells are innate lymphocytes best known for their role against viruses and tumors. In recent years it became clear that NK cells also play an important role in anti-fungal immunity. Here we show that while NK cells recognize and eliminate C. albicans, the fungal cells inhibit NK cells by manipulating the immune checkpoint receptor TIGIT (T cell immunoreceptor with Ig and ITIM domains) in both humans and mice. We identify the responsible fungal ligands as members of the Als (Agglutinin-Like Sequences) protein family. Furthermore, we show that blocking this interaction using immunotherapy with a TIGIT-blocking antibody can re-establish anti-Candida immunity and serve as a potential therapeutic tool.

NK-92 cells retain vitality and functionality when grown in standard cell culture conditions.

NK-92 cells are an off-the-shelf, cell-based immunotherapy currently in clinical trials for a variety of cancer types. As the most 'NK-like' cell line available, it is also an important research tool. To date, NK-92 cells have been cultivated in a costly and time-consumingly prepared specialized medium, complicating research with these cells. Here we show that NK-92 cells grow in the comparatively user-friendly RPMI medium supplemented with IL-2. We demonstrate that their metabolic activity and replication rates are even improved in RPMI. Furthermore, they can be grown in cell culture dishes and do not need to be expanded in ventilated flasks. We show that in RPMI the cells retain functional characteristics relating to receptor expression, IFN-γ secretion, and killing. Our findings will enable more researchers to work with and manipulate this cell line, hopefully leading to further discoveries and improved therapies.

The Utility of Functional Luminal Imaging Probes Measurements to Diagnose Dysmotility and Their Relationship to Impaired Bolus Clearance.

BACKGROUND: Functional luminal imaging probes (FLIP) have been used by multiple centers to assess esophagogastric junction (EGJ) function in patients at risk for esophageal obstruction but its role in diagnosing peristaltic disorders is less well studied. In particular, there are no studies comparing the sensitivity of FLIP to diagnose motility abnormalities and impaired bolus transit by high-resolution esophageal manometry with impedance. METHODS: We prospectively recruited 42 patients undergoing high-resolution esophageal manometry with impedance (HRIM) who also underwent FLIP between 2018 and 2020. HRIM parameters were analyzed using Swallow Gateway software to determine peristaltic and lower esophageal sphincter pressure measurements as well as bolus flow parameters. FLIP tracings were analyzed for the presence of repetitive antegrade contractions (RACs), EGJ distensibility, and associated parameters. RESULTS: Forty-two patients were included (11 controls, 7 achalasia, 16 fundoplication, 8 dysmotility). The mean age of patients was 10.1 ±â€Š0.9 years. There were significant differences in bolus flow parameters across diagnosis with longer bolus presence (BPT) in control patients compared with fundoplication and dysmotility patients. There was a significant correlation between EGJ diameter, EGJ distensibility and bolus flow time (BFT) for solid foods (r2 > 0.518, P < 0.02). The presence of RACs and EGJ relaxation during RACs was associated with a greater BFT and BPT across textures (P < 0.05). Forty-two percentage of patients with absent RACs, however, had clear peristalsis by HRIM. CONCLUSIONS: The presence of RACs and EGJ relaxation by FLIP correlate with improved bolus flow. Patients with an absence of RACs need HRIM to confirm any diagnoses of dysmotility.

Increasing Incidence of Type 1 and Type 2 Diabetes Among Canadian Children.

BACKGROUND: Diabetes mellitus is one of the most common pediatric chronic illnesses. Although a rising incidence of childhood type 1 diabetes (T1D) has frequently been documented, an almost 400-fold variation in incidence has been seen worldwide. We aimed to describe the trends in incidence of diabetes (type 1, type 2, all types) among children and adolescents living in the Greater Montréal area of Québec, Canada. METHODS: Using health administrative data (Québec Integrated Chronic Disease Surveillance System) and medical records from the 3 major pediatric diabetes centres in the Greater Montréal area, we conducted serial cross-sectional studies of children aged 1 to 15 years during the period from 2002 to 2010. We conducted a trend analysis of diabetes incidence over time using multivariate Poisson regression models. RESULTS: We identified 696 new cases of diabetes between 2002 and 2010. The age-standardized incidence of diabetes (all types) increased from 16.3 (95% confidence interval [CI], 12.4 to 21.2) to 27.8 (95% CI, 22.5 to 34.0) per 100,000, with annual incidence increasing, on average, by 5.2% per year (adjusted rate ratio [aRR], 1.052; 95% CI, 1.022 to 1.083). This was driven predominantly by the T1D annual increase of 5.4% (aRR, 1.054; 95% CI, 1.023 to 1.086). A low number of incident cases of type 2 diabetes limited trend analysis in this group. There were no significant interactions between year and sex or age. CONCLUSIONS: The annual incidence of T1D is increasing in Québec children and does not vary by sex or age. Further research into etiologic factors is indicated.

Teaching Medical Students to Teach: A Narrative Review and Literature-Informed Recommendations for Student-as-Teacher Curricula.

PURPOSE: Medical students play an important role as teachers. This narrative review synthesizes the student-as-teacher (SaT) literature that incorporates formal teaching skills training, with the goal of proposing literature-informed recommendations for SaT curriculum development within the context of competency-based medical education. METHOD: In January and August 2020, the authors searched Medline and Embase and conducted forward citation searches in Scopus to identify articles from 1985 to 2020 related to teaching medical students to teach. Search terms included "student(s) as teacher(s)," "near-peer teaching," and "teaching to teach." The findings from selected articles were summarized and synthesized. RESULTS: Forty-three articles met the inclusion criteria: 33 papers describing specific SaT curricula, 3 literature reviews, 6 stakeholder surveys, and 1 Delphi study. While students often engage in teaching roles, formal teaching skills training is not always provided. Existing curricula are usually optional, delivered as short courses, and offered to senior students. Course content commonly includes topics related to planning and delivering learning activities and providing feedback. Of the numerous teaching modalities employed, students indicate a preference for interactive and experiential learning. Methods used to assess students' teaching skills vary; however, direct observation and feedback are valued assessment methods. Program evaluations have shown positive outcomes, including high student satisfaction and enhanced self-confidence as teachers. CONCLUSIONS: Informed by these findings and outcome-based educational frameworks, the authors suggest 4 guiding principles for SaT curricula: (1) teaching skills training should be formally implemented in undergraduate medical education and should, whenever possible, be compulsory; (2) teaching skills should be taught longitudinally and progressively along the undergraduate to postgraduate continuum; (3) curriculum content should be aligned with a school's preexisting curriculum and local context; and (4) authentic opportunities for students to engage in teaching roles should be included. They also propose recommendations for curriculum content, teaching modalities, and assessment methods.

Impact of Coronavirus Disease 2019 on the Pediatric Population with Aerodigestive Disease.

OBJECTIVE: To determine the impact of the coronavirus disease 2019 (COVID-19) quarantine on baseline health, medication use, health anxiety, and healthcare use in pediatric patients with aerodigestive disease and to evaluate for associations of commonly prescribed medications with the risk of COVID-19 illness. STUDY DESIGN: Prospective study of patients presenting in person to pediatric neurogastroenterology clinics between July 2020 and March 2021. RESULTS: Of 202 recruited patients, 71.3% were seen in the aerodigestive diseases center and 28.7% in the functional abdominal pain (FAP)/motility clinic. Of all patients, 25.1% reported improved overall health during quarantine; patients with aerodigestive disease (35.3%) reported higher rates of improved overall health compared with patients with FAP/motility disorders (3.6%, P = .0001). Patients with aerodigestive disease had fewer airway symptoms (P < .05) and less medication use during quarantine (inhaled steroids, P < .05 and albuterol, P < .05). Despite objective improvement, there was significant health-related anxiety, with greater anxiety scores reported during and at the end of quarantine (P < .05), with no difference between patient groups (P > .11). Patients continued to access healthcare during quarantine. In total, 28.7% of patients were seen in the emergency department (patients with FAP more than patients with aerodigestive disease, P = .02), and 19.8% were hospitalized. COVID-19 testing was performed in 58.4% of patients and 2.0% (n = 4) of the entire cohort tested positive. CONCLUSIONS: Patients with aerodigestive disease show improvement of airway symptoms and decreased use of medications during the pandemic, despite increased health-related anxiety. Despite complexities of accessing care due to the widespread lockdown, all patient groups continued to access healthcare.

Processing of Task-Irrelevant Race Information is Associated with Diminished Cognitive Control in Black and White Individuals.

The race of an individual is a salient physical feature that is rapidly processed by the brain and can bias our perceptions of others. How the race of others explicitly impacts our actions toward them during intergroup contexts is not well understood. In the current study, we examined how task-irrelevant race information influences cognitive control in a go/no-go task in a community sample of Black (n = 54) and White (n = 51) participants. We examined the neural correlates of behavioral effects using functional magnetic resonance imaging and explored the influence of implicit racial attitudes on brain-behavior associations. Both Black and White participants showed more cognitive control failures, as indexed by dprime, to Black versus White faces, despite the irrelevance of race to the task demands. This behavioral pattern was paralleled by greater activity to Black faces in the fusiform face area, implicated in processing face and in-group information, and lateral orbitofrontal cortex, associated with resolving stimulus-response conflict. Exploratory brain-behavior associations suggest different patterns in Black and White individuals. Black participants exhibited a negative association between fusiform activity and response time during impulsive errors to Black faces, whereas White participants showed a positive association between lateral OFC activity and cognitive control performance to Black faces when accounting for implicit racial associations. Together our findings propose that attention to race information is associated with diminished cognitive control that may be driven by different mechanisms for Black and White individuals.

Associative memory persistence in 3- to 5-year-olds.

Adults struggle to recollect episodic memories from early life. This phenomenon-referred to as "infantile" and "childhood amnesia"-has been widely observed across species and is characterized by rapid forgetting from birth until early childhood. While a number of studies have focused on infancy, few studies have examined the persistence of memory for newly learned associations during the putative period of childhood amnesia. In this study, we investigated forgetting in 137 children ages 3-5 years old by using an interactive storybook task. We assessed associative memory between subjects after 5-min, 24-h, and 1-week delay periods. Across all delays, we observed a significant increase in memory performance with age. While all ages demonstrated above-chance memory performance after 5-min and 24-h delays, we observed chance-level memory accuracy in 3-year-olds following a 1-week delay. The observed age differences in associative memory support the proposal that hippocampal-dependent memory systems undergo rapid development during the preschool years. These data have the potential to inform future work translating memory persistence and malleability research from rodent models to humans by establishing timescales at which we expect young children to forget newly learned associations.

Ustekinumab for the treatment of refractory pediatric Crohn's disease: a single-center experience.

BACKGROUND/AIMS: Despite the well-established efficacy of tumor necrosis factor (TNF) antagonists as treatment options for Crohn's disease, many pediatric patients need a change in therapy due to adverse events and loss of response, highlighting the necessity for medications with a different mechanism of action. Ustekinumab has been shown to be effective in inducing clinical remission in some adults with disease refractory to anti-TNF agents, however, minimal data exists in the pediatric population. METHODS: We conducted a retrospective chart review of 11 pediatric patients receiving ustekinumab, specifically extracting baseline data, information on prior treatment and response, indications for starting ustekinumab, clinical information, and laboratory parameters pre- and post-therapy. Clinical response was defined as a decrease in abbreviated Pediatric Crohn's Disease Activity Index score. RESULTS: Patients ranged from 12 to 17 years of age upon initiation of treatment with ustekinumab. Five of 11 patients demonstrated a clinical response. Among these patients, 2 remained in clinical remission, while the remaining 3 experienced a secondary loss of response. The other 6 patients were primary nonresponders who either remained unwell or demonstrated slight clinical worsening. All patients who clinically responded to ustekinumab and had an initially elevated CRP experienced complete normalization of their values. Mucosal healing was seen on endoscopy in 1 responder, with 2 other patients showing endoscopic improvement. CONCLUSIONS: These results demonstrate for the first time that ustekinumab has the potential to induce not only clinical and biochemical remission, but also endoscopic improvement, in the pediatric population. Future research is needed to determine factors that influence response to therapy.