Author Archives: gutsandgrowth

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. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. 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 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, 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 15 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. For many families, more practical matters 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 – 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. I like to read, walk/hike, exercise, swim, and play tennis with my free time as well as go to baseball games. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have participated in industry-sponsored research studies.

Healthy Microbiome: A Work in Progress, Plus Microbiome-Drug Metabolism

Posted on by
Reply

A recent study (G Galazzo, N Van Best, et al. Gastroenterol 2020; 158: 1584-96) highlights the changes in microbiota diversity from birth until 11 years of age.

Full text: Development of the Microbiota and Associations With Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood

Methods: We collected 1453 stool samples, at 5, 13, 21, and 31 weeks postpartum (infants), and once at school age (6–11 years), from 440 children (49.3% girls, 24.8% born by cesarean delivery; all children except for 6 were breastfed for varying durations; median 40 weeks; interquartile range, 30–53 weeks).

Key findings:

  • Most bacteria within the Bacteroidetes and Proteobacteria phyla were already present at 5 weeks after birth, whereas many bacteria of the Firmicutes phylum were acquired at later times in infancy.
  • At school age, many new Actinobacteria, Firmicutes, and Bacteroidetes bacterial taxa emerged.
  • The largest increase in microbial diversity occurred after 31 weeks of life.
  • Vaginal, compared with cesarean delivery, was most strongly associated with an enrichment of Bacteroides species at 5 weeks through 31 weeks.
  • From 13 weeks onward, diet became the most important determinant of microbiota composition; cessation of breastfeeding, rather than solid food introduction, was associated with changes.
  • When we adjusted for confounding factors, we found fecal microbiota composition to be associated with development of atopic dermatitis, allergic sensitization, and asthma. Members of the Lachnospiraceae family, as well as the genera Faecalibacterium and Dialister, were associated with a reduced risk of atopy.

My take: We are still learning a lot about the microbiome.  Though a ‘healthy’ microbiome is still not straight-forward determination, a good diet with plenty of fruits and vegetables has been associated with more favorable attributes.

Plus One: Bahar Javdan, et al. Personalized Mapping of Drug Metabolism by the Human Gut Microbiome. Cell, 2020; DOI: 10.1016/j.cell.2020.05.001

In this study, the authors found how variations in the microbiome had unique effects on drug metabolism.  From ScienceDaily, Can gut microbiome alter drug safety and efficacy?  The authors tested 575 FDA-approved drugs to see if they are chemically modified by one of the 21 cultured microbiomes, and then tested a subset of the drugs with all the cultured microbiomes. Here, they found microbiome-derived metabolites that had never been previously reported

Related blog posts:

 

Reducing Gastrostomy Tube Placement in Children with Aspiration & COVID-19 Tracking

Posted on by
1

From The COVID Tracking Project: Effective Reproduction Number

These are up-to-date values for Rt, a key measure of how fast the virus is growing. It’s the average number of people who become infected by an infectious person. If Rt is above 1.0, the virus will spread quickly. When Rt is below 1.0, the virus will stop spreading.  All 50 states listed below (but hard to see) -these numbers adjust for testing frequency:

The site has each state -here are Georgia and Florida:

A recent study (McSweeney M, Meleedy-Rey P, Kerr J, Yuen JC, Fourneir G, Norris K, Larson K, Rosen R. A quality improvement initiative to reduce gastrostomy tube placement in aspirating patients. Pediatrics. 2020, 145: e20190325; DOI: https://doi.org/10.1542/peds.2019-0325) was highlighted by John Pohl in Practical Gastroenterology:

Full text summary: Reducing Gastrostomy Placement in Children with Aspiration

An excerpt:

Children equal to or less than 2 years of age with aspiration demonstrated on VFSS were included in the study…If a VFSS was abnormal and the child was less than 52 weeks gestational age, then the child either was admitted to the hospital for a trial of nasogastric (NG) breastmilk or oral thickened formula with NG breast milk. The patient then continued to work with SLP… If a repeat VFSS showed improvement in the swallowing mechanism, then work with SLP and trialing with thickened feeds continued until the aspiration had resolved as demonstrated by VFSS. However, if a repeat VFSS still showed aspiration, a child was considered a candidate for gastrostomy placement…

In total, 6125 patients at 2 years of age or less underwent a VFSS during the 4-year study period, and 1668 of these patients had aspiration or penetration… 94 of the patients with aspiration or aspiration and penetration on their first VFSS (12.2%) and 31 of the patients with penetration only on their first VFSS (3.4%) eventually required gastrostomy placement…

