Metagenomic next-generation sequencing, instead of procalcitonin, could guide antibiotic usage in patients with febrile acute necrotizing pancreatitis: a multicenter, prospective cohort study.

BACKGROUNDS: The effectiveness of procalcitonin-based algorithms in guiding antibiotic usage for febrile acute necrotizing pancreatitis (ANP) remains controversial. Metagenomic next-generation sequencing (mNGS) has been applied to diagnose infectious diseases. The authors aimed to evaluate the effectiveness of blood mNGS in guiding antibiotic stewardship for febrile ANP. MATERIALS AND METHODS: The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed. RESULTS: From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P <0.001). Moreover, mNGS outperformed procalcitonin (89.5 vs. 61.4%, P <0.01) and blood culture (89.5 vs. 69.0%, P <0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis, significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P <0.001) and lower fibrinogen level (OR=2.0, P <0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (Odds ratio=11.7, P =0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results. CONCLUSION: Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.

Exenatide-induced chronic damage of pancreatic tissue in rats.

OBJECTIVE: The study aimed to explore exenatide-induced damage of pancreatic tissue in rats. METHODS: At first stage, 30 male rats were randomly divided into exenatide and control groups. At second stage, 10 male and 10 female rats were treated according to sex, exenatide dose and time, and with or without inhibitor. Exenatide was injected subcutaneously twice a day, and body weights were measured once a week. At approximately 10 weeks, blood and pancreatic tissue samples were harvested. Amylase, lipase, interleukin 1, interleukin 6, and tumor necrosis factor α in serums were determined. Pancreatic tissues were divided for dry-wet ratio, myeloperoxidase, hematoxylin-eosin staining, and electric microscope imaging. RESULTS: Compared with the control group, myeloperoxidase in pancreatic tissue of rats administered with exenatide exhibited a significantly high level; dry-wet ratio of pancreatic tissue in rats administered with exenatide exhibited a significantly low level. Chronic pancreatic damage was observed in 30% of rats from exenatide group for both sexes and showed pycnosis of acinar cells, increased cytoplasmic vacuoles, widened cellular gap, and inflammatory cell infiltration in pancreatic tissue. No pancreatic damage was observed in the control and the inhibitor groups. Histopathological evaluation scores in exenatide group were significantly higher than those of the control group. CONCLUSION: Long-term administration of exenatide in rats can result in chronic pancreatic damage.

Influence of nuclear factor kappaB activation on inflammatory mediators of alveolar macrophages in rats with acute necrotizing pancreatitis.

AIM: To investigate the potential influence of nuclear factor kappaB (NF-kappaB) activation on the inflammatory mediators secreted by alveolar macrophages (AMs) in rats with acute necrotizing pancreatitis (ANP) and to evaluate the effect of an inhibitor of NF-kappaB-N-acetylcysteine (NAC). METHODS: Ninety male Sprague-Dawley rats were randomly divided into 3 groups, 30 of each: control, ANP, and ANP plus NAC groups. The ANP rat models were established by a retrograde injection of 5% sodium taurocholate into the pancreatic duct. In addition to sodium taurocholate, the ANP plus NAC group received intravenous infusion of NAC (25 mg/100 g). At the sixth hour after modeling, the protein content of the bronchoalveolar lavage fluid, the myeloperoxidase in the lung tissue, and the transforming growth factor alpha and the nitric oxide (NO) secreted by AMs were determined. The histopathologic changes of the pancreas and the lung were observed under light microscope, and NF-kappaB activation of AMs was detected. RESULTS: The protein content of the bronchoalveolar lavage fluid and the myeloperoxidase level of the lung tissue showed a significant increase in the ANP group as compared with the NAC-administered group. The levels of transforming growth factor alpha and NO secreted by AMs in the ANP and the ANP plus NAC group rose significantly over that in the control group, and there was a significant difference between them. Although they were still higher than those in the control group, the pancreas destruction and the lung injury were slighter in the ANP plus NAC group and the activation of NF-kappaB was lower in the ANP plus NAC group as compared with that in the ANP group. CONCLUSIONS: The correlation between the NF-kappaB activation, the up-regulation of the inflammatory mediators secreted by AMs, and the tissue damage suggests a key influence of NF-kappaB in the pathogenesis of ANP. Inhibition of NF-kappaB activation may reverse the lung injury of ANP.