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

Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E

The selective constraint of liver uptake and the sustained metabolism of tocotrienols (T3) demonstrate the need for a prompt detoxification of this class of lipophilic vitamers, and thus the potential for cytotoxic effects in hepatic and extra-hepatic tissues. Hypomethylated (γ and δ) forms of T3 show the highest in vitro and in vivo metabolism and are also the most potent natural xenobiotics of the entire vitamin E family of compounds. These stimulate a stress response with the induction of detoxification and antioxidant genes. Depending on the intensity of this response, these genes may confer cell protection or alternatively they stimulate a senescence-like phenotype with cell cycle inhibition or even mitochondrial toxicity and apoptosis. In cancer cells, the uptake rate and thus the cell content of these vitamers is again higher for the hypomethylated forms, and it is the critical factor that drives the dichotomy between protection and toxicity responses to different T3 forms and doses. These aspects suggest the potential for marked biological activity of hypomethylated “highly metabolized” T3 that may result in cytoprotection and cancer prevention or even chemotherapeutic effects. Cytotoxicity and metabolism of hypomethylated T3 have been extensively investigated in vitro using different cell model systems that will be discussed in this review paper as regard molecular mechanisms and possible relevance in cancer therapy

Examining the Effects of the Destroying Ammunition, Mines and Explosive Devices on the Presence of Heavy Metals in Soil of Open Detonation Pit; Part 2: Determination of Heavy Metal Fractions

As a result of the destruction of ammunition, mines, and explosive devices by the method of open detonation, the increased concentration of heavy metals is often recorded in the soil of military polygons, which is a serious ecological problem. However, in order to determine the potential risk of such locations to the environment, it is necessary to determine, in addition to the total content, the forms in which the metals are present. In this paper, a sequential extraction method was used to analyze the six fractions of five heavy metals (cadmium, lead, nickel, copper, and zinc) in the soil of the polygon for destruction of ammunition, mines, and explosive devices. Samples were collected from the place of direct detonation (so-called pits) and from the edge of the pit. The aim of this research is determination of metal speciation in order to obtain a better insight in their mobility and risk arising from this. The results showed that heavy metals are predominantly present in the residual, oxide, and organic fractions. Cd and Cu were also significantly present in the mobile fractions due to conducted activities on the polygon. To assess the potential environmental risk of soil, the risk assessment code (RAC) and individual (ICF) and global (GCF) contamination factors were used. According to the RAC, the mobility and bioavailability of the analyzed heavy metals decreases in the following order: Cd gt Cu gt Zn gt Pb gt Ni. ICF results show low to moderate risk, while GCF results show low risk in terms of heavy metal contamination in the examined area