Monthly Archives: May 2023

Prognostic Tool for Biliary Atresia after Kasai: Serum Bile Acids

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S Harpavat et al. Hepatology 2023; 77: 862-873. Open Access! Serum bile acids as a prognostic biomarker in biliary atresia following Kasai portoenterostomy

Methods: Participants with biliary atresia from the Childhood Liver Disease Research Network, in a prospective observational cohort, were included if they had normalized bilirubin levels 6 months after KP and stored serum samples from the 6‐month post‐KP clinic visit.

Key Findings:

  • The ≤40 μmol/L group (n=43) had a 10‐year cumulative incidence of liver transplant/death of 8.5% compared with 42.9% for the >40 μmol/L group (n=94) (p = 0.001).
  • At 2 years of age, the ≤40 μmol/L group had significantly lower total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma‐glutamyltransferase, bile acids, and spleen size, as well as significantly higher albumin and platelet counts.
  • In addition, during 734 person‐years of follow‐up, those in the ≤40 μmol/L group were significantly less likely to develop splenomegaly, ascites, gastrointestinal bleeding, or clinically evident portal hypertension.
  • The 137 patients included in this study were only a small fraction of the 756 children enrolled in these studies. 232 children failed to achieve normalized serum bilirubin levels by 6 months following KP, 279 children did not have a 6‐month post‐KP serum bilirubin value, and 108 children did not have serum available for bile acid testing.

My take: Only a fraction of children with BA normalize their bilirubin by 6 months after Kasai procedure. In those with normalized bilirubin (T bilirubin <1.5 mg/dL or conjugated <0.2 mg/dL), elevated serum bile acid levels indicate a high risk for progressive liver disease.

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Understanding Success and Failure

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NPR (5/1/23): Why an NBA star’s response to a reporter’s question about losing hit a nerve

Some excerpts:

Antetokounmpo, after being asked if he considered the past season a failure:

Do you get a promotion every year at your job? No, right? So every year, your work is a failure? No. Every year, you work towards something, which is a goal: It’s to get a promotion, to be able to take care of your family, provide a house for them, or take care of your parents. It’s not a failure, it’s steps to success. There’s always steps to it. Michael Jordan played for 15 years and won 6 championships. The other 9 years were a failure? That’s what you’re telling me.

There’s no failure in sports. There’s good days, bad days, some days you are able to be successful, some days you’re not, some days it’s your turn, some days it’s not your turn. That’s what sport’s about. You don’t always win, some other people are gonna win. And this year, someone else is gonna win. Simple as that. 

So 50 years from 1971-2021 that we didn’t win a championship, it was 50 years of failure? No it was not, there were steps to it, and we were able to win one, hopefully we can win another one.

Real Madrid manager Carlo Ancelotti’s reaction:

What Antetokounmpo said was fantastic … Failure is when you don’t try to do something as well as you can. When you try to do your best, you have a clear conscience, and that’s never a failure, not just in sport but in life.

My take: I like Giannis’ response so much (there’s a 2 minute video at the link). His sentiments align with my beliefs. If/when I work hard, this often leads to good outcomes. However, even if the outcome is not what I wanted, I have no regrets.

“When You Reach for the Stars You May Not Quite Get One, But You Won’t Come Up With a Handful of Mud Either” – Leo Burnett

How Does Bowel Ultrasound Stack Up to MRE for Crohn’s Disease?

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A Rispo et al. Inflamm Bowel Dis 2023; 29: 563-569. David Against Goliath: Direct Comparison of Handheld Bowel Sonography and Magnetic Resonance Enterography for Diagnosis of Crohn’s Disease

Lately, there has been a lot of ‘buzz’ about the potential use of point-of-care bowel sonography (aka intestinal ultrasound). This study (2019-2021) prospectively enrolled patients with a high likelihood of Crohn’s disease (CD) and compared handheld bowel sonography (HHBS), MRE (all patients, n=85, had ileocolonoscopy)

Key findings:

  • Sensitivity, specificity, positive predictive values, and negative predictive values for CD diagnosis were 87.50%, 91.89%, 93.33%, and 85% for HHBS; and 91.67%, 94.59%, 95.65%, and 89.74% for MRE, without significant differences in terms of diagnostic accuracy (89.41% for HHBS vs 92.94% for MRE, P = NS)
  • Magnetic resonance enterography was superior to HHBS in defining CD extension (r = 0.67; P < .01) with a better diagnostic performance than HHBS for detecting location (k = 0.81; P < .01), strictures (k = 0.75; P < .01), abscesses (k = 0.68; P < .01), and fistulas (k = 0.65; P < .01).

My take: In this study, MRE was clearly superior at defining CD complications. This study suggests that HHBS could be an effective screening tool but is not likely a definitive imaging study. In terms of bedside monitoring, it would be helpful to see how clinical monitoring with HBSS compares with a highly sensitive marker like a calprotectin. I also worry that HBSS could perform more poorly with more widespread application due to potential increase in operator error.

Can Ceftriaxone Be Given (Safely) to Infants with Unconjugated Hyperbilirubinemia?

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SB Amin. J Pediatr 2023; 254: 91-95. Bilirubin-Displacing Effect of Ceftriaxone in Infants With Unconjugated Hyperbilirubinemia Born at Term

This prospective study with 27 term infants (<7 days) with mild unconjugated hyperbilirubinemia (total bilirubin 6-12 mg/dL) (to convert to micromol/L multiple by 17.1) and with sepsis. Free bilirubin concentrations were measured by the peroxidase method using a UB analyzer and a Zone Fluidics device before (baseline) and 15 minutes after (follow-up) IV ceftriaxone administration on postnatal days 4 to 6.

Key findings:

  • The mean free bilirubin (μg/dL) at follow-up was not different from that at baseline when measured by the UB analyzer (P = .78). The mean free bilirubin was significantly lower at follow-up compared with baseline when measured by the Zone Fluidics device (P = .02). The ratio of a free bilirubin with and without ceftriaxone, an index of displacing effect, was 1.02 (95% CI 0.89-1.14) using the UB analyzer and 0.58 (95% CI 0.30-0.86) using the Zone Fluidics device.

Ceftriaxone has been considered contraindicated in the presence of neonatal unconjugated hyperbilirubinemia due to concern of bilirubin displacement from albumin, resulting in elevated serum free bilirubin (& risk of kernicterus). However, “most of the evidence for the bilirubin-displacing effect of IV ceftriaxone has been derived from in vitro studies.”

My take: This study indicates that there is no significant effect of ceftriaxone in increasing free bilirubin in term infants with mild unconjugated hyperbilirubin

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Lipid Emulsions and Cognitive Outcomes

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M Thanhaeuser et al. J Pediatr 2023; 254: 68-74. Open Access: A secondary Outcome Analysis of a Randomized Trial Using a Mixed Lipid Emulsion Containing Fish Oil in Infants with Extremely Low Birth Weight: Cognitive and Behavioral Outcome at Preschool Age

Methods: This was a retrospective secondary outcome analysis of a randomized controlled trial performed between June 2012 and June 2015. Infants with extremely low birth weight received either a mixed (soybean oil, medium chain triglycerides, olive oil, fish oil) or a soybean oil-based lipid emulsion for parenteral nutrition (up to 3 gm/kd/day). At 5 years 6 months of age, data of 153 of 206 infants (74%) were available for analysis.

Key findings:

My take: The discussion highlights the lack of a positive benefit from the mixed emulsion. However, one of the biggest concerns with lipid emulsions occurs in the setting of lipid emulsion restriction due to parenteral nutrition associated liver disease. Because mixed emulsions are better tolerated, this helps minimize lipid restriction which could result in worsened neurocognitive outcomes.

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Measurement of Exocrine Pancreatic Insufficiency in IBD and the Real-World

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J Fernandez et al. JPGN 2023; 76: 475-479. Prevalence of Exocrine Pancreatic Dysfunction Based on Direct Function Testing in Pediatric Inflammatory Bowel Disease

Methods: Direct stimulated endoscopic pancreatic function test (ePFT) was performed in 74 children with IBD

Key findings:

  • 42 (56.7%) children had either generalized or partial exocrine pancreatic insufficiency (EPI). 
  • Weight z scores were significantly lower in those with abnormal ePFT (Crohn cases: P = 0.008; UC cases: P = 0.046). 

In their discussion, the authors assert: “We can confidently recommend ePFT in established or new IBD patients who have stricturing and/or penetrating CD, weight loss, low weight Z-score, or qualify for the diagnosis of malnutrition.”

My take: In my real-world experience (~30 years), I have yet to have one patient presenting with IBD who needed pancreatic enzyme supplementation to reverse growth failure/malnutrition. As a consequence, I have a difficult time accepting the premise that more than 50% have EPI. To me, this suggests that testing children when they are acutely-ill or malnourished is yielding unreliable results.

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Acid Suppression and Antibiotics in Infancy Associated with Increased Risk of Celiac Disease

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M Boechler et al. J Pediatr 2023; 254: 61-67. Acid Suppression and Antibiotics Administered during Infancy Are Associated with Celiac Disease

Methods: A retrospective cohort study was performed using the Military Healthcare System database. N=968,524 children with 1704 cases of celiac disease (CD) in this group (from 2001 to 2013) with prescription for PPIs, H2RAs or antibiotics in first 6 months of life.

Key findings:

  • PPIs (HR, 2.23; 95% CI, 1.76-2.83), H2RAs (HR, 1.94; 95% CI, 1.67-2.26), and antibiotics (HR, 1.14; 95% CI, 1.02-1.28) were all associated with an increased hazard of CD.
  • The risk is increased by use of multiple categories of these medications and/or if acid suppression medications are used for longer periods

There have been previous studies indicating an increased risk of CD in patients given acid suppression (Lebwohl et al. Dig Liver Dis 2014; 46: 36-40) and conflicting data regarding the use of antibiotics. With regard to acid suppression, recent studies have indicated that these medications in infancy may increase the risk of food allergies as well. The authors speculate in their discussion that the increased risk for CD could be related to changes in protein degradation, mucosal permeability, microbiome changes, and immune reactivity. The authors note that their dataset did NOT show an increased risk of CD associated with C-section delivery.

One of the limitations of this study is that early presentations of CD could lead to prescriptions of agents to to help reduce symptoms rather than the medications increasing the risk of developing CD. However, this is unlikely as gluten introduction is often later in infancy.

My take: Better stewardship of antibiotics and acid blockers is needed. Use of acid suppression medications is associated with an increased risk of celiac disease as well as food allergies.

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Additional posts on Celiac Disease

Panoramic View of Tucson, AZ from Tumamoc Hill