Dear colleagues, 

Recent years have seen intense debate around the question of whether treatment with proton-pump inhibitors (PPI) might increase the risk of dementia. This was based on prior studies drawing on analyses of German health insurance data, yet the data is conflicting. In light of this controversy, a new prospective cohort study with over 18,000 individuals ages ≥ 65 delivers an important observation: The study detected no association between PPI or H2 antihistamine use and incident dementia or cognitive impairments (Mehta et al.). We are currently witnessing a revolution in the pharmacological treatment of obesity, spurred by the availability of GLP1 (glucagon-like peptide 1) analogs capable of achieving major reductions in body weight. The drug retatrutide – a triple agonist of glucose-dependent insulinotropic polypeptide, GLP1, and glucagon receptors – represents a promising next step in this therapeutic principle. In a phase 2 trial, treatment with retatrutide for 48 weeks resulted in a remarkable 24.2% reduction in body weight (Jastreboff et al.). In light of increasing antibiotic resistance, detection of Helicobacter pylori by culture testing and characterization by resistance testing are growing in importance. However, these methods are time-consuming and not universally available. Two studies have now shown that first-line and third-line eradication therapy based on PCR-based molecular testing is non-inferior to – i.e. is similarly effective as – resistance testing using culture-based methods. Given these findings, increased use of PCR-based diagnosis can be expected in coming years (Chen et al.) [...]

Mirikizumab recently became the first selective IL-23 antibody approved for the treatment of ulcerative colitis. In the pivotal LUCENT study, the remission rate after 12 weeks was 24.2% with mirikizumab versus 13.3% with placebo (D’Haens et al.). The large number of new treatment options for ulcerative colitis raises questions about the value of conventional therapies like thiopurines. A small, randomized trial now reports that steroid-free clinical remission and endoscopic response could be achieved by 48.3% of patients receiving optimized 6-mercaptopurine treatment, which included regular dose adjustments, versus 10% receiving placebo (Löwenberg et al.). It remains to be seen whether these results lead to a renaissance in thiopurine therapy. Chemoradiotherapy is often used as neoadjuvant therapy for advanced rectal cancer. A randomized trial now demonstrates that neoadjuvant chemotherapy with the FOLFOX regimen is non-inferior to chemoradiotherapy in the primary end point of disease-free survival among candidates for sphincter-sparing resection (Schrag et al.).  

Treatment of patients with biliary pancreatitis often raises the question of the optimal time point for ERCP and stone extraction. Recently, the APEC study reported no benefit of early ERCP in patients with severe acute biliary pancreatitis without cholangitis. These results raised the possibility that endoscopic ultrasonography performed prior to ERCP might have a beneficial impact on the clinical outcome of severe pancreatitis in the event of stone or sludge detection. However, this hypothesis was not confirmed in a prospective study: Even when gallstones or sludge were detected in the bile ducts by endoscopic ultrasonography followed immediately by ERCP, the risk of major complications or mortality was not improved compared with conservative treatment in a historical control group. Given these findings, a decision to perform ERCP for biliary pancreatitis should be made with caution (Hallensleben et al.). 

The Italian surveillance registry for acute viral hepatitis reveals that surgical and endoscopic interventions still harbor a major risk of infection with hepatitis B or hepatitis C virus, even in the 21st century (Caminada et al.). Bulevirtide has been conditionally approved in Europe for the treatment of chronic HBV/HDV co-infection since 2020. A recent phase 3 trial shows that nearly 50% of patients achieve combined response, defined as normalization of ALT levels and a decrease in HDV RNA by > 2 log steps after 48 weeks of treatment with bulevirtide (Wedemeyer et al.). The phase 3 KEYNOTE-966 trial has demonstrated that pembrolizumab in combination with gemcitabine and cisplatin prolongs median overall survival versus gemcitabine and cisplatin alone (12.7 vs. 10.9 months) in patients with advanced biliary tract cancer (Kelley et al.). 

Together with the entire team at the Falk Gastro Review Journal, we wish you a Merry Christmas, happy holidays, and a positive, healthy, fruitful, and most of all peaceful 2024! 

Happy reading, 

Christoph Neumann-Haefelin and Peter Hasselblatt 
Department of Internal Medicine II, Medical University Clinic of Freiburg (Germany) 

Christoph Neumann-Haefelin

Peter Hasselblatt

Current literature articles in this edition

Long versus short peroral endoscopic myotomy for the treatment of achalasia: Results of a non-inferiority randomized controlled trial

Gut. 2023;72(8):1442–50

Molecular testing-guided therapy versus susceptibility testing-guided therapy in first-line and third-line Helicobacter pylori eradication: Two multicenter, open-label, randomized controlled, non-inferiority trials

Lancet Gastroenterol Hepatol. 2023;8(7):623–34

Association of proton-pump inhibitor use with incident dementia and cognitive decline in older adults: A prospective cohort study

Gastroenterology. 2023;165(3):564–72.e1

Effect of Helicobacter pylori eradication therapy on the incidence of non-cardia gastric adenocarcinoma in a large diverse population in the United States

Gastroenterology. 2023;165(2):391–401.e2

Long-term exposure to fine particulate matter and incidence of esophageal cancer: A prospective study of 0.5 million Chinese adults

Gastroenterology. 2023;165(1):61–70.e5

Clinical relevance of random biopsies from the esophagogastric junction after complete eradication of Barrett’s esophagus is low

Clin Gastroenterol Hepatol. 2023;21(9):2260–9.e9

The effect of procedural time on dysplasia detection rate during endoscopic surveillance of Barrett’s esophagus

Endoscopy. 2023;55(6):491–8

Yield of repeat endoscopy for Barrett’s esophagus after normal index endoscopy

Am J Gastroenterol. 2023;118(7):1168–74

Life cycle assessment of routinely used endoscopic instruments and simple intervention to reduce our environmental impact

Gut. 2023;72(9):1692–7