Dupixent Data in 1-11 year olds:
Rumination -clinical diagnosis:
Dupixent for Eosinophilic Esophagitis (1-11 yrs) and Clinical Diagnosis of Rumination from DDW Tweets
Category Archives: Uncategorized
Lipid Changes with IBD Medications
JAM Sleutjes et al. Inflamm Bowel Dis 2023; 29: 531-538. Open Access! Lipid Changes After Induction Therapy in Patients with Inflammatory Bowel Disease: Effect of Different Drug Classes and Inflammation
In this prospective study (n=198), the authors examined lipid profile changes at week 10 in patients starting IBD medications: corticosteroids, thiopurines, methotrexate, anti-TNF-α agents, vedolizumab, ustekinumab, and tofacitinib.
Key findings:
- Relative increases in total cholesterol, HDL-c, and LDL-c were significant after prednisone (+26%, +31%, +12%) and tofacitinib therapy (+20%, +25%, +26%), respectively
- No changes were observed in other drug classes
- Findings did not correlate with calprotectin or CRP values, likely indicating a direct medication effect
My take: Recent studies have provided some reassurance regarding tofacitinib and the risk of major adverse cardiovascular events (MACEs) (see posts below). Nevertheless, it seems prudent to monitor lipids in patients receiving JAK inhibitors.
Related blog posts:
- Tofacitinib Induction and Maintenance for Ulcerative Colitis
- Treatments for “Bad” Inflammatory Bowel Disease (Part 2) & Reassuring Data on Tofacitinib
- Tofacitinib Outperformed Vedolizumab in Anti-TNF-experienced Ulcerative Colitis
- Practice Tips for New IBD Therapies
- IBD Updates: Understanding Newest IBD Therapies for Kids- Bowel Sounds, Hispanic Patients with IBD, More on Intestinal Ultrasound
How Effective and Safe is Fecal Microbiota Transplantation in Immunocompromised Pediatric Patients with Clostridioides difficile?
KR Conover et al. JPGN 2023; 76: 440-446. Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Pediatric Patients
In this multicenter retrospective cohort (n=42), the authors examined the efficacy and safety of fecal microbiota transplantation (FMT) in immunocompromised (IC) children with Clostridioides difficile infection (CDI). Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%)
Key findings:
- 23 (55%) of FMT was delivered via colonoscopy, 17 (40%) were delivered via enteric tube, and 2 (5%) via capsule
- Success rate was 79% after first FMT and 86% after 1 or more FMT.
- There were serious adverse events (SAEs) in 13 out of 42 (31%) patients; 4 (9.5%) of which were likely treatment-related (all patients recovered). These events included cecal perforation, aspiration pneumonitis, diarrhea and fever. Given retrospective design of study, AEs were likely underreported
My take: Though there are the potential for significant adverse effects, FMT is effective in a high percentage of immunocompromised children with CDI.
Related blog posts:
- Fecal Microbioata Transplantation for Recurrent Clostridium difficile — Position Paper (NASPGHAN-ESPGHAN)
- FDA Approves Pharmaceutical Fecal Transplant Product
- ACG Clostridium Difficile Guidelines Plus One
- Why It Is Still A Bad Idea To Test Asymptomatic Patients For Clostridium Difficile
- Fecal Microbial Transplantation -Evidence for Use Beyond Recurrent Clostridium Difficile
- Two Studies: 1. COVID-19 Transmissibility 2.Fecal Microbiota Transplantation in 372 Children
- Only 3% Make It Through the Donor Screening Process for Fecal Microbiota Transplantation
- FDA News: FDA Warning for FMT, IB-Stim Device Approval, Teduglutide Approval
Prognostic Tool for Biliary Atresia after Kasai: Serum Bile Acids
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.
Related blog posts:
- Cholangitis After Kasai Procedure for Biliary Atresia
- Biliary Atresia Biomarkers 2020
- Landmark Study on Universal Screening for Biliary Atresia -It Works!
- Online Aspen Webinar (Part 5) -Biliary Atresia Diagnosis and Screening
- High Survival Rates for Biliary Atresia Patients Needing Liver Transplantation
- What to Expect After Pediatric Liver Transplantation: Cognitive Function and Quality of Life
- 30 -Year Outcomes with Biliary Atresia
Measurement of Exocrine Pancreatic Insufficiency in IBD and the Real-World
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.
Related blog posts:
- Transient Exocrine Pancreatic Insufficiency or Misleading Tests?
- Endoscopic Pancreatic Function Testing -NASPGHAN Position Paper
- How Helpful is Endoscopic Pancreatic Testing in Pediatrics?
Acid Suppression and Antibiotics in Infancy Associated with Increased Risk of Celiac Disease
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.
Related blog posts:
- First Year of Life Antibiotics and Celiac Disease
- Origins of Hygiene Hypothesis
- Do Acid Blockers Given to Infants Increase the Risk of Allergic Disease?
Additional posts on Celiac Disease
- Northern Latitudes -Higher Celiac Disease Prevalence
- Dietary Patterns in First Year of Life May Increase Celiac Autoimmunity
- Global Prevalence of Celiac Disease ~1.4%
- Celiac Disease Epidemic (High rate of celiac disease reported in Denver children)
- Vaccine for Celiac Disease
- Celiac Disease Risk –TEDDY study
- Celiac Disease and Mode of Delivery -Perhaps Not Very Consequential
- Celiac disease and diabetes
- How Birth Can Affect Your GI Tract | gutsandgrowth
- How to Protect Children From Celiac Disease
- Why are we seeing so many more cases | gutsandgrowth
- Why is Celiac Disease Becoming More Prevalent?
Thrombosis in Pediatric Patients with Intestinal Failure
G Keefe et al. J Pediatr 2023; 253: 152-157. High Rate of Venous Thromboembolism in Severe Pediatric Intestinal Failure
This retrospective study (n=263) examined the rate of venous thromboembolism (VTE) in pediatric patients who required parenteral nutrition for at least 90 consecutive days.
Key findings:
- The cumulative incidence of VTE was 28.1%, with a rate of 0.32 VTEs per 1000 catheter-days
- The number of catheters and early gestational age were noted to be independent risk factors for VTE
- No patients had progression of thrombus while receiving therapeutic anticoagulation
- Of those with acute DVTs (n=47), 24 (51%)resolved on repeat imaging, 14 (30%)were stable, and and 9 (19%) had decreased
- 4.4% (2 of 45) had a major bleed while on anticoagulation
The authors note that the true rate of VTE is likely even higher because only 42% categorized as not having a VTE had undergone dedicated venous imaging.
My take: A lot of patients with intestinal failure develop VTE. Given the risks of treatment, the role of prophylactic anticoagulation remains unclear. This is where a prospective study would be helpful.
Related blog posts:
- Catheter-Related Venous Thrombosis in Pediatric Patients with Inflammatory Bowel Disease
- Latest on VTE in Pediatric IBD
“Tug” Sign For Eosinophilic Esophagitis and EoE Bowel Sounds Tips
EA Pasman et al. Clin Gastroenterol Hepatol 2023; 21: 1108-1110. Quantitative Analysis of Tug Sign: An Endoscopic Finding of Eosinophilic Esophagitis
Background: “Chronic inflammation can lead to tissue remodeling in the esophagus with fibrosis in the lamina propria that is partially responsible for symptoms and complications of EoE.3,4 At times, a firmness to the esophagus can be appreciated with a noticeable force required to obtain biopsies from EoE. This sensation has been described as the “tug” or “pull” sign.5,6“
Methods: in this prospective study with 159 patients (128 pediatric, 31 adult), the authors devised a digital force gauge to measure the force required to take biopsy specimens. The study included 88 patients with EoE and 71 controls.
Key finding:
- EoE patients showed an increase in the mean force required to obtain biopsies: 14.9 Newton (N) compared to 11.6 in control group
- Peak force was greater in EoE patients: 20.4 N compared to 15 N in control group.
- The pediatric subgroup had higher peak force in EoE patients: 22.4 N compered to 16.1 N for control group
My take: I had not heard of the term “Tug” sign for EoE, though it is something that is intuitive for GI providers who care for these patients. This study quantifies this problem.
“When you can measure what you are speaking about and express it in numbers, you know something about it; but when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind” –Lord Kelvin 1883
Related topic: Recent bowel sounds episode with Amanda Muir discussed eosinophilic esophagitis. A few pointers:
- Useful YouTube video explaining how to swallow inhaled steroid (from Glen Furuta/Colorado Chilren’s): How to Use an Inhaler for EoE
- Budesonide can be administered with 1 tsp honey, 1 tsp maple syrup or with 1 tsp apple sauce
- Approximate equivalent dose of Flovent 4 puffs of 220 mcg =~1 mg budesonide
- Elemental feedings are difficult to maintain and used much less, mainly in children who already have enteral tubes.
Dried Blood Spot Testing for Biliary Atresia
C-S Lee el al. JPGN 2023; 76: 418-423. A Pilot Study of Biliary Atresia Newborn Screening Using Dried Blood Spot Matrix Metalloproteinase-7
Methods: The study used stored DBS samples collected from 48 to 72 hours of life were retrieved from newborn screening centers in Taiwan (n=25 biliary atresia (BA), 107 non-BA)
Key findings:
- MMP-7 levels of BA patients on the DBS were significantly higher than those of non-BA patients (19.2 ± 10.4 vs 5.6 ± 2.7 ng/mL, P value < 0.0001).
- BA patients in this cohort underwent Kasai operation at a mean of 43 days. 32% (n=8) had surgery before 30 days of life, and 24% (n=6) had surgery after 60 days.
- In this cohort, at time of publication, 9 (36%) of BA patients had received a liver transplantation at a mean of 2.4 years. Patients with their native liver tended to have had an earlier Kasai (38 days vs 54 days, P=0.057).
In their discussion, the authors note that BA starts very early in life. Increase in MMP-7 within 3 days of birth, supports “speculation that most BA ” may start before birth (JPGN 2019; 69: 396-403, What Is The Evidence That Biliary Atresia Starts in Utero?).
My take: Incorporating MMP-7 testing with newborn screening needs to be looked at in a bigger study. Efforts to identify BA cases earlier have largely been unsuccessful over the past several decades despite the knowledge that delayed diagnosis leads to worse outcomes.
Related blog posts:
- MMP-7 Helps Sort Out Biliary Atresia from Parenteral Nutrition-Associated Liver Disease
- Landmark Study on Universal Screening for Biliary Atresia -It Works!
- More Data, More Nuance with MMP-7: Best Biliary Atresia Biomarker
- Online Aspen Webinar (Part 5) -Biliary Atresia Diagnosis and Screening (2020)
- How To Diagnose Biliary Atresia in 48 hrs
Risk of Recurrent Surgery in Pediatric Crohn’s Patients
MD Edberg et al. Crohn’s and Colitis 360, 2023; https://doi.org/10.1093/crocol/otad003 Open Access! Trends in Surgical Recurrence Among Pediatric Crohn’s Disease Patients Using Administrative Claims Data
Methods: This study analyzed postresection pediatric (≤18 years) CD patients (n=434) identified in the 2007–2018 IQVIA Legacy PharMetrics administrative claims database
Key findings:
- Risk of surgical recurrence was 3.5%, 4.6%, and 5.3% at 1, 3, and 5 years, respectively
- Postoperatively, patients were most commonly prescribed an immune modulator (33%), anti-tumor necrosis factor agent (32%), or antibiotic (27%)
- 24% underwent colonoscopy 6–15 months postoperatively
My take: Current recommendations include postoperative endoscopic surveillance 6-12 months after surgery. Would the surgical recurrence rate have been lower if there had been higher postoperatively endoscopic evaluation?
Related blog posts:
- Expert Guidance on Pediatric Postoperative Crohn’s Disease
- AGA 2017 Guidelines for Postoperative Crohn’s Disease
- Microscopic Disease Does Not Predict Relapse in Crohn’s Disease