Gastrostomy placement in this patient population fell from 10.9% at the beginning of the study to 5.2% at the end…

The number of emergency room visits and hospitalizations in the patient group without gastrostomies did not increase during the study with this same patient group having significantly less emergency room visits and hospitalizations compared to those children who had undergone gastrostomy placement

My take: This study shows that conservative therapy allows most children (<2 yrs) to avoid gastrostomy tube placement

Related blog posts:

 

Pandemic Is NOT Taking a Summer Holiday

Posted on by
1

More data indicate that the coronavirus pandemic is NOT taking a summer holiday.  Projections from IHME indicate that Georgia is likely to have 4 times as many deaths by October (~2500 to  >10,000) and Florida 6 times as many (~3000 to >18,000) due to COVID-19. If projections do not worsen, the U.S. will still have more than 200,000 deaths by October.

In Europe which had at one point accounted for ~80% of new infections, the daily toll is ~10%. From Financial Times website:

From Financial Times website

From Financial Times website

From CNN/Johns Hopkins

NPR: Younger Adults Are Increasingly Testing Positive for Coronavirus

The fact that younger adults account for a large fraction of the new cases is likely a significant reason why the number of daily deaths has not spiked (& improved).

Data from Broward County, FL

Related blog posts:

Can Microscopic Colitis Lead to Crohn’s Disease or Ulcerative Colitis?

Posted on by
Reply

A recent prospective cohort “ESPRESSO” study (H Khalili et al. Gastroenterol 2020; 158: 1574-83) from 1990-2017 examined the risk of incident inflammatory bowel disease (IBD) in subjects with microscopic colitis, n=13,957 (& each matched with 5 controls). ESPRESSO = Epidemiology Strengthened by histoPathology Reports in Sweden.

Key findings:

  • In the microscopic colitis group, there were 323 incident cases of ulcerative colitis (UC) and 108 cases of Crohn’s disease (CD)
  • Mean times to diagnosis were 3.2 years for UC and 3.3 years for CD
  • Microscopic colitis was associated with an aHR of 12.6 for CD and 17.3 fo rUC
  • The absolute excess risk compared to matched control over a 10-year period were 2.6% for UC and 0.9% for CD

My take: Individuals with microscopic colitis are at increased risk of developing UC and CD.

Related blog post/related article:

 

IBD Briefs June 2020

Posted on by
Reply

SA Draiweesh et al. Safety of Combination Biologic and Antirejection Therapy Post-Liver Transplantation in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2020; 26: 949-59. In this case series of 19 patients, 14 who had liver transplantation for PSC, there was no increased risk of serious infections among patients receiving biologic therapy in combination with antirejection medications.

A Malian et al. Pedictors [sic] of Perianal Fistula Relapse in Crohn’s Disease. Inflamm Bowel Dis 2020; 26: 926-31. In this retrospective study with 137 patients, fistula relapse rates were not different in patients receiving infliximab or adalimumab (P = 0.66). In patients treated by anti-TNF at inclusion, discontinuation of anti-TNF therapy (odds ratio 3.49, P = 0.04), colonic location (OR 6.25, P = 0.01), and stricturing phenotype (odds ratio 4.39, P = 0.01) were independently associated with fistula relapse in multivariate analysis.

M-H Wang et al. Unique Phenotypic Characteristics and Clinical Course in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis: A Multicenter US Experience. Inflamm Bowel Dis 2020; 26: 774-81. Among 522 patients with UC, 56 (10.7%) had PSC. Compared with UC alone, patients with UC-PSC were younger (younger than 20 years) at diagnosis (odds ratios [OR], 2.35; adjusted P = 0.02) and had milder UC severity (adjusted P = 0.05), despite having pancolonic involvement (OR, 7.01; adjusted P < 0.001).  In the biologics era (calendar year 2005 to 2015), patients with UC-PSC less commonly received anti-TNF therapy compared with patients with UC (OR, 0.38; adjusted P = 0.009), but their response rates were similar.

B Barberio et al. Matrix Metalloproteinase 3 Predicts Therapeutic Response in Inflammatory Bowel Disease Patients Treated with Infliximab. Inflamm Bowel Dis 2020; 26: 756-62. Retrospectively, 73 IBD patients who had received IFX for at least 1 year were enrolled: 35 patients were responders and 38 were nonresponders at 52 weeks…The MMP3 levels were similar at baseline (19.83 vs 17.92 ng/mL), but at postinduction, patients who failed to respond at 1 year had significantly higher levels than patients who responded (26.09 vs 8.68 ng/mL, P < 0.001); the difference was confirmed at week 52 (29.56 vs 11.48 ng/mL, P < 0.001)…The MMP3 serum determination may represent an early marker of response to infliximab.

