OBJECTIVES: To study innate immune pathways in @entity1 undergoing hepatopancreaticobiliary surgery to understand mechanisms leading to enhanced inflammatory responses and identifying biomarkers of adverse clinical consequences. BACKGROUND: @entity1 undergoing major abdominal surgery are at risk of life-threatening @entity1850 ( @entity1850 ) and @entity295 . Early identification of at-risk @entity1 would allow tailored postoperative care and improve survival. METHODS: Two separate cohorts of @entity1 undergoing major hepatopancreaticobiliary surgery were studied (combined n=69). Bloods were taken preoperatively, on day 1 and day 2 postoperatively. Peripheral blood mononuclear cells and serum were separated and immune phenotype and function assessed ex vivo. RESULTS: Early innate @entity1200 was evident in 12 @entity1 who subsequently developed @entity1850 (postoperative day 6) compared with 27 who did not, when no clinical evidence of @entity1850 was apparent (preoperatively or days 1 and 2). Serum @entity650 concentration and monocyte Toll-like receptor (TLR)/NF-kB/ @entity650 functional pathways were significantly upregulated and overactive in @entity1 who developed @entity1850 (P<0.0001). Interferon a-mediated @entity6897 phosphorylation was higher preoperatively in @entity1 who developed @entity1850 . Increased @entity2939 and @entity20040 gene expression in whole blood was demonstrated in a separate validation cohort of 30 @entity1 undergoing similar surgery. Expression of @entity69748 on monocytes, particularly intermediate CD14CD16 monocytes, on day 1 or 2 predicted @entity1850 with accuracy 0.89 to 1.0 (areas under receiver operator curves). CONCLUSIONS: These data demonstrate the mechanism for @entity650 overproduction in @entity1 who develop postoperative @entity1850 and identify markers that predict @entity1 at risk of @entity1850 5 days before the onset of clinical signs.

@entity1850 After Major Abdominal Surgery Predicted by Early Upregulation of @entity2939 and XXXX .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity650 :: ('3569', 'Gene') :: ['IL-6', 'interleukin (IL)-6'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity69748 :: ('7099;7100', 'Gene') :: ['TLR4/5'] @entity20040 :: ('7100', 'Gene') :: ['TLR5'] @entity1200 :: ('MESH:D007154', 'Disease') :: ['immune dysfunction'] @entity1850 :: ('MESH:D018746', 'Disease') :: ['systemic inflammatory response syndrome', 'SIRS'] @entity6897 :: ('6772', 'Gene') :: ['STAT1'] @entity2939 :: ('7099', 'Gene') :: ['TLR4']
@entity20040 :: (7100,Gene) :: ['TLR5']
