Category Archives: Pediatric Gastroenterology Intestinal Disorder

Histologic Healing and IBD Outcomes

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Several recent studies recently evaluated outcomes based on histologic healing compared to endoscopic remission.

RK Pai et al. Clin Gastroenterol Hepatol 2020; 18: 2510-2517. Full text link: Complete Resolution of Mucosal Neutrophils Associates With Improved Long-Term Clinical Outcomes of Patients With Ulcerative Colitis n=281.Key findings:

  • “We found histologic evidence of UC activity (Geboes score ≥ 2B.1) in biopsies from 182 patients (65%) and endoscopic evidence of UC activity in 149 patients (53%) (substantial agreement, κ = 0.60).”
  • “Histologic features of UC activity were associated with increased rates of systemic corticosteroid use, colectomy, and hospitalization in the entire cohort (P < .05 for all) and associated with increased rates of systemic corticosteroid use in an analysis limited to patients in endoscopic remission (P < .001).”

B Christensen et al. Clin Gastroenterol Hepatol 2020; 18: 2518-2525. Full text link: Histologic Healing Is More Strongly Associated with Clinical Outcomes in Ileal Crohn’s Disease than Endoscopic Healing This was a a retrospective study of 101 patients with CD (52% male) isolated to the terminal ileum. Key findings:

  • At ileo-colonoscopy, 63% of patients had endoscopic healing and 55% had histologic evidence of healing. The level of agreement between endoscopic and histologic activity was fair (62%, K = 0.2250, P = .0064)
  • On multivariate analysis, only histologic healing was associated with decreased risk of clinical relapse (hazard ratio [HR], 2.05; 95% CI, 1.07–3.94; P = .031), medication escalation (HR, 2.17; 95% CI, 1.2–3.96; P = .011), and corticosteroid use (HR, 2.44; 95% CI, 1.17–5.09; P = .018).
Kaplan-Meier analysis of effect of endoscopic and histologic activity on (A) clinical relapse-free survival versus histologic healing, (B) clinical relapse-free survival versus endoscopic healing

D Kevans et al. Inflamm Bowel Dis 2020; 26: 1722-1729. Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis Key finding: In endoscopically quiescent UC (n=76), active histological inflammation …[is] adjunctive histological marker associated with increased likelihood of disease relapse. The associated editorial (1730-32 by Asher Kornbluth) quotes Voltaire: “A wise Italian says that the best is the enemy of the good.” He notes that there is “a very real risk of abandoning an effective drug while chasing the goal of some yet to be universally defined histologic remission.” Currently organizational guidelines (ACG, AGA, ECCO, IOIBD) do NOT suggest the use of histologic normalization as an endpoint at this point.

My take: These studies show that histologic healing in ileal Crohn’s disease and in ulcerative colitis are associated with better outcomes that endoscopic appearance. However, there are a lot questions because many patients, possibly a majority, will not achieve histologic healing despite aggressive treatment. Related technical issues include how many biopsies are needed to assess histology and having a validated histologic assessment.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

In Case You Missed It: IBD Year in Review (Eric Benchimol)

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I did not have the opportunity to hear this #NASPGHAN20 lecture but Dr. Benchimol has shared his slides. Link to Dropbox Slides: IBD Clinical Science: Year in Review

Some of the key points on slides (links to articles below):

Some screenshots:

Links to many of the referenced papers:


Related links:

“Surprise Billing for Colonoscopy: The Scope of the Problem”

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JM Scheiman et al. Annals of Internal Medicine. 2020; https://doi.org/10.7326/M20-2928. Surprise Billing for Colonoscopy: The Scope of the Problem

Background: “Federal law eliminates consumer cost sharing for multiple methods of colorectal cancer screening, including colonoscopy when done by an in-network provider. However, some patients having screening incur considerable out-of-pocket costs because out-of-network bills are not included in federal mandates. “Surprise billing” articles are widespread in the research literature and lay press . To date, the frequency of unexpected patient costs for screening colonoscopy have yet to be rigorously quantified.”

This study with ~983,000 procedures, which was conducted between 2012-2017, shows that it is common to get additional charges from a screening colonoscopy (which is supposed to be covered). Despite using an in-network physician, these charges can be due to “out-of-network” costs from anesthesia or pathology. This can also occur when anesthesia bills the colonoscopy as a diagnostic procedure rather than as a screening procedure.

From Annals of Internal Medicine Twitter Feed

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Nutrition Pearls -Fiber in Short Bowel and Good Growth with Cystic Fibrosis

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One useful resource for NASPGHAN members (NASPGHAN Nutrition Pearls) has been the short monthly nutrition pearl videos (about 10 of them so far). Here are some pointers from the most recent of these.

In October: Fiber for Short Bowel Syndrome –Beneficial for those with a colon in continuity:

Commercial products with limited data supporting use in short bowel syndrome
All of the fiber products are fermented in colon and may be beneficial. Highlighted products are more likely to help with stool consistency (thickening).

In September: Growth in Cystic Fibrosis

Related blog posts for Short Bowel Syndrome:

Related blog posts for Cystic Fibrosis:

Ustekinumab Effectiveness for Ulcerative Colitis Over Two Years

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R Pannacionne et al. AP&T. 2020; https://doi.org/10.1111/apt.16119. Full text link: Ustekinumab is effective and safe for ulcerative colitis through 2 years of maintenance therapy

Methods: Overall, 399 (adult) “responders to intravenous ustekinumab induction and who were randomised to maintenance therapy were treated in the long‐term extension (115 received subcutaneous placebo, 141 received ustekinumab 90 mg every 12 weeks [q12w], and 143 received ustekinumab 90 mg q8w). Placebo treatment was discontinued at unblinding after week 44”

Key Findings:

  • Symptomatic remission rates (stool frequency = 0/1; rectal bleeding = 0) at week 92 were, 64.5% and 67.6% in the ustekinumab q12w and q8w groups, respectively ((Intent-to-treat population).
  • At week 44 of maintenance, measures of UC disease activity (eg Mayo scores) were generally comparable among patients randomised to ustekinumab q12w and q8w with 46.1% and 52.4% in clinical remission and 56.7% and 61.5% with endoscopic improvement respectively
  • Among randomised patients treated in the long‐term extension, 78.7% and 83.2% of patients receiving q12w and q8w, respectively, attained symptomatic remission at week 92; >95% of patients in symptomatic remission at week 92 were corticosteroid‐free
  • No new safety signals were observed
Steroid-free Remission (Intent-to-treat population)

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

The Link Between Celiac Disease and Inflammatory Bowel Disease

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IM Pinto-Sanchez et al. Gastroenterol 2020; 159: 884-903. Association Between Inflammatory Bowel Diseases and Celiac Disease: A Systematic Review and Meta-Analysis

Methods: The authors identified 65 relevant studies after searching databases including MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, DARE, and SIGLE through June 25, 2019 for studies assessing the risk of CeD in patients with IBD, and IBD in patients with CeD

Key findings:

  • Among patients with celiac disease, there was an increased risk of IBD vs controls (RR 9.88; 95% CI 4.03–24.21); the risk was greater for Crohn’s disease than ulcerative colitis
  • Among patients with inflammatory bowel disease, there was an increased risk of celiac disease vs controls (risk ratio [RR] 3.96; 95% confidence interval [CI] 2.23–7.02); however, this finding needs to be interpreted with a lot more caution.
    • The population-based studies that identified this risk relied on ICD codes.
    • Celiac diagnosis is much more difficult in patients with IBD. Overdiagnosis is possible due to increased surveillance, and misinterpretation of serology (eg. false positive serology). In addition, the pooled prevalence in this study of 0.75%, while greater than the controls of 0.3%, remains lower that the current worldwide prevalence of approximately 1%.
    • Only more prospective cohort studies will prove a definitive increase in risk.

My take: In patients with either IBD or celiac disease, clinicians should consider additional diagnoses in patients with ongoing symptoms.

Key to Reducing Unnecessary AXRs: Individualized Metrics

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Diagnosis of constipation is primarily based on history and physical exam –not abdominal xray (AXR). In a recent quality improvement study (G Moriel et al. J Pediatr 2020; 225: 109-116. Reducing Abdominal Radiographs to Diagnose Constipation in the Pediatric Emergency Department), ED physicians were trying to improve adherence to evidence-based guidelines for diagnosis of constipation in otherwise healthy children. In this article, the authors note evidence “has shown abdominal radiographs to be unreliable in establishing an association between clinical symptoms of constipation and fecal load on abdominal radiographs.”

As part of the study, the researchers provided two 20-minute presentations to the pediatric emergency department providers and sent emails to them and to resident housestaff. The email for ED provider’s included the provider’s baseline abdominal radiograph frequency. After study was initiated, a followup email was sent with similar information with key information on the project along with individualized data.

Key findings:

  • After the QI interventions, the total percentage of abdominal radiograph decreased to 18% (from 36% at baseline). This 18% decrease was significant ( P < .001) and sustained over a 12-month follow-up period.
  • The average length of stay was 1.07 hours longer for children who had an abdominal radiograph.
  • Clinically important return visits to the emergency department were uncommon during the postintervention phase (125/1830 [6.8%]), and not associated with whether or not an abdominal radiograph was performed at the initial visit.
  • While the study focused on healthy children, the authors noted that the overall population (6 mo-18 years) experienced a decline in AXR usage, regardless of exclusion criteria. At baseline the rate of AXR was 39.5% (1550/3926) which decreased to 20.7% (478/2311).

One interesting piece of data was showing that this intervention resulted in a sustained reduction for 12 months after the intervention observation period, which mitigates the potential influence of the Hawthorne effect.

My take: In my view, the keys to this intervention was providing individualized metrics as well as having leadership in establishing this project. The individualized metrics help physicians recognize when they are outliers and to motivate them to address this.

Related posts:

Faulty Narrative with Functional Nausea Study

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A recent study (SE Tarbell et al J Pediatr 2020 225: 109-108. Children with Functional Nausea—Comorbidities outside the Gastrointestinal Tract) highlights the frequent comorbidities in children with functional nausea. The authors have combined prospective and retrospective elements with specific questionnaires and review of the electronic medical records.

Key points:

  • High rates of comorbidities were noted: Abdominal pain 94%, Headache 83%, Orthostatic Intolerance 81%, Fatigue 75%, Disturbed sleep 71%, Anxiety 59%, and Constipation 57%. Other frequent findings included vomiting in 51%, Allergies 54%, , Joint Pain 46%, Hypermobility in 37%.
  • 69.5% of subjects missed more than 10 days of school due to their symptoms.
  • There was extensive testing in this cohort (n=63), including 96 endoscopies, and 199 radiologic tests. In addition, 4 patients had cholecystectomies.
  • Among 64 EGDs, 28 were considered abnormal. The authors claim that 6 had specific findings: H pylori (n=2), polyps (n=2), celiac disease (n=1), and lactase deficiency (n=1).
    • It is likely that H pylori and celiac disease could have been identified/suspected by non-invasive testing; these two findings may make a diagnosis of functional nausea more tricky.
    • Lactase deficiency could be considered a normal finding.
  • The authors state that 32 of 59 AXRs had “moderate to severe constipation” based on stool burden

Overall, this article makes some useful points about the high rate of comorbidities with functional nausea but I disagree with some of the other discussion points.

The authors claim that “negative tests can reassure families of the absence of a more serious underlying condition.” This assertion has been disputed in other studies. In one study (A Rolfe et al. JAMA Intern Med. 2013;173(6):407-416 Full text: Reassurance After Diagnostic Testing With a Low Pretest Probability of Serious Disease), the authors conclude that ‘diagnostic tests for symptoms with a low risk of serious illness do little to reassure patients, decrease their anxiety, or resolve their symptoms, although the tests may reduce further primary care visits.’

The authors also have a permissive attitude regarding AXRs saying “a radiograph may validate a diagnosis of constipation.” Yet the preponderance of evidence indicates that AXRs are not needed or recommended for the diagnosis of constipation. The juxtaposition of this statement on page 107 of this issue with the next article on page 109 which details a quality improvement process of reducing abdominal radiographs to diagnose constipation in the ED is interesting. The ED physicians in the next article are trying to adhere to evidence-based guidelines; in this article, the authors correctly note that evidence “has shown abdominal radiographs to be unreliable in establishing an association between clinical symptoms of constipation and fecal load on abdominal radiographs.”

My take: Tarbell et al show that in patients with functional nausea, nausea is the tip of the symptom iceberg. Generally, radiographic and endoscopic diagnostic studies have very low yield and should be discouraged.

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Anemia in IBD -NASPGHAN Position Paper

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A Goyal et al. JPGN 2020; 71: 563-582 Full text (free). Anemia in Children With Inflammatory Bowel Disease: A Position Paper by the IBD Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition.

Main Types of Anemia in Inflammatory Bowel Disease:

  • “IDA is the most common cause of anemia in children with IBD. True iron deficiency results from a number of factors, including chronic blood loss secondary to gastrointestinal bleeding, decreased iron absorption because of tissue or systemic inflammation and from reduced absorptive surface area. “
  • “Functional iron deficiency (FID) results from high levels of circulating hepcidin, which binds to and disables the iron transporter, ferroportin. Under the influence of hepcidin, ferroportin-mediated export of intracellular iron is stalled, leaving the iron trapped within the enterocytes and macrophages… the underlying inflammation, which induces hepcidin production can result in anemia secondary to FID.”
  • Anemia of chronic disease (ACD) “occurs from various downstream pathways secondary to inflammation.”

Table 4:

Recommended Testing

  • Screening Tests: “initially a complete blood count (CBC), CRP, and ferritin levels should be performed. If a patient is found to be anemic, then testing should include CBC with differential, including mean corpuscular volume (MCV), mean corpuscular Hgb concentration (MCHC), red cell distribution width (RDW), reticulocyte count, CRP, serum ferritin, and transferrin saturation (TSAT)”
  • Serum iron level … is … unreliable in the assessment of iron deficiency as the level fluctuates with several variables.
  • Transferrin saturation (TSAT) is a measure of the iron content in the circulating transferrin and reflects the availability of utilizable iron

Treatment of Anemia

  • In mild anemia (Hgb ≥10 g/dL) and/or quiescent disease, oral iron should be tried first.
  • Parenteral iron is indicated when oral iron is ineffective or poorly tolerated, in patients with moderate-severe anemia and/or with active inflammation.
  •  According to ECCO guidelines, an IV replacement goal of achieving of ferritin level of up to 400 μg/L is more likely to prevent recurrence of anemia…a transferrin saturation of 50% and serum ferritin of 800 μg/L should not be exceeded
  • Regarding iron effects on microbiome: studies indicate that dysbiosis at baseline worsens the unfavorable shifts in microbiome with oral iron therapy…Our position, however, is that further studies are required in humans before any reliable conclusions can be drawn. [My question: have the effects of oral iron supplementation on the microbiome been compared to IV iron supplementation on the microbiome?]
  • Table 6 lists various iron products including costs and dosing.
  • The hypersensitivity reactions to parenteral iron are mostly secondary to iron nanoparticles that trigger complement activation-related pseudo-allergy (CARPA)….It is important that parenteral iron be administered by trained personnel. Emergency medications and resuscitative equipment should be available during these infusions.

My take: This is a useful resource for a very common problem.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

More Evidence That A Proinflammatory Diet May Increase the Risk of Crohn’s Disease

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C-H Lo et al. Gastroenterol 2020; 159: 873-883. Full Text Link Dietary Inflammatory Potential and Risk of Crohn’s Disease and Ulcerative Colitis

The authors used Empirical dietary inflammatory pattern (EDIP) scores which were calculated based on the weighted sums of 18 food groups obtained via food frequency questionnaires. n=166,903 women and 41,931 men 

Key findings:

  • “In an analysis of 3 large prospective cohorts, we found dietary patterns with high inflammatory potential to be associated with increased risk of CD but not UC.”
    • Compared with participants in the lowest quartile of cumulative average EDIP score, those in the highest quartile (highest dietary inflammatory potential) had a 51% higher risk of CD (HR 1.51; 95% CI 1.10–2.07; Ptrend = .01).
  • There were 328 cases of CD and 428 cases of UC over 4,949,938 person-years of follow-up. The median age at IBD diagnosis was 55 years (range 29–85 years)

Discussion points:

  •  Food groups that are associated with unfavorable EDIP scores “are characterized by calorie-dense foods high in animal proteins, saturated fats, and glycemic carbohydrates, such as red meat, refined grain, and high-energy soft drinks.”
    • “Dietary patterns resembling the Western diet, characterized by higher intake of red meat, high-fat dairy, and refined grains, have been proposed to trigger the onset of intestinal inflammation by inducing changes in gut microbiome, altering host homeostasis, and regulating T-cell immune response.”
  • “In contrast, diets rich in fruit, vegetables, legumes, whole grains, fish, and poultry, resembling a more prudent and Mediterranean dietary pattern with high fiber and marine ω-3 content, may have anti-inflammatory effects.”

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