 

Growth in Children at Risk for Celiac Disease & Emapalumab for Hemophagocytic Lymphohistiocytosis

Posted on by
Reply

Briefly noted:  R Auricchio et al. Archives of Disease in Childhood 2020; http://dx.doi.org/10.1136/archdischild-2019-317976. Growth rate of coeliac children is compromised before the onset of the disease Thanks to Mike Hart for the reference.

Methods:   We analysed the growth patterns of infants at genetic risk of CD, comparing those who developed CD by 6 years of age (CD ‘cases’, 113 infants) versus those who did not develop CD by 6 years (no CD ‘controls’, 831 infants).

Key finding: The growth of children at risk of CD rarely fell below ‘clinical standards’. However, growth rate was significantly lower in cases than in controls. Our data suggest that peculiar pathways of growth are present in children who develop CD, long before any clinical or serological signs of the disease appear.

F Locatell et al. NEJM 2020; 382: 1811-22. This open-label study (n=34) investigated emapalumab, a human anti-interferon-gamma antibody, for the treatment of primary hemophagocytic lymphohistiocytosis (HLH). Of the 26 patients who completed the study, approximately 65% had a response (based on clinical and lab features) and were able to proceed to transplantation.

Related blog posts:

Summer Georgia AAP Board Meeting: COVID-19, Pediatric Practices, and Resources

Posted on by
Reply

This year’s Summer Georgia AAP Board Meeting included presentations from Kathleen Toomey (commissioner of the Department of Public Health), Sally Goza (National AAP President),Kristie Clarke/Anne Kimball (CDC Liaison) and Evan Anderson (infectious disease committee).  Also a fair amount of information was shared by more than 75 participants.

Useful Links:

  • RIVM Children and COVID-19 Describes experience with opening schools in Europe and Australia. “Schools have now reopened in various other European countries. RIVM is in close contact with sister organisations in these countries to evaluate the impact of this policy on the spread of the novel coronavirus there. Denmark was the first country to reopen childcare and primary education, as of 15 April. They have not reported any negative effects after reopening the schools and are not seeing any increase in the reproduction number. ”  There were several studies showing no transmission
  • Nature (June 11) Why children avoid the worst coronavirus complications might lie in their arteries Evidence is mounting that healthy blood vessels protect children from serious effects of COVID-19, such as stroke
  • Georgia Department of Public Health: DPH COVID-19 Website: One fatality due to COVID-19 in Georgia Pediatric population, 0-17 years.

From Dr. Goza -AAP website/resources/agenda:

From Dr Goza: AAP has been working on health equity and racism prior to recent events, including policy statement last year.  Now with additional input:

From Kristie Clarke/Anne Kimball –they note that recent MMWR reports that the pediatric population now representing 5% of COVID-19  cases with more widespread testing.

 

From Dr. Terri McFadden (Ga. AAP Chair):

Related material from The Children’s Care Network: Website: Call Your Pediatrician Video -Dr. Anna Kuo (2 minutes) “Now, more than ever, it is important that practices actively reach out to families to educate them on the importance of staying connected to their medical home. Kids Health First partnered with Dr. Anna Kuo from Peachtree Park Pediatrics, to create a video aimed towards parents. This video highlights the importance of scheduling patient visits, staying up-to-date on immunizations and assuring families of the safety measures practices are implementing to ensure the health and well-being for all. “

“No Solid Conclusions” for Alternative/Complementary Therapies for Inflammatory Bowel Disease

Posted on by
Reply

In this clinical review (N Chande et al Inflamm Bowel Dis 2020; 26: 843-51) assess evidence from Cochrane reviews of four popular nontraditional treatments for inflammatory bowel disease (IBD):

  • Fecal Microbiota Transplantation (FMT)
  • Nutritional Therapies including Enteral Nutrition (EN)
  • Naltrexone for Crohn’s Disease (CD)
  • Cannabis for IBD

So what does the literature have to say about these treatments:

  • FMT: FMT for mild to moderate ulcerative colitis (UC) increased the proportion of patients achieving clinical remission. “However, the number of included studies was small and the quality of evidence was low.”  Other problems included uncertainty regarding serious adverse events and short duration of followup.
  • “As a result, no solid conclusions [the authors did not indicate this as a pun] can be drawn at this time.”
  • Nutritional Therapies: For remission in CD, “EN may be more effective than corticosteroids in children, although the opposite was true in adults.”
  • “Exclusion diets did not promote clinical remission or reduce clinical relapse in UC”
  • “The overall certainty of evidence in these studies were generally very low, largely due to sparse data.”
  • Naltrexone for Crohn’s Disease (CD): “The paucity of data makes it impossible to draw any firm conclusions about the effectiveness and safety” of low dose naltrexone.
  • Cannabis for IBD: “The risk of adverse events was significantly higher in cannabis-treated patients”…though these events were generally mild (eg. sleepiness, confusion, nausea).
  • “The results of these studies suggest that cannabis is not effective for the treatment of IBD”  This conclusion is limited by the small number of patients in prior studies.  Cannabis may be helpful as an adjunct for some symptoms though this “warrants further study.”

Related blog posts:

 

 

Ionizing Radiation Exposure in Adults with Inflammatory Bowel Disease

Posted on by
Reply

From The Onion:

In the largest reported cohort to date, GC Nguyen et al (Inflamm Bowel Dis 2020; 26: 898-906) describe the ionization radiation exposure (IRE) in individuals (≥18 years) with inflammatory bowel disease (IBD).

Methods: N=72,933 with IBD,1994-2016. During 1st 5 yrs after diagnosis, IRE was estimated in a retrospective matched cohort in Ontario.

Key findings:

  • IBD patients were exposed to nearly 6-fold IRE due to abdominal imaging compared to controls: 18.6 mSv vs 2.9 mSv
  • Patients with CD had higher IRE than UC: 26 mSv vs 12 mSv (P<0.001).  CD patients were more likely to have >50 mSv exposure (15.6% vs 6.2%) and >100 mSv 5.0% vs 2.1%
  • Women were less likely to have high IRE compared to males
  • Residents in the poorest neighborhoods were 27% more likely to have IRE >100 mSv.  Socioeconomic status was an independent factor after accounting for comorbidities. The authors speculate that this could be related to increased use of emergency rooms where they may be more likely to receive a CT.
  • The use of CT scan began to decline after 2007…likely explained by the rise of MRE studies.

While strict guidelines on IRE are lacking, the International Commission on Radiological Protection has suggested that occupational exposure (eg. nuclear workers) should be limited to <100 mSv over 5 years and not more than 50 mSv in a single year.

My take: We need to continue efforts to reduce IRE due to concerns about subsequent secondary malignancies. This likely means avoiding CT for non-emergencies and working with our ED colleagues to think carefully about lifetime IRE in IBD patients.

Related blog posts:

Additional references:

  • -AJR 2001; 176: 289-96. Estimated risks of radiation-induced fatal cancer from pediatric CT
  • -Br J Radiol 2012; 85: 523-28.  Justification of CTs -some not needed
  • -AJR 2010; 194: 868-73.  Lower CT radiation doses in pediatric patients.  ‘Image gently’
  • -Arch Intern Med 2009; 169: 2078-86.

From LA Times:

 

Medical Progress: Toward Hepatitis C Elimination

Posted on by
Reply

JE Squires, WF Balistreri. J Pediatr 2020; 221: 12-22. Full text: Treatment of Hepatitis C: A New Paradigm toward Viral Eradication

This is a terrific article describing the improvements in treatment and challenges ahead for hepatitis C infection.

The authors note that widespread treatment has led to recommendations that primary health providers manage treatment in most adults.  Given the safety and effectiveness of these newer agents, the authors propose a similar algorithm for children (Figure 3).

The authors note the following:

“Just as has occurred in adults, the rate of discovery related to pediatric HCV therapy is outpacing traditional publication methods and many recommendations are no sooner published than they are “outdated” as newer data re-shapes the therapeutic landscape. To combat this challenge, the AASLD and IDSA have partnered to create an updated web experience resource to facilitate rapid access to treatment information (https://www.hcvguidelines.org/). A section of this document is dedicated to children, however, as of this writing, a similar comprehensive ‘living’ document is not available for pediatric populations, thus, care teams should be cognizant of the most current published data and increase their awareness of upcoming studies and DAA’s ‘in the pipeline’ that may soon be available.”

My take (borrowed from authors):

  • “Every child deserves equitable access to a cure for HCV.”
  • “Progress toward elimination of HCV infection in the US is at hand; however, both community/primary care practices and federal commitment will be required.”
  • “The role of the primary care practitioner will be enhanced [and needs to be incentivized]. It is likely that the new paradigm will be to screen and to initiate DAA treatment in patients with HCV infection.”
  • “Consultation with a hepatologist/infectious disease specialist would, thus, be reserved for selected patients (nonresponsive or those with advanced fibrosis).”

Related blog posts: