Category Archives: Pediatric Gastroenterology Intestinal Disorder

EEN: It Only Works If You Do It

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S Mckirdy et al. JPGN 2022; 74: 801-804. The Impact of Compliance During Exclusive Enteral Nutrition on Faecal Calprotectin in Children With Crohn Disease

The expression ‘90% of Success is Showing Up’ has been attributed to Woody Allen. With dietary and medical treatments, adherence is the equivalent of showing up.

In this study, the authors measured fecal gluten immunogenic peptides (GIP), a biomarker of gluten intake, in 45 children (3– 17 years) with Crohn’s disease to assess adherence to enteral nutrition. This, in turn, was correlated with fecal calprotectin (FC) levels.

Key findings:

  • FC decreased in patients with undetectable GIP at both 33 and 54 days of EEN (mean decrease, 33 days: −743 mg/kg, 54 days: –1043 mg/kg, P< 0.001) but not in patients who had detectable GIP levels
  • At EEN completion, patients with undetectable GIP had a lower FC by 717 mg/kg compared with patients with a positive GIP result (P = 0.042) and demonstrated a greater decline from baseline FC (–69% vs +5%, P = 0.011)
  • 13% and 23% had detectable GIP levels at 33 days and 54 days respectively. It is noted that GIP levels are only indicative of short-term consumption (eg. prior 1-2 days) of gluten-containing foods

My take: Dietary therapies are really difficult for most people. This study shows that those with poor compliance are unlikely to benefit.

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Related blog post: Why I No Longer Need to Be A Billionaire

Avoidant/Restrictive Food Intake Disorder (ARFID) with Irritable Bowel Syndrome and with Inflammatory Bowel Disease

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Last week, this blog highlighted a study regarding the prevalence of ARFID in pediatric neurogastroenterology (Prevalence of Avoidant/Restrictive Food Intake Disorders in Pediatric Neurogastroenterology).

Today, this post reviews a study with 955 adult patients from 4 prospective studies who had completed the IBS Quality of Life Instrument (IBS-QOL). The 3 questions constituting the food domain were used to identify patients with reported severe food avoidance and restriction.

Key findings:

  • In total, 13.2 % of the patients reported severe food avoidance and restriction, and in these patients all aspects of quality of life were lower (P < .01) and psychological, GI, and somatic symptoms were more severe (P < .05). 

The associated editorial provides a lot of information on ARFID in this setting.

Key points:

  • “The sine qua non of ARFID is a reduction in food intake, in terms of volume and/or variety, not primarily motivated by body image disturbance”
  • “Motivations behind changes in eating in ARFID need to be 1 or more of 3 prototypical presentations: (1) fear of aversive consequences (eg, IBS symptoms), (2) a lack of interest in eating or low appetite, and (3) sensitivity to sensory characteristics of food (eg, taste, texture, smell)”
  • “Weight suppression has similar deleterious health effects as is seen in anorexia nervosa, including cardiac abnormalities and bone mineral density loss”
  • “Up to 90% of patients in IBS reporting avoidance of specific foods”
  • “To identify presence of problematic avoidant/restrictive eating, there are ARFID measures validated with cutoffs (eg, the 9-item ARFID Screen;22,23 the PARDI-ARFID questionnaire).24 Nevertheless, more research is needed on the utility of these screening measures in IBS populations”

My take: Patients with ARFID and IBS need much more careful dietary counseling. So, it is important to consider the possibility of ARFID in this patient population.

Related article: E Yelencich et al. Clin Gastroenterol Hepatol 2022; 20: 1282-1289. Open Access PDF: Avoidant Restrictive Food Intake Disorder Prevalent Among Patients With Inflammatory Bowel Disease In this cross-sectional study of adults with IBD, 28/161 (17%) had a positive ARFID risk score (>/=24). Most participants (92%) reported avoiding 1 or more foods while having active symptoms, and 74% continued to avoid 1 or more foods even in the absence of symptoms. Patients with a positive ARFID risk screen were significantly more likely to be at risk for malnutrition (60.7% vs 15.8%; P < .01)

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Afraid to Eat -Could be “Avoidant Restrictive Food Intake Disorder”

Liver Update: Past Time to Split (2022) & Graft Fibrosis -Will the Liver Last?

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In previous posts (see below), the benefits of split-liver transplantation has been discussed, chiefly reducing pediatric waitlist mortality. A recent study (MG Bowring et al. Liver Transplantation 2022; 28: 969-982. Survival Benefit of Split-Liver Transplantation for Pediatric and Adult Candidates) shows split livers improve survival for pediatric and adult recipients.

Methods:  The researchers sought to determine the survival benefit associated with accepting a splittable graft offer for SLT versus declining and waiting for a subsequent offer using 2010 to 2018 Scientific Registry of Transplant Recipients (SRTR) data on 928 pediatric and 1814 adult liver transplantation candidates who were ever offered a splittable graft

Key findings:

  • Among adult candidates, split liver offer acceptance was associated with a 43% reduction in mortality (aHR, 0.390.570.83 [P = 0.005]; 92.2% versus 84.4% 1-year survival after decision)
  • Among pediatric candidates ≤7 kg, split liver offer acceptance versus decline was associated with a 63% reduction in mortality (adjusted hazard ratio [aHR], 0.170.370.80 [P = 0.01]; 93.1% versus 84.0% 1-year survival after decision). Among pediatric candidates >7 kg, there was no significant difference associated with acceptance of a split liver offer (aHR, 0.631.071.82 [P = 0.81]; 91.7% versus 94.4% 1-year survival after decision)

My take: These findings should spur more efforts at incentivizing the use of split livers.

Unrelated article: ER Perito et al. Liver Transplantation 2022; 28: 1051-1062. Graft Fibrosis Over 10 to 15 Years in Pediatric Liver Transplant Recipients: Multicenter Study of Paired, Longitudinal Surveillance Biopsies

Key findings (n=78):

  • The first biopsy, at a median 8.2 years (interquartile range, 5.9-11.6 years) after transplantation, showed moderate (LAFSc 4-6) in 55%, and severe (LAFSc 7 or higher) in 3% of patients.
  • The second biopsy, at a median 4.7 years (IQR, 4.3-5.1 years) later, showed moderate (LAFSc 4-6) in 62%, and severe (LAFSc 7 or higher) in 5% of patients.. Thus, there was fibrosis progression (LAFSc increased by ≥3) in 10 (13%) and regression (LAFSc decreased by ≥3) in 4 (5%) patients.

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Albuquerque, NM and a bridge over the Rio Grande

Targeted Therapy for Autoinflammatory Very Early Onset Inflammatory Bowel Disease

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S Rudra et al. Clin Gastroenterol Hepatol 2022; 20: 1408-1410. Ruxolitinib: Targeted Approach for Treatment of Autoinflammatory Very Early Onset Inflammatory Bowel Disease

As we start to understand the genetic basis for some of the cases of very early onset inflammatory bowel disease (VEO-IBD), identifying effective targeted treatment is needed. For example, abatacept has been shown to be helpful for CTLA4 deficiency. The report cited above reports the experience of ruxolitinib for autoinflammatory phenotype (AIP) of VEO-IBD.

AIP was defined by persistent fevers, leukocytosis, elevation of at least 2 cytokines: sIL2R, IL8, IL6, CXCL9 or IFN-gamma.

Ruxolitinib is a selective JAK1/2 inhibitor which is approved for treatment of polycythemia vera, myelofibrosis, and graft-versus-host disease. As an aside, its retail cost (with 10 mg, #60) is ~$15,000 per month.

In this case report, 6 children with severe VEO-IBD were treated with average starting dose of 5.6 mg/m2/dose twice daily. Most were receiving dual therapy –3 patients were treated with IL1 blockade and 2 patinents with anti-TNF therapy.

