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

Prolonged diet-induced obesity in mice modifies the inflammatory response and leads to worse outcome after stroke

BACKGROUND: Obesity increases the risk for ischaemic stroke and is associated with worse outcome clinically and experimentally. Most experimental studies have used genetic models of obesity. Here, a more clinically relevant model, diet-induced obesity, was used to study the impact of obesity over time on the outcome and inflammatory response after stroke. METHODS: Male C57BL/6 mice were maintained on a high-fat (60% fat) or control (12% fat) diet for 2, 3, 4 and 6 months when experimental stroke was induced by transient occlusion of the middle cerebral artery (MCAo) for either 20 (6-month diet) or 30 min (2-, 3-, 4- and 6-month diet). Ischaemic damage, blood-brain barrier (BBB) integrity, neutrophil number and chemokine expression in the brain were assessed at 24 h. Plasma chemokine levels (at 4 and 24 h) and neutrophil number in the liver (at 24 h) were measured. Physiological parameters (body weight and blood glucose) were measured in naïve control- and high-fat-fed mice at all time points and blood pressure at 3 and 6 months. Blood cell counts were also assessed in naïve 6-month control- and high-fat-fed mice. RESULTS: Mice fed a high-fat diet for 6 months had greater body weight, blood glucose and white and red blood cell count but no change in systolic blood pressure. After 4 and 6 months of high-fat feeding, and in the latter group with a 30-min (but not 20-min) occlusion of the MCA, obese mice had greater ischaemic brain damage. An increase in blood-brain barrier permeability, chemokine expression (CXCL-1 and CCL3), neutrophil number and microglia/macrophage cells was observed in the brains of 6-month high-fat-fed mice after 30-min MCAo. In response to stroke, chemokine (CXCL-1) expression in the plasma and liver was significantly different in obese mice (6-month high-fat fed), and a greater number of neutrophils were detected in the liver of control but not obese mice. CONCLUSIONS: The detrimental effects of diet-induced obesity on stroke were therefore dependent on the severity of obesity and length of ischaemic challenge. The altered inflammatory response in obese mice may play a key role in its negative impact on stroke

Arsenic Contamination of Groundwater in Indus River Basin of Pakistan

Arsenic (As) contamination of drinking water from groundwater sources is an issue of public health concern in many parts of the world, including South Asia. The presence of As in groundwater of Pakistan was reported around the city of Karachi as early as 1997. Widespread occurrences of As are reported in groundwater through a number of subsequent studies in the provinces of Punjab and Sindh, the two most populated provinces in the Indus River basin of Pakistan and thereby emerged as an issue of public health concern. These studies have revealed that concentrations of As are elevated by a factor of 10–250 as compared to the WHO drinking water guideline. Both natural and anthropogenic processes have been primarily indicated as cause for elevated As concentration in groundwater. An increasing number of studies also show evidence that irrigation with As contaminated groundwater is associated with elevated As concentrations in agricultural products. The future research should therefore focus on the detailed understanding of the complexities of the geological and hydrogeological setting of Pakistan and to outline the sources of As and the mechanisms of transport to the Indus basin aquifers

Genetics of Obesity

Obesity is caused by an imbalance between energy intake and output, influenced by numerous environmental, biological, and genetic factors. Only a minority of people with obesity have a genetic defect that is the main cause of their obesity. A key symptom for most of these disorders is early-onset obesity and hyperphagia. For some genetic obesity disorders, the hyperphagia is the main characteristic, often caused by disruptions of the leptin-melanocortin pathway, the central pathway that regulates the body's satiety and energy balance. For other disorders, obesity is part of a distinct combination of other clinical features such as intellectual disability, dysmorphic facial features, or organ abnormalities. This chapter focuses on genetic obesity disorders and also summarizes the present knowledge on the genetics of the more common polygenic/multifactorial obesity