Inpatient management of iron deficiency anemia in pediatric patients with inflammatory bowel disease: A single center experience.

BACKGROUND: Screening for iron deficiency anemia (IDA) is important in managing pediatric patients with inflammatory bowel disease (IBD). Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous (IV) iron to treat IDA in this population. AIM: To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center. METHODS: A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019. 92 patients met study criteria for IDA, of which 57 received IV iron, 17 received oral iron, and 18 were discharged prior to receiving iron therapy. RESULTS: Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9 (± 0.2) g/dL in mean (± SE) hemoglobin (Hb) concentration by the first ambulatory follow-up, compared to patients who received oral iron 0.8 (± 0.3) g/dL or no iron 0.8 (± 0.3) g/dL (P = 0.03). One out of 57 (1.8%) patients that received IV iron therapy experienced an adverse reaction. CONCLUSION: Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.

Efficacy and Safety of Tacrolimus or Infliximab Therapy in Children and Young Adults With Acute Severe Colitis.

INTRODUCTION: One-third of children and young adults admitted for management of acute severe colitis (ASC) fail intravenous corticosteroids. Infliximab (IFX) or tacrolimus (TAC) is often used to prevent urgent colectomy in these patients. However, no prior studies have reviewed the outcome of pediatric patients with ASC who were treated with either IFX or TAC. METHODS: We retrospectively identified 170 pediatric patients with ASC admitted to our institution who did not respond to intravenous corticosteroids and were subsequently treated with either IFX or TAC. We compared 6-month colectomy rates, time to colectomy, improvement in disease activity indices, and adverse effects. RESULTS: The mean age of patients in the IFX (n = 84) and TAC (n = 86) groups were 14 and 13.8 years, respectively. The median study follow-up time was 23 months. The rate of colectomy 6 months from rescue therapy was similar whether patients received IFX or TAC (22.6% vs 26.7%, respectively, P = 0.53). The mean decline in Pediatric Ulcerative Colitis Activity Index scores from admission to discharge in those treated with IFX (31.9) or TAC (29.8) was similar (P = 0.63). Three patients treated with IFX experienced infusion reactions. Six patients treated with TAC experienced changes in renal function or electrolytes, and 4 patients reported neurologic symptoms. CONCLUSIONS: There were no significant differences in the likelihood of colectomy 6 months after initiating IFX or TAC rescue therapy. Efficacy of both agents was comparable. The types of adverse effects differed by therapy. These data support the use of either TAC or IFX in children with ASC refractory to intravenous corticosteroids.

Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after Fecal Microbiota Transplant in Inflammatory Bowel Disease.

Background: Fecal Microbiota Transplant (FMT) has proven effective in treating recurrent Clostridioides difficile infection (rCDI) and has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. However, there is little known regarding predictors of engraftment. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Results: Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. The treatment arm received seven days of antibiotics followed by FMT enema and then capsules weekly for seven weeks. We enrolled four subjects with CD and 11 with UC, ages 14-29 years. Due to weekly stool sampling, we were able to create a time series of alpha diversity, beta diversity and engraftment as they related to clinical response. Subjects exhibited a wide range of microbial diversity and donor engraftment as FMT progressed. Specifically, engraftment ranged from 26% to 90% at week 2 and 3% to 92% at two months. Consistent with the current literature, increases over time of both alpha diversity (p< 0.05) and donor engraftment (p< 0.05) correlated with improved clinical response. Additionally, our weekly time series enabled an investigation into the clinical and microbial correlates of engraftment at various time points. We discovered that the post-antibiotic but pre-FMT time point, often overlooked in FMT trials, was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial with publicly available weekly sequencing data. Conclusions: We found that higher residual alpha diversity and Lactobacillus blooms after antibiotic treatment correlated with improved engraftment and clinical response to FMT. Future studies should closely examine the host microbial communities pre-FMT and the impact of antibiotic preconditioning on engraftment and response.

Overlap Between Irritable Bowel Syndrome Diagnosis and Endometriosis in Adolescents.

BACKGROUND & AIMS: Gastroenterologic symptoms often are reported by adults with endometriosis, leading to unnecessary diagnostic tests or complicated treatment. We investigated associations between endometriosis and irritable bowel syndrome (IBS) in adolescents and whether concurrent pain disorders affect these. METHODS: We collected data from within The Women's Health Study: Adolescence to Adulthood, which is a US longitudinal study of premenopausal females with and without endometriosis. Our study cohort included participants younger than 21 years enrolled from 2012 to 2018. Participants completed an extensive health questionnaire. Those with IBS based on a self-reported diagnosis or meeting Rome IV diagnostic criteria were considered cases and those without IBS were controls. Subjects without concurrent gastrointestinal disorders or missing pain data (n = 323) were included in the analyses. We calculated adjusted odds ratios using unconditional logistic regression. RESULTS: More adolescents with endometriosis (54 of 224; 24%) had comorbid IBS compared with adolescents without endometriosis (7 of 99; 7.1%). The odds of IBS was 5.26-fold higher among participants with endometriosis than without (95% CI, 2.13-13.0). In girls with severe acyclic pelvic pain, the odds of IBS was 35.7-fold higher in girls without endometriosis (95% CI, 4.67-272.6) and 12-fold higher in girls with endometriosis (95% CI, 4.2-36.3), compared with no/mild pain. For participants with endometriosis, each 1-point increase in acyclic pain severity increased the odds of IBS by 31% (adjusted odds ratio, 1.31; 95% CI, 1.18-1.47). CONCLUSIONS: In an analysis of data from a longitudinal study of girls and women with and without endometriosis, we found significant associations between endometriosis and IBS, and a linear relationship between acyclic pelvic pain severity and the odds of IBS. Increased provider awareness and screening for IBS and endometriosis will improve patient outcomes and increase our understanding of these complex disorders.

The pharmacotherapeutic management of pediatric Crohn's disease.

Introduction: Crohn's disease (CD) is a chronic inflammatory condition that can occur throughout the gastrointestinal tract. The aims of treatment of children with CD are to induce and maintain clinical remission of disease, optimize nutrition and growth, minimize adverse effects of therapies, and if possible, achieve mucosal healing.Areas covered: This review summarizes evidence for the various therapeutic options in the treatment of children with CD. Exclusive enteral nutrition, corticosteroids, and biologics may be used for induction of remission. Immunomodulators (thiopurines, methotrexate) and biologics (infliximab, adalimumab) may be employed for maintenance of remission to prevent flares of disease and avoid chronic steroid use. In cases of fibrotic disease, intestinal perforations, or medically refractory, surgery may be the best therapeutic option.Expert opinion: Exclusive enteral nutrition, corticosteroids, and biologics (including anti-TNF inhibitors) may be used for induction of remission in patients with active flare of their disease. Immunomodulators and TNF inhibitors may be used for maintenance of remission. Early use of anti-TNF inhibitors in patients with moderate to severe CD may improve efficacy and prevent penetrating complications of disease. While pediatric data is limited, newer biologics, such as vedolizumab and ustekinumab, are used off-label in anti-TNF refractory disease.

Postoperative complications of pediatric patients with inflammatory bowel disease treated with vedolizumab.

BACKGROUND: Vedolizumab is a biologic, which inhibits leukocyte adhesion in the gut and is used to treat ulcerative colitis (UC) and Crohn's disease (CD). Little is known of the surgical outcomes in patients treated with vedolizumab. We reviewed the postoperative complications in a cohort of pediatric UC and CD patients treated with vedolizumab. METHODS: We identified pediatric UC and CD patients treated with vedolizumab at our institution from 2014 to 2016. We compared postoperative outcomes in the vedolizumab exposed group to a cohort of vedolizumab naïve patients who required diverting ileostomy. RESULTS: Of the 31 patients who were treated with vedolizumab, 13 patients required surgery. Eight of 13 (62%) vedolizumab exposed patients had a postoperative complication, including mucocutaneous separation at the stoma (3), readmission for pain/dehydration (2), bowel obstruction at the ostomy, and intraoperative colonic perforation. In comparison, four of 16 (25%) vedolizumab naive patients had a postoperative complication, including readmission for ileus and for high stoma output with mucocutaneous separation. p=0.07. CONCLUSIONS: At our institution, patients treated with vedolizumab prior to surgery have a high prevalence of postoperative complications, notably mucocutaneous separation of the stoma. A prospective, multicenter study is needed to determine if these observed complications are attributable to vedolizumab. LEVEL OF EVIDENCE: Level III.

Postoperative Complications in Children With Crohn Disease Treated With Infliximab.

OBJECTIVES: Infliximab (IFX) has become a mainstay of therapy for children with Crohn disease (CD). Despite medical advances, many children with CD, however, still require operative interventions. The risk of complications following resection in children treated with IFX remains largely unknown. We compare surgical outcomes stratified by IFX therapy in a cohort of children with CD who require bowel resection. METHODS: We reviewed the postoperative complications in 123 children with CD who underwent bowel resection with primary anastomosis at our institution between 1977 and 2011. Demographics, medications, types of operations, and inpatient courses were analyzed. Complications and length of stay were compared based on medical therapy. RESULTS: Overall, the postoperative complication rate was 13%. Of the 123 surgical cases, 24 children had received IFX before their operation. In the children treated with IFX, we identified 3 major complications, including anastomotic leak, acute renal failure, and intraabdominal abscess. There were 9 major complications in the non-IFX group, including infections (2), intraabdominal abscesses (2), bowel obstruction, shock, supraventricular tachycardia, phlegmon, and anastomotic stricture. No significant differences in complication rates or postoperative lengths of stay were identified between those who did or did not receive IFX. CONCLUSIONS: In this cohort, surgical procedures in children and young adults treated with IFX were not associated with an increased number of complications or prolonged length of stay. Given that postoperative complications are infrequent in children, larger multicenter studies may be required to determine whether IFX therapy increases the risk of surgical complications in pediatric CD.

The power of (Mis)perception: Rethinking suicide contagion in youth friendship networks.

Suicide is a leading cause of death among youth. In the wake of peer suicide, youth are vulnerable to suicide contagion. But, questions remain about the mechanisms through which suicide spreads and the accuracy of youths' estimates of friends' suicidal behaviors. This study addresses these questions within school-aged youths' friendship networks. Social network data were drawn from two schools in the National Longitudinal Study of Adolescent to Adult Health, from which 2180 youth in grades 7-12 nominated up to ten friends. A measure of "perceived" friends' attempted suicide was constructed based on respondents' reports of their friends' attempted suicide. This measure was broader than a "true" measure of friends' attempted suicide, constructed from self-reports of nominated friends who attended respondents' schools. Sociograms graphically represented the accuracy with which suicide attempters estimated friends' suicide attempts. Results from cross-tabulation with Chi-square analysis indicated that approximately 4% of youth (88/2180) attempted suicide, and these youth disproportionately misperceived (predominantly overestimated) friends' suicidal behaviors, compared to non-suicide-attempters. Penalized logistic regression models indicated that friends' self-reported attempted suicide was unrelated to respondent attempted suicide. But, the odds of respondent attempted suicide were 2.54 times higher (95% CI, 1.06-6.10) among youth who accurately perceived friends' attempted suicide, and 5.40 times higher (95% CI, 3.34-8.77) among youth who overestimated friends' attempted suicide. The results suggest that at-risk youth overestimate their friends' suicidal behaviors, which exacerbates their own risk of suicidal behavior. Methodologically, this suggests that a continued collaboration among network scientists, suicide researchers, and medical providers is necessary to further examine the mechanisms surrounding this phenomenon. Practically, it is important to screen at-risk youth for exposure to peer suicide and to use the social environment created by adolescent friendship networks to empower and support youth who are susceptible to suicidal thoughts and behaviors.

Evaluation and treatment of constipation in children and adolescents.

Childhood constipation is common and almost always functional without an organic etiology. Stool retention can lead to fecal incontinence in some patients. Often, a medical history and physical examination are sufficient to diagnose functional constipation. Further evaluation for Hirschsprung disease, a spinal cord abnormality, or a metabolic disorder may be warranted in a child with red flags, such as onset before one month of age, delayed passage of meconium after birth, failure to thrive, explosive stools, and severe abdominal distension. Successful therapy requires prevention and treatment of fecal impaction, with oral laxatives or rectal therapies. Polyethylene glycol-based solutions have become the mainstay of therapy, although other options, such as other osmotic or stimulant laxatives, are available. An increase in dietary fiber may improve the likelihood that laxatives can be discontinued in the future. Education is equally important as medical therapy and should include counseling families to recognize withholding behaviors; to use behavior interventions, such as regular toileting and reward systems; and to expect a chronic course with prolonged therapy, frequent relapses, and a need for close follow-up. Referral to a subspecialist is recommended only when there is concern for organic disease or when the constipation persists despite adequate therapy.

Predictors of abdominal pain in depressed pediatric inflammatory bowel disease patients.

BACKGROUND: Pediatric patients with inflammatory bowel disease (IBD) have high rates of abdominal pain. The study aims were to (1) evaluate biological and psychological correlates of abdominal pain in depressed youth with IBD and (2) determine predictors of abdominal pain in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Seven hundred sixty-five patients aged 9 to 17 years with IBD seen over 3 years at 2 sites were screened for depression. Depressed youth completed comprehensive assessments for abdominal pain, psychological (depression and anxiety), and biological (IBD-related, through disease activity indices and laboratory values) realms. RESULTS: Two hundred seventeen patients with IBD (161 CD, 56 UC) were depressed. One hundred sixty-three (120 CD, 43 UC) patients had complete abdominal pain index scores. In CD, abdominal pain was associated with depression (r = 0.33; P < 0.001), diarrhea (r = 0.34; P = 0.001), erythrocyte sedimentation rate (r = 0.22; P = 0.02), low albumin (r = 0.24; P = 0.01), weight loss (r = 0.33; P = 0.001), and abdominal tenderness (r = 0.38, P = 0.002). A multivariate model with these significant correlates represented 32% of the variance in pain. Only depression (P = 0.03), weight loss (P = 0.04), and abdominal tenderness (P = 0.01) predicted pain for patients with CD. In UC, pain was associated with depression (r = 0.46; P = 0.002) and nocturnal stools (r = 0.32; P = 0.046). In the multivariate model with these significant correlates, 23% of the variance was explained and only depression (P = 0.02) predicted pain. CONCLUSIONS: The psychological state of pediatric patients with IBD may increase the sensitivity to abdominal pain. Thus, screening for and treating comorbid depression may prevent excessive medical testing and unnecessary escalation of IBD medications.

The effect of immunomodulators and biologics on indication for surgical bowel resection in children with Crohn's disease.

BACKGROUND: Despite advances in medical therapies, many children with Crohn's disease (CD) will require bowel resection. Although previous registry studies have attempted to identify risk factors for surgery, the effect of immunomodulators and biologics (IMB) on surgical indications has not been well characterized. METHODS: We reviewed a series of 125 children with CD who underwent bowel resection with reanastomosis between 1977 and 2011 and were followed up for at least 6 months. We compared patients who underwent surgery for perforating disease (abscess or internal fistula) and patients who were operated on for medically refractory or fibrostenosing disease. Between these 2 groups, we examined medications received before surgery. Other demographic and disease-specific covariates were examined. RESULTS: Of the 82 patients who received IMB before surgery, only 19 patients (23%) required surgery for a perforating complication of CD, whereas 63 patients (77%) required surgery for strictures or medically refractory disease. In contrast, of the 43 patients who did not receive IMB preoperatively, 20 patients (45%) developed a perforating complication and 23 patients (53%) required surgery for strictures or refractory disease. These differences across groups were significant, with a lower rate of operation for perforating disease among patients receiving preoperative IMB therapy (P = 0.007). CONCLUSIONS: In our surgical cohort, children with CD who were treated with IMB were less likely to have surgery for perforating disease. This finding raises the possibility that the administration of IMB in children who require surgery may be associated with a difference in disease behavior.

The overlap of functional abdominal pain in pediatric Crohn's disease.

BACKGROUND: Children with Crohn's disease (CD) may report abdominal pain despite clinical remission, suggesting that functional abdominal pain (FAP) may be playing a role. The aim of this study was to explore the presence and impact of FAP in children with CD in remission. METHODS: Children, aged 9 to 17 years, with CD were enrolled. Demographic information, the Pediatric Crohn's Disease Activity Index, and the Children's Depression Inventory were obtained. Disease remission was defined by physician global assessment, normal laboratories findings, absence of 3 or more stools a day, nocturnal stooling, bloody diarrhea, concurrent steroid therapy, strictures, or disease flare within 6 months. FAP was defined as patients with abdominal pain and CD remission. Rates of depression (Children's Depression Inventory >9) were compared. RESULTS: Of 307 children, 139 reported abdominal pain. Of this group, 18 of 139 (13%) children met the criteria for FAP. Despite clinical remission, 8 of 18 patients with CD having FAP were classified with active disease by Pediatric Crohn's Disease Activity Index. These patients had a higher rate of depression than patients with CD in remission with no abdominal pain (55.6% versus 29.9%; P = 0.03), similar to patients with abdominal pain from active CD (55.6% versus 44.8%; P = 0.62). CONCLUSIONS: A proportion of children with CD in remission have FAP. These children are at significant risk of depression. Future studies are needed to determine whether depression contributes to functional pain development or if pain itself leads to depression. Especially given that functional pain may exaggerate disease activity, clinicians caring for children with CD and FAP should consider evaluating for depressive disorders before escalating therapy.