Category Archives: Uncategorized

ADMIRE Study: Use of Stem Cell Therapy for Complex Perianal Fistulas in Crohn’s Disease

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A recent phase 3 randomized, double-blind, placebo-controlled study (J Panes et al. Gastroenterol 2018; 154: 1334-42) examined the use of stem cell therapy for the treatment of complex perianal fistulas in Crohn’s disease (CD).

They used a single local injection of 120 million Cx601, a suspension of allogeneic expanded adipose-derived stem cells, and compared to a placebo injection.  This study comprised 212 patients from 49 centers. The primary endpoint, labelled “combined remission,” was based on absence of draining fistulas and MRI findings.

Key Findings:

  • As noted in Figure 1 (below), combined remission occurred in 51.5% of Cx601-Rx patients compared with 35.6% for placebo at week 24; at week 52, combined remission occurred in 56.3% of Cx601-Rx patients compared with 38.6%

My take: This local therapy improved outcomes for 1 year after a single injection and appears promising for refractory perianal fistulas.  It may help avoid surgery or systemic immunosuppression.

 

Closer Look at Data Then Image Below

“A Guide to Gutsy Living”

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A recent article ( David JG, Jofriet A, Seid M, et al. “A Guide to Gutsy Living”: Patient-Driven Development of a Pediatric Ostomy Toolkit. Pediatrics. 2018;141(5): e20172789) describes “A Guide to Gutsy Living”: Patient-Driven Development of a Pediatric Ostomy Toolkit (Full Text)

From ImproveCareNow: Download a free copy of the Ostomy Toolkit

Background:

The education we received about our ostomy surgery was brief and focused only on basic skills regarding caring for an ostomy, including changing and emptying the bag, but did not address concerns we had about living with ostomies as part of our everyday lives. This educational void placed the burden on us as patients to find resources on our own, decide if the information was appropriate, and determine if it was reliable and accurate.

In this article, we describe how we, as patients, harnessed the capacity of a collaborative chronic care network1 and were supported to develop a resource that patients needed.

Methods:

We started a national task force of interested patients and parents who had experiences with ostomies to develop a pediatric ostomy toolkit. The task force was composed entirely of patients and parents and consisted of 7 patients and parents

After a literature review, we asked task force members to identify questions and topics related to living with an ostomy, including questions members had preoperatively, immediately postoperatively, and in the extended time since their surgeries. From this prompt, our group generated a list of topics all patients and parents agreed on based on the shared concerns, insights, or questions our task force members had around ostomy surgery… After the creation of the toolkit, we reached out to clinicians to provide clinical review.

Results:

Our final 19-page, colorful toolkit included topics relating to friends, school, travel, ostomy supplies, clothing, playing sports, using humor to cope, emergency kits, educational issues (eg, 504 plans), “Gastronauts” (Gastronauts are freely available puppets with ostomies), and ostomy medical language…The pediatric ostomy toolkit was posted on the ICN Exchange platform

My take (borrowed from authors): In our patient- and parent-led toolkit project, we demonstrate how patients and families can self-organize and ask clinicians to consult to create needed resources within a network

Resources:

  • The Oley Foundation website is a good link for patients with enteral tubes, ostomies, and central lines. http://oley.org/
  • From ImproveCareNow: Download a free copy of the Ostomy Toolkit

View from Pine Mountain

 

Point-of-Care Calprotectin Values in Preterm Infants at Risk for Necrotizing Enterocolitis

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It doesn’t look like calprotectin measurement in newborns is going to be terribly useful for detecting necrotizing enterocolitis.  A recent study (W Nakayuenyongsuk et al. J Pediatr 2018; 196: 98-103) showed a great deal of variability in the calprotectin values in their cohort of 62 infants.

Methods:

  • All infants had a birth weight of <1500 g
  • Stools collected daily (first stool of the day) either for 30 days or postmenstrual age of 32 weeks (whichever was longer)

Results: Calprotectin Values in microgram/gram

  • 1st week of life: All patients: Mean 637 +/- 638, Median 273
  • 2nd week of life: All patients: Mean 349 +/- 414, Median 180
  • 3rd week of life: All patients: Mean 486 +/- 470, Median 316
  • 4th week of life: All patients: Mean 488 +/- 385, Median 412
  • 5th week of life: All patients: Mean 358 +/- 339, Median 226
  • 6th week of life: All patients: Mean 370 +/- 334, Median 295
  • 7th week of life: All patients: Mean 240 +/- 191, Median 184
  • 8th week of life: All patients: Mean 445 +/- 110, Median 466

The highest subset scores for calprotectin was noted in the 1st week of life among preterm infants with gestational age >30 weeks.  In this group, the mean value was 799 +/- 651 and the median value was 718.

There were only two patients who developed necrotizing enterocolitis, both of whom did have an early rise in calprotectin

My take: This data shows elevated and highly variable calprotectin values in the neonatal period.  There was also a trend towards higher values among those with postnatal age >30 weeks.

Related blog post: Fecal calprotectin values in first years of life

 

 

Eosinophilic Esophagitis -Three Subtypes

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Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study

T Shoda et al. The Lancet Gastroenterology & Hepatology, published online May 2, 2018. DOI: https://doi.org/10.1016/S2468-1253(18)30096-7

Abstract:

Background

Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical–pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states.

Methods

We did a cross-sectional study across ten hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. We analysed oesophageal biopsy specimens taken from paediatric and adult patients with eosinophilic oesophagitis (discovery cohort), using the eosinophilic oesophagitis diagnostic panel (EDP), a set of 96 informative transcripts. Histological and endoscopic features were assessed by quantification of oesophageal eosinophils and use of the eosinophilic oesophagitis histology scoring system (HSS) and the eosinophilic oesophagitis endoscopic reference score (EREFS). Associations among the various histological, endoscopic, and molecular features were analysed by Spearman correlation. Results were replicated in a biologically independent, single-centre, validation cohort of patients with active eosinophilic oesophagitis.

Findings

The discovery cohort contained 185 samples and the validation cohort comprised 100 specimens. In the discovery cohort, EDP showed intersite consistency, significant correlation with oesophageal eosinophils (p<0·0001), and similar findings between paediatric and adult patients. Of eight HSS domains, basal zone hyperplasia correlated with the EDP (median Spearman ρ 0·47 [IQR 0·36–0·60]). Of five EREFS features, distal furrows correlated with the EDP (median Spearman ρ 0·42 [0·32–0·50]). By analysing active eosinophilic oesophagitis in the discovery cohort, the EDP identified three clusters associated with distinct endotypes (termed EoEe1–3) despite similar eosinophil levels. EoEe1 was associated with a normal-appearing oesophagus (risk ratio [RR] 3·27, 95% CI 1·04–10·27; p=0·0443), an inverse association with a history of oesophageal dilation (0·27, 0·09–0·82; p=0·0105) and showed relatively mild histological, endoscopic, and molecular changes. EoEe2 showed an inflammatory and steroid-refractory phenotype (RR 2·77, 95% CI 1·11–6·95; p=0·0376) and had the highest expression of inflammatory cytokines and steroid-responding genes. EoEe3 was associated with a narrow-calibre oesophagus (RR 7·98, 95% CI 1·84–34·64; p=0·0013) and adult onset (2·22, 1·19–4·12; p=0·0155), and showed the highest degree of endoscopic and histological severity and the lowest expression of epithelial differentiation genes. These endotypes were replicated in the validation cohort by clustering and with an eosinophilic oesophagitis endotype-prediction algorithm.

Interpretation

Our new disease classification stratifies patients with eosinophilic oesophagitis into subgroups with potential clinical and therapeutic significance and provides a framework for a precision medicine approach to eosinophilic oesophagitis.

Related blog entries:

Sub-Analysis of DIAMOND Study

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K Watanabe et al. Clin Gastroenterol Hepatol 2018; 16: 542-9.

The DIAMOND study evaluated monotherapy with adalimumab (n=85) compared with combination therapy of adalimumab with azathioprine (n=91).

Key findings:

  • In this subanalysis of patients with moderate and severe Crohn’s disease (CD), endoscopic response (defined by SES-CD drop of at least 8 points or SES-CD <4) was significantly higher at week 26: 71.6% vs 54.4%. The OR for endoscopic response was 2.12 at week 26 with combination therapy.
  • At week 52 the endoscopic response difference was not statistically significant: 60% vs. 50%.
  • Similarly, mucosal healing was more common (but not statistically significant) in the combination group compared with monotherapy: 20.9% vs 103% at week 26, and 21.5% vs 12.2% at week 52.
  •  While not statistically significant, the combination group had ADA trough that was higher (7.6 compared with 6.5).

My take: The results described above for endoscopic responses and mucosal healing rates are depicted in figure 2 (I do not have a digital copy of figure or permission to use).  After one looks at this figure, depicting the data noted above, there certainly appears to be an advantage for the use of combination therapy in patients with moderate-to-severe CD.

Related blog posts:

 

 

I have not independently verified the claims on this tweet

Don’t Forget the Kidneys in Children with Intestinal Failure

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Increasingly, kidney problems are recognized in children with intestinal failure/short bowel syndrome who receive long-term parenteral nutrition.  A recent study (H Billing et al JPGN 2018; 66: 751-54) highlights the experience with this issue at a pediatric intestinal rehabilitation center in Germany.

Key findings:

  • Among 50 patients with a median age of 4.2 years, 76% had proteinuria
  • 30% had chronic kidney disease –indicated by reduced creatinine clearance of <90 min (1.73 squared)/min
  • Hypercalciuria was identified in 30 patients (60%)
  • Nephrocalcinosis was identified in 9 patients (18%)

The authors note that end-stage renal failure has not been reported in association with intestinal failure, though proteinuria is associated as a risk factor.

My take: This observational study shows a high frequency of kidney issues in children with intestinal failure. With improvements in survival, chronic kidney disease could become a more significant clinical issue.

 

Tweet below indicates need for careful nutrition input when children are placed on unusual diets, including the ketogenic diet.

Super Poopers –CCFA Take Steps 2018

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Yesterday, I was fortunate to participate in Crohn’s and Colitis Foundation of America (CCFA) “Take Steps” walk with a big contingent of our team.  A shout out to Melissa Sheffer who was honored as Adult Volunteer of the year and to Jacqueline Akin who was honored as a pediatric hero.

Melissa along with Dr. Larry Saripkin (not pictured but also at event/walk) have been the crucial volunteers to run Camp Oasis for the last 14 years.  Jacqueline said in her speech that she is followed by our team and also described some of the issues she has faced in trying to manage Crohn’s disease.

Also, I want to thank Jacob Schoeff and Dr. Dinesh Patel for team leadership and organizing our participation.  Great work!

For those so inclined, it’s not too late to donate to our CCFA team: CCFA Super Poopers Donation Link

Endoscopy for Graft-versus-host Disease

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Briefly noted: T Martensson et al. JPGN 2018; 66: 744-50.

This retrospective study with 44 children (81 procedures) examined the yield of endoscopy for graft-versus-host disease (GVHD).  They found that sigmoidoscopy had a sensitivity of 85% whereas Ileocolonoscopy OR combined EGD-sigmoidoscopy both had a sensitivity of 97.4%.  The authors, thus, advocate more extensive evaluation in the majority of children with possible GVHD.  “Sigmoidoscopy may be an approach to consider in severely ill children with contraindications to full endoscopy, for example, general anesthesia.”

Related blog post: Image Only: GVHD

Big Creek Greenway, near McFarland

From ImproveCareNow: Resources for Mind Body Interventions

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From ImproveCareNow: Resources for Mind Body Interventions

The above linked-website has links to many others for patients and providers: meditation, mindfulness, yoga and guided imagery.  The links on this page borrowed from Chelly Dykes and KT Park who credits Dr. Sindu Vellanki and Dr Ann Ming Yeh from Stanford.

 

Literature on these topics (also from ImproveCareNow): Mind Body Interventions and IBD

Mind Body Interventions and IBD – Journal Articles

Overview:

  • Yeh, A. M., Wren, A., & Golianu, B. (2017). Mind–Body Interventions for Pediatric Inflammatory Bowel Disease. Children, 4(4), 22. doi:10.3390/children4040022
  • Mindfulness/ Meditation/ Mindfulness based Stress Reduction (MBSR):
  • Kabat-Zinn, J., Lipworth, L., Burney, R., & Sellers, W. (1987). Four-Year Follow-Up of a Meditation-Based Program for the Self-Regulation of Chronic Pain: Treatment Outcomes and Compliance. The Clinical Journal of Pain, 3(1), 60.

**Note: This is an overview of MBSR, not IBD specific

Mindfulness:

  • Neilson, K., Ftanou, M., Monshat, K., Salzberg, M., Bell, S., Kamm, M. A., . . . Castle, D. (2016). A Controlled Study of a Group Mindfulness Intervention for Individuals Living With Inflammatory Bowel Disease. Inflammatory Bowel Diseases, 22(3), 694-701.
  • Jedel, S., Hoffman, A., Merriman, P., Swanson, B., Voigt, R., Rajan, K., . . . Keshavarzian, A. (2014). A Randomized Controlled Trial of Mindfulness-Based Stress Reduction to Prevent Flare-Up in Patients with Inactive Ulcerative Colitis. Digestion, 89(2), 142-155.
  • Hood, M. M., & Jedel, S. (2017). Mindfulness-Based Interventions in Inflammatory Bowel Disease. Gastroenterology Clinics of North America, 46(4), 859-874.
  • Berrill, J. W., Sadlier, M., Hood, K., & Green, J. T. (2014). Mindfulness-based therapy for inflammatory bowel disease patients with functional abdominal symptoms or high perceived stress levels. Journal of Crohns and Colitis,8(9), 945-955. doi:10.1016/j.crohns.2014.01.018
  • Gerbarg, P. L., Jacob, V. E., Stevens, L., Bosworth, B. P., Chabouni, F., Defilippis, E. M., . . . Scherl, E. J. (2015). The Effect of Breathing, Movement, and Meditation on Psychological and Physical Symptoms and Inflammatory Biomarkers in Inflammatory Bowel Disease.Inflammatory Bowel Diseases,21(12), 2886-2896.

Clinical Hypnosis:

  • Keefer, L., Taft, T. H., Kiebles, J. L., Martinovich, Z., Barrett, T. A., & Palsson, O. S. (2013). Gut-directed hypnotherapy significantly augments clinical remission in quiescent ulcerative colitis. Alimentary Pharmacology & Therapeutics,38(7), 761-771.
  • Mawdsley, J. E., Jenkins, D. G., Macey, M. G., Langmead, L., & Rampton, D. S. (2008). The Effect of Hypnosis on Systemic and Rectal Mucosal Measures of Inflammation in Ulcerative Colitis. The American Journal of Gastroenterology,103(6), 1460-1469.
  • Shaoul, R., Sukhotnik, I., & Mogilner, J. (2009). Hypnosis as an Adjuvant Treatment for Children With Inflammatory Bowel Disease. Journal of Developmental & Behavioral Pediatrics,30(3), 268.
  • Vlieger, A., Govers, A., Frankenhuis, C., & Benninga, M. (2010). Hypnotherapy for children with functional abdominal pain or irritable bowel syndrome: Long term follow-up. European Journal of Integrative Medicine,2(4), 191.

Yoga: 

IBS + Yoga:

  • Schumann, D., Anheyer, D., Lauche, R., Dobos, G. Langhorst, J., Cramer, H. Effect of Yoga in the Therapy of Irritable Bowel Syndrome: A Systematic Review. Clin. Gastroenterol. Hepatol.  2016, 14, 1720-1731.
  • Selvan, S. R., Kavuri, V., Selvan, P., Malamud, A., & Raghuram, N. (2015). Randomized clinical trial study of Yoga therapy for Irritable Bowel Syndrome (IBS). European Journal of Integrative Medicine,7, 23.
  • Kuttner, L., Chambers, C., Hardial, J., Israel, D., Jacobson, K., Evans, K. A Randomized Trial of Yoga for Adolescents with Irritable Bowel Syndrome. Pain Research & Management 2006, 11, 217-223.
  • Evans, S., Lung, K., Seidman, L., Sternlieb, B., Zeltzer, L., & Tsao, J. (2014). (567) Iyengar yoga for adolescents and young adults with irritable bowel syndrome (IBS). J. Pediatri. Gastroenterol. Nutri. 2014, 59, 244-253.

IBD + Yoga:

 

Concurrent Infections in Inflammatory Bowel Disease Flares

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Briefly noted: Y Hanada et al. Clin Gastroenterol Hepatol 2018; 16: 528-33.

In this retrospective review with 9247 patients with IBD, the incidence of bacterial pathogens (non-C diff) identified was <3% of those who were tested; in this group (n=25), Aeromonas was detected in 8,Salmonella in 7, Plesiomonas in 4, Campylobacter in 2, and Yersinia in 2.  From authors: “These infections did not have a significant negative impact on patient outcomes.  Given these findings, routine testing for infections other than CDI is not recommended.”

Chattahoochee River