Category Archives: Pediatric Gastroenterology Intestinal Disorder

NASPGHAN Postgraduate Course 2014 -Intestinal Inflammation

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This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Link: PG Course Syllabus – FINAL (entire syllabus)

The speakers reviewed a lot of IBD material (both at the postgraduate course and at the meeting); much of it has been has been covered in previous blog posts:

Early Onset Inflammatory Bowel Disease –Scott Snapper (Boston Children’s Hospital) pg 170 in Syllabus

  • If one has a 1st degree relative with Crohn’s disease: 26-fold increased risk for IBD compared with 8-fold increased risk if 1st degree relative has ulcerative colitis
  • 30% of children have one or more family members with IBD
  • Concordance rate much greater in monozygotic vs dizygotic twins: 10-15% in UC and 25-30% in Crohn’s with monozygotic

Infantile IBD (age <2 years)

  • Often isolated colonic disease
  • Severe course – refractory to multiple immunosuppressant medications, often requiring surgery, occasionally fatal
  • > 40 % with one or more family members with IBD
  • 25% with infantile IBD have this as their first manifestation of underlying immunodeficiency (pg 174): IPEX, CGD, NEMO, Wiscott-Aldrich, XIAP, common variable immunodeficiency
  • NEOPICS: interNational Early Onset Pediatric IBD Cohort Study. Expanded to 80 Centers (250 scientists) on 5 continents with access to over 1000 VEO-IBD patients
  • IL10 Receptor defect results in infantile onset IBD. Hematopoietic stem cell therapy can be curative. Increased risk of B-cell lymphomas.
  • NCF2 variant (NADPH Oxidase Gene) found in 4% of   (n=11/268)
  • TTC7A mutations (identified by whole exome sequencing) cause apoptotic enterocolitis, intestinal atresias, and SCID (severe combined immunodeficiency) –may not benefit by stem cell transplantation
  • Immune workup for VEO-IBD: immunoglobulins, DHR for CGD, lymphocyte subsets. If negative, further genetic testing (candidate gene testing &/or exome sequencing)

Surgery in Crohn’s Disease –Jason Frischer (Cincinnati Children’s)

  • 28% of CD patients need surgery within 10 years of CD diagnosis; 5.7% within one year.
  • Reviewed principles: conserve bowel, reserved for complications/does not cure Crohn’s disease, strictures can be treated without resection.

Perioperative care

  • Preop-“no answer with regard to biologics,” steroids are detrimental (goal <20 mg of prednisone).  Biologics may increase risk of infections (could be related to specific level) but this is unclear.
  • Postop: thromboprophylaxis

Surgical problems (JPGN 2013; 57: 394 NASPGHAN Guidelines): Abscess, Fistula, Stricture

  • Abscess: percutaneously drain abscess if >2 cm and can remove drain when having less than 10 mL/day. Surgery reserved if refractory to conservative treatment –?timing
  • Strictures: steroids to minimize acute inflammation.  Stricturolplasty rare in pediatrics –used only in those without fistulas. Most common stricturolplasty: Heineke-Mikulicz.
  • In Crohn’s patients at Cincinnati children’s who have undergone ileostomy, long-term only 46% able to have intestinal continuity

Crohn’s and UC ‐ What to do when anti‐TNF isn’t working? –Athos Bousvaros (Boston Children’s) pg 190 in Syllabus

Off-label IBD drugs in children for medically-refractory disease.

Potential Rescue treatments

  •  Calcineurin inhibitors for UC (eg. tacrolimus, cyclosporine)
  •  Thalidomide for Crohn disease
  •  Natalizumab for Crohn disease –>not being used anymore. PML risk
  •  Vedolizumab for Crohn disease and UC
  •  Ustekinumab for Crohn disease
  •  Tofacitinib for UC

Before off-label drugs:

  • Optimize TNF: Make sure the diagnosis is right (eg. exclude CGD), Minimize risk of loss of response (combination therapy, optimize dose, scheduled infusions)
  • Consider surgery -strictures, ulcerative colitis, limited disease

Data for tacrolimus from Boston. n=46. (Watson et al, IBD Journal 2011).  Used most frequently with severe UC.

Data for thalidomide –31 of 49 achieved remission. Lazzerini et al, JAMA. 2013;310(20):2164‐2173.  Side effects -birth defects, neuropathy.  STEPS program.

