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.

Physician Team Cohesiveness

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Recently, I attended our medical staff semi-annual meeting.  Two speakers (Dr. Usha Sathian and Dr. Lucky Jain) provided some impressive information about the growth of the hospital system’s outreach with ambulatory care services and about the development of Emory/associated institutions’ academic medicine advances.  The latter includes graduate medical education, extensive grants, and involvement in more than 1000 current clinical studies.  The number of trainees at all levels has grown incredibly.  These trainees are much more likely to stay in Georgia than trainees in many other parts of the country.

This growth corresponds to increases in the hospital’s bed capacity and technical abilities.  A third speaker, Dr. Joseph Rosenfeld, was honored for being both a community physician and attending physician for 40 years!  When he first arrived, there were eight pediatric ICU beds at Egleston Children’s hospital.  Now, there has been about an 8-fold increase.  The number of hospital beds has more than tripled.

Yet, sadly in my view, only a tiny number of physicians attended this meeting, a fraction that attended when the medical staff was much smaller.  Despite the huge increase in staff physicians, there is a dwindling number who attend meetings; this is true for grand rounds as well.  When I first arrived in town about 20 years ago, I looked forward to these meetings to engage and meet my colleagues.  In addition, due to ever larger number of subspecialists, it is much less frequent that when I rotate on hospital service that I will see the well-known neurologist, pulmonologist, endocrinologist, infectious disease expert and so many others.

I came away from the staff meeting with a tangible feeling that despite the incredible success of the system in developing improved capabilities that the feeling of working together as a team of subspecialists and generalists has diminished.  This makes me wonder whether other aspects of modern medicine and the worry over physician burnout are not related to increased isolation of physicians into their specialty silos and to cloistering into our computers and smartphones.

Though I feel grateful to be able to help children in my work, the biggest reason that I chose pediatrics was because of my admiration for the pediatricians I had met and my desire to both emulate their work and to work with them.  I think working closely together is one aspect that makes being a pediatric specialist worthwhile.

My take: Experts have recommended “peer support” to prevent burnout and increase job satisfaction.  My experience, which I suspect is shared widely, indicates that engaging with our peers is becoming less frequent.

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Drug Development for Eosinophilic Esophagitis

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Full text link: White Paper AGA: Drug Development for Eosinophilic Esophagitis (EoE)

I Hirano et al. Clin Gastroenterol Hepatol 2017; 15: 1173-83. This article reviews diagnostic criteria for EoE, clinical endpoints, and current/emerging treatments.

From AGA website-an excerpt:

Four important points from the white paper:

1. There is a complex inter-relationship between EoE, gastroesophageal reflux disease (GERD) and proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). A substantial proportion of patients with esophageal eosinophilia will improve with PPI treatment.

2. The clinical features and presentation of EoE differ between children and adults. Poor symptom specificity among children has limited the ability to identify appropriate candidates for enrollment into clinical trials and has impeded the development of pediatric patient-reported outcome instruments.

3. Aside from pharmacologic approaches, EoE can be addressed with dietary modifications and/or endoscopic dilation.

4. We should remember that the diagnosis of EoE carries a potentially major financial burden on patients’ families, making identifying new, effective and affordable treatment options a priority.

Great Story -How CAR-T Came About

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While chimeric antigen receptor T-cell (CAR-T) therapy does not have much to do with pediatric gastroenterology, the development of this therapy, described recently (L Rosenbaum NEJM 2017; 377: 1313-5), holds lessons about perseverance and chance that are widely applicable.

CAR-T involves genetically engineering the patient’s own T cells to kill tumor cells. It recently received FDA approval to treat patients up to 25 years of age with relapsed or refractory acute lymphoblastic leukemia.

The story of the survival of Emily Whitehead, the index patient for this therapy, is suitable for Hollywood.  The groundwork for this very expensive treatment dates back to 1893 with William Coley’s recognition of the immune system’s potential for treating cancer –he injected streptococcus into an inoperable osteosarcoma and observed tumor shrinkage.

Key Steps in this Story:

  1. University of Pennsylvania’s immunologist Carl June spent his career working on CAR-T. His wife died of ovarian cancer in 2001 and he resolved to develop this emerging immunotherapy that he had wanted for her.
  2. Barbara and Edward Netter provided key funding for this project in 2008.  They too had lost a close family member to cancer.
  3. Emily Whitehead nearly died due to CAR-T therapy which triggered cytokine-release syndrome, which was not a recognized entity at the time.  In part due to chance, extremely high levels (>1000-fold) of interleukin-6 (IL-6) were detected quickly due to the ability of the institution and prodding by the researchers to their colleagues.  This allowed the experimental use of tocilizumab, a monoclonal antibody that targets IL-6.
  4. Her survival helped reenergize this line of research.

My take (borrowed from author): “Therapeutic advances are motivated by more than money –that it’s the hope, vision, and perseverance of both patients and investigators that made this …possible.”

Acute esophageal necrosis ina a 63 year-old that resolved with conservative treatment.  “The cause is unknown..[it] occurs most commonly in the distal third of the esophagus, which is hypovascular” often in the setting of chronic disease.

Do these antibiotics make me look fat?

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There has been a lot of interest and conflicting reports about whether antibiotics contribute to obesity.  Another interesting study on this theme:

  • ET Rogawski et al. JPGN 2017; 65: 350-6. 

The authors followed 1954 children twice weekly from birth to 2 years of age as part of the MAL-ED study.  There were 8 study sites, including in Bangladesh, India, Brazil, Pakistan, Nepal, South Africa, Peru, and Tanzania. Key finding:

  • Antibiotic use before 6 months of age was associated with increased weight from 6 months to 2 years of age.
  • Antibiotic use after 6 months did not affect growth.

The authors speculate: “If treatment of infections were the main mechanism, we would expect antibiotic exposure after 6 months to also have an impact.” Thus, they conclude that effects on the microbiome are likely a more important explanation.

My take (borrowed from te authors):  “Antibiotic use in low-resource settings” can improve growth, though the long-term consequences are not known.  In high-income settings, weight gain secondary to antibiotic exposure is more likely to be detrimental.

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Patient T-shirt

 

Diet and Stress in Pediatric Eosinophilic Esophagitis

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When it comes to eosinophilic esophagitis (EoE), I sometimes worry that some treatments are worse than the disease, depending on the severity of the EoE. A recent study (C Case et al. JPGN 2017; 65: 281-84) indicates that dietary therapy is often stressful for families.

This study examined children ages 2-18 during an annual American Partnership for Eosinophilic Diseases (APFED.org) patient education conference. What I found most interesting was Table 3. “Stress associated with eosinophilc esophagitis.”

Some of the data:

  • In response to ‘how stressful do you find the following since your child’s diagnosis of EoE?’ Family structure at mealtimes: Not stressful 13.5%, somewhat stressful 21.6%, moderate stressful 16.2%, significant stressful 32.4%, and severe stressful 16.2%
  • In response to ‘how stressful do you find the following since your child’s diagnosis of EoE? Buying and cooking separate foods/meals for your child: Not stressful 2.6%, somewhat stressful 21.1%, moderate stressful 21.1%, significant stressful 31.6%, and severe stressful 23.7%
  • In response to ‘how stressful do you find the following since your child’s diagnosis of EoE? Financial strain due to cost of food: Not stressful 10.5%, somewhat stressful 21.1%, moderate stressful 18.4%, significant stressful 23.7%, and severe stressful 36.3%
  • What is your current stress level in response to your child’s EoE? Not stressful 2.6%, somewhat stressful 15.8%, moderate stressful 36.8%, significant stressful 42.1%, and severe stressful 2.6%
  • 62% of respondents indicated that child’s EoE has affected marital relationship.

In addition, the study documented that “half of youth were affected by worry, anger, and sadness related to specialized diets.”  As this study relied on participants at an APFED meeting, this could skew the EoE population to be more severely affected.

My take: This study shows the emotional burden that dietary treatment of EoE places on families.

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Berry College

Top Anti-TNF for Ulcerative Colitis

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A recent retrospective cohort study (S Singh et al. Clin Gastroenterol Hepatol 2017; 15: 1218-25) compared infliximab and adalimumab in a nationwide Danish cohort of adults with ulcerative colitis (UC) from 2005-2014. The authors used propensity score and selected 171 patients who received infliximab (IFX) from a total of 1580 and 104 patients who received adalimumab (ADA) among a total of 139.

Key findings:

  • Patients who received ADA had higher hospitalization rates (HR 1.84) and a trend toward higher UC-related hospitalization (HR 1.71, CI 0.95-3.07) compared to IFX
  • Risk of abdominal surgery was not significantly higher in ADA patients (HR 1.35) compared to IFX
  • Serious infections were higher in ADA group, HR of 5.11 of needing hospitalization due to infections

There have been no randomized clinical trials  to determine if a specific anti-TNF agent is superior to another. In an associated editorial (MT Osterman, GR Lichtenstein, 1197-99), the authors note that while we don’t know which agent is superior, by comparing similar trials (ACT 1 & 2 for IFX and ULTRA 1 & 2 for ADA), “raw week 8 induction rates of clinical remission, clinical response, and mucosal healing are approximately 16%, 18%, and 19%, respectively, higher for infliximab”..”less dramatic differences favoring infliximab (approximately 9%, 13%, and 15%, respectively) are seen during maintenance at 1 year.”

My take: Due to the lack of randomized head-to-head studies, we do not know with certainty which anti-TNF is best for UC.  However, the data we have from retrospective cohort studies and from using raw data from prospective studies suggests that infliximab is effective in more patients.

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University of Virginia Rotunda Pctures

 

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Briefly: Notable Recent IBD Publications

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Vermeire S et al. Lancet 2017; 389: 266-75.  The “FITZROY ” study examined clinical remission in patients with moderate-to-severe Crohn’s disease treated with filgotinib, a orally administered selective JAK inhibitor.  This agent is 30 times more selective fo rJAK1 over JAK3. This study enrolled 174 patients in a phase II study. Key findings:

  • Among patients naive to anti-TNF agents, clinical remission (based on CDAI <150 at week 10) noted in 47% of filgotinib-treated compared with 23% of placebo group (P=.0077)
  • Among patients naive to anti-TNF agents, clinical response was noted in 67% of filgotinib-treated compared with 44% in the placebo group.

H Singh et al. Gastroenterol 2017; 153: 430-8.  Using the large Manitoba Epidemiology Database with 1.3 million population (2005-2014), the authors found that individuals with IBD had a 4.8 fold increase risk of Clostridium difficile infection.

T-D Kanneganti. NEJM 2017; 377: 694-6. This review examined the NLRP3 Inflammasome.  Neudecker et al (J Exp Med 2017; 214: 1737-52) identified microRNA miR-223 which functions “to suppress the Nlrp3 inflammasone during acute colitis.” Other useful points in this review of basic research:

  • “The majority of the immune cells in the body are located in the intestine, where they are spatially separated from more than 10 trillion microorganisms by a layer of mucus and a layer of epithelial cells.  Deterioration of this physical barrier …underlies inflammatory bowel disease.”
  • miR-223 is increased in the inflamed colon. “During inflammation, the expression of miR-223 is also upregulated..and the molecule binds to its complementary sequence in a regulatory part of Nlrp3 mRNA…lead[ing] to decreased Nlrp3 expression and the consequent dampening of interleukin-1β maturation and associated inflammation.”

Autoimmune Hepatitis and Hepatocellular Carcinoma

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Briefly noted:

A Tansel et al. Clin Gastroenterol Hepatol 2017; 15: 1207-17.  This systematic review and meta-analysis identified 25 studies and 6528 patients examining the relationship between autoimmune hepatitis (AIH) and hepatocellular carcinoma (HCC) .  In these studies the median followup was 8.0 years.  Key findings:

  • The pooled incidence of HCC was 3.06 per 1000 patient-years
  • 92 of 93 patients who had HCC had evidence of cirrhosis before or at the time of their diagnosis

My take: This study demonstrates that AIH patients with cirrhosis are at increased risk for HCC.  In patients with AIH who do not have cirrhosis, there does not appear to be a significant risk of HCC.

Also: Link for Online Resource for Hepatopulmonary Syndrome (Canadian Sponsored site). This site has content for patients and for practitioners, including a useful video.

 

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Probiotics Lower Risk of Sepsis in Newborns

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Summary of recent study from NPR: Probiotic Bacteria Can Protect Newborns from Deadly Infections

Previous studies have shown that probiotics lower the risk of necrotizing enterocolitis in premature infants.  Now, a study (full text link below) from India examines whether probiotics could lower other infections.

An excerpt:

Feeding babies the microbes dramatically reduces the risk newborns will develop sepsis, scientists report Wednesday in the journal Nature.

Sepsis is a top killer of newborns worldwide. Each year more than 600,000 babies die of the blood infections, which can strike very quickly…

Babies who ate the microbes [Lactobacillus plantarum] for a week — along with some sugars to feed the microbes — had a dramatic reduction in their risk of death and sepsis. They dropped by 40 percent, from 9 percent to 5.4 percent.

But that’s not all. The probiotic also warded off several other types of infections, including those in the lungs. Respiratory infections dropped by about 30 percent…

The only significant side effect seen in the study was abdominal distension, which occurred in six babies. But there were more cases reported in the placebo group than in the group that got the probiotic.

Full text link (thanks to Kipp Ellsworth’s twitter feed for this link): A randomized synbiotic trial to prevent sepsis in newborns in rural India. P Panigrahi et al.

My take: Whether probiotics would be useful broadly in full-term infants in developed countries is uncertain –more studies are needed.

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We Are Last in Health Care Among High-Income Countries

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In a recent commentary (EC Schneider, D Squires. NEJM 2017; 377: 901—4) explains why the U.S. Health Care System is last among high-income countries.

Overall, the U.S. “begins with a challenge: its population is sicker and has higher mortality than those of other high-income countries.”  The U.S. has a rate of death from “conditions that can be managed and treated effectively (referred to as ‘mortality amenable to health care’) is far higher than in other high-income countries.

Four areas that have to be addressed to help U.S. move from last to first:

  • U.S. must confront lack of access to health care. The top-ranked countries offer universal insurance coverage with minimal out-of-pocket costs for preventive and primary care.
  • Underinvestment in primary care. In other countries, a higher percentage of “the professional workforce is dedicated to primary care than to specialty care.”
  • Administrative inefficiency. “Both patients and professionals In the United States are baffled by the complexity of obtaining care and paying for it.”
  • Disparities in the delivery of care. This may be mediated in part by a less robust social safety net than other high-income countries.  “Social spending [for] stable housing, educational opportunities, nutrition, and transportation may reduce the demand for” many health care services.

My take: It makes me mad that our health care system performs so poorly compared to other countries.

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