Prognostic factors after acute mesenteric ischemia: which patients require specific management?

PURPOSE: Diagnosis and treatment of AMI are a real issue for implicating physicians. In the literature, only one AMI stroke center has reported its results so far, with increasing survival rates. Our aim was to analyze acute mesenteric ischemia (AMI) related mortality and predictive factors, in a single academic center, before creating a dedicated intestinal stroke center. METHODS: All the patients with an AMI, between January 2015 and December 2020, were retrospectively included. They were divided into 2 groups according to the early mortality: death during the first 30 days and alive. The 2 groups were compared. RESULTS: 173 patients (57% of men), were included, with a mean age of 68 ± 16 years. Overall mortality rate was 61%. Mortality occurred within the first 30 days in 78% of dead cases. Dead patients were significantly older, more frequently admitted from intensive care, with more serious clinical, laboratory and radiological characteristics. We have identified 3 protective factors - history of abdominal surgery (Odd Ratio = 0.1; 95%CI = 0.01-0.8, p = 0.03), medical management with curative anticoagulation (OR = 0.09; 95%CI = 0.02-0.5, p = 0.004) and/or antiplatelets (OR = 0.04; 95%CI = 0.006-0.3, p = 0.001)-, and 2 predictive factors of mortality - age > 70 years (OR = 7; 95%CI = 1.4-37, p = 0.02) and previous history of coronaropathy (OR = 13; 95%CI = 1.7-93, p = 0.01). CONCLUSIONS: AMI is a severe disease with high morbidity and mortality rates. Even if its diagnosis is still difficult because of non-specific presentation, its therapeutic management needs to be changed in order to improve survival rates, particularly in patients older than 70 years with history of coronaropathy. Developing a dedicated organization would improve the diagnosis and the management of patients with AMI.

A pancreatic ductal adenocarcinoma subpopulation is sensitive to FK866, an inhibitor of NAMPT.

Treating pancreatic cancer is extremely challenging due to multiple factors, including chemoresistance and poor disease prognosis. Chemoresistance can be explained by: the presence of a dense stromal barrier leading to a lower vascularized condition, therefore limiting drug delivery; the huge intra-tumoral heterogeneity; and the status of epithelial-to-mesenchymal transition. These factors are highly variable between patients making it difficult to predict responses to chemotherapy. Nicotinamide phosphoribosyl transferase (NAMPT) is the main enzyme responsible for recycling cytosolic NAD+ in hypoxic conditions. FK866 is a noncompetitive specific inhibitor of NAMPT, which has proven anti-tumoral effects, although a clinical advantage has still not been demonstrated. Here, we tested the effect of FK866 on pancreatic cancer-derived primary cell cultures (PCCs), both alone and in combination with three different drugs typically used against this cancer: gemcitabine, 5-Fluorouracil (5FU) and oxaliplatin. The aims of this study were to evaluate the benefit of drug combinations, define groups of sensitivity, and identify a potential biomarker for predicting treatment sensitivity. We performed cell viability tests in the presence of either FK866 alone or in combination with the drugs above-mentioned. We confirmed both inter- and intra-tumoral heterogeneity. Interestingly, only the in vitro effect of gemcitabine was influenced by the addition of FK866. We also found that NAMPT mRNA expression levels can predict the sensitivity of cells to FK866. Overall, our results suggest that patients with tumors sensitive to FK866 can be identified using NAMPT mRNA levels as a biomarker and could therefore benefit from a co-treatment of gemcitabine plus FK866.