Background: Post-ERCP pancreatitis (PEP) is significantly influenced by the reflux of duodenal fluid. While gastrointestinal decompression represents a fundamental approach in acute pancreatitis management, the effectiveness of immediate duodenal decompression following ERCP to prevent PEP remains uncertain. This study aimed to investigate the impact of immediate duodenal decompression after ERCP on reducing the incidence of hyperamylasemia and PEP.
Methods: This retrospective study encompassed patients with native papilla who underwent therapeutic ERCP for choledocholithiasis at the Department of Gastroenterology, Chun'an Branch of Zhejiang Provincial People's Hospital (Zhejiang, China) between January 2020 and June 2023. Based on the immediate placement of a duodenal decompression tube post-ERCP, patients were categorized into two groups: the duodenal decompression group and the conventional procedure group. Primary outcomes included the incidence of PEP and hyperamylasemia.
Results: A total of 195 patients were enrolled (94 in the duodenal decompression group and 101 in the conventional procedure group). Baseline clinical and procedural characteristics exhibited no significant differences between the two groups. PEP occurred in 2 patients (2.1%) in the duodenal decompression group, in contrast to 11 patients (10.9%) in the conventional procedure group (Risk difference [RD] 8.8%; 95% confidence interval [CI] 1.7%-16.5%, P = 0.014). Hyperamylasemia was observed in 8 patients (8.5%) in the duodenal decompression group, compared to 20 patients (19.8%) in the conventional procedure group (RD 11.3%; 95% CI 1.4%-21.0%; P = 0.025). Patients with PEP in both groups showed improvement after receiving active treatment. No severe cases of PEP occurred in either group, and no serious adverse events related to duodenal catheter decompression were reported.
Conclusion: Immediate duodenal decompression following ERCP demonstrates an effective reduction in the incidence of hyperamylasemia and PEP.
Background: Since boosting stem cell resilience in stressful environments is critical for the therapeutic efficacy of stem cell-based transplantations in liver disease, this study aimed to establish the efficacy of a transient plasmid-based preconditioning strategy for boosting the capability of mesenchymal stromal cells (MSCs) for anti-inflammation/antioxidant defenses and paracrine actions in recipient hepatocytes.
Methods: Human adipose mesenchymal stem cells (hADMSCs) were subjected to transfer, either with or without the nuclear factor erythroid 2-related factor 2 (Nrf2)/Dickkopf1 (DKK1) genes, followed by exposure to TNF-α/H2O2. Mouse models were subjected to acute chronic liver failure (ACLF) and subsequently injected with either transfected or untransfected MSCs. These hADMSCs and ACLF mouse models were used to investigate the interaction between Nrf2/DKK1 and the hepatocyte receptor cytoskeleton-associated protein 4 (CKAP4).
Results: Activation of Nrf2 and DKK1 enhanced the anti-stress capacity of MSCs in vitro. In a murine model of ACLF, transient co-overexpression of Nrf2 and DKK1 via plasmid transfection improved MSC resilience against inflammatory and oxidative assaults, boosted MSC transplantation efficacy, and promoted recipient liver regeneration due to a shift from the activation of the anti-regenerative IFN-γ/STAT1 pathway to the pro-regenerative IL-6/STAT3 pathway in the liver. Importantly, the therapeutic benefits of MSC transplantation were nullified when the receptor CKAP4, which interacts with DKK1, was specifically removed from recipient hepatocytes. However, the removal of the another receptor low-density lipoprotein receptor-related protein 6 (LRP6) had no impact on the effectiveness of MSC transplantation. Moreover, in long-term observations, no tumorigenicity was detected in mice following transplantation of transiently preconditioned MSCs.
Conclusions: Co-stimulation with Nrf2/DKK1 safely improved the efficacy of human MSC-based therapies in murine models of ACLF through CKAP4-dependent paracrine mechanisms.