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.

Can We Learn to Live With Germs Again?

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Correction made on blog post on 5/12/21 Humira Dosing Guidelines. For Crohn’s induction >/= 40kg, there is not an 80mg dose on day 8, just 160mg day 1 and 80mg day 15. Blog post: Ustekinumab for Refractory Pediatric Ulcerative Colitis and Updated Adalimumab Dosing

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NY Times: Can We Learn to Live With Germs Again? (4/23/21)

An excerpt:

Almost everything we know about the microbiome is uncertain, including how our activities and environments influence its makeup...

Despite the now consensus recognition that air transmission, …we continue to annihilate every microbe in our midst, even though most are harmless…

Excessive hygiene practices, inappropriate antibiotic use and lifestyle changes such as distancing may weaken those [microbial] communities going forward in ways that promote sickness and imperil our immune systems. By sterilizing our bodies and spaces, they argue, we may be doing more harm than good…

Dr. Graham Rook, an emeritus professor of medical microbiology at University College London, likens the immune system to a computer. He says that the microbes we encounter in daily life — on other people and in our spaces — are the data that the immune system relies on to program and regulate its operations.

Deprived of these exposures, especially at the start of life, the immune system is prone to malfunction. The result can be allergies, asthma, autoimmune disorders, obesity, Type 2 diabetes and other chronic medical conditions...

 “Even before the pandemic, we know that half of antibiotic use was inappropriate.”…

For those who aren’t yet able to mix and mingle — and right now, that’s most of us — there are other ways to support microbial health. “If you want to do something proactive right now, I would put eating a healthy diet high on your list,” says Dr. Emeran Mayer… plant foods (legumes, greens, whole fruits, a variety of vegetables), as well as fermented foods, support the richness and diversity of the gut microbiome. So, too, does limiting one’s intake of processed and fast foods, especially those that contain added sugar…

Before the pandemic, only one of the top 10 causes of death in America — influenza — was attributable to an infectious disease that someone could “catch.” Nearly all the rest, such as heart disease and stroke, cancer, brain disease and diabetes, are associated with poor microbiome health or dysfunction.

Related blog posts:

World Obesity Day was March 4, 2021

AGA: Best Practice Advice for Refractory H pylori

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SC Shah et al. Gastroenterol 2021;  160: 1831-1841. Full text: AGA Clinical Practice Update on the Management of Refractory Helicobacter pylori Infection: Expert Review

Key recommendations:

  • Best Practice Advice 4: If bismuth quadruple therapy failed as a first-line treatment, shared decision making between providers and patients should guide selection between (a) levofloxacin- or rifabutin-based triple-therapy regimens with high-dose dual proton pump inhibitor (PPI) and amoxicillin, and (b) an alternative bismuth-containing quadruple therapy, as second-line options
  • Best Practice Advice 5: When using metronidazole-containing regimens, providers should consider adequate dosing of metronidazole (1.5–2 g daily in divided doses) with concomitant bismuth therapy, because this may improve eradication success rates irrespective of observed in vitro metronidazole resistance.
  • Best Practice Advice 6: In the absence of a history of anaphylaxis, penicillin allergy testing should be considered in a patient labeled as having this allergy in order to delist penicillin as an allergy and potentially enable its use. Amoxicillin should be used at a daily dose of at least 2 g divided 3 times per day or 4 times per day to avoid low trough levels.
  • Best Practice Advice 8:Longer treatment durations provide higher eradication success rates compared with shorter durations (eg, 14 days vs 7 days). Whenever appropriate, longer treatment durations should be selected for treating refractory H pylori infection.
  • Best Practice Advice 10: After 2 failed therapies with confirmed patient adherence, H pylori susceptibility testing should be considered to guide the selection of subsequent regimens.
  • Table 1 in report details specific regimens

Related blog posts:

Cool Perfusion –Better Liver Transplant Outcomes

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R van Rijn et al. NEJM 2021; 384: 1391-1401. Hypothermic Machine Perfusion in Liver Transplantation — A Randomized Trial

Background: Nonanastomotic biliary strictures are a major complication after liver transplantation, and ischemia–reperfusion injury is a key mechanism in their development. Although static cold preservation provides some protection against injury, preclinical studies have shown that a short period of hypothermic oxygenated machine perfusion restores mitochondrial function and reduces damage.

Methods: In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial).

Key points:

  • Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group, risk ratio, 0.36
  •  Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group; risk ratio, 0.43
  • Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers; risk ratio, 0.61

My take: Hypothermic oxygenated machine perfusion led to lower risk of nonanastomotic biliary strictures

Related blog posts:

Ustekinumab for Refractory Pediatric Ulcerative Colitis and Updated Adalimumab Dosing

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As noted in previous blog posts (see below), adult guidelines for ulcerative colitis favor ustekinumab over vedolizumab for ulcerative colitis patients who have had anti-TNF therapy; recent pediatric guidelines appeared to do the opposite, possibly due to limited data with ustekinumab.

A recent study (J Dhaliwal et al. AP&T 2021; https://doi.org/10.1111/apt.16388. One‐year outcomes with ustekinumab therapy in infliximab‐refractory paediatric ulcerative colitis: a multicentre prospective study) provides prospective data on ustekinumab effectiveness when given to children with UC refractory to other biologics; n=25. Thanks to Ben Gold for this reference.

Key findings:

  •  All patients had failed prior infliximab therapy, and 12 (48%) also had failed vedolizumab.  Five patients discontinued ustekinumab after IV induction (four undergoing colectomy).
  • On intent to treat basis, 44% (n=11) achieved the primary endpoint of steroid‐free remission at week 52, including nine (69%) of 13 who previously treated with anti‐TNF only vs two (17%) of 12 who previously failed also by vedolizumab. Seven of 11 remitters met the criteria for endoscopic improvement.
  • Higher trough levels were not associated with a superior rate of clinical remission; the median (IQR) trough levels (μg/mL) were greater with q4 vs q8 weekly dosing (8.7 [4.6‐9.9] vs 3.8 [12.7‐4.8]) P = 0.02.
  • No adverse events were associated with therapy.

My take: Ustekinumab is a good option for pediatric patients with ulcerative colitis who are refractory to anti-TNF agents. More data are needed to help in positioning therapies.

Also, Humira (adalimumab) is now FDA-approved for children as young as 5 years with ulcerative colitis: FDA Approves Adalimumab as Treatment for Children With Ulcerative Colitis (2/25/21). “This approval is based on results from the phase 3, randomized, double-blind, multicenter ENVISION I (NCT02065557) study.” Abbvie has now updated their Humira dosing recommendations (Reference:  https://www.rxabbvie.com/pdf/humira.pdf). Thanks to Clair Talmadge for this update.

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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.

No Benefit of Combination Therapy with Ustekinumab or Vedolizumab

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C Yzet et al. Clin Gastroenerol Hepatol 2021; 19: 668-679. Full Text: No Benefit of Concomitant Immunomodulator Therapy on Efficacy of Biologics That Are Not Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases: A Meta-analysis

In a systematic review, key findings:

  • Combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84; 95% CI, 0.68–1.05; I2=13.9%; Q test P = .17); n= 933 and n=2378 with combination therapy and monotherapy, respectively
  • Combination therapy was not associated with better clinical outcomes in patients receiving ustekinumab (15 studies: OR, 1.1; 95% CI, 0.87–1.38; I2 = 11%; Q test P = .28); n=856 and n=1926 patients with combination therapy and monotherapy, respectively

Why don’t immunomodulators seem to help? “Unlike anti-TNF, prospective studies as well as post hoc analysis of randomized controlled trial consistently reported a low immunogenicity [with ustekinumab and vedolizumab]…all the prospective studies available to date have shown no impact of immunomodulator on the trough serum level of vedolizumab or ustekinumab.”

Limitation: patients treated with combination therapy in the included studies could be more severe

My take: “This meta-analysis found that overall the use of combination therapy in patients treated with vedolizumab or ustekinumab was not associated with a clinical benefit in comparison with the use of monotherapy.”

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It’s About Time: No Surprises Act

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Pleasant surprises often don’t work out. Case in point: a colleague sent me an email to our joint email account letting me know that he would not be able to come to my wife’s surprise party (she probably knew anyway).

When it comes to medical billing, surprises are never intended to be pleasant. “As many as one in five patients visiting an emergency department or undergoing elective surgery receives an out-of-network bill from a clinician whom they had no ability to choose.”

It appears that improvement in this area is on the horizon. KR Chhabra et al. NEJM 2021; 384:1381-1383. No More Surprises — New Legislation on Out-of-Network Billing

Key points:

  • “Effective January 1, 2022, patients receiving an out-of-network emergency services, air-ambulance transportation, or out-of-network nonemergency services at in-network facilities may be billed only the amount they would owe for an in-network provider.”
  • “Out-of-network providers and insurers will have 30 days to agree on payment and then may invoke a binding arbitration process.”
  • “Three days before scheduled procedures, clinicians and insurers must inform patients of their expected out-of-pocket costs and clinicians’ network status and consenting to out-of-network bills can patients be balance-billed.
  • “This notice-and-consent doesn’t apply to emergency services [and] situations in which there are no in-network alternatives…patients cannot be balance billed in these cases…, even if they provide consent.”
  • “The Congressional Budget Office estimates that the law will reduce payments for some clinicians, reduce insurance premiums by up to 1%, and save the federal government nearly $17 billion over 10 years.”
  • “The law’s transparency provisions–particularly the requirements to provide advance price and network-participation information –may have a larger effect on day-to-day practice than its balance-billing provisions.”
  • Omission in law: ground-ambulance surprise bills
  • Potential effect: insurers may leverage the law to drop high-priced providers and potentially the law may lead to low-price providers to drop out of network

My take: This is a huge advance for patients/families; it is likely to reduce financial harm to patients and improve trust in the health care system.

Related blog posts:

Targeting on Social Media

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A recent survey (n=464) study (TR Pendergrast et al. JAMA Intern Med 2021; 181: 550-552. Prevalence of Personal Attacks and Sexual Harassment of Physicians on Social Media) describes personal attacks that physicians experience due to social media presence.

Key findings:

  • 108 (23%) physicians reported being personally attacked on social media with no significant differences between males and females
  • Women were significantly more likely than men to report online sexual harassment: 44 (16%) vs. 3 (1.5%)
  • Attacks were common within some topics like vaccines and gun control

The authors note that their study is limited by potential sampling error and may not be representative of the physician workforce.

My take: Online harassment is common, particularly with controversial topics. The effects of these attacks is to create distress and reluctance to engage in social media.

Related blog posts:

What Happens With Double Switches of Infliximab Products

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N Trystram et al. Alimentary Pharmacology & Therapeutics, 01 Mar 2021, 53(8):887-899 Outcomes after double switching from originator Infliximab to biosimilar CT-P13 and biosimilar SB2 in patients with inflammatory bowel disease: a 12-month prospective cohort study.

Key findings:

  • Drug persistence was high (94.9%) after 54 weeks in cohort of 158 patients
  • Double switching from the originator Infliximab to CT-P13 and then to SB2 was associated with continued effectiveness; this study did not identify issues related to immunogenicity or safety of anti-TNF therapy after 54 weeks of follow-up.

My take: There is very limited data on repeated infliximab product changes; this small study did not identify any problems. Due to mandates from insurance, more frequent switching is likely to be more widespread and more definitive outcome data will emerge.

Abstract:

Related blog posts:

Combating Anti-Drug Antibodies with Immunomodulators in Pediatric IBD

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RJ Colman et al. Inflamm Bowel Dis 2021; 27: 507-515. Favorable Outcomes and Anti-TNF Durability After Addition of an Immunomodulator for Anti-Drug Antibodies in Pediatric IBD Patients

In this retrospective review with 89 patients who developed antidrug antibodies (ADAs), the authors identified 30 who started an immunomodulator (IM) within 3 months of developing an ADA and compared with 59 who did not start an IM. The main IM used was methotrexate (n= 28, 93%)

Key findings:

  • 61 of the 89 patients (69%) had quiescent disease based on physician global assessment at their previous clinic visit
  • The initial anti-TNF was stopped shortly after ADA detection in 36% of the No-IM patients vs none of the IM patients. Thus, anti-TNF agents durability was prolonged in the IM group.
  • Dose intensification was also undertaken at the time of ADA detection: 25 (83%) of IM group and 28 (48%) of non-IM group.
  • At 12 months, steroid-free clinical and biochemical remission on the same anti-TNF occurred in 53.9% of the IM group vs 26.8% in the No-IM group (P = 0.025).
  • Drug levels rose higher (P = 0.003) and ADA levels fell farther (P = 0.037) in the IM group than in the No-IM group
  • Lower ADAs often improved without IM: An ADA level <329 ng/mL had a 76.2% sensitivity and an 83.3% specificity for ADA reversal without IM.

My take: If a patient develops a significantly elevated anti-drug antibody, addition of methotrexate/immunomodulator along with dose intensification increases the likelihood that the anti-TNF agent will continue to be effective.

Related blog posts: