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

Studies towards the total synthesis of the pyrronazols

In 2014, the pyrronazols, a family of closely related natural products were isolated from a soil dwelling myxobacteria, Nannocystis pusilla strain Ari7. The family represent a novel structural class of secondary metabolites, containing a conjugated chlorinated pyrrole-oxazole unit. The total synthesis of pyrronazols A and A2, 20 and 21, has still to be accomplished and is of specific interest, not only for its unusual and interesting structure, but also to expand on the very limited biological profile. This could be probed further through the synthesis of structural analogues, thus requiring a synthetic strategy that tolerates rapid modifications to probe SAR. A synthetic strategy for the pyrronazol family must be flexible to allow for the synthesis of both isomers from a single privileged intermediate. Through our attempts towards the synthesis of the pyrronazol family this work details a highly syn-selective, substrate controlled vinylogous Mukaiyama aldol reaction (vMAR) which has been developed and optimised to install the required stereocentres on the pyranone ring. The (4S,5S) C₁-C₇ pyranone fragment has been utilised in the synthesis of two advanced intermediates, both a single reduction step away from pyrronazol A2, that have proved resistant to reduction. The alkene geometry, directing the synthesis towards pyrronazol A2, was set by an unprecedently selective Knoevenagel condensation between 5-chloro-2-formylpyrrole and amidoester partners. Our C₁-C₇ fragment has also been used in a convergent, modular synthesis of pyrronazol B, which afforded the natural product alongside an isomeric product

Asymmetric isothiourea-catalysed formal [3+2] cycloadditions of ammonium enolates with oxaziridines

The authors thank the Royal Society for a University Research Fellowship (A.D.S.) and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007—2013), ERC Grant Agreement No. 279850 (C.F. and J.E.T.), GSK (CASE award to S.R.S.) and EPSRC grant No. EP/J018139/1 (D.S.B.D.) for funding.A highly enantioselective Lewis base-catalysed formal [3+2] cycloaddition of ammonium enolates and oxaziridines to give stereodefined oxazolidin-4-ones in high yield is described. Employing an enantioenriched oxaziridine in this process leads to a matched/mis-matched effect with the isothiourea catalyst and allowed the synthesis of either syn- or anti-stereodefined oxazolidin-4-ones in high dr, yield and ee. Additionally, the oxazolidin-4-one products have been derivatised to afford functionalised enantioenriched building blocks.Publisher PDFPeer reviewe

Novel ether and thioether macrocycles from phthalaldehyde

By reaction of phthalaldehyde (benzene-1,2-dicarbaldehyde) with ethane-1,2-diol or 2-mercaptoethanol, macrocycles containing respectively 14- and 12-membered polyether/thioether rings were obtained in low but reproducible yield and their structures confirmed by X-ray diffraction. The simple compounds (2-vinylphenyl)oxirane and 2-oxiranylbenzaldehyde have also been prepared and characterised for the first time

Data underpinning Ross Sinclair McLennan's PhD thesis

The data files are embargoed until 19/02/202