Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Impact of gastric emptying and small intestinal transit on blood glucose, intestinal hormones, glucose absorption in the morbidly obese

First published: 25 September 2015NQ Nguyen, TL Debreceni, JE Burgess, M Bellon, J Wishart, S Standfield, CK Rayner, M Horowit

Arterial flow induces changes in saphenous vein endotheliumproteins transduced by cation channels

Objectives: expression of leukocyte adhesins and proteins controlling thrombosis is likely to be an important determinant of graft patency early following vein bypass. We have previously demonstrated rapid increase in endothelial ICAM-1 and nitric oxide synthase (eNOS) concentrations in human saphenous vein exposed to arterial flow. The aim of this study was to investigate whether ion-channel-blocking drugs could alter these flow-induced changes. Methods: human saphenous vein segments, freshly excised from patients, were placed in a validated in vitro circuit using flow conditions shown to simulate arterial or venous circulations for 90 min, in the presence or absence of ion-channel blockers. The concentrations of ICAM-1, VCAM-1, eNOS and tissue factor (TF) were assessed by quantitative immunohistochemistry in vein exposed to flow and compared with that in freshly excised vein from the same patient. The endothelial protein concentration was calculated as the mean area of staining as percentage of that for the control protein CD31, using computer-aided image analysis. Results: after arterial flow conditions the area ratio of ICAM-1 increased from 21.4±1.4 to 44.6±2.0%, of eNOS increased from 50.0±5.6 to 70.1±5.0%, of VCAM-1 decreased from 16.6±3.4 to 3.6±1.0%, whereas TF staining area ratio was unchanged. Inclusion of the non-selective K+channel blocker, tetraethylammonium, in the arterial perfusion solution abolished all these arterial flow-induced changes. Inclusion of the K+ATP channel blocker, glibenclamide, selectively abolished the arterial flow-induced changes in ICAM-1 and VCAM-1. Inclusion of the calcium channel blocker, nifedipine, abolished the arterial flow-induced changes in eNOS and VCAM-1 but increased the TF staining area ratio from 3.0±0.4 to 8.5±0.7%, p=0.01. Inclusion of the stretch-activated cation-channel blocker, gadolinium, enhanced the arterial flow-induced increase in eNOS, but prevented the arterial flow-induced increase in ICAM-1.Conclusions: perfusion of veins under arterial flow conditions with gadolinium was associated with low endothelial concentrations of ICAM-1, VCAM-1 and TF, but high levels of eNOS. Such a concentration of endothelial proteins may be advantageous in newly implanted vein grafts. In contrast, nifedipine could have adverse effects by promoting increase in TF concentration. © 2000 Harcourt Publishers Ltd

Arterial flow induces changes in saphenous vein endothelium proteins transduced by cation channels

Objectives: expression of leukocyte adhesins and proteins controlling thrombosis is likely to be an important determinant of graft patency early following vein bypass. We have previously demonstrated rapid increase in endothelial ICAM-1 and nitric oxide synthase (eNOS) concentrations in human saphenous vein exposed to arterial flow. The aim of this study was to investigate whether ion-channel-blocking drugs could alter these flow-induced changes. Methods: human saphenous vein segments, freshly excised from patients, were placed in a validated in vitro circuit using flow conditions shown to simulate arterial or venous circulations for 90 min, in the presence or absence of ion-channel blockers. The concentrations of ICAM-1, VCAM-1, eNOS and tissue factor (TF) were assessed by quantitative immunohistochemistry in vein exposed to flow and compared with that in freshly excised vein from the same patient. The endothelial protein concentration was calculated as the mean area of staining as percentage of that for the control protein CD31, using computer-aided image analysis. Results: after arterial flow conditions the area ratio of ICAM-1 increased from 21.4 ± 1.4 to 44.6 ± 2.0%, of eNOS increased from 50.0 ± 5.6 to 70.1 ± 5.0%, of VCAM-1 decreased from 16.6 ± 3.4 to 3.6 ± 1.0%, whereas TF staining area ratio was unchanged. Inclusion of the non-selective K+ channel blocker, tetraethylammonium, in the arterial perfusion solution abolished all these arterial flow-induced changes. Inclusion of the K+(ATP) channel blocker, glibenclamide, selectively abolished the arterial flow-induced changes in ICAM-1 and VCAM-1. Inclusion of the calcium channel blocker, nifedipine, abolished the arterial flow-induced changes in eNOS and VCAM-1 but increased the TF staining area ratio from 3.0 ± 0.4 to 8.5 ± 0.7%, p = 0.01. Inclusion of the stretch-activated cation-channel blocker, gadolinium, enhanced the arterial flow-induced increase in eNOS, but prevented the arterial flow-induced increase in ICAM-1. Conclusions: perfusion of veins under arterial flow conditions with gadolinium was associated with low endothelial concentrations of ICAM-1, VCAM-1 and TF, but high levels of eNOS. Such a concentration of endothelial proteins may be advantageous in newly implanted vein grafts. In contrast, nifedipine could have adverse effects by promoting increase in TF concentration

Effects of fat and protein preloads on pouch emptying, intestinal transit, glycaemia, gut hormones, glucose absorption, blood pressure and gastrointestinal symptoms after Roux-en-Y gastric bypass

BACKGROUND: The aim was to determine the effects of fat and protein preloads on pouch emptying (PE), caecal arrival time (CAT), glucose absorption, blood glucose (BSL), gut hormones, haemodynamics and gastrointestinal (GI) symptoms in subjects who had undergone Roux-en-Y gastric bypass (RYGB) >12 months previously. METHODS: Ten RYGB subjects were studied on three occasions, in randomised order, receiving 200 ml preloads of either water, fat (30 ml olive oil) or whey protein (55 g), 30 min before a mixed meal. PE, CAT, BSL, plasma 3-O-methyl-D-glucopyranose (3-OMG), insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and glucagon, blood pressure (BP), heart rate (HR) and GI symptoms were assessed over 270 min. RESULTS: Although fat and protein preloads did not alter PE of either solids or liquids, the CAT of solids, but not liquids, was longer than that after the water preload (fat 68 ± 5 min and protein 71 ± 6 min vs. water 46 ± 5 min; P = 0.02). BSL elevated promptly after the meal on all days (P < 0.001), but after protein, the magnitude and integrated increases in the first 75 min were less than fat and water preloads (area under the curve (AUC(0-75 min)), 18.7 ± 18.2 vs. 107.2 ± 30.4 and 76.1 ± 19.3 mmol/L/min; P < 0.05). Compared to water preload, the protein and fat preloads were associated with greater increases in plasma insulin, GLP-1 and glucagon concentrations, a reduction in BP, and greater increases in HR, fullness, bloating and nausea. Plasma 3-OMG levels were lower after the protein than after the water and fat preloads (P < 0.001). CONCLUSIONS: Given its effects to attenuate post-prandial glycaemia, reduce intestinal glucose absorption and potentiate the "incretin response", without inducing more adverse post-prandial GI symptom, protein preload may prove clinically useful in RYGB patients and warrant further evaluation, particularly in those with type 2 diabetes (T2DM) and/or dumping syndrome.Nam Q. Nguyen, Tamara L. Debreceni, Carly M. Burgstad, Melissa Neo, Max Bellon, Judith M. Wishart, Scott Standfield, Dylan Bartholomeusz, Chris K. Rayner, Gary Wittert, and Michael Horowit