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A Diaz-Gonzalez et al. Hepatology 2023; 77: 1095-1105. Open Access! Budesonide as first-line treatment in patients with autoimmune hepatitis seems inferior to standard predniso(lo)ne administration
Background: AASLD guidelines also suggest the use of budesonide with azathioprine as an alternative agent (to prednisone with azathioprine) in patients without cirrhosis or a severe acute presentation.1–3 However, particularly in pediatrics, there is concern that it is not as effective.
Methods: This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone.
Key findings:
My take: “The use of budesonide in the real-life setting was low and was associated with a lower probability of achieving BR with respect to prednisone.” It likely needs to be restricted to those with mild disease, and those with adverse events with prednisone. Cost is less of an issue as budesonide can be obtained as a generic (Mark Cuban Costplus pharmacy: Budesonide).
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MR Ingrosso et al. Gastroenterol 2023; 164: 642-654. Open Access! Efficacy and Safety of Drugs for Gastroparesis: Systematic Review and Network Meta-analysis
The authors examined 29 RCTs (3772 patients). Key findings:
In the associated editorial (pg 522-524, Drug Treatments for Gastroparesis—Why Is the Cupboard So Bare?), the authors note that the label “gastroparesis” applies to a heterogeneous population.
Key points:
My take: Currently, pharmaceutical agents geared towards symptoms like nausea and sensory disorders are much more promising than prokinetic agents for gastroparesis
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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 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.
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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:
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:
Y Usui et al. NEJM 2023; 388: 1181-1190. Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer
Background: Gastric cancer is the fifth most common neoplasm and the fourth leading cause of death from cancer worldwide.1 Helicobacter pylori has been classified as a group I carcinogen and is an environmental risk factor for gastric cancer.2 Although H. pylori infection affects more than half the world population
Methods: This study evaluated the association between germline pathogenic variants in 27 cancer-predisposing genes and the risk of gastric cancer in a sample of 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan. This retrospective study also assessed the combined effect of pathogenic variants and H. pylori infection status on the risk of gastric cancer and calculated the cumulative risk in 1433 patients with gastric cancer and 5997 controls from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC).
Key findings:
My take: H. pylori infection has a synergistic effect in increasing the risk of gastric cancer in individuals with germline pathogenic variants in homologous-recombination genes. To minimize the risk of gastric cancer, H pylori eradication is important; however, it is especially in those with cancer-predisposing variants.
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FDA 3/13/23: FDA approves first treatment for Rett Syndrome
FDA has approved Daybue (trofinetide) oral solution as the first treatment for Rett syndrome, a rare, genetic neurological disorder. Daybue is approved for the treatment of Rett syndrome in adults and children 2 years of age and older.
Patients take Daybue either orally or via gastrostomy tube. The recommended dose is based on patient weight. Daybue is taken twice daily, morning and evening, with or without food.
Rett syndrome is a rare, genetic neurological and developmental disorder that affects the way the brain develops. Patients with Rett syndrome experience a progressive loss of motor skills and language. Most babies with Rett syndrome seem to develop as expected for the first six months of life. These babies then lose skills they previously had attained at approximately six to 18 months of age — such as the ability to crawl, walk, communicate, or use their hands. The hallmark of Rett syndrome is near constant repetitive hand movements, such as rubbing or clapping. Rett syndrome leads to severe impairments affecting nearly every aspect of life, including the ability to speak, walk, eat, and breathe.
The syndrome primarily affects females (1 in 10,000) and even more rarely affects males.
The efficacy and safety of Daybue was evaluated in a randomized, double-blind, placebo-controlled, 12-week study (Study 1; NCT04181723) of patients with Rett syndrome five to 20 years of age. Patients were randomized to receive Daybue (N=93) or matching placebo (N=94) for 12 weeks. The dose of Daybue was based on patient weight to achieve similar exposure in all patients.
The co-primary efficacy measures were change from baseline in the Rett Syndrome Behavior Questionnaire (RSBQ) total score and the Clinical Global Impression-Improvement (CGI-I) score at week 12. The RSBQ is a 45-item rating scale completed by the caregiver that assesses a range of signs and symptoms of Rett syndrome. Lower scores represented lesser severity in signs and symptoms of Rett syndrome. The CGI-I is a 7-point scale rated by clinicians to assess how much a patient’s illness has improved or worsened. A decrease in CGI-I score indicates improvement.
Patients treated with Daybue demonstrated a statistically significant difference compared to placebo on the co-primary efficacy endpoints, as measured by the change from baseline in the RSBQ total score and the CGI-I score at week 12.
Most common adverse reactions, occurring in at least 10% of Daybue-treated patients and twice the rate of placebo, included diarrhea (81%) and vomiting (27%).
See full prescribing information for additional information on risks associated with Daybue.
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:
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.
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S Travis et al. NEJM 2023; 388: 1191-1200. Vedolizumab for the Treatment of Chronic Pouchitis
Methods: This was a a phase 4, double-blind, randomized trial (n=102 adults,EARNEST trial) to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis.All patients received 4 weeks of ciprofloxacin and the treatment group received standard vedolizumab dosing. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)–defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings.
Key findings:
My take: Vedolizumab is an effective treatment for chronic pouchitis.
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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:
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?
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