Data for vedolizumab. Feagan et al NEJM 2013; 369:699.  Remission (in the responders) for ulcerative colitis at 52 weeks:

  • 45% of patients getting vedolizumab monthly
  • 42% of patients getting it every other month
  • 16% of patients randomized to placebo

For Crohns’ disease , Vedolizumab also works in Crohn’s disease, but it takes time (Sands et al: Gastroenterology 2014 147:618‐627)

Off-label does not equate to experimental! pg 199:

FDA Statement: The FD&C Act does not, however, limit the manner in which a physician may use an approved drug. Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in approved labeling. Such “unapproved” or, more precisely, “unlabeled” uses may be appropriate and rational in certain circumstances, and may, in fact, reflect approaches to drug therapy that have been extensively reported in medical literature.

 

“Luminitis:” When Inflammation is Not IBD (Microscopic Colitides) –Robbyn Sockolow (Weill Cornell Medical School) pg 180 in Syllabus

Microscopic Colitis -pediatric prevalence unknown (JPGN 2013;57:557-561). Nonbloody diarrhea with normal-appearance grossly.

  • Lymphocytic Colitis (>20 intraepithelial lymphocytes/100 colonocytes) -Normal crypt architecture
  • Collagenous Colitis -Thick layer (up to 30 micrometers) of collagen in the tissue and increased lymphocytes in colon

Eosinophilic colitis

  • At-risk groups?  Infants & post-transplant patients (tacrolimus trigger?) (Saeed et al Pediatr Transplantation 2006: 10: 730–735)
  • Associated with food allergy, IBD, autoimmune diseases
  • Elevated serum IgE.

 

 

Microbial Signature in Crohn’s

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This recent study (summarized in earlier post today/Dr. Barnard’s talk) provides more information on the microbiome in patients with pediatric Crohn’s.  Here’s a link to full article: Specific transcriptome and microbiome signature in pediatric Crohn’s   Here’s the abstract:

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.

From Cincinnati Children’s Pediatric Insights (summary of findings):

“The discovery of specific bacterial populations and a core gene signature associated with Crohn’s disease could lead to new diagnostic testing and improved treatment for inflammatory bowel disease (IBD), according to a study led by researchers at Cincinnati Children’s.

‘This study identifies a set of bacteria that are associated with symptoms, and a group of anti-inflammatory genes that are associated with intestinal damage in children with Crohn’s disease,’ says Lee (Ted) Denson, MD, Medical Director of the Inflammatory Bowel Disease Center, senior investigator for the study, published online July 8 in the Journal of Clinical Investigation. Yael Haberman Ziv, MD, was the study’s first author.

Denson’s team studied tissue samples from the ileum, the lowermost portion of the small intestine, in a large number of children with Crohn’s disease. They found specific types of bacteria and a “core” gene expression signature, both of which appear to affect inflammatory changes in the gut. Certain genes in the core signature appeared to be specifically associated with intestinal damage from deep ulcers.”

 

Basic Science Year in Review –#NASPGHAN 2014

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John Barnard –Basic Science Year in Review

“Emerging Trends and Provocative Findings in Basic Science”

This blog entry has abbreviated/summarized this terrific presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.  To minimize these issues, I have placed a link to most of Dr. Barnard’s slides which he shared:

2014 John Barnard Slides

“Big Data” –big increase in “big data” cited in pubmed over past year.

  • Good read on this subject: Foreign Affairs: The Rise of Big Data Kenneth Cukier

Scientific fraud –more attention to this issue this past year. Two papers in Nature were retracted. One researcher committed suicide and one arrested. Scientific fraud undermines important messages & ruins credibility of other important advances.

CRISPR-Cas9: Gene editing.  CRISPRs –“RNA guides”  Cas9: “molecular scissors” (endonucleases)

“Genome editing has never been easier.”  Examples:

  • Cell Stem Cell 2013: 13: 653-58. “Functional repair of CFTR by CRISPR-Cas9”
  • Also, genome editing has been used in mouse model of tyrosinemia.

Liver regeneration in zebrafish. Implication: Liver cells will be regenerated in humans. Gastroenterol 2014; 146: 789.

Microbiome Big Data:

  • J Clin Invest 2014; 124: 3617. This was a very important and complex study.  The slides explaining this study start at slide 35.
  • Pediatric Crohn disease exhibit specific ileal transcriptome and microbiome signature.
  • RISK study (CCFA). Treatment-naïve, 28 sites.
  • 1281 ileal host genes in ileocolonic Crohn’s, 1055 in Colonic Crohn’s had ileal host genes =82% similar, 232 host genes in ulcerative colitis –18% similar to ileocolonic Crohn’s.
  • Tissue microbiomes are where changes are noted; changes are not evident in luminal microbiome.
  • Antibiotics worsen dysbiosis.
  • Microbiome at diagnosis strongly correlates with Crohn’s disease.

Microbiome –affects the entire body:

  • J Clin Invest 2014; 124: 3391. Incorporation of microbes with genetically-engineered E coli can prevent obesity in mice

Recommended Reading by Dr. Barnard: “Missing Microbes” How the overuse of antibiotics is fueling our modern plagues. Martin Blaser

 

NASPGHAN Postgraduate Course 2014 -Endoscopy Module

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This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.  Link to full syllabus:

PG Course Syllabus 2014

The Dreaded Wake-Up Call (Part A) –Maercedes Martinez (NY Presbyterian Hospital) (pg 55 syllabus)

Variceal Bleeding – “When RED is not attractive”

Discussed presentation of varices (gastric/esophageal), etiologies, association with portal hypertension. Reviewed variceal grading.

Medical management:

  • PICU admit
  • Avoid over-transfuse (goal ~ 8 g/dL)
  • Correct coagulopathy
  • Role of platelets is controversial/if trouble with endoscopy, may be helpful
  • Suggested dosing for octreotide/somatostatin: 2 mcg/kg bolus then 1-2 mcg/kg/hr (typically max 100 mcg/hr), antibiotics
  • Most patients do not require emergency overnight endoscopy.
  • Sclerotherapy and banding reviewed -including complications.
  • Transjugular intrahepatic portosystemic shunts (TIPS) and Surgical options briefly discussed

The Dreaded Wake-Up Call (Part B) –Lee Bass (Children’s Hospital of Chicago) (pg 67 in syllabus)

Nonvariceal GI Bleeding Management

  • Start with ABCs -airway, breathing, cardiovascular –fluid resuscitation/blood products
  • Restrictive transfusion strategy (Hgb <7 as threshold) (Villanueva et al NEJM 2013) helpful for survival in adults
  • Treatment with PPI improves rates of high risk stigmata on endoscopy
  • Prokinetics can improve identication of bleeding lesions
  • Preparation for endoscopy is most important (slide on page 70 of syllabus)
  • Also on page 70, pictures of typical findings with GI bleeding: nonbleeding vessel, adherent clot, spurting blood, oozing blood, and flat pigmented spot and clean base
  • Endoscopic management -combination of two techniques appears to be more effective than single method. injection, thermal probe, hemoclips, hemospray (not available in U.S.

Endoscopic Interventions for Biliary Tract Disease — Victor Fox (pg 75 in Syllabus)

Choledocholithiasis is most common need for interventional biliary endoscopy and increasing related to increase risk with increase in obesity.(Buxbaum J. Gastrointest Clin N Am 2013;23:251‐75)

Requires advanced training to achieve high level of skill and experience

  • >200 cases needed to achieve selective cannulation required for interventions
  •  Acquisition and maintenance of skills by pediatricians is controversial

Other points:

  • No equipment is favorably designed for young or small children
  • Success and complication rates are similar as in adults (Varadarajulu S, et al. Gastrointest Endosc 2004;60:367)
  • Discussed biliary strictures (etiologies, management/stents), choledochocele, papillotomy, bile leak (Soukup ES et al. J Pediatr Surg 2014;49:345‐8)

  • “Most strictures and leaks can be successfully managed endoscopically without need for surgical intervention”

Take-home message: Endoscopic biliary interventions are increasingly employed in children with similar safety and technical success as adult patients

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

 

 

 

 

 

NASPGHAN Postgraduate Course 2014 -3rd Module

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This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.  All of the speakers had terrific presentations.  The course syllabus is attached:

PG Course Syllabus 2014

The 3rd Module had a “potpourri” of GI problems.

Extraesophageal Manifestations of Gastroesophageal Reflux –Ben Gold, MD (GI Care For Kids, Atlanta) (pg 86)

“Is reflux really the scurge of the earth and the cause of every malady known to human-kind in the head, neck, and lungs…?“

Key points:

Airway protection: “Aerodigestive disease reflexes are intact by 38 weeks gestation.”

Central deglutition apnea: a normal protective mechanism to prevent aspiration during swallowing. (Hasenstab KA, Jadcherla, S. J Pediatr 2014; 165:250-255).  No proof at present that central apnea is caused by reflux though there is a biologic plausibility.

“Although reflux causes physiologic apnea, it causes pathologic apneic episodes in only a very small number of newborns and infants.”  “When reflux causes pathological apnea, the infant is more likely to be awake and the apnea is more likely to be obstructive in nature.”

Laryngeal Reflux:

  • Chronic cough, chronic laryngitis, hoarseness, and asthma may be associated with GERD BUT the data showing a relation between reflux and upper airway disease are weak
  • Airway symptoms attributed to reflux in adults include hoarseness, chronic cough, and globus sensation
  • Affected adults rarely have typical reflux symptoms
  • The sensitivity of laryngoscopic findings to identify reflux disease are poor. Sherman et al. Am J Gastroenterol. 2009;104:1278-95. Vandenplas et al. J Pediatr Gastroenter Nutr. 2009;49:498-547.

Asthma:

“Chronic cough, chronic laryngitis, hoarseness and asthma are multifactorial disease processes and acid reflux can be an aggravating cofactor.” GER is an unlikely contributor to asthma if reflux testing is negative.

“Two NIH-funded blinded, randomized placebo-controlled trials (RCT), one in adults (using esomeprazole), one in children (using lansoprazole) showed NO difference in asthma outcomes comparing placebo and acid suppression therapy”

Multi-Channel Intraluminal Impedance/pH probe studies: Pediatric studies are critically needed to determine if knowing the amount of nonacid reflux changes treatment or outcome

Proton Pump Inhibitors can cause gastric bacterial overgrowth (Rosen R et al JAMA Pediatr 2014; JAMA Pediatr. doi:10.1001/jamapediatrics.2014.696)

Ben Gold (speaker) and Jay Hochman prior to 5K Run

Ben Gold (speaker) and Jay Hochman prior to 5K Run

Related blog posts:

EoE: PPI, PPI-REE, TCS, OVB, SFED, 4FED….…Alphabet Distress — Sandeep K Gupta, MD (Indiana University) pg 105 in Syllabus

Treatment endpoints discussed -histologic, symptomatic, fibrosis, etc.

  • Proton pump inhibitor responsive eosinophilic esophagitis (PPI-REE) may work by blocking STAT6 binding to Eotaxin-3 promoter rather than by acid suppression (PLos ONE 2012;7:e50037).  PPIs work (eos <6/hpf) in in 30-40%.  May need high dose to work long-term (Dr Molina-Infante – DDW 2014)
  • Topical corticosteroids (TCS) -higher dose = better response.  (Budesonide. Gupta SK, Vitanza J, Collins, MH Clin Gastro Hepatol 2014 [ePub], Fluticasone. Butz BK. Gastroenterology 2014). Clinical symptoms do not correlate with histologic response. Discussed long term safety concerns.
  • Reviewed diets -elemental, targeted, 4-food elimination and 6-food elimination.

Related blog posts:

“Gotta keep on movin”: New tricks and treatments for motility disorders –Carlo DiLorenzo (Nationwide Children’s Hospital) pg 116 in Syllabus

Key points:

  1. Most important motility study is a normal study.  If normal study, then there is more concern for sensory dysfunction.   Look for significant findings on motility studies not minor changes.
  2. Key to confirm if motility disorder is present. Hx/o small intestinal transplant in medical child abuse/Munchausen syndrome by proxy (Trans Proc 1996; 28: 2790)
  3. New tool: wireless motility capsule (J Pediatr. 2013;162:1181-7)
  4. Easier to obtain full thickness biopsies (Gastrointest Endosc 2011;73:949-54)

Treatments reviewed -“try everything”

  • prucalopride (JPGN 2014; 57: 197-203
  • cisapride -still available
  • lubiprostone (JPGN 2014;58:283–291)
  • linaclotide boxed warning not for <17 years of age –though has been used by motility specialists
  • cyproheptadine (J Pediatr 2013; 163: 261-7) –use in dyspepsia
  • fludrocortisone -used in orthostatic intolerance
  • augmentin -for small bowel motility (JPGN 2012;54: 780–784)
  • octreotide -for bowel motility
  • pyridostigmine (Colorectal Disease 2010 12, 540–548)
  • iberogast
  • botulinum toxin (Gastrointest Endosc. 2012 ;75:302-9)
  • treat bacterial overgrowth
  • surgery: Jube, GJ tube, ileostomy. “Every child with pseudoobstruction on TPN needs a gastrostomy and an ileostomy –(me, now)”
  • gastric electrical stimulation
  • emerging treatment: Elobixibat (for constipation) Expert Opin. Investig. Drugs

Related blog posts:

What’s New in the Diagnosis and Management of Constipation –Manu Sood (Children’s Hospital of Wisconsin) -page 130 in Syllabus

Reviewed recent guidelines from NASPGHAN

“Miralax is considered a 1st line agent”

Outcomes in children with constipation:

  • Almost 50% of patients experienced at least one relapse in first 5 yrs.
  • Almost 20% of children were symptomatic at 10 yrs. follow up (Bongers ME, et al. Pediatrics. 2010)

Pointers:

  • Slow transit is common
  • Rectal compliance does not predict success with treatment. Van den Berg MM, et al. Gastroenterology 2009.  Patients with mega-rectum may have motility disturbance as well.
  • Success rates for antegrade continence enemas (ACE) 65% to 89%. Colon manometry can help predict ACE success.  Up to 40% may be able to stop ACE w/in 2 years

Related blog posts:

Clinical Science Year in Review in Pediatric GI – NASPGHAN 2014

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For many participants at NASPGHAN, the “year in review” presentations are a highlight.  This year was no exception.

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

William Balistreri –Clinical Science Year in Review 

Lay press remains excellent source of information.

Benefit of microbiome. (from NPR) Now there is elephant poop coffee -$645/lb ($70/cup).  Link: No. 1 Most Expensive Coffee Comes From Elephant’s No. 2 : The ... Collecting elephant poop is probably a less ideal job than what most of us have.  As for coffee, “make mine de-crap.”

Elephant Microbiome Collector

Topic of the year: Hepatitis C

  • 25 years since identification of Hepatitis C in 1989
  • Now approaching cure (Related blog post: Wiping out Hepatitis C | gutsandgrowth). All-oral highly effective regimen –newest regimen as easy as one pill per day for 8-12 weeks. Direct-acting antivirals (DAAs). Moving past 1st generation of DAAs: telaprevir/boceprevir with interferon/ribavirin.(refs = Pawlotsky, Gastroenterology 146:1176, 2014 and Schmidt, Clinical Gastroent Hepatol 12:728, 2014)
  • New drugs for HCV –just in time –increasing risk of HCV complications. Ann Intern Med 2014; 160: 293.
  • Goal –SVR –sustained virological response
  • Reviewed large number of articles: Sofosbuvir, Simeprevir, Sofosbuvir/Ledipasvir (Harvoni).  3-D regimen: ABT-450, ABT-267, ABT-333 –will be approved in coming weeks (Related blog post:Have You Heard of Harvoni? | gutsandgrowth)
    • Gane, NEJM 368:34, 2013
    • Zeuzem, NEJM 370:1993,2014
    • Kowdley, N Engl J Med 370:1879, 2014
    • Lawitz, Lancet 383:515, 2014
    • Feld, New England Journal of Medicine, 370:1594, 2014
  • Mild side effects with newer drug therapies
  • Awaiting pediatric studies.
  • Costly $1000/pill –“if dog swallows it,” may have to look for it in the stool
  • Stay updated with recommendations: www.hcvguidelines.org  (AASLD/IDSA)

Hepatitis B –success of vaccination.

  • Preventing perinatal transmission with HBIG/vaccine. JAMA 2013; 310: 974. Those born after 1984, with much lower HCC. Ann Intern Med 2014; 160: 828; Hepatology 2014; 60: 448
  • Give antivirals (eg. telbivudine) for HBeAg-positive mothers prior to delivery. (Related blog post: Hepatology Update -Summer 2014 | gutsandgrowth) Greenup, Journ of Hepatology 61:502, 2014 AND Zhang, Hepatology 60:468, 2014
  • Antiviral therapy lowers the risk of HCC. Hepatology 2014; 147: 143 (Wu et al).
  • Make sure children with IBD are being screened for hepatitis B. ~13% may not be immune. Moses, Am J Gastro 107:133, 2012

Trend of the Year: Social Media

  • Genome sequencing –tremendous advance. Families may push for this option on their own.
  • Magnets –banned. Social media allowed this problem to be quickly identified. (Related blog post: Buckyball Recall –It’s Official | gutsandgrowth)
  • Social media allows family to share information and get answers. Internet blogging allows families to reach out to scientists.
    • Schumacher, Pediatrics 133:e1345, 2014
    • Enns, Genetics in Medicine, March 2014
  • BiliCam –can take picture with mobile phones.

Biliary Atresia

Threat of the Year: Obesity along with NAFLD

  •  NAFLD can have significant liver histologic abnormalities even with normal ALT levels. J Pediatr 2014; 164: 707.
  • Clinical burden of NAFLD is not restricted to liver-related morbidity or mortality Armstrong, HEPATOLOGY 59:1174, 2014. Also, concern for obstructive sleep apnea and cardiovascular disease.  Sundaram, J Pediatr 164:699, 2014. Pacifico, HEPATOLOGY 59:461, 2014
  • Elastography is promising tool. Xanthakos, J Peds 164:186, 2014
  • Current treatment –lifestyle changes. Snacking contributes to fatty liver. Sleep curtailment is associated with obesity. Spaeth. SLEEP 36:981, 2013, Taveras, Pediatrics 133:1013, 2014, Mitchell, Pediat 131:e1428, 2013
  • Increased antibiotics in early life associated with obesity due to alteration of microbiome. Bailey, JAMA Pediatrics, Sept 29, 2014
  • Suggestion for future: “Diet Water.”

Diet Water.jpg

For those who want to learn more from Dr. Balistreri directly, I would recommend the Aspen Conference:

Aspen Meeting

Related link: Dr. Balistreri’s Review of the Growth and Development of the Pediatric Gastroenterology Specialty.

 

Diabetes and Hepatitis C –A Bad Combination

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Until recently (see next post tomorrow), it has been well-recognized that there is a connection between chronic hepatitis C infection and diabetes mellitus (DM) (related previous post: Treating HCV Helps Diabetics | gutsandgrowth).  More data confirms that the development of diabetes is associated with increased risk of poor outcomes in HCV-infected patients.

  • Hepatology 2014; 60: 807-14
  • Hepatology 2014; 60: 823-31

In the first study, the authors used a nation-wide cohort comprising >99% of the Taiwanese population.  Among a random sample of 1 million enrollees, 6,251 adult chronic HCV patients were identified from 1997-2009.  Among those who developed DM during the study period (not before), after adjustment for confounding variables, diabetes was an independent predictor for cirrhosis (hazard ratio (HR) =2.5, P<0.001) and hepatic decompensation (HR=3.56, P+0.003).

In the second study, the authors identified consecutive chronic HCV-infected patients with cirrhosis who were hospitalized between 2006-2008 (n=348).  At baseline, 40% had DM.  DM was independently associated with development of ascites (P=0.057), renal dysfunction (P=0.004), bacterial infections (P=0.007), and hepatocellular carcinoma (P=0.016).  The authors suggest that improving diabetes control may improve the outcome of cirrhosis.

Take-home message: New-onset diabetes is a marker for progressive liver disease in patients with chronic HCV infection.  Whether diabetes has a causal role in HCV patient deterioration remains unclear.

Also noted, from Healio Gastroenterology, a recent study suggests that sofusbuvir/ledipasvir reduces HCV-related complications, here’s link: Sofusbuvir/ledipasvir Abstract

NASPGHAN Awards 2014

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I wanted to congratulate/recognize this year’s awardees at NASPGHAN and to summarize some of the associated presentations.

This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Major Awards:

  1. Harry Shwachman Award: Peter Whitington (Children’s Hospital of Chicago) This award is given for major life long scientific contribution to the field of pediatric gastroenterology.
  2. Distinguished Service Award: Melvin Heyman (UCSF Division Chief and JPGN editor). This award is given for excellence and service in the field of pediatric gastroenterology.
  3. AAP Murray Davidson Award: Jeffrey Hyams (Division Chief Connecticut Children’s)This award is given to an outstanding clinician, scientist and educator.

Fellow Research Award: “Bile Acid Signatures in Children Confer Protection From Clostridium Difficil Infection” ME Tessier et al (Baylor College of Medicine). Conclusions: Stool bile acids profiles are different in children with C difficile infection and could be a predisposing factor.  C diff toxins may alter bile acid profiles via inducing epithelial FGF-19 production.

Young Investigator Award “Analysis of Candidate Genes by Whole Exome Sequencing in Very Early-Onset IBD” J Kelsen (CHOP), et al. VEO-IBD cohort. Excellent presentation! (Related blog post: Just the Beginning: Mutations in Very Early Onset ..)

  • Children <5 years/extensive controls.
  • Mutation Findings: IL10RA/IL21R variants, RAG2/PIK3R1 variants
  • Presentation included phenotypic description (clinical and immunity/functional analysis)
  • Gut microbiome development being studied as well
  • Trying to combine microbiome data with genomic data.

William Balistreri Prize “A Prospective Newborn Screening Study for Biliary Atresia” Sanjiv Harpavat (Baylor College of Medicine) et al.   Excellent talk!

Background: 67 infants with biliary atresia (2007-2014) on retrospective review—ALL had elevated conjugated/direct bilirubin levels in first 24-48 hours of life. (Related blog post: Diagnosing biliary atresia earlier | gutsandgrowth)

Repeat testing at 2 weeks can identify those infants that need to be followed closely.  Workup needed for those who remained abnormal at 2 weeks of life.

This algorithm was studied at 4 different hospitals in Houston with 2-12% premature infants)

In newborn period:

  • N=11,636 –121 abnormal on newborn testing (based on hospital’s normative values -usually direct bilirubin >0.4)
  • When repeated at 2 weeks: 102 of these 121 were normal/only 12 continued to test high (2 with BA, 1 A1AT, 1 Rh disease, 8 resolved).  The two patients detected with biliary atresia is in line with the expected frequency of ~1 in 5000.
  • 7 missed retesting. 3 died (congenital heart disease), 2 missed followup, 2 had PCP refuse retesting.
  • Testing results: 100% sensitivity. Good specificity with repeat testing.

Baylor Workup approach to cholestasis:

  • 3-4 day evaluation
  • Day 1: liver panel, A1AT typing, U/S, CXR
  • Days 2-4: liver biopsy/percutaneous cholangiogram, +/- Kasai

Current AAP recommendation (per Ronald Sokol) is for all infants to have fractionated bilirubin.

Take-home message: How can we diagnose every infant on time? Possibly check every infant for direct/conjugated bilirubin in first 48 hours.

Young Clinical Investigator Award: “Poop-MD: A mobile health application accurately identifies acholic stools.” Douglas Mogul

Problem of delayed diagnosis has been improved in some studies with stool color cards. With emergence of smart phones (80% of 18-35 year olds have smart phones), opportunity to identify echoic stools with new technology.

  • PoopMD. Software determines whether stool is bloody, acholic, etc. Can email doctor and place reminder. FREE app.
  • Parents takes the picture of stool and then app analyzes.
  • Pilot study with 45 initial photographs reviewed by panel of 7 pediatricians
  • When at least 6 physicians agreed on stool color as being acholic (n=7), this was tested against app
  • App: 100% sensitivity for acholic stools. 89% specificity.
  • Working on Spanish version and improved interface.

Other awards:

NASPGHAN Foundation Awards

NASPGHAN Foundation Awards

Sponsored Awards

Sponsored Awards

NASPGHAN Postgraduate Course 2014 -Nutriton Module

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Thanks to those who attended yesterday’s talk (10/24/14) at the clinical practice session and to those who provided helpful feedback.

This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.  If you make it to the bottom of this post, you will find some useful patient resources along with previous related blog entries.

Diet and the Microbiome –Robert Baldassano (CHOP) pg 140 in Syllabus

This was a very effective lecture; it brought together a lot of useful information.

Trying to sort out balance between health and disease and role of dysbiosis (altered microbiome)

  • Things that we ingest such as food (diet), antibiotics, and xenobiotics shape the composition of the gut microbiota and serve as substrates for the gut microbiota to produce metabolites
  • We are not the only organism consuming what we eat

Specific studies:

  • Wu G, et al. Science. 2011 Oct 7;334(6052):105-8  The Bacteroides enterotype was highly associated with animal protein and saturated fats, which equates to frequent meat consumption as in a Western diet. The Prevotella enterotype high values for carbohydrates and simple sugars, indicating association with a carbohydrate-based diet more typical of agrarian societies.
  • De Filippo C, et al. PNAS 2010: 14691-96: African children (compared with European) with more bacterial diversity & richness along with higher levels of short-chain fatty acids
  • Holmes et al. Cell Met 2012; 16: 559. Diet serves as a substrate for the microbiota to produce certain metabolites.

IBD and diet (Hou JK et al. American Journal of Gastro 2011;106:563-73)

  • High dietary intakes of total fats, PUFAs, omega-6 and meat were associated with an increased risk of CD and UC
  • High fiber and fruit intakes were associated with decreased CD risk
  • High vegetable intake was associated with decreased UC risk.
  • Consumption of meat, particularly red and processed meat increased the likelihood of relapse (Jowett et al Gut 2004)
  • Enteral diet for IBD can improve stool calprotectin within 1-2 weeks.

Take-home messages: Don’t tell your patients with non-stricturing IBD to eat a low fiber diet.  Reduced red meat and reduced oral iron may be helpful.  Vegetarian diet and Mediterranean diets may be helpful.

Related blog posts:

FODMAP: Navigating this Novel Diet –Bruno Chumpitazi, MD, MPH (Texas Children’s Hospital) -page 152 in Syllabus

  • Fermentable Oligosaccharides Disaccharides and Polyols (FODMAPs): Poorly absorbed, osmotically active, rapidly fermented (produce gas)
  • Higher FODMAPs increase breath hydrogen (Murray K et al. Am J Gastroenterol 2014;109:110-9)
  • Higher FODMAPs increase stool/ileostomy output (Barret JS et al. Aliment Pharmacol Ther 2010;31:874-882,Halmos EP J Gastroenterol Hepatol 2013;28(Suppl4):25-28)

Evidence for use of low FODMAPs diet is best in adult irritable bowel syndrome.

  • Shepherd SJ et al. Clin Gastroenterol Hepatol 2008;6:765-71
  • Staudacher HM et al J Nutr 2012;142:1510-18
  • Ong DK et al. J Gastroenterol Hepatol 2010;25:1366-1373
  • Halmos EP et al. Gastroenterology 2014;146:67-75

Limited studies in children.

  • Chumpitazi BP et al. NASPGHAN 2014 abstract n=33 pediatric IBS.  Favorable response noted to low FODMAP diet.

Dietary recommendations were reviewed along with the caveat that obtaining the assistance of a dietician/nutritionist is recommended.

Resources:

Related blog posts:

Nutrition in the Child with Neurological Disabilities –Kathleen Motil (Baylor College of Medicine) pg 162 in Syllabus

  • Nutritional disorders are highly prevalent in children with neurological disabilities: 29-46% are underweight; 8-14% are overweight.
  • Improved nutrition improves behavior, activity level, improves growth, and reduces infections.
  • Cause of nutritional disorders mostly related to inappropriate dietary intake but other factors can play a role
  • Growth/anthropometric measures are key determinant of nutritional assessment
  • Key questions: Is child taking all day to eat? Is child choking with feedings?
  • Critical BMI <12 kg/m-squared
  • Goal for BMI ~25%

Reasons for gastrostomy:

  • Flat growth >6 months/weight below curve
  • Parental request
  • Medication administration
  • Aspiration

Resource:

www.feedingtubeawareness.com  This site contains a terrific PDF download which explains enteral tubes in an easy to understand style along with good graphics. “What You Need to Know Now, A Parent’s Introduction to Tube Feeding is the guide book that every parent wished they had when they were first introduced to feeding tubes.”

Related blog posts: