Author Archives: gutsandgrowth

Unknown's avatar

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.

Thrombophilia and Portal Vein Thrombosis

Posted on by

Most cases of portal vein thrombosis (PVT) remain without apparent explanation (JPGN 2012; 55: 599-604).

In this study from Brazil, 32 children with portal vein clots (1990-2011) were reviewed in this cross-sectional study.  The median age at diagnosis was 2.4 years.  Hereditary or acquired thrombophilia was detected in 34% and 9 of these patients had identified risk factors.

The most common thrombophilia factor was the presence of heterozygous state for methylenetetrahydrofolate reductase (MTHFR) C677T which was present in 11 patients.   2 of these patients had a cofactor, including G20210A prothrombin gene, and factor V Leiden.

Risk factors included umbilical catheterization in 13 patients (40.6%).

18 (56%) had no risk factors. 

Related blog entry:

VTE with IBD | gutsandgrowth

Additional references:

  • -Hepatology 2009; 39: 1729.  AASLD practice guidelines on vascular disorders. Recs mesoRex shunt for PVT.
  • -JPGN 2008; 47: 630. n=108. Infrequent thrombophilia d/o with PVT. Banding/sclero -effective.
  • -J Pediatr 2006; 148: 735. PVT more common than previously thought; umbilical vein catheter, esp if misplaced, is risk factor.
  • -NEJM 2011; 365: 147. Review. In cirrhosis pts, platelet count as low as 60K usually sufficient to preserve thrombin generation equivalent to lower limit of normal range in healthy subjects. PVT occurs in 8-25% of pts listed for OLTs. Thus, many procoagulant factors as well as potential propensity for bleeding.
  • -J Pediatr 2003; 142: 197. Rex procedure corrects clotting abnormalities.
  • -J Pediatr 2005; 146: 568. Portal vein -cavernous transformation –associated with cholestasis.
  • -J Pediatr 2000; 136: 805. 49% of children with PV clot had bleeding by 16 yrs & 76% by 24 yrs. (n=44).
  • -Gastroenterol 2001; 120: A-49, #256. Attention span deficits can be corrected c REX.
  • -Hepatology 2000; 31: 345-348 & 587-591. Hyperhomocysteine mutation frequent when PVT assoc c cirrhosis. Etiologic factors. 87% c thrombophilic d/o.
  • -Gastroenterol 2001; 120: 490-497 & 579. Anticoagulation helpful.
  • -J Peds 2006; 149: 275. Reference values.
  • -NEJM 2005; 352: 1791. Thrombosis of cerebral veins & sinuses (review); includes assoc c IBD.  Specific thrombophilia disorders: Antithrombin deficiency, protein S and C deficiencies,Factor V Leiden mutation, (the A for G 20210) prothrombin gene mutation, lupus anticoagulant, antiphospholipid antibodies, factor XI, and MTHFR-hyperhomocysteinemia (thermolabile variant of methylenetetrahydrofolate reductase- C677T MTHFR-). The later was paricularly interesting in view of the recent report of hyperhomocysteinemia in patients with inflammatory bowel disease (Thromb Haemost 1998,80;542-5)

For the smoking skeptics

Posted on by

How bad is secondhand tobacco smoke (SHS)?  This has been debated.  When I come out of an office room and the entire room smells of smoke, even though no one has smoked in the room, I know this is detrimental.  More proof of this comes from an article which shows that SHS is associated with an increase in the severity of children hospitalized with influenza (J Pediatr 2013; 162: 16-21).

In this study of 117 children, 40% were exposed to SHS.  They had increased need for intensive care (30% vs. 10%), increased intubation (13% vs. 1%), and longer length of stay (LOS) (4 days vs. 2.4 days). In children with chronic conditions, the LOS was 10 vs. 3.5.  After controlling for multiple variables, the authors found that SHS exposure was associated with a 4.7 fold increase in the likelihood of ICU admission and a 70% LOS.

This study had many limitations.  It was a retrospective chart review.  Patients between 2002-2009 were identified initially by the discharge diagnosis of influenza.  Among the 171 charts identified, 117 had a positive influenza culture and adequate data to retrieve.  As a retrospective review, it is possible that screening for smoke exposure was more common in the more severely affected cases.

Additional references:

Predictors of colectomy in pediatric UC

Posted on by

A recent review of children in the Pediatric Inflammatory Bowel Disease Consortium (PediIBDC) examined risk factors for proctocolectomy in children with Ulcerative Colitis (UC) (JPGN 2012; 55: 534-40).  Two of the investigators (Stanley Cohen and Ben Gold) are colleagues of mine at GI Care for Kids.