Key findings:

  • Over 6-months, all patients had clinical response, especially with regard to fever and stool frequency
  • All patients had improvement in lab studies
  • Among the 3 with endoscopic followup, 1 had deep mucosal healing and 2 had endoscopic improvement
  • Three mild infections occurred while on treatment, but no bone marrow suppression was noted

My take: Patients with VEO-IBD represent a huge challenge. Trying to target specific therapies is difficult given that there are more than 70 monogenic defects that have been identified and many of the therapies are quite expensive (and difficult to get).

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Near Santa Fe, NM

Useful (Open Access) Reference for Colonic Motility Studies

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A Rybak et al. JPGN 2022; 74: 681-692. Open Access: Colonic Function Investigations in Children: Review by the ESPGHAN Motility Working Group

This article reviews the following:

  • Colonic Transit Radiomarker Studies (aka Sitz markers)
  • Colonic Scintigraphy
  • Colonic Manometry
  • Wireless Motility Capsule (aka SmartPill)
  • Electromagnetic Capsule Tracking System
  • CINE Motility MRI

The article provides useful information for indications and for interpreting these studies along with some terrific figures.

For colonic transit radiomarkers:

  • Fecal impaction should be addressed prior to study
  • Figure 1 algorithm: If >80% of markers remain in colon on day 4 or 5, this is an abnormal study. “Children are considered as having slow transit constipation when there is a delay in transit, with the pellets spread throughout the colon. When the delay occurs and over 50% of the markers are held up in the rectosigmoid colon, children are labeled as having rectal outlet obstruction”

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The Curtain or The Box: Therapeutic Dilemmas

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X Roblin et al. Inflamm Bowel Dis 2022; 28: 720-727. Swapping Versus Dose Optimization in Patients Losing Response to Adalimumab With Adequate Drug Levels

Many times, treatment decisions are like on “Let’s Make a Deal.” That is, should I stick with what I’ve got or should I try for something better & sometimes wind up with a goat. In this referenced article, patients were under maintenance therapy with adalimumab (ADA) monotherapy (40 mg every 14 days) and had experienced a secondary loss of response (LOR) despite trough levels > 4.9 μg/mL. In this nonrandomized prospective study, patients were either swapped to vedolizumab (VDZ) or optimized on adalimumab (ADA) treatment.

Key findings:

  • At 24 months, 11 out of 70 patients (16%) in the swap group discontinued treatment compared with 36 out of 61 (59%) patients in the optimization group (P < 0.001)
  • In the optimization group, treatment discontinuation was positively associated with baseline fecal calprotectin >500 μg/g (HR, 3.5)
  • In patients selected for optimization, 56% (34/61) remained on ADA at 1 year and 41% (25/61) at 2 years

In their discussion, the authors state “current guidelines recommend switching to another class of biologics in case of LOR to ADA with therapeutic drug levels.” However, the authors note that their therapeutic level cut-off of >4.9 mcg/mL is lower than the latest recommendations. In addition, in their conclusion, they note that due to limited biologic options, “ADA optimization strategy might be considered” in a subgroup.

My take: Despite better results in the patients that swapped to VDZ in this study, I think it is important to assure adequate drug levels before choosing a new drug class. For ADA, expert recommendations have suggested a level of 8-12 as therapeutic and to avoid discontinuation if ADA level is less than 10. In this study, more than 40% remained on ADA two years after LOR in those with dosing optimization.

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Panoramic View -Sandia Mountain, NM

IBD -Briefly Noted: Intestinal U/S and Anxiety/Depression Not Worsening Pediatric IBD Activity

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EA van Wassenaer et al. Inflamm Bowel Dis 2022; 28: 783-787. Open Access PDF: Intestinal Ultrasound in Pediatric Inflammatory Bowel Disease: Promising, but Work in Progress

Key points from this review:

  • Research has shown that IUS has the potential to be a valuable additional point-of-care tool to guide treatment choice and to monitor and predict treatment response, although evidence of its accuracy and value in clinical practice is still limited
  • The utility may be operator-dependent as well

My take: Due to low upfront costs, IUS would be appealing adjunct to current monitoring. However, one could envision IUS leading to more downstream studies (& costs), especially if its sensitivity and specificity are not very high.

EJ Brenner et al. Inflamm Bowel Dis 2022; 28: 728-733. Anxiety and Depressive Symptoms Are Not Associated With Future Pediatric Crohn’s Disease Activity

In this internet-based cohort of 9-17 yr olds (n=159, 96% white), the authors found no association between baseline PROMIS Pediatric anxiety score and subsequent sCDAI (change in sCDAI for 3-point change in PROMIS Pediatric −0.89; 95% CI −4.81 to 3.03). This study is in contrast to studies in adults which have shown a bidirectional relationship between anxiety/depression and IBD activity.

My take: It is difficult to know with certainty whether anxiety/depression may trigger IBD activity; more studies are needed. Treatment of mental health is important regardless of its effects on IBD activity.

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“We Can’t Wait” App

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CCFA: We Can’t Wait: New app helps inflammatory bowel disease patients find available restrooms nearby

An excerpt: “The Crohn’s & Colitis Foundation…launched the We Can’t Wait app, which provides an interactive map that allows users to find a restroom near them across the U.S.  Driven by crowd-sourced submissions and major retail and restaurant partners that contributed their restroom location data, the app empowers IBD patients – and all users – with a tool to find restrooms more easily, both in emergency and everyday situations. The app is free and available for download now.  

Related blog post: When you gotta go…looking for a clean bathroom

Improving Mortality in Spain After Nationwide Access to Direct-Acting Antivirals

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J Politi et al. Hepatology 2022; 75: 1247-1256. Favorable impact in hepatitis C-related mortality following free access to direct-acting antivirals in Spain

Background: Free treatments for HCV infection with direct-acting antivirals (DAAs) became widespread in Spain in April 2015

Key findings:

  • After the intervention, there was a great acceleration of the downward mortality trend from HCV, whose annual percent change (APC) went from −3.2% (95% CI, −3.6% to −2.8%) to −18.4% (95% CI, −20.6% to −16.3%). There were also significant accelerations in the downward trends in mortality from HCC.

My take: More proof that DAAs can be life-saving.

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Can You Give Ustekinumab Subcutaneously After IV Reaction?

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J Sunny et al. JPGN Reports: May 2022 – Volume 3 – Issue 2 – p e205 Open Access: Hypersensitivity Reaction to Ustekinumab in Pediatric and Young Adult Inflammatory Bowel Disease Patients: A Case Series

This is a case series of six pediatric patients and young adults who developed hypersensitivity reactions during intravenous infusion with ustekinumab (UST).

Key findings:

  • Hypersensitivity reactions during intravenous (IV) induction dose of UST, ranging from mild allergic reactions to anaphylaxis, with no antibodies detected in the two who had testing
  • Reactions occurred 0-30 minutes after start of infusion
  • Management was with methylprednisolone in 5 of 6 patients, diphendyramine in 3 of 6, and epinephrine in 1. One patient was managed with IV diphenhydramine alone.
  • Four of six continued with UST subcutaneously without reactions. ***Change of formulation of UST from IV to subcutaneous was done in a controlled hospital-based setting. The other two 33% were switched to another biologic due to physician preference and were never exposed to the subcutaneous formulation
  • Although the exact pathogenesis of this infusion reaction remains unknown, it has been attributed to EDTA

My take: It appears that patients with UST hypersensitivity reactions can be changed to SC formulation. The authors recommend to trial a subcutaneous dose of UST in a controlled setting; in addition, they suggest testing with skin prick testing or specific IgE levels to EDTA done by allergy and immunology.

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Sandia Mountain, near Albuquerque