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.

IBD Briefs: May 2019 (Part 1)

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H Khalili et al. Clin Gastroenterol Hepatol 2019; 17: 123-29.  Using data from two prospective Swedish cohort sutdies with 83,042 participants (age 44-83 yrs), the authors determined that there was “no evidence for association between consumption of sweetened beverages and later risk of” Crohn’s disease or Ulcerative Colitis.

WJ Sandborn et al. Gastroenterol 2019; 156: 946-57.  This study published data from 354 patients who received subcutaneous abrilumab, an anti-alpha4beta7 antibody as a treatment for moderate-to-severe colitis. This 8 week treatment increased the odds of remission compared with placebo.

B Wynne et al. Gastroenterol 2019; 156: 935-45. This study showed that a psychological intervention termed “acceptance and commitment therapy (ACT)” was effective in a randomized controlled trial in reducing stress and depression in patients with quiescent or mildly-active IBD (n=122). With ACT, the “primary aim is to encourage subjects to adopt positive life values and to accept adverse experiences, including thoughts, feelings and sensations that are an inevitable consequence of life.”  All program materials are available in article supplement: Full text and supplement: https://doi.org/10.1053/j.gastro.2018.11.030

D Duricova et al. Inflamm Bowel Dis 2019; 25:789-96. This study included 72 consecutive children born to mothers with IBD treated with anti-TNF therapy during pregnancy (2007-16) along with 69 unexposed controls.  Key findings: Anti-TNF therapy exposure in utero was NOT associated with a negative impact on postnatal complications, including infections, allergy, growth, or psychomotor development. Findings are limited by the small number of participants.

AW Gridnal et al. Inflamm Bowel Dis 2019; 25:642-45.  The authors examined the frequency of financial conflicts of interest (FCOI) among authors of 11 relevant clinical practice guidelines for IBD in the US,  the UK, Canada, and Europe. Key finding: FCOI were frequently present with 19% prevalence among US authors, 56% in UK, 84% in Canada, and 94% in Europe.

KN Weaver et al. Inflamm Bowel Dis 2019; 25:767-74. This retrospective study examined the efficacy of ustekinumab for Crohn’s disease of the pouch in 56 patients; 73% had previously been treated with anti-TNF therapy, vedolizumab or both. Key finding: 83% demonstrated a clinical response 6 months and 60% with endoscopic improvement after induction with ustekinumab. Clinical response was defined as “any improvement in symptoms …including a decrease in bowel movements, pain, or fistula drainage.”

Retiro Park, Madrid
Thanks to Jennifer

 

How Quickly Does Tofacitinib Work for Ulcerative Colitis?

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The second study reference yesterday:

A recent study (S Hanauer et al. Clin Gastroenterol Hepatol 2019; 17: 139-47) shows that tofacitinib can work quickly to reduce symptoms in ulcerative colitis.

In a post-hoc analyses of data from OCTAVE induction 1 and 2 (n=905 patients, n=234 placebo), the authors determined that tofacitinib reduces symptoms within 3 days.

Key findings:

  • By day 3, there was a reduction in stool frequency (-1.06 vs. -0.27 for placebo) and a reduction in rectal bleeding subscore (-0.30 vs -0.14 for placebo)
  • 28.8% of tofacitinib-treated patients had a reduction in stool frequency subscore by >1 point compared to 17.9% for placebo.  For rectal bleeding subscore, tofacitinib-treated patients had a reduction by >1 point in 32% compared to 17.9% for placebo 20.1%.

My take: This study reinforces the impression that tofacitinib works rapidly.

Related blog posts:

La Boqueria, Barcelona

How Quickly Does Vedolizumab Work?

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Two recent studies highlight more rapid onset of action for vedolizumab and tofacitinib than previous reports.

In the first study (BG Feagan et al. Clin Gastroenterol Hepatol 2019; 17: 130-8), the authors performed a post-hoc analysis of data from phase 3, randomized controlled trials of vedolizumab vs placebo in adult patients (UC, N=374; CD, N=784).

Key findings:

  • In patients with UC, 19.1% overall and 22.3% of anti-TNF naive achieved a composite score of rectal bleeding of 0 and stool frequency of ≤1 at week 2 compared to 10% and 6.6% respectively in the placebo group. By 6 weeks, this response rate was 40.8% among anti-TNF naive patients.
  • In patients with CD, 15.0% of anti-TNF naive patients achieved a composite score of abdominal pain ≤1 and loose stool frequency ≤3 at week 2 compared to 7.9% of placebo; at 4 weeks, the vedolizumab group, the rate was 23.8% compared to 10.3% with placebo.

My take: This study shows that a substantial portion of patients respond fairly quickly to vedolizumab, especially among patients who are naive to anti-TNF therapy.  This is in contrast to the impression that vedolizumab is slow-acting and needs closer to 14 weeks to see clinical effects.

Related blog posts:

Jardines de Cecilio Rodríguez; Retiro Park, Madrid

Favorable “Break”through Data for Proton Pump Inhibitors and Bone Density

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Franklin Roosevelt’s secretary of state, Cordell Hull, wrote: “A lie will gallop halfway round the world before the truth has time to pull its breeches on.”

This saying came to my mind as I read a recent study (KE Hansen et al. Gastroenterol 2019; 156: 926-34) titled: “Dexlansoprazole and esomeprazole do not affect bone homeostasis in healthy postmenopausal women.”

In this study, the authors performed a prospective double-blind study with 115 healthy postmenopausal women who were treated with one of these two PPIs or placebo daily for 26 weeks.

Key findings:

  • PPI therapy did not reduce true fractional calcium absorption
  • There were no significant difference between groups in serum or urine levels of minerals, bone mineral density, or parathyroid hormone

Previous studies have found conflicting results of PPIs on bone density.  Studies suggesting that PPIs could affect bone density have been questioned due to “low odds ratios (<2), lack of dose response, biological implausibility, and uncontrolled potential confounders.”  The authors note that they chose bone turnover rather than changes in BMD as a primary outcome as bone turnover precede changes in BMD and should serve as an early marker of adverse effects.

My take: This study, while short in duration and with limited numbers of participants found no harmful effects of PPIs on skeletal health.

Related blog posts:

Tajo River, Toledo Spain

Mortality Rate with Autoimmune Hepatitis –Increased if Cirrhosis

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Briefly noted: Using a Dutch database to identify 449 patients with autoimmune hepatitis, a recent study (FF van den Brand et al. Clin Gastroenterol Hepatol 2019; 17: 940-7) found that having associated cirrhosis increased the mortality rate over a 10-year followup.  In this circumstance, the standardized mortality ratio (SMR) was 1.9.  In contrast, if cirrhosis was not present, there was no significant increase in SMR (1.2).  Patients with overlapping PSC had the greatest increase in mortality with an SMR of 4.7.

View from Sofia Reina museum. Madrid

How Often Do Children with Obesity Have a Fatty Liver?

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According to a recent study (EL Yu et al. J Pediatr 2019; 207: 64-70), about one-third of boys and one-fourth of girls with obesity have nonalcoholic fatty liver disease (NAFLD).

This study from San Diego with 408 children aged 9-17 years (mean 13.2 years) with obesity evaluated for NAFLD with laboratories (to exclude other etiologies) and with liver MRI proton density fat fraction (PDFF), with ≥5% considered the threshold for NAFLD.

Key findings:

  • Prevalence of NAFLD was 26% in this population, with 29.4% in males and 22.6% in females
  • The optimal cut offs of ALT for detecting NAFLD in this study were ≥30 U/L for females and ≥42 U/L for males. These are much lower than NASPGHAN guidelines which proposed ≥80 U/L or twice the ULN as thresholds for further investigation.  (The NASPGHAN recommendations are likely to have higher specificity in identifying children at greater risk for nonalcoholic steatohepatitis (NASH).)

Limitations:

  • 77% of this cohort were hispanic, thus prevalence may vary significantly in other populations.
  • MRI-PDFF -the exact cut off is unclear.  The authors note that if 3.5% were chosen, the NAFLD prevalence jumped to 49.3% (according to Table II –though the discussion stated 53.2%)

My take: Understanding the likelihood of NAFLD in children at risk is a helpful first step.  This study points to the growing use of non-invasive diagnosis with MRI.

On a related topic, briefly noted: “Obesity in Adolescents and Youth: The Case for and against Bariatric Surgery” (A Khattab, MA Sperling. J Pediatr 2019; 207: 18-22). In this review, the authors refer frequently to endocrine society guidelines (J Clin Endocrinol Metab 2017; 102: 709-57).    These guidelines generally recommend bariatric surgery only under specific conditions (eg. completion of Tanner 4 or 5 along with a BMI of 40 kg/m-squared or BMI of 35 with significant extreme comorbidities after failure of lifestyle modifications & without untreated psychiatric illness).  This review predicts increasing use of bariatric surgery in adolescents “as more data on long-term outcomes in larger cohorts become known.”

Related blog posts on fatty liver disease:

Related blog posts on bariatric surgery:

 

New Way to Diagnose Biliary Atresia

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Case report: Recently, our group consulted on a 3 week old infant (ex34 week) who weighed 2.8 kg and had cholestasis. In addition, he had a GGT in the 400s and an ultrasound notable for a “small” gallbladder.  Due to the patient’s small size, he underwent a HIDA (no excretion).   The GGT was actually improving but the clinical situation was concerning for biliary atresia.

Instead of arranging a liver biopsy, we were able to perform a MMP-7 (Serum Matrix Metalloproteinase-7) assay which will be commercially available soon.  The result, which returned in 48 hours, indicated that the child had a >95% likelihood of biliary atresia. Subsequently, this infant is recovering from a hepatoportoenterostomy. No liver biopsy was needed prior to surgery.

My take: The MMP-7 assay is a remarkable test which is going to rapidly change the approach to infants with cholestasis.  I expect that this test will be ordered along with a serum alpha-one antitrypsin phenotype and an ultrasound.  In those with persistent cholestasis with negative initial testing, it is likely that, in the majority, a genetic cholestasis panel would be pursued rather than a liver biopsy.

Related blog posts:

Mesquite Flat Sand Dunes

Tofacitinib Case Reports for Acute Severe UC and Pyoderma Gangrenosum

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Two recent case reports indicate that Tofacitinib may be useful in refractory cases of acute severe ulcerative colitis (ASUC) (JA Berinstein et al. Clin Gastroenterol Hepatol 2019; 17: 988-90) and for pyoderma gangrenosum (PG) (B Kochar et al. Clin Gastroenterol Hepatol 2019; 17: 991-93)

The case report for ASUC described 4 patients who received off-label high-intensity tofacitinib.  Initially dosing was 10 mg 3 times a day for 9 doses with subsequent transition to standard dosing.  All four patients had a rapid improvement, though one patient required a colectomy 6 months later and one patient required urgent colectomy after rapid return of symptoms when tofacitinib dose was reduced.

The case report for PG involved 3 patients -two healed with tofacitinib and one improved considerably; the latter patient required dose escalation to 10 mg twice a day.  To understand the mechanism of action further, the authors performed immunohistochemical staining from skin biopsy specimens from two patients and detected “strong staining of phosphorylated JAK-1, phosphorylated JAK-2, phosphorylated JAK-3…in the epidermis.”  Tofacitinib is an oral JAK-1/JAK-3 inhibitor.  In all of these patients, inflammatory arthritis was the indication for tofacitinib.

My take: Due to tofacitinib’s rapid onset of action as well as its rapid clearance, it is a promising agent for both acute severe ulcerative colitis and pyoderma gangrenosum.  More clinical trials are needed.

Related blog posts -Tofacitinib:

Related blog posts -ASUC:

Related blog posts -PG:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

Image below is from an unrelated tweet.

How Hepatitis C Therapy Affects Cardiovascular Outcomes

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Briefly noted: A recent retrospective study (AA Butt et al. Gastroenterol 2019; 156: 987-96) utilized a Veterans HCV database (n=242,680) and determined that HCV therapy improved cardiovascular outcomes.

Key finding: Treatment with a direct-acting antiviral regimen lowered the risk of cardiovascular events by more than 40% (hazard ratio of 0.57) compared to no treatment.

This finding is limited based on the reliance of a retrospective study and not being able to control for factors that may have led some patients to not receive treatment.

Related blog posts: