Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: a proof-of-concept clinical trial.

BACKGROUND: Vagus nerve stimulation is an investigational anti-inflammatory therapy targeting the nervous system to modulate immune activity. This study evaluated the efficacy and safety of transcutaneous auricular VNS (ta-VNS) in patients with pediatric-onset Crohn's disease (CD) or ulcerative colitis (UC). METHODS: Participants were 10-21 years of age with mild/moderate CD or UC and fecal calprotectin (FC) > 200 ug/g within 4 weeks of study entry. Subjects were randomized to receive either ta-VNS targeting the cymba conchae of the external left ear, or sham stimulation, of 5 min duration once daily for a 2-week period, followed by a cross over to the alternative stimulation for an additional 2 weeks. At week 4, all subjects received ta-VNS of 5 min duration twice daily until week 16. Primary study endpoints were clinical remission, and a ≥ 50% reduction in FC level from baseline to week 16. Heart rate variability measurements and patient-reported outcome questionnaires were completed during interval and week 16 assessments. RESULTS: Twenty-two subjects were enrolled and analyzed (10 CD, 12 UC). Six of 10 with CD had a wPCDAI > 12.5 and 6/12 with UC had a PUCAI > 10 at baseline, correlating to mild to moderate symptom activity. Among the 12 subjects with active symptomatic disease indices at baseline, clinical remission was achieved in 3/6 (50%) with CD and 2/6 (33%) with UC at week 16. Despite all subjects having FC levels ≥ 200 within 4 weeks of enrollment, five subjects (4 UC, 1 CD) had FC levels < 200 at the baseline visit and were excluded from the FC analysis. Of the remaining 17, median baseline FC was 907 µg/g (IQR 411-2,120). At week 16, 11/17 (64.7%) of those with baseline FC ≥ 200 had a ≥ 50% reduction in FC (95% CI 38.3-85.8). In the UC subjects, there was an 81% median reduction in FC vs baseline (833 µg/g; p = 0.03) while in the CD subjects, median reduction in FC at 16 weeks was 51% (357 µg/g; p = 0.09). There were no safety concerns. CONCLUSION: Noninvasive ta-VNS attenuated signs and symptoms in a pediatric cohort with mild to moderate inflammatory bowel disease. TRIAL REGISTRATION: NCT03863704-Date of registration 3/4/2019.

The Future of Advanced Therapies for Pediatric Crohn's Disease.

Pediatric Crohn's disease commonly presents with moderate-to-severe intestinal inflammation with a greater risk of complications if remission is not achieved. Anti-tumor necrosis factor therapies have offered the possibility of deep and durable remission; however, many children do not respond or no longer respond over time. Further, some children do not require broader systemic immunosuppression to achieve remission and are better served by an alternative treatment strategy. Proper utilization of advanced biologic and small-molecule therapies, which have become available for adult patients since anti-tumor necrosis factor medications, is paramount for tighter disease control for a large proportion of children. Newer advanced therapies such as anti-integrin and anti-interleukin biologics, and several small-molecule agents capitalize on various mechanisms through narrower immunologic targets and reduced immunogenicity. Given limited regulatory approvals of these agents for use in children with Crohn's disease, clinicians continue to rely on data extrapolated from clinical trials in adult patients, sparse pediatric studies, and a growing real-world experience for treatment selection and optimization. In this article, we discuss currently available treatment options, pipeline drugs, and relevant data as they pertain to some of the most pressing clinical challenges faced in treating pediatric Crohn's disease.

The safety of COVID-19 vaccination in immunocompromised children and young adults with immune-mediated inflammatory disease.

AIM: To assess safety of COVID-19 vaccination in paediatric patients with immune-mediated inflammatory disease (IMID). METHODS: Subjects of 5-21 years of age with IMID who received at least one COVID-19 vaccine completed electronic surveys after each vaccine to assess side effects within 1 week of vaccination, current medications and COVID-19 testing after vaccination. Charts were reviewed for COVID-19 polymerase chain reaction and IgG response to SARS-CoV-2 spike protein results and for disease flare during the study period. RESULTS: Among 190 enrolled subjects, 71% were female, with median age 17 (range 6-21) years. The most common diagnosis was juvenile idiopathic arthritis/rheumatoid arthritis (55%). 78% of subjects were taking immunosuppressive medication. At least one side effect was reported in 65% of subjects after any dose of the vaccine; with side effects in 38%, 53% and 55% of subjects after the first, second and third vaccine doses, respectively. The most common side effects were injection site pain (59%), fatigue (54%) and headache (39%). No anaphylaxis or myocarditis was reported. Three subjects (2%) experienced disease flare. CONCLUSION: In our cohort of paediatric patients with IMID, observed side effects were found to be mild and disease flare rates were found to be low following COVID-19 vaccination.

Coil-Localized Laparoscopic-Assisted Resection of Symptomatic Gastrointestinal Vascular Malformations in Children and Young Adults.

Gastrointestinal (GI) bleeding from pediatric vascular malformation is uncommon and difficult to diagnose and manage. The preferred treatment is surgical resection; however, it can be challenging to precisely localize the lesion, particularly if it is not serosal. Objectives: To describe a technique of intentional preoperative coil localization of symptomatic pediatric GI vascular malformations by pediatric interventional radiology to facilitate fluoroscopically assisted laparoscopic resection. Methods: We searched the electronic privacy information center and picture archive and communication system in our center and found 3 cases. The electronic privacy information center and picture archive and communication system databases were the sources for retrieval of demographic, medical, radiological, and procedural information in all 3 cases. Results: After many nondiagnostic investigations in all 3 patients, a GI vascular malformation as a cause of GI bleeding was diagnosed with computed tomography angiography/magnetic resonance angiography and catheter angiography. A preoperative 0.018-inch Hilal coil was placed as close as possible to the vascular malformation during super selective angiography. Laparoscopic surgery was performed within 24 hours of coil placement. In all cases, histology confirmed the resected bowel lesions to be vascular malformations. Conclusions: Intentional endovascular coil localization has the potential to increase the precision of lesion localization and may reduce laparoscopic operative time, when guided by the coil position.

P072 Non-invasive Vagal Nerve Stimulation to Treat Crohn Disease and Ulcerative Colitis in Children and Young Adults: A Proof-of-Concept Clinical Trial.

BACKGROUND: Current inflammatory bowel disease (IBD) therapies are limited by incomplete efficacy, loss of response, side effects and high costs. Vagal nerve stimulation (VNS) is an investigational Bioelectronic Medicine therapy targeting the nervous system to treat IBD through an 'inflammatory reflex' that reduces systemic inflammation. Data in humans with IBD are promising but limited to two small studies using a cervically implanted VNS device in adults with Crohn disease (CD); no data exist to date using a non-invasive VNS modality in IBD. This study aimed to evaluate the efficacy and safety of transcutaneous auricular VNS (ta-VNS) in children and young adults with CD or ulcerative colitis (UC). METHODS: IBD patients 10-21 years of age with mild/moderate CD or UC who did not achieve remission with conventional therapy, and a fecal calprotectin (FC) >200 ug/g within 4 weeks of study entry were enrolled. Subjects were randomized to receive either ta-VNS using a transcutaneous electrical nerve stimulator unit targeting the cymba conchae of the external left ear, or sham stimulation of the posterior lower leg, for 5 minutes once daily for a 2-week duration followed by a switch to the alternative stimulation for an additional 2 weeks. At week 4, all subjects were assigned to receive active ta-VNS for 5 minutes twice daily until week 16 so that all received 14 weeks of active ta-VNS by the end of the study. Primary study endpoint was defined as ∆FC ≥50% reduction from baseline to week 16. Secondary endpoints included improvement in weighted Pediatric Crohn Disease Activity Index (wPCDAI) or Pediatric Ulcerative Colitis Activity Index (PUCAI). RESULTS: Twenty-two subjects were enrolled (12 UC, 10 CD; median age 14.4 years [range 10-21] 54.5% male). Median baseline FC was 587 (range 18 - 3828, SD 1074). 5 subjects (4 UC, 1 CD) had FC levels 12.5 at baseline, 3 (50%) achieved clinical remission (wPCDAI ≤ 10) at week 16. In the full UC cohort (n = 12), baseline PUCAI ranged from 0-45. In the 6 with PUCAI > 10 at baseline, 2 (33%) achieved clinical remission at week 16. There were no safety concerns. CONCLUSION: Non-invasive ta-VNS reduced FC levels and improved symptoms in a pediatric cohort with mild/moderate IBD. Further research is needed to identify optimal electrical dose and settings to achieve peak anti-inflammatory effect and to identify the mechanistic principles for this therapy.

Features of Intestinal Disease Associated With COVID-Related Multisystem Inflammatory Syndrome in Children.

ABSTRACT: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified syndrome that appears to be temporally associated with novel coronavirus 2019 infection. MIS-C presents with fever and evidence of systemic inflammation, which can manifest as cardiovascular, pulmonary, neurologic, and gastrointestinal (GI) system dysfunction. Presenting GI symptoms are seen in the majority, including abdominal pain, diarrhea, and vomiting. Any segment of the GI tract may be affected; however, inflammation in the ileum and colon predominates. Progressive bowel wall thickening can lead to luminal narrowing and obstruction. Most will have resolution of intestinal inflammation with medical therapies; however, in rare instances, surgical resection may be required.

Pediatric Endoscopy and High-risk Patients: A Clinical Report From the NASPGHAN Endoscopy Committee.

Pediatric gastrointestinal endoscopy has been established as safe and effective for diagnosis and management of many pediatric gastrointestinal diseases. Nevertheless, certain patient and procedure factors should be recognized that increase the risk of intra- and/or postprocedural adverse events (AEs). AEs associated with endoscopic procedures can broadly be categorized as involving sedation-related physiological changes, bleeding, perforation, and infection. Factors which may increase patient risk for such AEs include but are not limited to, cardiopulmonary diseases, anatomical airway or craniofacial abnormalities, compromised intestinal luminal wall integrity, coagulopathies, and compromised immune systems. Examples of high-risk patients include patients with congenital heart disease, craniofacial abnormalities, connective tissues diseases, inflammatory bowel disease, and children undergoing treatment for cancer. This clinical report is intended to help guide clinicians stratify patient risks and employ clinical practices that may minimize AEs during and after endoscopy. These include use of CO2 insufflation, endoscopic techniques for maneuvers such as biopsies, and endoscope loop-reduction to mitigate the risk of such complications such as bleeding and intestinal perforation. Endoscopic infection risk and guidance regarding periprocedural antibiotics are also discussed.

Foreign body ingestion in pediatric patients.

PURPOSE OF REVIEW: The purpose of this article is to review clinical manifestations and management of common pediatric foreign body ingestions, with a particular focus on some of the current trends. RECENT FINDINGS: Foreign body ingestion (FBI) is a problem that is frequently encountered by pediatric providers. As new toys and products enter the marketplace, there may also be new dangers from those objects not initially recognized. Some of the recent trends and findings in pediatric FBI include an increase in adolescent injury from ingestion of laundry detergent pods because of a popular game where participants are encouraged to bite or swallow the pods, and injuries associated with ingesting parts of a popular toy known as a 'Fidget Spinner'. SUMMARY: Adverse events resulting from FBI range the entire gamut from nonexistent or minor symptoms to moderate injury and rarely may be fatal. Factors such as age, type of object ingested, anatomic location of the foreign body, and timing from ingestion to receipt of medical attention all determine the risk posed to the child and guide management decisions. Because of the constant development of products, and the potential for the emergence of new and dangerous trends among children, continued surveillance by the medical community is important in monitoring and managing injuries associated with FBI.

Button Battery Powered Fidget Spinners: A Potentially Deadly New Ingestion Hazard for Children.

Toys entering the marketplace may have unrecognized hazard risks until data on injury become known. The fidget spinner is a new popular toy mass marketed to children and is primarily sold without warning labels. The US Consumer Product Safety Commission has recently issued a formal statement on potential safety concerns related to ingestion of the toy parts and other hazards. Button batteries within this toy pose the greatest danger to children as ingestion can lead to lethal injury. We report 2 cases of children who swallowed a button battery from a fidget spinner, causing severe esophageal injury. Various aspects of this type of ingestion important for clinicians to be aware of are reviewed.

Histological features of ileitis differentiating pediatric Crohn disease from ulcerative colitis with backwash ileitis.

BACKGROUND/AIM: Pediatric ileocolonic Crohn disease (CD) may be difficult to distinguish from ulcerative colitis (UC) with backwash ileitis (BWI). The primary aim of the study was to determine the probability of CD in children with a confluent colitis and ileitis when newly diagnosed with inflammatory bowel disease (IBD). METHODS: A retrospective observational study of 100 newly diagnosed patients with IBD was performed. Two pathologists reviewed ileal biopsy specimens for 8 histological features. Biopsy and clinical features were evaluated for predictive ability of a final diagnosis of CD. RESULTS: The presence of crypt distortion, lamina propria (LP) expansion, and acute LP inflammation combined with 4 clinical variables in multivariate regression analysis had adequate discriminative validity when comparing the mean probability of a final CD diagnosis between CD and not-CD groups (0.90 vs. 0.59, p value <0.001). When crypt distortion, LP expansion, and acute LP inflammation are present in any combination, the sensitivity and specificity for presence of CD ranges 38.4-57% and 92.9-100%, respectively. CONCLUSIONS: Combining histological features of ileitis and clinical variables can adequately discriminate between the presence and absence of Crohn disease in children who present with confluent colitis and ileitis. Combined presence of certain histological features has high specificity for CD.

Endoscopic ultrasound with or without fine-needle aspiration has a meaningful impact on clinical care in the pediatric population.

BACKGROUND AND OBJECTIVES: The safety and utility of endoscopic ultrasound (EUS) for the evaluation and management of gastrointestinal (GI) tract disorders among adults has been established. The literature on safety and efficacy in a pediatric referral population (under 21 years of age) is limited. We hypothesized that EUS is safe and useful in the pediatric population. We reviewed the pediatric EUS experience at a single tertiary-care system. We describe the indications, findings, safety, technical success rate, and impact on clinical outcomes. PATIENTS AND METHODS: All patients 21 years of age or younger referred for EUS between 5, 2007 and 11, 2012 were identified from our electronic medical record databases. Retrospective chart review was then conducted to document demographics, procedure indications, procedure type (diagnostic or therapeutic), type of anesthesia used, EUS findings, and the clinical impact of EUS on the subsequent management of the patients. RESULTS: Seventy EUS procedures were attempted in 58 patients during the study. Of these, two EUS procedures were aborted due to inadequate moderate sedation and 68 were successfully completed. The median age at initial endoscopy was 18 years (range 6-21 years), 50% were male and 65% were Caucasian. Four patients underwent EUS-guided pseudocyst drainage. Among the remaining 54 patients, the indications for EUS were the evaluation of GI mucosal/submucosal lesions (n = 14), acute or recurrent pancreatitis (n = 10), localization of suspected insulinoma (n = 8), evaluation of pancreatic abnormalities seen on prior imaging (n = 6), surveillance of tumors or evaluation of luminal lesions in hereditary syndromes (n = 6), abdominal pain of suspected pancreatobiliary origin (n = 5), and other rare indications (n = 5). Fine-needle aspiration was performed in 13 (9 diagnostic, 4 therapeutic) and trans-gastric fine-needle contrast injection of the pancreatic duct was performed in one patient without any complications. Sedation (data available for 66 procedures) included general endotracheal anesthesia in 38 (57%), monitored anesthesia care (MAC) in 19 (29%), and moderate sedation in 9 (14%). There were 4 minor intra-procedural anesthesia-related complications (laryngospasm in 2 and hypoxemia from airway obstruction and secretions in 2) in MAC and general endotracheal anesthesia (GA) cases, and 1 postprocedural complication (fever after pseudocyst drainage). EUS can achieve the diagnostic or therapeutic goal and ruled out suspected pathology in 88% of cases precluding need for additional testing. CONCLUSIONS: (1) EUS in the pediatric population is technically successful and efficacious. (2) Therapeutic and diagnostic EUS impacted clinical care decisions. (3) There is a low risk of immediate significant complications. (4) The overall efficacy and safety support the performance of EUS in a pediatric population by experienced endoscopists.

NASPGHAN Capsule Endoscopy Clinical Report.

Wireless capsule endoscopy (CE) was introduced in 2000 as a less invasive method to visualize the distal small bowel in adults. Because this technology has advanced it has been adapted for use in pediatric gastroenterology. Several studies have described its clinical use, utility, and various training methods but pediatric literature regarding CE is limited. This clinical report developed by the Endoscopic and Procedures Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition outlines the current literature, and describes the recommended current role, use, training, and future areas of research for CE in pediatrics.

Lower Gastrointestinal Bleeding in Children.

This article provides an overview of the evaluation and management of lower gastrointestinal bleeding (LGIB) in children. The common etiologies at different ages are reviewed. Conditions with endoscopic importance for diagnosis or therapy include solitary rectal ulcer syndrome, polyps, vascular lesions, and colonic inflammation and ulceration. Diagnostic modalities for identifying causes of LGIB in children include endoscopy and colonoscopy, cross-sectional and nuclear medicine imaging, video capsule endoscopy, and enteroscopy. Pre-endoscopic preparation and decision-making unique to pediatrics is highlighted. The authors conclude with a summary of current and emerging therapeutic hemostatic techniques that can be used in pediatric patients.

Safety of a 1-Day Polyethylene Glycol 3350 Bowel Preparation for Colonoscopy in Children.

OBJECTIVES: Electrolyte-free polyethylene glycol powder (PEG-3350) has been widely used for colonoscopy preparation (prep); however, limited safety data on electrolyte changes exists with 1-day prep regimens. The primary aim of this study was to determine the proportion of patients with significant serum chemistry abnormalities before and at the time of colonoscopy. Secondary aims included evaluation of prep tolerance and bowel cleansing efficacy. METHODS: We performed a prospective descriptive observational study of pediatric patients scheduled for outpatient colonoscopy who received our standard 1-day, weight-based 4 g/kg PEG-3350 prep with a single stimulant laxative dose and had serum chemistry testing within 60 days before and at the time of colonoscopy. A standardized bowel cleanliness tool (Aronchick scale) was completed by the endoscopist. RESULTS: One hundred fifty-five patients had serum electrolytes data pre- and postprep. Comparison of each patient's chemistries demonstrated statistical equivalence with the 1 exception of blood urea nitrogen levels (P = 0.56). Hypokalemia was detected postprep in 37 subjects (24%), but none had a serum level <3.3 mmol/L, which was deemed to be of no clinical significance. Five patients were hypoglycemic post prep; 3 were 7 years or younger (P = 0.02). The colon cleanliness rating was excellent or good in 77% and suboptimal in 23% of patients. CONCLUSIONS: A 1-day, weight-based PEG-3350 bowel prep in children appears safe. Changes in electrolyte levels and renal function were not clinically significant. Children of 7 years or younger seem to be at a higher risk of hypoglycemia compared with older children.

Duodenal hematoma following EGD: comparison with blunt abdominal trauma-induced duodenal hematoma.

BACKGROUND: Duodenal hematoma (DH) is a rare complication of esophagogastroduodenoscopy (EGD) with duodenal biopsy and uncommon, but better described following blunt abdominal trauma (BAT). We aimed to describe DH incidence and investigate risk factors for DH development post-EGD and compare its features to those post-BAT. METHODS: Multiple electronic databases were searched for the diagnosis of DH from 2000 to 2012. Inclusion criteria were patients 0 to 21 years of age who developed a DH following EGD with biopsy or BAT. Exclusion criteria were DH secondary to any other mechanism, EGD performed at another medical center, and insufficient information in the electronic medical record to determine treatments or outcomes. RESULTS: A total of 14 post-EGD and 15 post-BAT patients with DH were included in the study. There were 26,905 EGDs with duodenal biopsies performed during the study period, for an incidence of 1:1922 procedures. Thirteen of 14 (93%) post-EGD DH events occurred between 2007 and 2012 (P < 0.001). The proportion of procedures performed under general anesthesia versus moderate sedation, and performed in the supine position versus left lateral decubitus were close to but did not reach statistical significance. DH-related complications and time to hematoma resolution was similar between groups. CONCLUSIONS: In a 13-year study period, 14 patients developed DH after EGD, for an incidence of 1:1922. Method of sedation and supine positioning of the patient during endoscopy warrant further investigation as potential risks. The clinical course and time to recovery with conservative management are similar between patients with EGD and BAT-induced DH.

Bowel preparation for pediatric colonoscopy: report of the NASPGHAN endoscopy and procedures committee.

Pediatric bowel preparation protocols used before colonoscopy vary greatly, with no identified standard practice. The present clinical report reviews the evidence for several bowel preparations in children and reports on their use among North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition members. Publications in the pediatric literature for bowel preparation regimens are described, including mechanisms of action, efficacy and ease of use, and pediatric studies. A survey distributed to pediatric gastroenterology programs across the country reviews present national practice, and cleanout recommendations are provided. Finally, further areas for research are identified.

Review of foreign body ingestion and esophageal food impaction management in adolescents.

Foreign body ingestion is a common clinical scenario among patients of all ages. The immediate risk to the patient ranges from negligible to life threatening. Initial and follow-up management strategies depend on multiple patient and ingested object-related factors. Available literature on this topic tends to focus on the small child or adult, leaving the clinician caring for adolescents to extrapolate this information to guide decision making for individual patients. This article reviews foreign body ingestion literature with important implications to the adolescent patient and raises awareness of some highly dangerous objects such as large button batteries, high-powered magnets, long sharps, narcotic packages, and super absorbent objects. An additional focus includes the management of esophageal food impaction. We highlight the unique aspects to the care of the adolescent with intentional ingestion and co-morbid psychiatric illness. The article concludes by discussing the challenges to prevention of ingestion in the at-risk patient.