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.

EPT for Achalasia

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EPT or esophageal pressure topography (using high-resolution manometry) can help predict outcomes for achalasia (Gastroenterol 2013; 144: 718-25, editorial 681-83).

Background:  Patients with achalasia often present with dysphagia, chest pain, and regurgitation.  These symptoms result from impaired lower esophageal sphincter relaxation and aperistalsis.  While the main treatment has focused on disruption of the sphincter, esophageal body pressures may be important in long-term outcomes.

Three patterns of esophageal body pressures with achalasia:

  • type 1 absence of peristalsis and minimal pressurization
  • type 2 absence of peristalsis with panesophageal pressurization (≥30 mm Hg)
  • type 3 evidence of spasm

According to the cited study which reviewed data from 176 patients in the European achalasia trial (time period: 2003-2008, 18-75 year old), success rates were better with type 2 achalasia (96%, n=114) compared with type 1 (81%, n=44) or type 3 (66%, n=18).

In addition, the EPT findings may influence treatment selection.  Pneumatic dilation (PD) was more successful than Heller myotomy (HM) for type 2 patients (100% vs. 93%, p < 0.05).  However, HM was considered successful more frequently for patients with type 3 achalasia (86% vs. 40% –though not statistically significant due to small numbers).  For type 1, no significant difference was noted between HM and PD at 2 year followup, 81% vs. 85% respectively.

The commentary discusses some of the pertinent issues.   For example, HM may be better than PD among type 1 patients; the exclusion of patients with severe dilatation of esophagus.

Take-home message (from editorial) “The task at hand is to determine whether these distinct categories truly matter in clinical practice…it seems that the subtypes of achalasia do have prognostic value…we …need to determine…whether subtypes can inform treatment options.”

Elevated Celiac Serology Associated with Reduced Infant Birth Weights

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Using a population-based study of 7046 singleton pregnancies (from the Netherlands), the authors of a recent study have shown an inverse relationship between levels of anti-tissue transglutaminase IgA (TTG) antibodies and fetal growth (Gastroenterol 2013; 144: 726-35).

Results:

  • Newborns of positive TTG (>6 U/mL) weighed 159 g less at birth than newborns of mothers who tested negative for TTG.  In addition, newborns with mothers who had intermediate TTG levels ( 0.8 U/mL to 6 U/mL) had growth restriction of 53 g.
  • Among the intermediate TTG group, the results were more pronounced (2-fold greater) in those carrying the HLA risk molecules for celiac disease.
  • These birth weight changes were not associated with maternal nutritional status or deficiencies related to hemoglobin, iron, folate, or vitamin B12 deficiency.
  • Gestational age was not affected by TTG titers.

In the discussion, the authors note that other studies have shown that undiagnosed celiac disease increases the risk for intrauterine growth retardation; this risk can be eliminated by treating celiac disease.  The latter is a risk factor for lower neuropsychological performance.  This study was the first that took into effect the different TTG titers and correlated with additional nutritional parameters.

The authors speculate that celiac disease could have direct effects on the placenta.  In addition, other nutritional parameters could play a role such as vitamin D and calcium which were not included in this study.  Another important consideration is that celiac disease can result in increased miscarriages.  As a result, the “true” effect on newborn growth may be underestimated due to a “survivor bias.”

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Fecal Transplants -NY Times Opinion Piece

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The following link (thanks to Kayla Lewis) to a recent NY Times article provides a first hand anecdotal account of fecal microbiota transplant for an adult patient with ulcerative colitis and discusses the use of FMT for Clostridium difficile infections.

http://opinionator.blogs.nytimes.com/2013/07/06/why-i-donated-my-stool/?ref=health

Bottom-line: Expect more questions about this emerging treatment.

Also, a quick way to keep up on NY Times -follow the twitter feed: @nytimesHealth

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Could antibiotics make you fat?

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Studies in mice have shown that those exposed to antibiotics had higher total fat mass/body fat without additional weight gain.  In addition, a study of infants indicated that early antibiotic exposure may also be a risk factor for increased weight gain.

From Gastroenterology and Endoscopy News, June 2013: http://www.gastroendonews.com/ViewArticle.aspx?d=In%2bthe%2bNews&d_id=187&i=June+2013&i_id=961&a_id=23385

“Ilseung Cho, MD, MS, assistant professor of medicine, associate program director, Division of Gastroenterology, NYU School of Medicine, New York City, said, “Many investigators who study the gut microbiome think that it plays a significant role in the obesity epidemic in concert with a variety of other risk factors, such as poor dietary habits or a sedentary lifestyle. The microbiome plays a key role in a variety of host functions, including immune response and metabolism.”

Effect of Antibiotics

Dr. Cho was the lead investigator on a study in mice that demonstrated that antibiotics altered the gut microbiome in such a way as to affect murine metabolism and cause increased adiposity (Cho I et al. Nature 2012;488:621-626). Investigators administered subtherapeutic doses of penicillin, vancomycin, penicillin plus vancomycin, or chlortetracycline to young mice in their drinking water; a control group received no antibiotics. There were 10 mice per group. After an exposure period of seven weeks, the mice did not differ significantly in weight gain, but all four antibiotic-exposed groups had significantly higher total fat mass (P<0.05) compared with controls, and most (with the exception of the vancomycin group) had higher percent body fat (P<0.05).

The antibiotic exposure caused taxonomic changes in the microbiome, with the ratio of the phylum firmicutes to the phylum Bacteroidetes elevated in the antibiotic-exposed mice. Additionally, there was evidence of metabolic changes. For example, glucose-dependent insulinotropic polypeptide was elevated in the antibiotic-exposed mice, and glucose tolerance tests showed a trend toward hyperglycemia.

“In our paper, we describe a model where, by exposing mice to low-dose antibiotics, we were able to alter their microbiome,” said Dr. Cho. “Altering their microbiome resulted in a metabolic change in the mice that led to increased adiposity. The paper demonstrates that we are able to affect host metabolism by altering the gut microbiome.”

Around the same time that Dr. Cho and his colleagues published their results, a related paper about antibiotic exposure in infants was published in advance online (Trasande L et al. Int J Obes 2012 Aug 21 [Epub ahead of print]).

“Knowledge of the importance of the microbiome in human development raises new issues about antibiotic use in children, as such exposures may disrupt the microbial ecology,” the authors wrote.

In the longitudinal birth cohort study, investigators analyzed data from 11,532 children. Exposure to antibiotics during three early-life time periods (ages <6 months, 6-14 months, 15-23 months) was assessed by questionnaires that had been administered to the parents near the measured time interval. Body mass indices (BMIs) were examined at five time points (six weeks, 10 months, 20 months, 38 months and seven years).

Exposure to antibiotics during the period before 6 months of age—and only during that period, of those studied—was consistently associated with increases in BMI from 10 to 38 months. At 38 months, children who had been exposed to antibiotics before 6 months had significantly higher standardized BMI scores (P=0.009) and were 22% more likely to be overweight than children who had not been exposed (P=0.029). The researchers controlled for known social and behavioral risk factors for obesity.”

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Risk from CT scans -Best Data to Date

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Thanks to Mike Hart for forwarding the following reference:

BMJ 2013; 346: f2360 doi: 10.1136/bmj.f2360

This study examines the risk of cancer among a cohort of nearly 11 million Australian children and adolescents since 1985.  Among this cohort, 680,000 (6.2%) pediatric patients were identified who had been exposed to a CT scan. This study was accomplished by analyzing CT scans funded by the Australian Medicare system which provides health services for all Australians.

One of the remarkable aspects of this study was the efforts the authors took to exclude reverse causation.  First of all, the data was analyzed with an exclusion period of a year “because of the possibility that the scan was part of the cancer diagnostic procedure…but we repeated the main analyses with lag periods of five and 10 years to explore the possibility of reverse causation.”  In addition, the authors analyzed all non-brain cancers in patients who had had cranial CT scans.  Despite all of the parameters, an increased risk of cancer was maintained among those who had prior CT and the risk was heightened by obtaining studies at younger ages and by having increased number of CT scans.

Key findings:

  • Almost 60% of CT scans were of the brain. Only 5% of CT scans were of abdomen or pelvis.
  • CT scan incidence increased over time.  Between 1985-89, 95,249 (14%) CT scans were ordered.  Whereas between 2000-2005, 266,971 (39%) were ordered.
  • The average CT dose was about 4.5 mSv per scan.
  • The increased relative risk (IRR) for brain cancers after a scan to a site other than the brain was 1.51 (confidence interval 1.19-1.91).
  • Each seivert (Sv) of effective dose was associated with 0.125 cancers; thus, by 2007, with average followup of 9.5 years, one cancer resulted from every 1800 CT scans.  This number is likely to climb with more time.
  • Among brain CT scans, the numbers are trickier due to the possibility of slow-growing tumors (which could trigger symptoms for imaging and still be difficult to detect).  However, up to one excess brain cancer would occur for every 4000 brain scans.
  • All solid cancers IRR 1.25, All lymphoid/hematologic cancers IRR 1.19, Brain cancers after CT IRR 2.44, Brain cancer after other scans 1.51.

There are several limitations to the study including the difficulty of knowing specific doses of radiation at various CT scanners, the possibility of CT scans funded outside the Australian Medicare system, or obtaining screening scans due to precancerous genetic conditions. Nevertheless, the magnitude of the cohort in this study along with its general agreement with a number of other studies provide ample evidence that these risks are real.

Take-home point: While CT scans have the potential for great benefits, they increase the risk of developing cancer; in many cases, an MRI or an ultrasound can provide similar information without this risk.  In this study, for lag (exclusion) period of one, five, and 10 years, the incidence rate for all cancers combined increased by 24%, 21%, and 18% respectively in the CT exposed group.  Eventual lifetime risk is likely to climb with longer followup.

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Tattoos: a marker for Hepatitis C

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A recent study has found that tattooing was independently associated with hepatitis C virus (HCV) infection, even in those without traditional risk factors (Hepatology 2013; 57: 2117-23).

The authors of this large, multicenter, case-control study analyzed demographics and risk factors for HCV among 3,871 patients including 1,930 who had chronic HCV infection.  As in previous studies, a history of injection drug use (IDU) and blood transfusion prior to 1992 were associated with an increased risk of HCV.

After excluding patients with these risk factors, there were 465 patients with HCV and 1,421 controls.  Among these individuals, after controlling for age, sex and ethnicity, HCV-positive patients had an OR of 5.17 of having had one or more tattoos compared to the control patients.

Previous studies have not been definitive about whether tattoos represent a specific risk factor or an epiphenomenon.  That is, tattoos are known to be more common among individuals with IDU.  And, this study does not really settle the question either.  “Underrepresentation due to self-reporting of intravenous drug use is a concern that could confound our result.”  In addition, the authors note that commercial parlors have not been implicated in HCV transmission.

Bottomline: Individuals with tattoos are more likely to have HCV.  For individuals who insist on tattoos, avoid nonprofessional settings to limit the risk of HCV acquisition.

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Uncertainty and Mindfulness

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Two complementary perspective articles are worth a look:

  • NEJM 2013; 368: 2445-48
  • NEJM 2013; 368: 2448-50.

The first article discusses cognitive bias. The authors note that diagnostic failure rates are typically in the range of 10-15%, but lower for “visual specialties” like radiology and pathology where the rate is closer to 2%.  Why is the diagnostic failure rate so high?  The authors describe the mind’s vulnerability due to biases, and assumptions. “More than 100 biases affecting clinical decision-making have been described.”

The authors note that decision-making relies on either intuitive processes or analytic processes.  Intuitive processes are either hard-wired or acquired through repeated experiences.  These processes are subconscious and fast.  In contrast, analytic processes are deliberate, slower, but much more reliable.  “Despite the ubiquity and usefulness of intuitions, they are not reliable enough for us to use them to send a spaceship to Mars.”  In more complex issues, analytic processes are needed.

The main problem with analytical thinking is that it is more time-consuming and more resource-intensive.  “It would be impractical to deal with each clinical decision analytically.”  Keeping mindful of when critical thinking is needed is the challenge.

The second article discusses uncertainty, especially with regard to prognosis.  Key points:

  • Normalize the issue of uncertainty with patients. “Patients are bombarded…with the notion that high-tech advances…have resulted in definitive answers.” “Clinicians should be honest…’I understand that you want more accurate information about the future.  The reality is that it’s like predicting the weather–we can never be absolutely certain about the future. I wish I could be more certain.'”
  • Help families manage uncertainty.  “The search for certainty may impede the ability …to live in the present.” Clinicians should avoid propagating this issue.  Instead of “We need more time to be sure,” the authors suggest “What can we do to help you now, given that we are unsure of exactly what the future will bring?”

Wireless motility capsule -emerging for pediatrics?

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Currently, there are limited options for detecting gastrointestinal motility abnormalities.  The most definitive current evaluation is antroduodenal manometry (ADM) which remains restricted to a few specialized pediatric centers (coming soon to Children’s Center for Digestive Healthcare/Children’s Healthcare of Atlanta –Fall 2013).  And, of course, in many cases of defined motility disorders there are limited available treatments.  This situation has prompted one of my colleagues to state that motility testing is like getting the license plate of the bus that hit you.

A wireless motility capsule has the potential to facilitate motility testing.  A recent study explores it use in 22 patients (8-17 years) referred to a motility center (J Pediatr 2013; 162: 1181-7). The wireless motility capsule, also marketed as the SmartPill, has received FDA approval for use in the diagnosis of gastroparesis and constipation.  It measures intraluminal pressure, temperature, pH, and allows calculation of transit times in different segments of the GI tract.

Methods:

All patients underwent antroduodenal manometry, gastric empyting study (GES), and wireless motility capsule study.  The GES was performed with a 2-hour protocol.  The patient was given a standardized meal of 2 eggs, toast, and jelly with Tc-99m labeled eggs.  A GES was abnormal if >50% of labelled material was in the stomach at 2 hours. Similarly, the wireless motility capsule was ingested immediately prior to a similar standardized meal; this test was performed on a consecutive day with ADM testing.

Results:

  • In the paper, Table II & III lists the values for each test and includes which data was missing.
  • Based on ADM testing: 8 patients had rumination, 10 had normal motility, and 3 had abnormalities (1 with antral hypomotility, 1 with neuropathic dysmotility, 1 with hyperactivity/rumination).
  • Based on wireless capsule, 10 patients had severe gastroparesis.  Of these 10 patients, the ADM was normal in 4 and abnormal in 6.

The authors point out that the wireless motility capsule had excellent sensitivity but only moderate correlation between scintigraphic GES as well as ADM studies.  One possible reason for increased identification of gastric emptying disorders for the capsule include the use of 2-hour rather than 4-hour GES.  In addition, in symptomatic patients, those with normal GES and normal ADM may still have contractility abnormalities  that can be identified with capsule test.

One limitation of the study was the fact that migrating motor complexes (MMCs) was detected in all patients by ADM (as well as by capsule).  As such, there was no opportunity to identify potential false-positive in patients without MMCs.  Similarly, healthy children were not studied and this limits the findings to a highly selected cohort of children referred for motility evaluation.

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Hemorrhoids and asstronauts

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A recent review on hemorrhoids (Clin Gastroenterol Hepatol 2013; 11: 593-603) had a few useful quotes:

“Why are hemorrhoids called hemorrhoids and asteroids called asteroids? Wouldn’t it make more sense if it was the other way around? But if that were true, then a proctologist would be an astronaut.”  Robert Schimmel

“My troubles are all behind me” George Brett (on returning to World Series after treatment for a thrombosed external hemorrhoid)

Besides the quotes, the review article provides a concise approach to the epidemiology, anatomy, pathophysiology, diagnosis, and management of hemorrhoids.

Specific points:

  • The word ‘Hemorrhoid’ is derived from the Greek words “haima” meaning blood and “rhoos” meaning flow.  The word “pile” is derived from the Latin word “pila” meaning a ball.
  • Conservative treatment: increasing fiber, avoidance of straining/minimizing time on toilet, and sitz baths several times per day.
  • “Well-designed studies have found no evidence to support the use of any of the myriad of over-the-counter topical preparations that contain low-dose local anesthetics, corticosteroids, keratolytics, protectants, or antiseptics.”  “Long-term use of these products, particularly steroid preparations, …should be discouraged.”
  • Rubber band ligation: “highly effective…in a meta-analysis of 18 prospective, randomized trials, RBL was overall superior to injection sclerotherapy or infrared coagulation in the treatment of grades I, II, and III (internal) hemorrhoids.”  “Risk of complications is low <1-3%, including pain, bleeding, and vasovagal symptoms.” Higher rates of pain are reported in some studies and may be dependent on location of RBL.
  • Cryosurgery and Lord’s procedure ..”have lost favor in the United States.”
  • Surgical treatment: “Nonsurgical approaches are successful in 80-99% of patients.” “Surgical hemorrhoidectomy is more effective than RBL in the treatment of grade III hemorrhoids but incurs additional complications, pain, and disability.”  Complications have included urinary retention, bleeding, infection, anal stenosis, and incontinence (2-12%)–Ouch!

Celiac hepatopathies

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There has been a longstanding recognition that celiac disease can be associated with elevated liver enzymes.  Two articles provide further information about celiac hepatopathies.

  • JPGN 2013; 56: 663-70
  • JPGN 2013; 56: 671-74

The first study describes a review of nine studies identified in a MEDLINE search for celiac disease and hypertransamminasemia (HTS) or autoimmune hepatitis (AIH). In total 2046 patients were identified.

Key findings:

  • 12% of patients with mild persistent HTS had celiac disease.  Among individuals with HTS, the relative risk for celiac disease was 11.59 compared to general population.
  • 36% of newly diagnosed children with celiac disease, has elevated aminotransferases.  A gluten-free diet normalized transaminases in 77% within 4 to 8 months.
  • Among children with celiac disease, 1.4% had AIH.  Among children with AIH, 6.3% had celiac disease.

While this meta-analysis had many limitations, it is clear that celiac disease needs to be considered in patients presenting with elevated aminotransferases and in patients with AIH.  In addition, other liver conditions like primary biliary cirrhosis and sclerosing cholangitis, which are infrequent in the pediatric population, are more common in patients with celiac disease.

The second study involved both retrospective (1995-2000) and prospective evaluation (2000-2012) of patients followed at a single center.  The authors sought to determine the long-term response to immunosuppressive treatment in children with autoimmune hepatitis (AIH) and celiac disease.

In their cohort of 79 AIH patients, 15 (9%) had celiac disease.  There was a similar frequency of type 1, type 2 and seronegative AIH among the celiac patients (47%, 20%, and 33%) compared with the entire cohort (55%, 34%, and 11%).  All 15 patients responded to treatment with prednisone and azathioprine or cyclosporine, along with a gluten-free diet.  When immunosuppressive treatment was withdrawn in 9 patients, 4 relapsed and 5 were maintained off immunosuppression for a mean period of 89 months. A much lower rate of immunosuppression withdrawal was achieved in those AIH patients without celiac disease.  24 of 64 attempted to stop immunosuppression; 5 (8%) were successful.

Take-home point of second study: All AIH patients should be screened for celiac disease as a gluten-free diet may increase the likelihood of withdrawal of immunosuppression.