Category Archives: Pediatric Gastroenterology Intestinal Disorder

How Common are Clostridium difficile infections?

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In 2011, Clostridium difficile was estimated, by a recent report from the CDC (NEJM 2015; 372: 825-34) to result in 453,000 infections in the U.S. based on surveillance data from 10 geographic regions.

Other key findings:

  • Approximately 29,000 deaths were attributed to Clostridium difficile infections
  • 65.8% of cases were health care associated.
  • 24.2% had onset in the hospital
  • Increased risk was particularly notable among the elderly, with an rate ratio of 8.65 in those 65 years of age or older
  • The aggressive NAP1 strain was evident in 30.7% of health-care associated infections compared with 18.8% of community-associated infections

Related posts:

Note to blog followers: Yesterday’s blog was retitled to “Radiologic Image for St. Patrick’s Day” rather than “Endoscopic Image for St. Patrick’s Day”

Withdrawing Therapy Leads To Relapse, Even if in Deep Remission

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A recent study, presented as an oral abstract (thanks to Jeff Lewis for forwarding this reference), indicates that even in patients in deep remission, withdrawal of anti-TNF therapy leads to relapse in about 50% even when thiopurines are continued; this is in agreement with previous posts (see below).

Full abstract: OP007 Relapse after Deep Remission in Crohn’s disease. Here are the results and conclusion from the abstract:

Results

Sixty one patients were included and followed-up for a median of 28 months (range 7-47). After withdrawal of anti- TNFa therapy (44 infliximab and 17 adalimumab) 47 (77%) patients continued thiopurines. 32 (52.5%) patients relapsed until the end of follow-up with a median time to relapse of 8 months (range 1-25). The cumulative probability of maintaining remission was 82% at 6 months, 59% at 1 year and 51% at 2 years. Analysis of 28 patients who were in deep remission (endoscopic healing; faecal calprotectin <150mg/kg; CRP <5mg/l) revealed no better survival (82%, 64% and 40% at 6 months, 1 and 2 years, respectively). Four (8%) of relapsing CD patients required surgery 5 to 19 months after anti-TNFa cessation (2 for new stricture development, 1 for medically refractory flare and 1 for high grade dysplasia). In multivariate model only disease localization was risk factor of disease relapse (colonic vs. ileal/ileocolonic: OR 0.16, 95%CI: 0.03-0.72; p=0.02). Type of anti- TNFa preparation, smoking, disease behaviour, corticosteroid or thiopurine therapy, biological markers and anti-TNFa trough levels did not impact disease relapse.

Conclusion

Approximately half of CD patients relapsed within 2 years after anti- TNFa discontinuation despite being in endoscopic remission when anti-TNFa was stopped. The highest relapse rate was observed during the 1st year. Ileal disease increased the risk of disease flare, while no other risk factor was identified.

Related blog posts:

Bryce Canyon

Bryce Canyon

Breath Testing for Bacterial Overgrowth

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A recent review (Clin Gastroenterol Hepatol 2014; 12: 1964-72) provides useful advice on testing for bacterial overgrowth and explains the limitations/obstacles in determining whether bacterial overgrowth is present.

Their recommendations:

  • Preparation: avoid antibiotics for 4 weeks prior to testing, avoid bismuth for 2-4 weeks, avoid probiotics for 2-3 weeks before testing, avoid consumption of non absorbable carbohydrates (eg. pasta, bread, fiber cereal, beans) the night prior
  • Glucose substrate for hydrogen breath testing is likely most suitable.  50 g in 250 mL.  Check baseline and then every 15 minutes over 120 minute testing interval.  Positive study: increase of 12 ppm (or more) over baseline and/or baseline >20 ppm (if proper test conditions)
  • Glucose breath test (GBT): sensitivity 20-93%, specificity 30-86%.  False-positive results can occur with rapid small-bowel transit.  GBT may not detect distal small bowel bacterial overgrowth.  Lactulose breath test (LBT) generally has lower specificity.
  • If breath testing is not available, small-bowel aspiration for quantitative culture is a reasonable consideration (challenging methodology).  Alternatively, a trial of empiric antibiotics may be considered if pretest probability is high.

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In NASH, is ALT Wrongly Used as a Marker of Liver Injury?

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According to a recent report (Hepatology 2015; 61: 153-60), elevation of alanine aminotransferase (ALT) which is frequently used as an indicator to select patients for further investigations (eg. liver biopsy) is NOT a good indicator of liver parenchymal injury in patients with nonalcoholic fatty liver disease (NAFLD).

The researchers enrolled 440 patients and divided them into three groups: no NAFLD (n=60), NALFLD with normal ALT (n=165), and NAFLD with elevated ALT (n=215). The patients were overweight/obese patients prospectively recruited from newspaper ads, general medicine clinics and hepatology clinics at several VA hospitals. Those with history of alcohol abuse were excluded.

Numerous investigations were performed including liver fat by proton magnetic resonance spectroscopy (H-MRS), liver biopsy (n=293), and insulin resistance measurements.

Key findings:

  • NAFLD & NASH patients with elevated ALT had higher liver triglyceride content (P<0.0001), worse adipose tissue insulin resistance (ATIR) (P<0.0001), and lower plasma adiponectin (P<0.05).
  • Steatosis was worse on liver biopsy in those with NASH and elevated ALT (P<0.0001).
  • There were no differences in liver inflammation (P=0.62), ballooning (P=0.13), or fibrosis (P=0.12). Thus, patients with normal versus elevated ALT had similar severity of NASH liver histology.

Take-home message:  In adults, ALT values are “poor surrogate markers of disease activity” in NAFLD.  ALT values, in these patients, are indicative of metabolic disease.  Given the staggering numbers of individuals, adults and children, with fatty liver disease, the lack of simple screen tool is quite problematic.  Equally problematic is a lack of a simple treatment approach.

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Refractory Constipation -Terrific Update

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Recently I attended a terrific talk by my partner, Jose Garza.  This lecture provided a great deal of information on refractory constipation for both pediatricians and pediatric gastroenterologists alike.

Elements of the talk included diagnosis, pathophysiology and differential diagnosis.

Rome III Criteria -Helpful in Diagnosis of Constipation

Rome III Criteria -Helpful in Diagnosis of Constipation

JG1 pathophys

Is it Hirschsprung's Disease?

Is it Hirschsprung’s Disease?

Some of the more useful points.

  1. AXR should not be used to make diagnosis of constipation.
  2. Many refractory constipation patients are stooling fine and actually labeled as constipation instead of a functional abdominal pain disorder.  That is, they are complaining of stomach pain and have been erroneously told they are constipated (see point #1).
  3. Miralax remains a 1st line agent for constipation. In individuals with fecal soiling, if miralax is not working and they have had appropriate cleanout, then senna laxative may be helpful.
  4. Sitz markers are particularly helpful in proving stooling when teenager claims to not be stooling for a month and in proving functional fecal retention rather than nonretentive soiling.
  5. If good treatment is not working, then refer to neurogastroenterology.

Related blog posts:

JG3 -Help

 

FMT for Crohn’s Disease -Small Study

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A recent prospective open-label study (Suskind DL, et al. Inflamm Bowel Dis 2015; 21: 556-63) adds a bit more information on fecal microbial transplantation (FMT) for individuals with Crohn’s disease (CD). This study included 9 patients, ages 12-19, and 11 authors.

Study details:

  • Pretreated with rifaximin 200 mg TID x 3 days and Miralax 17 gm TID x 2 days prior, and omeprazole day before and morning of procedure
  • Patients continued on prior treatment: 4 on methotrexate, 2 on thiopurine, and 3 on mesalamine (1 mesalamine patient was receiving methotrexate also)
  • Stool donor was a screened parent
  • Stool administered via NG
  • Stool DNA studied –>metagenomic sequencing

Key findings:

  • FMT engraftment was demonstrated in 7 of 9 patients
  • Mean PCDAI improved –baseline 19.7 –>6.4 at 2 weeks–>8.6 at 6 weeks
  • 5 of 9 patients who did not receive additional medical therapy were in remission at 6 and 12 weeks.

One particular advance with this study was the correlation between microbial species before and after FMT.  One speculation from the authors was that “the more divergent a Crohn’s patient is from his donor the more the potential benefit of transplantation.”  Thus, this same study with unrelated donor stool (eg. OpenBiome) would be of interest as well.

My Take: While this study offers encouragement for bigger studies, we will not know if FMT is effective (& how to administer optimally) until we have studies with more patients than authors.

Related blog posts:

 

 

Short Takes on IBD Articles

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Singh S, et al. Gastroenterol 2015; 148: 64-76.  In this study, the authors identified 21 trials with 2006 participants to examine the comparative efficacy of pharmacologic interventions to prevent relapse of Crohn’s disease (CD) after surgery.  Conclusion: “anti-TNF monotherapy appears to be the most effective strategy for postoperative prophylaxis for CD.” The relative risk of clinical relapse and endoscopic relapse with anti-TNF monotherapy was estimated to be between 0.02-0.20 and 0.005-0.04, respectively. Thus, those at highest risk for recurrence, including younger individuals, smokers, penetrating CD, perianal CD, and recurrent surgeries) are most likely to benefit.(Related blog post: More Lessons in TNF Therapy (Part 1) | gutsandgrowth)

Pariente B, et al. Gastroenterol 2015; 148: 52-63. The researchers in this cross-sectional study developed the Lémann Index which measures cumulative structural bowel damage in patients with CD.  My only complaint with this study was the associated editorial on pages 8-10, titled “The Holy Grail, or Only Half Way There?”  There are too many medical advances compared to ‘the holy grail’ and, in my opinion, this shouldn’t be one of them.

Zitomersky NL et al. Inflamm Bowel Dis 2015; 21: 307-14.  In this study the authors examine the relationship between the development of antibodies to infliximab (ATI) and the risk of surgery in a cross-sectional cohort of pediatric and young adult patients.  Not surprisingly, development of ATI, which was noted in 20% of cohort, correlated with reductions in infliximab levels and higher risk of surgery.  Interestingly, prior (but not current) immunomodulator therapy was associated with lower antibody levels (P=0.007).  Perhaps, “step-up” therapy may lower the risk of ATI. (This was a point noted by James Markowitz in a previous post: More NASPGHAN Meeting Notes: IBD Hot Topics | gutsandgrowth)

Rogler G, Vavricka S. Inflamm Bowel Dis 2015; 21: 400-08. This review article discusses the exposome in IBD.  Exposures include air pollution, diet, drugs, infections, water pollution, food additives, and smoking.  These exposures influence the gut microbiome and genetic susceptibility. “Only environmental influences…explain the rising incidence in IBD worldwide. The investigation of the exposome…is an enormous challenge…[but] of crucial importance.” (Related blog post: What do you know about the “exposome”? | gutsandgrowth)

Kalmon RS. Inflamm Bowel Dis 2015; 21: 428-35. Review article provides information when there is a prior personal or family history of malignancy (=avoid thiopurines).  Figure 2 is a suggested algorithm for those with IBD and a previous diagnosis of cancer.

  • In those in which the cancer is adequately controlled, the recommendations indicate that if it has been more than 2 years since completion of therapy to use a ‘step-up’ management and favor methotrexate over thiopurines
  • In those with less than 2 years since completion of cancer treatment and not responsive to 5-ASAs/antibiotics, then “consider monotherapy with biologic agents.”
  • In those still receiving chemotherapy, the authors suggest “hold immunosuppression and follow course of IBD.  If IBD not well controlled despite chemotherapy, 5-ASAs and antibiotics, treat flares with steroids, then consider biologic agents.”

An Oral Oligonucleotide in the Crohn’s Treatment Pipeline & Smart Patients

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The preliminary data are in from a phase II study regarding Mongerson, a oral pill for Crohn’s disease.

Here’s the link: Oral oligonucledotide shows efficacy, safety in Crohn’s

Here’s an excerpt from GI & Hepatology News:

Fourteen days of daily treatment with mongersen, an oral, antisense oligonucleotide, safely produced remissions in two-thirds of patients with Crohn’s disease in a phase II study with a total of 163 patients…

Mongensen “is not an anti-inflammatory drug. It removes a brake on the normal immunosupressant mechanism in the gut, and that is why the effect is long lasting. It allows TGF [transforming growth factor]-beta to work again [as an endogenous immunosuppressant] and promote healing,” said Dr. Monteleone, a professor of gastroenterology at the University of Rome Tor Vergata.

Oligonucleotide blockade of the production of the Smad7 intracellular protein prevented the inhibitory effect of Smad7 on TGF-beta and thus allowed TGF-beta to inhibit cytokine production and T lymphocyte signaling (J. Clin. Invest. 2001;108:601-9).

From ImproveCareNow — Smart Patients Online Community -may be helpful resource for families:

There are many social networks and online communities for IBD, but we have chosen to partner with the Smart Patients team because their custom-built, disease-specific forums offer a truly safe, warm and engaging experience for users. Smart Patients also offers conversation tagging, and clearly defined community norms, which means community members are highly likely to find the answers they need and highly unlikely to be trolled. And because the conversations are arranged using tags and completely searchable, you can always find what you’re looking for.

The Smart Patients team and ImproveCareNow have partnered to create an online IBD community that is supportive and also powerful. The Smart Patients IBDcommunity has the power to improve health and health care systems through patient and family peer-to-peer learning.

 

Taking One ‘Bite’ At A Time -For Celiac Diagnosis

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A small study (reference from KT Park’s Twitter feed –Gastrointestinal Endoscopy DOI: http://dx.doi.org/10.1016/j.gie.2014.10.024) suggests that taking a single biopsy per pass rather than two biopsies per pass results in better quality specimens:

Link: Endoscopic Biopsy Technique in the Diagnosis of Celiac Disease

Here are the results and conclusion of the abstract:

Results

Patients (N = 86) were enrolled, 47% with known celiac disease, 36% with suspected celiac disease, and 17% with an unknown celiac disease status. Well-oriented biopsy specimens were noted in 66% of patients with the single-biopsy technique and 42% of patients with the double-biopsy technique (P < .01). Analysis of matched pairs showed improved orientation with the single-biopsy technique (odds ratio 3.1; 95% confidence interval, 1.5-7.1; P < .01). This persisted in subgroup analysis of patients with known celiac disease (P = .02), villous atrophy (P = .02), and a final diagnosis of celiac disease (P < .01).

Conclusion

The single-biopsy technique improves the yield of well-oriented duodenal biopsy specimens. Endoscopists should consider taking only 1 biopsy specimen per pass of the forceps in patients undergoing biopsies of the duodenal mucosa.

Related blog posts:

I'm the one on the right

I’m the one on the right