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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Risankizumab Receives FDA Approval for Crohn’s Disease

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Abbvie Press Release: SKYRIZI® (risankizumab-rzaa) Receives FDA Approval as the First and Only Specific Interleukin-23 (IL-23) to Treat Moderately to Severely Active Crohn’s Disease in Adults

– Third approved indication for SKYRIZI (risankizumab-rzaa) is supported by safety and efficacy data from two induction and one maintenance clinical trials evaluating SKYRIZI in moderately to severely active Crohn’s disease, ADVANCE, MOTIVATE and FORTIFY1-4

– As early as week 4 in the induction studies, clinical response and clinical remission were achieved by significantly more subjects treated with SKYRIZI versus placebo, as were co-primary endpoints of endoscopic response and clinical remission at week 12 and week 521-4

About SKYRIZI® (risankizumab-rzaa)
SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit.9,10 IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases, including Crohn’s disease.10 The approved dose to treat adults with moderately to severely active Crohn’s disease is 600 mg administered by intravenous infusion over at least one hour at week 0, week 4, and week 8, followed by 360 mg administered by subcutaneous injection at week 12, and every 8 weeks thereafter.4 SKYRIZI is also approved in the U.S. to treat moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, as well as to treat active psoriatic arthritis in adults, and the recommended dosage is 150 mg administered by subcutaneous injection at week 0, week 4, and every 12 weeks thereafter.4 Phase 3 trials of SKYRIZI in psoriasis, Crohn’s disease, ulcerative colitis and psoriatic arthritis are ongoing

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NASPGAN Paper: Surgery for Chronic Pancreatitis: Choose Your Operation and Surgeon Carefully

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JD Nathan et al. JPGN 2022; 74: 706-719. Open Access: The Role of Surgical Management in Chronic Pancreatitis in Children: A Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee

This society paper provides a terrific review of potential operations and rationale in children with chronic pancreatitis. Some of the highlights from this open access article include figures detailing the anatomical considerations of the operations (eg. Frey, Modified Puestow, TPIAT, Berger, Whipple, and Berne) and an algorithm in choosing which procedure should be considered.

Key points:

  • Surgery is indicated for children with debilitating CP who have failed maximal medical and endoscopic interventions.
  • A conventional surgical approach (eg, drainage operation, partial resection, combination drainage-resection) may be considered in the presence of significant and uniform pancreatic duct dilation or an inflammatory head mass.
  • Total pancreatectomy with islet autotransplantation is the best surgical option in patients with small duct disease.
  • The presence of genetic risk factors often portends a suboptimal outcome following a conventional operation.

My take: Fortunately, very few children need operations for chronic pancreatitis. As such, surgical expertise/judgement is particularly important.

Figure 1

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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

Prevalence of Avoidant/Restrictive Food Intake Disorders in Pediatric Neurogastroenterology

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HB Murray et al. JPGN 2022; 74: 588-592. Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in Pediatric Neurogastroenterology Patients

Associated commentary by SB Oliveira, A Kaul: Invited Commentary Re: Prevalence and Characteristics of Avoidant/ Restrictive Food Intake Disorder in Pediatric Neurogastroenterology Patients

This was a retrospective study with 129 consecutive neurogastroenterology patients. Key findings:

  • Eleven cases (8%) met the full criteria for ARFID (DSM, 5th ed) and 19 cases (15%) had clinically significant avoidant/ restrictive eating behaviors with insufficient information for a definitive ARFID diagnosis
  • In a separate retrospective study, the same center published data on ARFID in a general pediatric population, showing 1.5% meeting the full criteria and 2.4% with some features (KT Eddy et al. Int J Eat Disord . 2015 Jul;48(5):464-70. Prevalence of DSM-5 avoidant/restrictive food intake disorder in a pediatric gastroenterology healthcare network)

The discussion notes that while elimination diets (eg. low FODMAPs diets) are frequently used for disorders of brain-gut interaction, they may increase the risk of ARFID. “Some children may develop fear of what will happen when they try foods again.”

The insightful commentary makes several useful points:

  • A retrospective study is not the best way to determine prevalence of ARFID particularly as many practitioners have limited familiarity and documentation may be inadequate
  • Nutritional rehabilitation can improve GI function. It has been shown that patients with anorexia nervosa have delayed gastric emptying which improved with refeeding. More broadly, it is often challenging to definitively determine the cause and effect in patients with malnutrition and gut dysmotility. (This is why I rarely obtain gastric emptying studies in patients with poor nutritional status)

My take: ARFID can be difficult to manage and is important to consider in our patient population, and probably even more so in patients seen in neurogastroenterology programs. The exact prevalence of ARFID in these programs is uncertain and prospective studies are needed.

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I-SEE for Eosinophilic Esophagitis

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ES Dellon et al Gastroenterol 2022; DOI: https://doi.org/10.1053/j.gastro.2022.03.025 Open Access: A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions “The Index of Severity for Eosinophilic Esophagitis (I-SEE)—that can be completed at routine clinic visits to assess disease severity using a point scale of 0–6 for mild, 7–14 for moderate, and ≥15 for severe EoE.”

From AGA: Eosinophilic Esophagitis Index

“The Index of Severity for EoE (I-SEE) is now available for you to use as a tool to help assess EoE patients. Developed by a multidisciplinary team of experts, the new tool is now published in Gastroenterology.”

Details about I-SEE 

  • “The I-SEE has three domains: (1) symptoms and complications, (2) inflammatory features and (3) fibrostenotic.
  • I-SEE can be used at initial diagnosis and then at each subsequent visit, with the recall being only between visits so that the severity can be assessed over time and ultimately (when data supports this step) treatment and monitoring adjusted based on severity.
  • As the number of children and adults with EoE increases worldwide, a simple system to assess and track disease activity in a meaningful way in a clinical setting is needed.
  • I-SEE is for use in adult and pediatric patients with EoE. It was created by an international team of more than 30 experts in allergy, gastroenterology and pathology.”

Link: I-SEE Tool Scoring Table

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.

Related blog post:

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.

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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A (Virtual) Reality Without Pain?

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NY Times Magazine, Helen Ouyang 5/22/22: Can Virtual Reality Help Ease Chronic Pain?

This lengthy article describes the emerging therapy of virtual reality to help with chronic pain. Some of the article focuses on chronic abdominal pain.

Here are some excerpts:

  • Brennan Spiegel, a gastroenterologist and researcher at Cedars-Sinai .. runs one of the largest academic medical initiatives studying virtual reality as a health therapy…
  • As Daniel Clauw, who runs the Chronic Pain and Fatigue Research Center at the University of Michigan, put it in a 2019 lecture, there isn’t “any drug in any chronic-pain state that works in better than one out of three people.” He went on to say that nonpharmacological therapy should instead be “front and center in managing chronic pain — rather than opioids, or for that matter, any of our drugs…”
  • In November, the Food and Drug Administration gave authorization for the first V.R. product to be marketed for the treatment of chronic pain.…
  • [In one] virtual environment … built specifically for patients with chronic gastrointestinal symptoms…[the patient] used hand controls. Inside a virtual clinic, a robot named Maia — short for “mixed-reality artificial-intelligence assistant” — guided her to a young blond woman, who expressed frustration with abdominal symptoms. [The patient] examined the [virtual] patient with her virtual hands, placing a stethoscope on her stomach to listen to the sounds of digestion. Maia explained how the brain and the gut work together. As she spoke, an image of a brain popped up, connected to intestines by a yellow flashing line. When the brain became stressed, it turned fuchsia in color, and the yellow line to the gut metamorphosed into a stream of fire...
  • Scientists knew that the brain has some control over pain, but that insight was mostly confined to the situations described by Patrick Wall’s and Ronald Melzack’s gate-control theory, which helps explain why, say, a person running from a house on fire may not realize that she sprained her ankle until she is a safe distance away. The brain, so intent on escaping the fire, shuts the gate, blocking pain signals coming up the spinal cord from the ankle. “You could close the gate,” says Clifford Woolf, a neurobiology professor at Harvard Medical School who worked in Wall’s lab, but “essentially there was nothing about the opposite possibility — which is that the brain, independent of the periphery, could be a generator of pain.”
  • “Woolf was conducting his own experiment in Wall’s lab, applying painful stimuli to rats’ hind legs. The animals developed large “fields” of pain that could easily be activated months later with a light tap or gentle warmth, even in spots that weren’t being touched directly. “I was changing the function of the nervous system, such that its properties were altered,” Woolf says. “Pain was not simply a measure of some peripheral pathology,” he concluded; it “could also be the consequence of abnormal amplification within the nervous system — this was the phenomenon of central sensitization.”
  • V.R.’s “unique ability to convey a sense of just ‘being there,’ wherever there happens to be,” as he [Spiegel] puts it in his book “VRx: How Virtual Therapeutics Will Revolutionize Medicine.” “All of its revolutionary potential tumbles out of its ability to compel a person’s brain and body to react to a different reality.” 
  • RelieVRx also has modules that prompt patients to redirect their attention through game play or by allowing scenes — waves washing onto a sunny coast, say — to soothe their nervous systems. The average session lasts seven minutes, and patients are directed to do just one a day for eight weeks…
  • A recently published study by researchers affiliated with the company [AppliedVR], for which they recruited subjects during the pandemic through Facebook ads and pain organizations, reported an average drop in chronic back pain by nearly 43 percent for the RelieVRx group compared with 25 percent for the control group. For those who used RelieVRx, pain also interfered less with their activity and sleep. Three months after the last V.R. session, these gains were mostly found to endure…
  • In chronic pain, the body part that hurts may be undamaged and even seem healthy; what’s altered is the area of the brain that corresponds to its anatomical location...
  • If doctors do start prescribing V.R., there’s another hurdle to clear: Who will pay for it? 

My take: I am looking forward to the pediatric studies which will be needed before this technology can be promoted. I would think pediatric patients with chronic pain may respond even more favorably than adults. If this technology were in our clinic, I am certain that are “no show” rate would be lower.

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This could be me in a virtual reality. Picture taken at Connie’s Photo Park in Madrid, NM.

“Waste” of a CT Scan

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M Alsayid, V Kotwal. Clin Gastroenterol Hepatol 2022; DOI:https://doi.org/10.1016/j.cgh.2021.06.030. Open Access: Chronic Constipation With Fecal Stasis

A 50 year old with a history of abdominal distention for a week and chronic constipation had a CT with intravenous contrast. Ultimately he had a disimpaction under general anesthesia and a flexible sigmoidoscopy.

My view: A complete examination with digital rectal exam (if feasible) or an AXR would have been sufficient for diagnosis.

Blog note: Link for We Can’t Wait App updated in yesterday’s post.