In total, 406 children with UC were reviewed.  The average age at diagnosis was 10.6 years.  The average followup was 6.8 years.  57 (14%) underwent surgery with a median time to surgery of 3.8 years.  Overall risk factors for colectomy included the following:

  • Presenting with weight loss, HR 2.55
  • Presenting with hypoalbuminemia (<3.5 g/dL), HR 6.05
  • First-degree relative with UC, HR 1.81
  • Treatment with cyclosporine, HR 6.11
  • Treatment with tacrolimus, HR 3.66

While this data expands on the knowledge of these factors in children, the findings are not unexpected.  Low albumin levels and poor nutritional status have been identified in other studies as risk factors for UC relapse and for colectomy.

With regard to first-degree relatives, the findings imply that children with a first-degree relative are more likely to have a more severe form of UC.

The use of calcineurin inhibitors, cyclosporine and tacrolimus, are given only in the presence of severe disease.  Thus, while use of these agents is associated with an increased risk of colectomy, it is unlikely that this is a causal relationship.  Interestingly, the use of infliximab was not identified as a risk factor.  However, this retrospective study examined patients between 1999-2003.  Since this timeframe, there has been increased use of infliximab for refractory UC.

Going forward, it is likely that contemporary studies would incorporate PUCAI (pediatric UC activity index) measurements and would have the ability to enroll far greater numbers of patients from database consortiums.

Related blog posts:

Outgrowing the growth charts

Posted on by

Unfortunately, there is a need for extreme growth charts (Pediatrics 2012; 130: 1136-40).

The authors of this study designed growth charts for morbidly obese children.  The reason for these charts is that there are many pediatric patients who cannot be plotted using the CDC  growth chart which has a maximum BMI of 36 kg per meter-squared.  The CDC charts are based on a preobesity epidemic population data set (1963-94) and has sparse data for those above the 97th percentile.  The manuscript describes how these initial charts were derived.

These new growth charts calculate the BMI as a percentile of the 95th percentile.  For example, multiplying the BMI 95th % by 1.2 would yield a result of 120% of the 95th%.  The authors calculated 1.1 through 1.9 multiples of the 95% for all ages between 2 and 20 years.  On their curve, a BMI as high as 64 kg per meter-squared can be plotted.  This allows easier visual tracking of a patient’s progress.

Drawbacks:

  • Difficult to explain to parents due to confusing phraseology –use of two percentages
  • Many of the patients are now on the growth curve and could appear to be graphically normal despite being morbidly obese

The authors note that their growth charts were incorporated into their electronic medical record (Epic software).

Related blog entry:

Advice for doctors after the death of a child

Posted on by

Abraham Lincoln (in a letter to a girl whose father died in the civil war): “It is with deep grief that I learn of the death of your kind and brave father; and especially that it is affecting your young heart beyond what is common in such cases.  In this sad world of ours, sorrow comes to us all; and to the young it comes with bitter agony because it takes them unawares.  The older have learned ever to expect it.”

Fortunately in pediatric care, the death of a child is uncommon.  When it occurs, it can have a devastating effect on the family; a recent article provides a lot of useful advice for this situation (Pediatrics 2012; 130: 1164-69).

Key points:

  • Most parents experience a profound sense of guilt when harm comes to their child even if through no fault of their own.  The duration and intensity vary considerably.
  • Parents invest much of their hopes for the future in their children; this extends to fetuses and infants.
  • Family events may reawaken grief.  In addition, many parents report that their greatest fear is that the child will be forgotten.
  • Even in children with severe disabilities, the parents’ sense of loss is not usually diminished.
  • Peer-support groups can be very helpful (see below).
  • Complicated grief which occurs more often in the setting of previous psychiatric problems often require mental health support.  Previous parent-child troubled relationships may intensify grief as well.
  • Certain types of death like suicide, homicide, or due to drugs/alcohol can contribute to more intense grief.
  • Siblings are often considered ‘the forgotten mourners.’  Grieving parents may not be able to provide adequate support. Sibling issues include ‘survivor guilt’ (especially in the setting of intense sibling rivalry), overprotection, idealization/replacement child, and general issues of sibling grief.
  • Most helpful for pediatricians: provide an opportunity to meet with family members to listen.  “The pediatrician might say, simply ‘I’m so sorry to hear about _____’s death.  What a terrible loss for you and your family.’ Recommends avoiding expressions like “he/she is better off now” which parents may perceive as diminishing the value of the child.

Resources recommended by article:

  1. Compassionate Friends 877-969-0010 –self-help groups
  2. http://www.nationalshare.org –newborn death or stillbirth support
  3. http://www.bereavedparentsusa.org –support for bereaved family members
  4. http://www.survivorsofsuicide.com –support for those who have lost loved ones to suicide

Additional resources/references:

  • Useful Books recommended by previous article (Pediatrics 2000; 105: 445):

“The Fall of Freddie the Leaf” Leo Buscaglia
“When dinosaurs die: a guide to understanding death” Laurie Brown
“Caring for your grieving child” Martha Wakenshaw

  • NEJM 2001; 344: 1162. Suggestions for Writing a Condolence Letter:

There are ways to make the difficult task of writing a condolence letter easier. The letter may describe in detail the extent and depth of the relationship between the physician and the patient, or it may be a much shorter expression of sympathy. Whatever one writes, it is important to avoid superficial attempts to assuage grief, such as, “It was meant to be” or “I know how you feel.” In order to avoid issues of legal liability, the letter should focus on the sadness of death rather than revisit the clinical details of the illness..

One can begin the letter with a direct expression of sorrow about the death, such as “I am writing to send you my condolences on the death of your husband.” In our condolence letters, we try to include a personal memory of the patient and something about the patient’s family or work. Specific references to achievement at work, devotion to family, courage during the illness, or the patient’s character can bring life to the letter. We also state that it was a privilege to have participated in the patient’s care. We point out the comfort the patient received from the family’s love. We conclude the letter with a few words of support to let the family know our thoughts are with them. These suggestions are intended not as a substitute for the expression of genuine thoughts and feelings but as an aid in approaching the task.

Are we missing Vitamin B12?

Posted on by

This is the question that I wonder after reading a recent review (NEJM 2013; 368: 149-60) -especially since effective treatment is readily available.

While vitamin B12 deficiency is most common in individuals 70 to 80 years, it affects all age groups.  A particularly vulnerable group are infants of mothers with vitamin B12 deficiency.  These infants may be born with deficiency or it may develop if exclusively breast-fed, usually between 4 and 6 months of age.  Indications of this deficiency include failure of brain development, poor growth, hypotonia, and feeding difficulties.  Some infants develop tremors, lethargy, and hyperirritability.  Imaging may show atrophy and delayed myelination.

Mothers who are at most risk:

  • unrecognized pernicious anemia
  • history of gastric bypass
  • short gut syndrome
  • long-term vegetarian or vegan diet

Other pediatric conditions that cause B12 deficiency: ileal resections, Imerslund-Grasbeck syndrome (Imerslund–Gräsbeck syndrome (selective vitamin B12 malabsorption ..), inflammatory bowel disease, and pernicious anemia.

Other Key Points from this review:

  • B12 deficiency causes reversible megaloblastic anemia, demyelinating neurologic disease or both
  • B12 deficiency is the major cause of hyperhomocysteinemia in countries with folate-fortified food and contributes to a risk of vascular disease and thrombosis
  • Autoimmune gastritis (pernicious anemia) is the most common cause of severe deficiency (in adults).  Tests to determine underlying reason for B12 deficiency include the following: anti-intrinsic factor antibodies (must be checked off treatment for at least 7 days), anti-parietal cell antibodies -both help detect pernicious anemia, gastrin level (high level) & pepsinogen I (low levels) both suggestive of atrophic gastritis.  The Schilling test of radioactive B12 is no longer available.  Endoscopy is frequently performed in adults with B12 deficiency.
  • Methylmalonic acid (MMA) is the best indicator for untreated B12 deficiency; MMA >400 nmol/L has 98% sensitivity for B12 deficiency.  Other causes of increased MMA include renal failure and volume depletion.
  • Serum B12 has poor sensitivity and specificity -though performs adequately at higher cut-off value (<350pg/mL has 90% sensitivity)
  • Many individuals require lifelong treatment with either parenteral B12 or high-dose oral tablets (see article for dosing recommendations)

Additional references:

  • -J Pediatr 2010; 157: 162.  B12 deficiency in newborns –especially if mother has had bariatric surgery or vegan diet.
  • -J Pediatr 2001; 138: 10 (review) At risk for deficiency: strict veggie, abnl absorption (gastric resection, pernicious anemia), long term PPI, bacterial overgrowth, ileal disruption (Crohn’s), or ileal receptor d/o (Imersund-Grasbeck),  inborn B12 metabolism d/o

Clinical Sx: FTT, weakness, anorexia, neuro/psych sx, macrocytic anemia, pancytopenia, glossitis, vomit/diarrhea

Dx: low vit B12, incr methylmalonic acid & incr homocysteine.  MMA specific for B12; homocysteine incr also if folate deficient.

If Vit B12 deficient, reason for this needs to be determined.

UVA Links

Posted on by

My alma mater, the University of Virginia, has a fair amount of useful GI educational material on their website.

Here are a few links:

Low FODMAP Diet

Irritable Bowel Syndrome (IBS) diet

Short Bowel Syndrome Diet (Long Version)

Nutritional Considerations for Patients with Inflammatory Bowel Disease

Fiber (dietary recommendations handout)

Gluten-free Diet

Transfusion strategy in acute GI bleeding

Posted on by

A recent study shows that holding off on blood transfusions can improve survival with severe acute upper gastrointestingal bleeidng (NEJM 2013; 368: 11-21).  This finding is not unexpected as this has been shown in observational studies.  In addition, in critical care patients without acute GI bleeding, a restrictive approach to transfusions has also been beneficial.

This study which enrolled 921 patients (>18 years) assigned 461 to a restrictive transfusion strategy (transfusion if <7 g/dL or at discretion of physician) and 460 to a “liberal” strategy (transfusion if <9 g/dL).

In additon to fewer transfusions, the restrictive group had improved survival:

  • 225 in the restrictive group did not require a blood transfusion compared with 65 in the liberal group
  • Survival at 6 weeks: 95% in the restrictive group compared with 91% in the liberal group.  Hazard ratio 0.55 (confidence interval 0.33 to 0.92) –a 45% reduction in the relative risk of 45-day mortality.
  • Recurrent bleeding occurred in 10% of the restrictive group compared with 16% of the liberal group.
  • The patients with cirrhosis (and Child-Pugh class A or B) were most likely to benefit from a restrictive approach with hazard ratio of 0.30.  Child-Pugh class C did not have a benefit from a restrictive approach with hazard ratio of 1.04.  With the liberal approach, there was a higher portal-pressure gradient within the first five days.

The reasons for bleeding in this study included peptic ulcers in about 50%, and varices in 24%.  The other causes included Mallory-Weiss tears, erosisve gastritis/esophagitis, and neoplasms.

Why does giving less blood result in better outcomes?

  1. Transfusion may impair hemostasis in several ways.  It may result in abnormalities in coagulation properties.  It may counteract splanchnic vasoconstrictive response.  And, in those with cirrhosis, it can increase portal pressure (even in the presence of somatostatin).  All of these mechanims may increase rebleeding.
  2. In addition, systemic effects from transfusion can include circulatory overload and pulmonary edema.

Also (unrelated to this posting), a thoughtful comment to a recent post on FDA regulations was posted by Ben Gold (Can the FDA prohibit free speech? | gutsandgrowth).

Related blog references:

Hepcidin for sepsis recognition

Posted on by

While this blog has discussed hepcidin’s essential role in iron homeostasis (see below), it performs well as a marker of sepsis as it is also an acute phase reactant (J Pediatr 2012; 162: 67-71).

Hepcidin is known to contribute to host defense by depriving microbes of access to iron and through direct antimicrobial properties.  In this study, the authors compared the performance of hepcidin to C-reactive protein (CRP) from the serum of 44 infants with late-onset sepsis.  Specimens were obtained in the acute and convalescent periods.

Results:

  • Hepcidin levels were increased 4-fold in infants with sepsis compared without infants who were not septic (P<.0001).  Levels returned to normal following therapy.
  • Hepcidin levels >92.2 ng/mL correctly identified 91% of all infants (PPV 100%, NPV 87%, specificity 100%, sensitivity 76%)
  • Models combining hepcidin with CRP did not perform better than hepcidin alone.
  • Hepcidin values were comparable to CRP, and possibly more useful.  The authors stated that a CRP value of >7.95 mg/dL had a PPV of 89%, NPV 74%, specificity of 96%, and sensitivity of 47%.
  • Hepcidin has been reported to peak at 6 hours after interleukin-6 injection in humans whereas CRP peaks 24-48 hours after an inflammatory stimulus.

Related blog entries:

Can the FDA prohibit free speech?

Posted on by

Maybe not (NEJM 2013; 368: 103-05).

While the FDA is responsible for overseeing the safety of pharmaceuticals and veracity of marketing, its authority does not extend to the practice of medicine.  This enables the widespread practice of using medications for “off-label” purposes.  Physicians can use approved drugs for nonapproved uses.  FDA regulations have restrained marketing of off-label uses of prescription medications by pharmaceutical representatives.

However, a recent appellate ruling in United States v. Caronia has stated “the government cannot prosecute pharmaceutical manufacturers…for speech promoting the lawful, off-label use of an FDA-approved drug.”  According to this perspective article, the ruling stemmed from the argument that refusing to “allow the free flow of information would result in …limitations, and side effects of the drug.”

At stake is whether the ability of the FDA to combat false or misleading speech.  In addition, limiting the FDA’s authority may lead to fewer studies documenting the effectiveness of medications for various indications.  If the medication is approved for one use and there are no constraints on marketing, there will be little incentive to complete additional studies.

Additonal references:

UNITED STATES V. CARONIA 09-5006-cr Unofficial Oral Argument …

United States v. Caronia – Reed Smith