Purpose Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP. Methods We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission. Results A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI − 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%). Conclusion The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06745-7.

No abstract

No abstract

Pancreatic adenocarcinoma (Paad) is one of the most fatal types of cancer in humans. However, the molecular mechanisms underlying the migration and invasion abilities of Paad cells remain unclear. The aim of the present study was to explore the regulatory roles of microrna (mir)-32-5p in Paad cells. mir-32-5p mimic and inhibitor were used to transfect the human Paad asPc-1 cell line to determine the role of mir-32-5p in cell proliferation and metastasis. The starBase database predicted the binding of mir-32-5p to the target gene TBc/lysM-associated domain containing 1 (Tldc1). Further analyses were performed to assess mir-32-5p and Tldc1 expression levels in healthy and Paad tissues, as well as the association between mir-32-5p or Tldc1 expression and the prognosis of patients with Paad. The interaction between miR-32-5p and TLDC1 was verified using the dual-luciferase reporter assay. mir-32-5p and Tldc1 expression levels were detected by reverse transcription-quantitative Pcr and western blotting, respectively. The cell counting Kit-8 assay was utilised to assess cell proliferation, whereas the wound-healing and Transwell assays were conducted to assess cell migration and invasion, respectively. mir-32-5p expression levels were markedly lower in Paad tissue compared with those in healthy tissue, and were significantly lower in Paad cell lines compared with those in the human pancreatic duct cell line HPde6, which corresponded with poor prognosis. miR-32-5p significantly inhibited the proliferation of Paad cells and markedly reduced migration and invasion compared with the negative controls. mir-32-5p was shown to target Tldc1, with mir-32-5p expression in Paad being negatively correlated with Tldc1 expression. High Tldc1 expression levels were associated with a poorer prognosis compared with low Tldc1 expression levels. co-transfection of mir-32-5p mimic and pcdna/Tldc1 demonstrated that TLDC1 significantly reversed miR-32-5p-mediated inhibition of the proliferation, migration and invasion of Paad cells. overall, the present study demonstrated that mir-32-5p may serve as a tumor-suppressor gene by inhibiting the proliferation and migration and invasion of Paad cells via the downregulation of Tldc1. Therefore, mir-32-5p may serve as a potential diagnostic or prognostic marker for Paad.

Background: Pancreatic duct (PD) obstruction and hypertension may play a central role in the onset and progression of acute pancreatitis (AP). However, only a few studies have reported using pancreatic stenting to relieve PD obstruction in the early phase of AP, with conflicting results. Whether pancreatic stenting is effective in the early phase of AP remains unknown. We conducted this experiment in order to study the therapeutic efficacy and safety of pancreatic stenting in the early stage of AP.Methods: We conducted a retrospective analysis of 336 AP patients from 2011 to 2018 who underwent pancreatic stenting within 48 hours of admission.Results: A total of 330 (98.2%) patients underwent successful pancreatic stenting, of whom 23 (7.0%) had severe AP, 178 (53.9%) had moderately severe AP, and 129 (39.1%) had mild AP. Visible PD obstructive material was observed in 94 (28.5%) patients. The mean oral refeeding time since admission and length of hospital stay were 3.5±2.7 and 7.4±6.7 days, respectively. Procedure-related adverse events, in-hospital mortality, and local complication rates were 0.3%, 0.3%, and 7.6%, respectively. Conclusions: Early endoscopic pancreatic stenting in AP patients effectively shortened the fasting time and length of hospital stay and did not increase the risk of adverse events, death, or local complications.A further prospective randomized controlled clinical trial is currently underway to validate the safety and efficacy of this procedure.