SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study.

OBJECTIVE: There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection. DESIGN: A prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups. RESULTS: 1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection. CONCLUSION: Patients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.

Inhibition of tyrosine-kinase-mediated cellular signaling by tyrphostins AG 126 and AG556 modulates murine experimental acute pancreatitis.

BACKGROUND: The effects of the tyrosine kinase inhibitors, tyrphostin AG126 and AG556 in a murine model of acute pancreatitis are investigated. METHODS: Intraperitoneal injection of cerulein in mice resulted in a severe, acute pancreatitis, which was characterized by edema, neutrophil infiltration, tissue hemorrhage, and cell necrosis as well as elevation in the serum activities of amylase or lipase. RESULTS: Infiltration of the pancreatic tissue of these animals with neutrophils (measured as increase in myeloperoxidase activity) was associated with signs of enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination showed a marked increase in immunoreactivity for nitrotyrosine and poly (ADP-ribose) polymerase (PARP) in the pancreas of cerulein-treated mice. Pretreatment or posttreatment with tyrphostin AG126 and AG556, 2 different tyrosine kinase inhibitors, significantly reduced the degree of pancreatic inflammation and tissue injury (histologic score). In particular, the treatment with the 2 tyrosine kinase inhibitors reduced the cerulein-induced nitrotyrosine formation and PARP activation in the pancreas as well as the systemic release of tumor necrosis factor alpha. CONCLUSIONS: This study provides the first evidence that (1) prevention of the activation of protein tyrosine kinases reduces the development of acute pancreatitis, and (2) inhibition of the activity of certain tyrosine kinases may represent a novel approach for the therapy of acute pancreatitis.

Systematic appraisal of the management of the major vascular complications of pancreatitis.

BACKGROUND: This study is a systematic appraisal of the management of major vascular complications of pancreatitis conducted by collating individual patient-episode data from published literature. METHODS: Searches identified 79 papers of which 62 provided detailed information on the clinical course of 214 patients. Principal outcomes were modes of presentation, results of diagnostic angiography, and embolization and overall outcome. RESULTS: There were 160 "spontaneous" and 40 postoperative episodes of hemorrhage. Underlying pancreatic disease was chronic pancreatitis (40), pseudocyst (135), and acute pancreatitis in 39. Angiography was undertaken in 173 (81%) with embolization attempted in 115 and achieving hemostasis in 85 (75%). There were 40 (19%) deaths. Mortality was greater in patients undergoing surgery as first intervention compared with angiography first (P = .01, Fisher exact test). CONCLUSION: This analysis of pooled data provides evidence of a central role for mesenteric angiography in the diagnosis of major vascular complications of pancreatitis and for angiographic embolization as a powerful tool for achieving hemostasis.

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis.

BACKGROUND: Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. METHODS: We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty-three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE-II score and hospital site, and delivered groups that were similar at baseline. RESULTS: Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. CONCLUSIONS: This study provides no evidence to justify continued use of n-acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study.