Author Archives: gutsandgrowth

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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Bone health in pediatrics

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Due to the survival of chronically ill children, exposure to skeletal toxic treatments, and wider availability of bone health measurement technology, osteoporosis in pediatrics has become a widespread problem.  A useful concise review is available (J Pediatr 2012; 161: 983-88).

One of the biggest problems is the limited pediatric evidence on which to base treatment decisions.

Specific points regarding osteoporosis and bone health:

  1. Bone accretion: most of one’s bone mass is reached by late adolescence or early adulthood
  2. Frequency of bone fractures: in the general population, 1/2 of boys and 1/3rd of girls have sustained a fracture by 16 years of age.  Thus, bone pathology should be suspected in those with unusual fractures.
  3. Pathological fractures: “meaningful” history of fracture history includes a lower extremity long bone fracture, 2 or more upper extremity long bone fractures and/or vertebral compression fracture.
  4. Testing: due to cost and precision, dual-energy x-ray absorptiometry (DXA) remains most widely used measurement tool. However, quantitative computed tomography (QCT) has some advantages.  It is less biased by bone size and directing generates a measurement of volumetric bone mineral density.
  5. Primary osteoporosis: osteogenesis imperfecta (OI), idiopathic juvenile osteoporosis (IJO), and osteoporosis-pseudoglioma syndrome (related to loss of function in low-density lipoprotein receptor-related protein 5 [LRP5]).
  6. Secondary osteoporosis: neuromuscular diseases, malabsorption syndromes, medication-induced (glucocorticoids, diuretics), chemotherapy, and radiation treatments.
  7. 1st line treatment: adequate nutrition –especially adequate calcium and vitamin D and exercise (especially weight-bearing exercise).  It is noted that with cystic fibrosis patients there has been a better response to vitamin D3 (cholecalciferol) than D2 (ergocalciferol); as a consequence, the CF Foundation recommends all CF patients receive vitamin D3.  With regard to weight-bearing exercise, the data are conflicting regarding its efficacy.
  8. 2nd line treatment: treat underlying disorder.  For example, with inflammatory bowel disease (IBD), treatment of chronic inflammation with infliximab has been shown to improve markers of bone formation.  Inflammation in IBD has been shown to play a more important role than glucocorticoid dosing in terms of predicting bone health.
  9. 3rd line treatment ??? a) “Currently, teriparatide is the only available treatment with anabolic actions on bone.” But, a black box warning has cautioned against its use in pediatric patients   b) bisphosphonates: pamidronate, aleondronate, and zoledronic acid. A review of the small pediatric studies, primarily in OI patients, have shown some improvement in fractures, skeletal pain, and mobility.  Optimal dose, frequency, and duration remain unknown.
  10. Safety of bisphosphonates: potential problems include ‘acute phase reaction,’ hypocalcemia, musculoskeletal pain, gastrointestinal side effects, and many other adverse reactions. Atypical fractures and jaw osteonecrosis have been reported in adults.

Related blog posts:

Update on pertusis epidemic

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Two previous blog entries have discussed the issue of pertusis resurgence:

More details on this epidemic have been published (J Pediatr 2012; 161: 1091-6, editorial 980).  There have been more Pertusis cases than in any period in the past 50 years.  Part of the problem is due to pertusis’ high reproduction number, 92-95% of the population must be protected against pertusis to halt transmission.

Specific issues highlighted in the report include the highest risk of severe disease occurring in the first 6 months of life, increased risk of disease in Hispanic infants despite similar immunization rates, and waning immunity in preadolescence.

Someone should figure this out for the esophagus

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A recent letter to the editor describes a cool approach to treating the midaortic syndrome (NEJM 2012; 367: 2361-62).

In this 3-year-old girl, after IRB approval, a tissue expander was placed in the lower abdomen and placed tension on the aortic bifurcation.  Over a nine month period, saline was added.  This enabled stretching and subsequently a 4 cm resection of the mid-aorta.  Subsequent to the operation, the anastomosis appears patent and the patient’s hypertension is much easier to manage with two antihypertensives rather than five.

Perhaps a similar approach would improve the outcomes of our patients with refractory esophageal strictures.  In the case report, the treatment was based on studies that had previously shown that arteries and veins elongate in response to longitudinal stretch.  I don’t know whether the esophagus would have the same response.

Related references:

  • -Refractory strictures (NASPGHAN 2011): -if not >14 mm after 5 sessions Complex strictures: >2 cm long, tortuous, or if scope cannot be passed predilatation. Consider Fluoro for complex strictures. Described technique of endoknife if only one-sided stricture –hard to dilate.
  • -Am J Gastroenterol 2005; 100: 2419.  Double-blind, randomized trial showed benefit of steroid injection for Rx of recalcitrant peptic strictures. Consider triamcinolone along length of stricture; max ~10mg (2-4mg/injection)
  • -JPGN 2007; 44: 336. n=16 pts. Mitomycin 0.1mg/mL; apply for 2-3min c pledget.
    -JPGN 2006; 42: 437.  Case report of using indwelling balloon for daily dilatation in refractory patients.
  • -Endoscopy. 2006 Apr;38(4):404-7).  Mitomycin C: an alternative conservative treatment for refractory esophageal stricture in children?
  • -JPGN 2005; 41: 35A (pg503).  use of stents for refractory benign strictures, n=10.
  • -Gastroenterol 1999; 117: 229 & 233. AGA position statement and technical review.

**Dosing regarding triamcinolone or mitomycin C has not been clearly established for esophageal strictures.  Doses listed above are based on my reading of the references but no specific dose is advocated on this posting.

Expert advice on portal hypertension

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A consensus report on portal hypertension has helpful advice on a broad range of management issues and should be kept in mind as a handy reference (Pediatr Transplantation 2012; 16: 426-37).  The report is concise and full of bullet points.  It is based on a meeting of pediatric experts to modify adult guidelines (Baveno V) for pediatrics.

In many instances, the experts indicate that there is not enough pediatric data. Specific subjects include the following (along with some points):

  • Treatment options for portal hypertension -consider screening for varices if thrombocytopenia and splenomegaly.  ‘No indication to use beta-blockers to prevent varices.’
  • Prevention of first bleeding episode -in the presence of varices (grade II or III), variceal ligation reasonable in selected children and/or within context of defined research protocols. Grade I varices can be flattened with insufflation, and grade III varices are confluent around circumference of esophagus (per Japanese Research Society for Portal HTN analysis)
  • Role of hepatic venous pressure gradient measurement (HVPG) -‘panel was undecided as to whether HVPG measurements in children’ should be ‘part of specialized clinical practice or’ a research tool.
  • Blood volume restitution -suggests use of platelets in cases of bleeding with profound thrombocytopenia (<20,000).
  • Antibiotic prophylaxis -unclear whether empiric antibiotics in children are needed in the presence of variceal bleeding.
  • Management of treatment failures -can retry endoscopy and if fails, consider transjugular intrahepatic portosystemic shunting (TIPS)
  • Management of gastric varices -only case reports in children, thus no evidence-based recommendations.
  • Prevention of rebleeding -variceal ligation (EVL) preferred in patients with cirrhosis.  EVL should be performed every 2-4 weeks up to five sessions to eradicate varices after 1st bleed.
  • Treatment of portal vein obstruction -diagnosis, natural history, anticoagulation, use of MesoRex bypass procedure, associated portal biliopathy -diagnosis and treatment.  With regard to MesoRex, ‘controversy exists as to the appropriateness of ..this procedure in an asymptomatic child.’ Surveillance endoscopy may assist in decision-making.
  • Hypersplenism with portal vein obstruction-in the presence of platelet count <50,000 and portal vein obstruction, strong consideration should be given to MesoRex procedure.
  • Portopulmonary hypertension and hepatopulmonary syndrome -important to monitor oxygen saturation in patients with portal vein obstruction/other causes of portal hypertension. If <97%, additional investigation may be needed.  Portopulmonary hypertension is best characterized with cardiac catheterization and hepatopulmonary syndrome with saline echocardiography.
  • Other topics: Prevention of hepatic encephalopathy, managing bleeding episodes, endoscopic treatment

Related blog entries:

Does NAFLD cause hepatocellular cancer?

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Probably (Clin Gastroenterol Hepatol 2012; 10: 1342-59).

The authors of this study reviewed original reports between 1992-2011 and narrowed them to those with pertinent information regarding evidence of whether non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) contributed to a higher risk of hepatocellular carcinoma (HCC).

17 cohort studies, 18 case-control and cross-sectional studies, and 26 case series were identified.

Results:

  • Cohorts with NASH and cirrhosis had a consistently higher risk of HCC; cumulative risk ranged from 2.4% over seven years to 12.8% over 3 years.
  • Cohorts with few or no cases of cirrhosis had a minimal risk of HCC; cumulative risk of HCC mortality was 0-3% for study periods up to 20 years.

The results of patients with NASH and cirrhosis are in agreement with a recent presentation at AASLD meeting; however, there may be a small risk even in the absence of cirrhosis (Fatty Liver Disease Cited for Rise in Hepatocellular Carcinoma November 2012):

“Of 17,895 HCC cases in the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, 2,863 (16%) had only NAFLD without any other risk factors or etiologies for HCC. The linked database covers 30% of the U.S. Medicare population. SEER itself contains data from 18 cancer registries covering 28% of the U.S. population.” In addition, “Cirrhosis was not present in 36% of the NAFLD-related HCC cases.” In the SEER database, the odds ratio for developing HCC with cirrhotic NAFLD was 16.5 compared with those with noncirrhotic NAFLD.

Related blog entry:

NAFLD Guidelines 2012 | gutsandgrowth

Teduglutide for Short Bowel Syndrome

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More data on teduglutide indicate its potential for short bowel syndrome (SBS) (Gastroenterol 2012; 143: 1473-81, editorial 1416-20).  Treatments for SBS are needed.  One year of parenteral nutrition often costs the health care system in excess of $100,000 per year.  This cost does not account for laboratory studies, health care visits, complications, and hospitalizations.  Treatment of intestinal failure with transplantation “may cost upwards of $1 million.”

In this study of adult patients with an average of 50 years, teduglutide was given in a prospective randomized double-blind study to 42 patients and another 43 patients received placebo. The dose of 0.05 mg/kg/day via subcutaneous injection was chosen based on a previous trial which showed that a higher dose was less effective.  Among these patients, the most common reasons for SBS were vascular disease (34%), Crohn’s disease (21%), volvulus (11%), and injury ((9%).

Bottom line:

  • Teduglutide over a 24-week study was more effective than placebo.  63% of study patients had a drop in parenteral nutrition requirement of more than 20% compared with only 30% of the placebo group.
  • The mean reduction in parenteral nutrition support of teduglutide-treated patients was 4.4 L/week compared with 2.3 L/week for placebo-treated patients.
  • Citrulline, a biomarker of mucosal mass, was increased in the teduglutide group.  In the treatment group, citrulline increased by 20.6 μmol/L compared with 0.7 μmol/L for the placebo group.

How does teduglutide work?  Teduglutide is a much more stable analog of glucagon-like peptide-2 (GLP-2).  The latter is released by the distal small bowel and colon.  GLP-2 promotes intestinal epithelial growth and increases transit time.

What are the adverse effects of teduglutide? First, there is a concern that teduglutide could promote colonic adenomas based on studies in mice.  GLP-2 receptors are present in the lung, and brain (including hypothalamus); its effects in these areas is poorly understood.  In addition, abdominal pain, distention, nausea, peripheral edema, and nasopharyngitis were more common in the treatment group. The long-term consequences of teduglutide therapy are not known.

Related posts:

Quality improvement and better outcomes in Pediatric Inflammatory Bowel Disease

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More information on outcomes and quality improvement (QI) efforts are available from Cincinnati Children’s Hospital (JPGN 2012; 55: 679-88).  The QI efforts at Cincinnati are part of a broader effort in QI in pediatric IBD that has been discussed on a previous post (see below).

Our group has rejoined Improve Care Now (ICN) and I look forward to gaining more first hand experience.  Some of the ICN target goals:

  • 80% remission rate among each center and sustained remission rate of 45%
  • 76% steroid-free remission
  • 90% checking TPMT if using thiopurine
  • 95% checking PPD/chest xray if using biologic therapy
  • 95% using accepted methotrexate dosing

As I look at these goals, I wonder whether the remission rate is feasible and about the variation in different centers. For example, among the groups with >75% enrollment of their patients, one center reports a 89% remission rate and another center 64% remission rate.  Given the limited number of therapeutic agents, how could there be such a difference?  Some explanations could include variation in the use of more potent biologic agents as well as capturing/assuring followup of more patients who are doing well.

Given this backdrop, I looked at this most recent publication to learn how their QI practices could translate into better care for my patients.

In this retrospective chart review study of 505 patients, who were followed from 2007-2010 at the IBD center, the remission rate increased from 59% to 76%.  The data were captured prospectively.  This corresponded to improved patient global assessment (>7) from 69% to 80%.  Repeated steroid use dropped from 17% to 10%.  Vitamin D (25-OH D) improved and this also correlated with quiescent disease.

Remission rates were defined by a pediatric Crohn clinical disease index, the sPCDAI, or PUCAI for Ulcerative colitis.

Key observations:

  • There was a trend towards increased use of anti-TNFα therapy (along with decreased use of 6-mercaptopurine) during the study period, but this did not reach statistical significance. No statistical difference was identified in the use of any major IBD medication class.
  • Despite target goals, the only drug class with a statistically significant change in dosing was 5-ASA (from 42 mg/kg to 50 mg/kg).
  • Fecal calprotectin monitoring increased.  The QI team recommended that IBD patients with ‘inactive’ disease have a fecal calprotectin measured every 6 months.  Those with elevated values had therapeutic drug monitoring implemented.  “Fecal calprotectin >400 μg/g is associated with a higher chance of relapse in a pediatric cohort.”
  • Starting in 2009, increased vitamin D monitoring was implemented (every 6 months).  In patients with a serum 25-OHD level < 30 ng/mL, treatment with 50,000 units weekly (for 6-8 weeks) was recommended (8000 units if weight <20 kg).  Once serum 25-OHD was >30 ng/mL, patients were maintained on monthly dosing.
  • Preclinic planning also increased and corresponded to improved remission rates which were 67% in 2009 and 76% in 2010.
  • The authors conclude: “Our results show that significant improvement in patient outcomes were achieved following QI efforts that did not rely on new medications or therapies, rather through initiating novel care processes and standardization of care.”

I think this conclusion is misleading.  First of all, as the authors point out, they did change their therapeutic approach.  They started vitamin D in more patients, used anti-TNFα therapy in more patients, and increased dosing of 5-ASA agents.  Other gains in remission rate could have been related to improved followup of patients who were doing well.

Despite my skepticism about the conclusion, I think the overall achievements are laudable.  Decreasing variation of care and assuring that all patients receive the best care possible with our diagnostic tests and current therapies is certainly worthwhile.  When patient care is studied carefully, this makes sure that “standard” practice like checking TPMT status before thiopurine use, checking PPDs before anti-TNFα therapy, and using optimal drug dosing occur in virtually all patients.

Developing a checklist for each patient can help assure that best practices occur.  For those with electronic medical records, this may mean putting in more “hard stops.”  A hard stop means the physician cannot sign out of a chart without paying attention to a specific detail.  For example, if a physician orders methotrexate, a “hard stop” could come up if the dosing was not in the typical target range.

Useful link:

Link for disease classification (quiescent, mild, moderate, severe):

http://links.lww.com/MPG/A129

Related blog entries:

Helping children cope after a disaster

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From the American Academy of Pediatrics:

One of the resources included in this listing is entitled, “Tips for Talking With and Helping Children and Youth Cope After a Disaster or Traumatic Event: A GUIDE FOR PARENTS, CAREGIVERS, AND TEACHERS.” This resource can be printed and shared with your patients and their families.  The direct link for this resource is the following:

http://store.samhsa.gov/shin/content/SMA11-DISASTER/SMA11-DISASTER-09.pdf.

Acupuncture for irritable bowel syndrome

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No medical therapy has been shown to alter the natural history of irritable bowel syndrome (IBS).  A number of therapies have been used to improve the symptoms.  More data has been published on whether acupuncture is an effective therapy (Am J Gastroenterol 2012; 107: 835-47)

A number of treatment approaches have shown that several medical treatments are more effective than placebo, including soluble fiber, some antispasmotics, peppermint oil, antidepressants, and agents that act on the 5-HT receptor.  In addition, cognitive-behavioral therapy and hypnotherapy seem to be more effective than placebo.  Dietary therapies (see blog links below) are helpful in some patients.  However, many patients have a poor response to all of these approaches.

To examine whether acupuncture may be effective for IBS, the authors of the current study reviewed 1421 citations and identified 17 eligible randomized controlled trials (RCTs) with >1800 patients.  Only trials that used accepted traditional Chinese medicine methods of acupuncture were included.

Key findings:

  • Among the five sham-controlled trials, there was no significant difference detected between true acupuncture and sham acupuncture in terms of effects on symptoms or quality of life.  The standardized mean difference in post-treatment between the groups was -0.11 (difference between two groups) –confidence limits -0.35 to 0.13 for symptom severity and -0.03 for quality of life –confidence limits -0.27 to 0.22.
  • A selected summary on this article in Gastroenterology (2012; 143: 1683-84) notes that the largest RCT in the U.S. found that sham acupuncture and true acupuncture were both superior to a control arm (Am J Gastroenterol 2009; 104: 1489-97).
  • When acupuncture was compared with medical therapies in 5 trials (4 with antispasmodic, 1 with sulfasalazine), acupuncture was more effective, RR=1.28 for symptom improvement.  These studies were non blinded and the overall effect was modest.
  • When acupuncture was added to traditional Chinese medicine in 4 RCTs, the addition of acupuncture improved the endpoints of IBS symptom severity (RR=1.17).

This study should reduce the stress of practitioners of acupuncture.  Whether they apply true acupuncture or sham acupuncture, the results may be equivalent.  In these studies, sham acupuncture did have a high “placebo effect.” At the same time, this study indicates that the comparison medical treatments (most in these RCTs are not used in Western medicine) were less effective than acupuncture.  So where does that leave us?

Related blog entries:

Preventing lethal antibiotic resistant outbreaks

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Establishing “rigorous infection-control procedures” remain the main tool to reign in these lethal outbreaks (NEJM 2012; 367:   2168-70).

While that message has been said before, the referenced article concisely discusses issues regarding multidrug-resistant gram-negative rods (MDR-GNRs) which are now much “more menacing” than methicillin-resistant Staphylococcus aureus (MRSA).  The reason: there are no effective drugs available to treat some life-threatening MDR-GNR infections.

With resistance to cephalosporins increasing, clinicians have turned to carbapenems; as a consequence, resistance is emerging to these agents as well.  Multidrug-resistant organisms (MDROs) are increasing; in addition, resistance that develops in one place of the world can quickly spread as shown by the MDR-GNRs with the New Delhi metallo-beta-lactamase 1.

Key points:

  • MDROs are transmitted mainly on the hands of caregivers.  The most effective aspect of “rigorous infection-control procedures” remains hand washing.
  • Some infections survive for prolonged periods on surfaces.  For example, during an NIH outbreak of a MDR-GNR Klebsiella pneumoniae, klebsiella survived on a ventilator that had been cleaned three times with two different disinfectants.
  • Antimicrobial stewardship is an important aspect of decreasing resistance. This includes sending cultures prior to antibiotics to tailor regimens, specifying the indication, documenting the expected duration of treatment, and assessing at 72 hours whether an ongoing antibiotic course is needed.
  • If we adhere to established practices, infections due to invasive devices which are the source of most ICU infections can be minimized.  For example, incorporating evidence-based “bundles” of care have been effective in reducing central line infections.

Related blog entry: