Does C-section Increase Risk of Celiac Disease? Probably Not

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Using data from the prospective TEDDY (The Environmental Determinants for Diabetes in the Young) from 2004-2010, a recent study (S Koletzko et al. JPGN 2018; 66: 417-24) has shown that cesarean section is not associated with an increased risk of celiac disease (CD) or celiac disease autoimmunity (CDA). TEDDY participants are at increased risk for CD and type 1 diabetes (T1D) based on HLA-risk genotypes.

Key findings:

  • Of the 6087 singletons, 1600 (26%) were born via C-section
  • C-section was associated with a lower risk for CDA (HR 0.85) and a lower risk of CD (HR 0.75)

My take: While environmental factors are likely to be responsible for increasing incidence of CD, C-section compared to vaginal delivery does not appear to be a risk factor.

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Baclofen for Rumination

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A recent randomized, placebo-controlled cross-over study by A Pauweis et al (Am J Gastroenterol 2018; 113: 97-104) indicated that baclofen improved rumination syndrome in adults (mean age 42 years). Thanks to Ben Gold for this reference.

Baclofen (dosed at 10 mg TID) had the following effects:

  • reduced rumination episodes from 13 (8-22) to 8 (3-11) (P=0.004)
  • increased lower esophageal sphincter (LES) pressure (17.8 vs. 13.1, P=0.0002) and lowered number of transient LES relaxations (4 vs 7, P=0.17)
  • overall treatment evaluation was superior after baclofen compared to placebo (P=0.03)

My take: In this study, baclofen improved symptoms of rumination and regurgitation, but not supragastric belching.

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Eluxadoline and Pancreatitis

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It looks like eluxadoline, recently FDA-approved for IBS-D, is associated with a significant rate of pancreatitis.  The most recent report: AJ Gawron, K Bielefeldt. Clin Gastroenterol Hepatol 2018; 16: 378-84.

The authors extracted reports of eluxadoline adverse events using the Federal Adverse Event Reporting System.

  • Of the 597 reports, 98 (16.4%) were due to pancreatitis; 53 cases required hospitalization.  (The FDA separately reported 120 cases of pancreatitis –https://www.fda.gov/Drugs/DrugSafety/ucm546154.htm)
  • The FDA report, which noted the risk primarily in those with prior cholecystectomy, “listed 1 fatality caused by pancreatitis..which manifested within the first day of therapy.”

My take: This study showing a significant risk of pancreatitis changes the risk-benefit ratio of eluxadoline.  Since pancreatitis can result in hospitalization and even death, alternative therapies for IBS will be favored.

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Tenofovir to Prevent Perinatal Transmission of Hepatitis B

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Mother-to-child transmission of hepatitis B virus (HBV) accounts for the majority of cases of chronic HBV infection.  HBV infection affects more than 250 million people worldwide and in many cases results in cirrhosis or hepatocellular carcinoma.  As such, there has been interest in preventing perinatal transmission.

The most recent study (C Jourdain et al. NEJM 2018; 378: 911-23) again showed that tenofovir administration to pregnant women with HBV can prevent transmission.  This study enrolled 331 women.  Key findings:

  • 0% (0/147) infants in the tenofovir group developed HBV infection compared to 2% (3/147) in the control group. This did not reach statistical significance
  • The placebo group received HBV vaccination and hepatitis B immune globulin 1.2 hours and 1.3 hours after birth (median time).  This rapid provision of treatment along with completion of four doses of HBV vaccine likely helped keep the placebo group HBV infection rate low

In the related editorial (G Dusheiko. pg 952-3), it is noted that “current levels of evidence supporting antiviral therapy with TDF [tenofovir] (or possbily lamivudine or telbivudine) to reduce levels of maternal HBV DNA during pregnancy have been accepted by the” AASLD.

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Childhood Obesity: It is NOT Getting Better

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A recent study (AC Skinner et al. Pediatrics 2018; 141: e20173459) examined obesity prevalence data in children 2-19 years of age from a nationally representative sample (n=3340).  Specifically, the authors used NHANES data from 1999-2016. Thanks to John Pohl’s twitter feed for pointing out this reference.

PDF Link: Prevalence of Obesity and Severe Obesity in US Children, 1999-2016

This article is packed with data and breaks down obesity in categories: overweight, class I obesity, class II obesity & class III obesity.  It provides data based on gender, age, and ethnicity.

The trend in obesity prevalence is best captured in Figure 1.

Among girls:

  • In 1999-2000: class I obesity noted in 14.6% –>17.8% in 2015-16
  • In 1999-2000: class II obesity noted in 4.0% –>5.2% in 2015-16
  • In 1999-2000: class III obesity noted in 0.9% –>1.8% in 2015-16

Among boys:

  • In 1999-2000: class I obesity noted in 14.7% –>19.1% in 2015-16
  • In 1999-2000: class II obesity noted in 4.1% –>6.7% in 2015-16
  • In 1999-2000: class II obesity noted in 1.0% –>2.0% in 2015-16

My take: This article indicates that the prevalence of childhood obesity in the U.S. is not improving and does not appear to have leveled off as has been suggested by some studies.

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Autoimmune Hepatitis Associated with Anti-TNF Therapy

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A recent study (A Ricciuto et al. J Pediatr 2018; 194: 128-35) identified an index case of autoimmune hepatitis (AIH) associated with anti-tumor necrosis factor (TNF) therapy and reviewed liver biochemistries in a cohort of 659 children.

Key findings:

  • In the index case, features of autoimmune hepatitis (AIH) on liver biopsy were noted 23 weeks after starting infliximab.   These findings resolved entirely within 4 months after withdrawal of infliximab
  • Overall, 7.7% of cohort had elevations of ALT while receiving anti-TNF therapy.  Most were mild and attributable to other causes than drug toxicity. No other cases of AIH were identified.

The authors recommend a careful investigation in those with elevations >2-3 times ULN which persists >3 months. Livertox (NIH) website notes the following for infliximab:

“The liver injury caused by infliximab is usually mild and rapidly reversed once therapy is stopped.  However, fatal instances of HBV reactivation and induction of autoimmune hepatitis due to infliximab have been reported, and regular monitoring of patients early during the course of infliximab is recommended.”

My take: Serious liver injury related to anti-TNF therapy is rare. A great place to understand the spectrum of liver problems potentially related to infliximab is the livertox website:

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AIH:

Views from inside Hoover Dam, including Mike O’Callaghan–Pat Tillman Memorial Bridge

Mechanisms in Fatty Liver Disease Improved After Bariatric Surgery

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A recent prospective study (V Nobili et al. J Pediatr 2018; 194: 100-8) consecutively enrolled 20 severely obese adolescents with biopsy-proven nonalcoholic fatty liver disease (NAFLD). The authors used liver histology, immunohistochemistry and cytokine analysis to assess the changes (after 12 months) induced by bariatric surgery with laparoscopic sleeve gastrectomy (LSG).

Key findings:

  • NAFLD Activity Score and fibrosis improved after LSG. Steatosis, hepatocyte ballooning, and NAS score showed a significant improvement (Z=-2.7; P=.007) at 12 months following surgery. Fibrosis improvement (Z=-2.449) was noted as well.
  • The histologic improvement “is associated with activation of local cellular compartments (hepatic progenitor cells, hepatic stellate cells, and macrophages), thus, strengthening the role of cellular interactions and hepatic adipocytokine production in the pathogenesis of NAFLD.”

This study has a large number of figures illustrating the changes in liver architecture and immunohistochemistry changes.

My take: This study shows specific improvements following LSG and shows correlation with cytokines and immunohistochemistry providing a mechanistic explanation for these improvements.

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2018 Pediatric Gastroesophageal Reflux Clinical Practice Guidelines

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Full text: NASPGHAN Pediatric Gastroesophageal Reflux Clinical Practice Guidelines (R Rosen et al. JPGN 2018; 66: 516-54)

This is a lengthy report with ~50 recommendations/302 references –many with several subrecommendations. I will highlight a few below. Tables 2 defines “red flags” that suggest the need for additional diagnostic tests and Table 3 provides a lengthy differential diagnosis (=everything).

R Rosen et al. JPGN 2018; 66: 516-54

The article reviews several frequent clinical diagnostic/management issues and provides two algorithms with suggested evaluation/treatment for infants and older children.  The older child algorithm (algorithm 2) suggests referral to GI if not improved with acid suppression or unable to wean after course of treatment.  For pediatric GI physicians, this algorithm suggests use of endoscopy if persistent symptoms on PPI or inability to stop PPI; pH-MII or pH-metry recommended if normal-appearing endoscopy.

Key point:

  • For infants: “if excessive irritability and pain is the single manifestation, it is unlikely to be related to GERD.”

Some of the Recommendations -My Top Ten:

  • 3.5 We suggest not to use esophago-gastro-duodenoscopy to diagnose GERD in infants and children.
  • 3.13 We suggest not to use a trial of PPIs as a diagnostic test for GERD in infants.
  • 3.14 We suggest a 4 to 8 week trial of PPIs for typical symptoms (heartburn, retrosternal or epigastric pain) in children as a diagnostic test for GERD
  • 3.15 We suggest not to use a trial of PPIs as a diagnostic test for GERD in patients presenting with extraesophageal symptoms.
  • 5.1 We suggest not to use antacids/alginates for chronic treatment of infants and children with GERD.
  • 5.4 We recommend not to use H2RA or PPI for the treatment of crying/distress in otherwise healthy infants.
  • 5.5 We recommend not to use H2RA or PPI for the treatment of visible regurgitation in otherwise healthy infants
  • 5.7 We suggest not to use H2RAs or PPIs in patients with extraesophageal symptoms (ie, cough, wheezing, asthma), except in the presence of typical GERD symptoms and/or diagnostic testing suggestive of GERD.
  • 5.10 We suggest to consider the use of baclofen prior to surgery in children in whom other pharmacological treatments have failed.
  • 6.4 We suggest to consider the use of transpyloric/jejunal feedings in the treatment of infants and children with GERD refractory to optimal treatment as an alternative of fundoplication.

My take: This is an excellent updated summary of current best clinical practices for evaluation/management of pediatric GERD.

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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.

 

Note full text link available online identified in Google Search

Isopropyl Alcohol -Antiemetic Aromatherapy

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April MD et al. Aromatherapy versus oral ondansetron for antiemetic therapy among adult emergency department patients: A randomized controlled trial. Ann Emerg Med 2018 Feb 17; [e-pub]. (https://doi.org/10.1016/j.annemergmed.2018.01.016) Thanks to Ann Beach for this reference.

Review/excerpt of this study from NEJM Journal Watch: by Daniel J. Pallin, MD, MPH.

In the current trial, 120 adult ED patients with nausea or vomiting who did not require intravenous access were randomized to inhaled isopropyl alcohol plus 4 mg oral ondansetron; inhaled isopropyl alcohol plus oral placebo; or inhaled saline plus 4 mg oral ondansetron. Isopropyl alcohol was provided in the form of a standard alcohol swab. Patients received a single dose of the oral intervention but could sniff alcohol or saline swabs repeatedly. Nausea was measured on a 100-mm visual analog scale at baseline and 30 minutes.

Mean nausea scores decreased by 30 mm in the alcohol/ondansetron group, 32 mm in the alcohol/placebo group, and 9 mm in the saline/ondansetron group. Rescue antiemetic therapy was given to 28%, 25%, and 45% of each group, respectively. Differences between alcohol and saline groups were statistically significant. Patients in the inhaled alcohol groups also had better nausea control at the time of discharge and reported higher satisfaction with nausea treatment. No adverse events occurred. The mechanism of action is currently unknown.

Dr. Pallin’s comments on study:

It is uncommon for us to assign a rating of “Practice Changing” to a small, single-center study, but these results are truly remarkable and are consistent with prior research. For patients not obviously requiring IV therapy, we should treat nausea with repeated inhalations from an isopropyl alcohol swab instead of administering any other drug. And, although this study provides no direct evidence of benefit to patients who do require IV therapy, there would seem to be little downside to trying this simple and safe intervention in that group, too.

My take: Who is doing the pediatric study to try to replicate these results in the pediatric population?

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How to Cultivate Clostridium difficile Infections

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The emergence of more frequent and virulent Clostridium difficile infections (CDIs) has generally been attributed to antibiotic usage.  A recent study (J Collins et al Nature 553, 291–4.  doi:10.1038/nature25178) suggests that changes in our diet are a contributing factor as well.

From Abstract:

Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.

From GI & Hepatology News: Food additive makes C difficile more virulent: “Prior to 2000, trehalose was limited by a relatively high cost of production.”  However, with innovations in production, trehalose concentrations in food increased, particularly in ice cream, pasta, and ground beef; “concentration in food skyrocketed form around 2% to 11.25%.”  In addition, the FDA in 2000 noted that trehalose as “generally recognized as safe.”

My take: “On the basis of these observations, we propose that the widespread adoption and use of the disaccharide trehalose in the human diet has played a significant role in the emergence of these epidemic and hypervirulent strains,” Dr. Collins and his colleagues wrote in Nature.

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