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.

Pediatric NAFLD histology score

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Pathologists may be more interested in this article than many pediatric gastroenterologists (J Hepatol 2012; 57: 1312-18).  Yet, the development of the pediatric NAFLD (non-alcoholic fatty liver disease) histological score (PNHS) is likely to be helpful, particularly in research of NAFLD.

In this study, an initial training set of 203 children with biopsy-proven NAFLD were examined.  After designing a scoring system, the PNHS was validated in another 100 children.  The mean age was 12.4 years.

PNHS = 100 x esp(Zphs)/[1 + exp(Zphs)]

Zphns = -8.4 + (2.5 x steatosis) + (3.5 x ballooning) + (3.4 x lobular inflammation) + (0.87 x portal inflammation)

This score is easily calculated by entering the individual histological features at the following website:

  • steatosis 1-3 (1=5%-33%, 2=34%-65%, 3=≥66%)
  • ballooning 0-2 (0=none, 1=few, 2=many)
  • lobular inflammation 0-3 (0=none, 1=<2 under 20x, 2=2-4 under 20x, 3=>4 under 20x)
  • portal inflammation 0-2 (0=none, 1=mild, 2=more than mild)
  • http://rcc.simpal.com/RCEval.cgi?RCID=RPCxtv#Result

Results:

  • In NASH patients, the mean PNHS was 89 ± 20.5 compared to 21.9 ± 24.5 in the non NASH patients.
  • There was a high level of agreement between categorization of NAFLD cases using PNHS compared with pathologist diagnosis.
  • NASH patients were much more likely to have metabolic syndrome (64%) compared with 38% for non-NASH patients
  • Of the histologic features, ballooning was the feature that most distinguished the cohorts.  In 66% of NASH patients, few or many ballooning hepatocytes were noted, whereas 96% of non-NASH patients had no ballooning noted.
  • With PNHS of ≥85, the sensitivity is 76-77% and the specificity is 91-97% for NASH.  This will decrease the number of ‘borderline NASH’ cases in pediatric cohorts.

Related blog posts:

Vaccine successes and ambitions

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“Designing Tomorrow’s Vaccines” is a fascinating assessment of the success of vaccines as well as a look into the what future vaccines may accomplish (NEJM 2013; 368: 551-60).

First, I like the quote from Thomas Jefferson noted in the article:

“I avail myself of this occasion of rendering you a portion of the tribute of gratitude due to you from the whole human family.  Medicine has never before produced any single improvement of such utility…mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated.”  Letter to Edward Jenner (May 14, 1805).

Jefferson’s enthusiasm was not without merit.  “In the 20th century alone, smallpox claimed an estimated 375 million lives.”  Yet, “since 1978, not a single person has died from smallpox.” Unfortunately, at this time, every year “more than 1.5 million children (3 per minute) die from vaccine-preventable diseases.”

Previous success in the U.S: Comparison of the estimated number of cases per year in the 20th century with the number of deaths in the year 2002 from the same diseases:

  • Poliomyelitis: 1.63 million vs 0
  • Diptheria: 17.6 million vs 0
  • Measles: 5.03 million vs 36
  • Pertusis: 1.47 million vs 6632
  • Rubella: 4.77 million vs 20
  • Smallpox: 4.81 million vs 0

Despite these advances, vaccines have “yet to realize their full potential.”  Effective vaccines are needed for malaria, HIV, and tuberculosis.  Vaccines for influenza which rely on 50-year-old technology need to be improved.

So how can this be achieved?

  • Improved knowledge of atomic structure/structural biology has provided new insights into neutralizing antibodies along with specific antibody reactions. This can counter immune evasion by targeting highly conserved regions
  • Millions of gene sequences encoding antibodies within a single individual can be analyzed to improve vaccine design
  • Genomewide sequencing of microbes has improved selection of vaccine targets
  • Improvements in delivery systems, like using viruslike particles or nanoparticles; alternatively, gene-based delivery of vaccines is feasible
  • Recombinant techniques has allowed a shift from egg-based methods

What is not on the horizon  — a vaccine for the half-truths that permeate the discussion.

Related posts:

Aptly titled “The Cost of Technology”

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A brief commentary in JAMA makes some real useful observations regarding the effects of the electronic medical record on patient care (JAMA 2012; 2497-98).   The article describes a drawing by a 7-yer-old girl of her doctor who has an outstanding reputation among his peers.  Yet, in the drawing he is staring at the computer, and his back is to the patient.

The author notes that “when a physician focuses on a patient with complete attention, this simple act of caring creates a connection between two human beings. Almost immediately, the patient begins to feel, well, cared for, and this becomes a first step toward helping that person feel better.”

The computer is now a third player in this dynamic.  We “find ourselves entering more and more data while we are trying to listen to and talk with our patients.”  “By default, the patient moves down to second place…it is becoming the new reality.”

Physicians have to develop electronic records that allow us to record our thinking and improve efficiency so that we have more time to communicate with patients.  Can this be accomplished?

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Liver transplant outcomes in the boonies

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It looks like living in the boonies (URBAN DICTIONARY: BOONIES) does not make a big difference in pediatric liver transplantation (LT) outcomes (J Pediatr 2013; 162: 313-8).

The authors analyzed 3307 pediatric patients using the United Network Organ Sharing (UNOS) database between 2004-09.

Key outcomes for rural location:

  • Associated with greater risk of allograft rejection in the first 6 months after LT with an OR 1.27 (27% compared with 22.9% of urban patients).  The risk allograft rejection was not statistically significant at 1 year post LT (OR 1.18).
  • Associated with lower risk of post transplantation lymphoproliferative disorder (PTLD) with an OR of 0.64.  In total, 2.4% of rural patients experienced PTLD compared with 3.8% of urban patients.
  • Allograft loss and survival were similar for rural patients as for patients: 21.3% and 14.1% respectively compared with 20.7% and 12.7%.

The opposite risk ratios with regard to rejection and PTLD indicates that rural status may have greater rates of nonadherence with maintenance immune-suppression. However, the lack of a larger discrepancy in outcomes comes as a pleasant surprise, particularly as rural status is a known risk factor for worse health outcomes in many other complex chronic diseases.  Perhaps, this study validates the high level of skill and teaching on the part of pediatric liver transplant teams as well.

Related link:

Practice guidelines and 93 OLTx recommendations

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While checklists have a role (Checklists for Crisis and Daily Care | gutsandgrowth), most will not be workable if each has 93 recommendations like the 2012 AASLD Adult Liver Transplant Practice Guidelines (Liver Transplantation 2013; 19: 3-26).

While the guidelines are comprehensive including topics like vascular thrombosis, immunosuppression, late rejection, bone health, kidney diseases, metabolic syndrome, reproductive health, and infectious disease, they are not easily organized.  Some recommendations include the following:

  1. “the frequency of monitoring with liver tests should be individualized by the transplant center (grade 1, level a)”
  2. “depending on the pattern of liver tests, magnetic resonance imaging, computed tomography, ERCP, and ultrasound may be appropriate (grade 1, level a)”
  3. “frequent handwashing reduces the risk of infection…(grade 1, level a)”
  4. “shoes, socks, long-sleeve shirts and long pants should be worn for activities that will involve soil exposure..(grade 1, level a)”
  5. Patients “with PSC and inflammatory bowel disease…should undergo an annual screening colonoscopy ..(grade 1, level b)”
  6. “the ideal immunosuppression for pregnancy is tacrolimus monotherapy”

Thus, the recommendations are sometimes almost worthless like #1-3, sometimes difficult to implement like #4, and sometimes specific like #5-6.

Bottom-line:

While not useful as a practical checklist for routine care, this guideline offers useful information on a broad range of problems for transplant recipients.

Born this way

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“Baby I was born this way” is applicable to more than just Lady Gaga.  It looks like this mantra extends to functional somatic symptoms (FSS) (J Pediatr 2013; 162: 335-42).

This study which was part of a longitudinal birth cohort study, Copenhagen Child Cohort CCC2000, included 6090 children born in a well-defined geographical area around Copenhagen, Denmark in 2000.  At 5-7 year follow-up, a random sample of 3000 members of the cohort were selected; only 2912 were included as 79 were unreachable and 9 had died.  Subsequently, 1327 had complete data and were the final study sample.

FSS were measured by the Soma Assessment Interview.  In the first 10 months of living, regulatory problems which included at least 2 of 3 problems of feeding, sleeping, or tactile reactivity predicted impaired FSS at 5-7 years with aOR 2.9.  Maternal psychiatric illness during the child’s first year of life conveyed an aOR of 7.1.

FSS (ie, headache and recurrent abdominal pain) could develop due to a number of possible mechanisms:

  • hypersensitivity to stimuli
  • autonomic hyper-reactivity
  • regulatory problems may be risk factors for mood and anxiety disorders

While the strengths of this study included prospective data collection by health professionals and a fairly large sample size, there were still numerous limitations.  Measuring regulatory problems in infancy is not fully validated.  In addition, the designation of FSS is problematic as it is difficult to fully exclude organic etiologies which could present with similar complaints.

The association of maternal psychopathology with the development of FSS in their children is of interest.  It is not clear if this risk is due to nurturing effects (i.e., child’s capacity to self-regulate) or due to nature (i.e., inherited susceptibility).

Taking Folic Acid for Autism Prevention

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A large study in JAMA shows an association between taking folic acid and reducing the risk of autism by about 40% (JAMA. 2013;309(6):570-577. doi:10.1001/jama.2012.155925). JAMA Network | JAMA | Association Between Mater

“The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study.”  The study took place between 2002-2008.  Pregancies in which mothers received folic acid for 4 weeks before the last menstrual period and for at least 8 weeks into the pregnancy were compared with those unexposed to folic acid.

Results:

“At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61,042) had autistic disorder, compared with 0.21% (50/24,134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use.”

While this study does not prove a causal relationship between maternal folic acid intake and autism, since folic acid is already recommended to prevent neural tube defects, this provides another potential benefit to this intervention.

From ABC news coverage:

Smoking-related mortality

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“The time is always right to do what is right.”  Martin Luther King

When it comes to almost any situation, including smoking cessation, this quote is probably appropriate.  The hazards of smoking are detailed in recent several articles/editorial (NEJM 2013; 368: 341-350, 351-64, 389-90).

In the first article, the authors reviewed smoking-cessation histories from 113,752 women and 88,496 men.  All participants were older than 25 years and interviewed between 1997-2004.  These participants were from a cohort in U.S. National Health Interview Survey (NHIS).  The NHIS is a nationally representative cross-sectional health survey.

The second study involved large populations from the Cancer Prevention Study I (CPS I) which started in 1959 and CPS II which started in 1982.  These were prospective studies followed the mortality associated with smoking.  In all, the populations of these two studies exceeded 1.2 million.

What were the key findings?

1. The benefits of smoking cessation were noted in all age groups.  Those who quit between 25-34 years of age lived 10 years longer.  Those who quit between 35-44 years of age lived 9 years longer. Those who quit between 45-54 years of age lived 6 years longer. Those who quit between 55-64 years of age lived 4 years longer.

2. Smokers mortality worsened compared to the general population over a 50-year period. During the three time periods (1959-65, 1982-88, 2000-10), the mortality dropped by 50% in the overall study population.  However, female smokers mortality remained unchanged and male smokers experienced only a 24% reduction.

Specific hazard ratios (HR) for a large number of conditions are detailed in these studies.  For example, among men, the HR for death due to lung cancer was 24.97 in the contemporary cohort.  Due to the nature of these large cohorts, there are many limitations and it is difficult to draw conclusions about a specific threshold in terms of amount of smoking.  However, the conclusions may actually underestimate the effects of smoking due to undersampling of certain high risk populations, like incarcerated persons and those with mental illness.

The editorial notes that more women die from lung cancer than breast cancer.  Yet, due to smoking’s stigma, there are no ‘race for the cure’ promotions.  In addition, increasingly smoking is a behavior concentrated in persons of lower social status.  As such, it “risks becoming invisible to those who set health policies and research priorities.”

Even Nick Naylor might consider a career change if he read these studies (Thank You for Smoking (film) – Wikipedia, the free encyclopedia).

Shout out for Gluten-Free Camp

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One enjoyable aspect about my work with my colleagues has been their willingness to use their free time to participate and develop programs for children.  For many years, this has included several camps at Camp Twin Lakes, particularly Camp Oasis for children with inflammatory bowel disease. Most of the physicians in our group have given their time to support this camp.  In recent years, Larry Saripkin has spent a week there every summer  and Stan Cohen really established this camp in Atlanta.  In addition, our nurses have volunteered their time as well; they stay busy attending to the medical needs of these kids so they can enjoy a camp experience.

More recently, a camp for kids with celiac disease has been started, Camp WeeKanEatIt.   Under Jeff Lewis’ direction and fundraising, this camp has been started and allows kids  (8-17 yrs) who need to be maintained on a gluten-free diet to experience camp.  Siblings are allowed to attend as well.  Don’t forget this year’s camp dates: June 23-28!

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New lipid emulsions — lacking data to support usage

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According to a systematic review of the literature regarding ω-3 (n-3FA) fatty acid lipid emulsions, there is a “lack of sufficient high-quality data to support the use of parenteral n-3FA lipid emulsions in children” (JPEN 2013; 37: 44-55). Thanks to Kipp Ellsworth for this reference.

The authors of this study researched 4 databases up to March 2011 and extracted relevant studies.  Five randomized controlled trials and 3 high-quality prospective cohort studies were included.  The strength of evidence was “consistently low or very low across all lipid emulsion comparisons and outcomes.”

Specific criticisms:

  • Few studies examined important outcomes like length of hospital stay or intensive care stay.
  • There was lack of data on growth, cognitive development or potential long-term effects/harms.
  • All of the studies in children varied considerably with regard to the dosing regimens, duration of administration, and duration of followup.
  • The studies were small with sample sizes ranging from 28-91 patients.
  • The 5 RCTs had unclear risk of bias due to inadequate blinding of participants and study personnel.
  • All of the RCTs were funded by the manufacturer.
  • While some biochemical outcomes improved, no difference in mortality has been identified.  A biochemical response is a poor measure of effectiveness.  In fact, several studies have shown deterioration in liver histology and fibrosis despite improved biochemical measures in infants on Omegaven.
  • For Omegaven (fish oil) treatment, all studies used a historical control group.  In these studies, typically the Omegaven dose was half the dose of Intralipid used in the control group.

This article (in its Table 1) identifies the constituents in the commercial available lipid products which include Intralipid, Clinoleic, Liposyn II, Omegaven, SMOFLipid, and Lipoplus.  Intralipid which is widely used is devoid of substantial arachidonic acid (ARA) and docosahexaenoic adic (DHA).  This is particularly important in premature infants as noted in recent blogs:

Omegaven, in particular, and SMOFLipid, to a lesser degree, have much more AA and DHA.  As such, both of these emulsions have the potential improve vision and cognitive outcome in premature infants.

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