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

The Zinc Dyshomeostasis Hypothesis of Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized microtubules, their binding to MAP-tau, and molecular dynamics involved in cognition. Further, our theory supports novel AD therapeutic strategies targeting intra-neuronal zinc homeostasis and microtubule dynamics to prevent neurodegeneration and cognitive decline

Developing a tool to assess motivation among health service providers working with public health system in India

BACKGROUND: Addressing the shortage of health service providers (doctors and nurses) in rural health centres remains a huge challenge. The lack of motivation of health service providers to serve in rural areas is one of the major reasons for such shortage. While many studies have aimed at analysing the reasons for low motivation, hardly any studies in India have focused on developing valid and reliable tools to measure motivation among health service providers. Hence, the objective of the study was to test and develop a valid and reliable instrument to assess the motivation of health service providers working with the public health system in India and the extent to which the motivation factors included in the study motivate health service providers to perform better at work. METHODS: The present study adapted an already developed tool on motivation. The reliability and validity of the tool were established using different methods. The first stage of the tool development involved content development and assessment where, after a detailed literature review, a predeveloped tool with 19 items was adapted. However, in light of the literature review and pilot test, the same tool was modified to suit the local context by adding 7 additional items so that the final modified tool comprised of 26 items. A correlation matrix was applied to check the pattern of relationships among the items. The total sample size for the study was 154 health service providers from one Western state in India. To understand the sampling adequacy, the Kaiser-Meyer-Olkin measure of sampling adequacy and Bartlett’s test of sphericity were applied and finally factor analysis was carried out to calculate the eigenvalues and to understand the relative impact of factors affecting motivation. RESULTS: A correlation matrix value of 0.017 was obtained narrating multi-co-linearity among the observations. Based on initial factor analysis, 8 out of 26 study factors were excluded from the study components with a cutoff range of less than 0.6. Running the factor analysis again suggested the inclusion of 18 items which were subsequently labelled under the following heads: transparency, goals, security, convenience, benefits, encouragement, adequacy of earnings and further growth and power. CONCLUSIONS: There is a great need to develop instruments aimed at assessing the motivation of health service providers. The instrument used in the study has good psychometric properties and may serve as a useful tool to assess motivation among healthcare providers

Post traumatic intra thoracic spleen presenting with upper GI bleed! – a case report

<p>Abstract</p> <p>Background</p> <p>Isolated splenic vein thrombosis with left sided portal hypertension is a rare cause of upper gastrointestinal bleed. Diagnosis is difficult and requires a high index of suspicion, especially in patients presenting with gastrointestinal bleed in the presence of splenomegaly and normal liver function tests.</p> <p>Case presentation</p> <p>A 64 year old male presented with haematemesis and melaena. An upper gastrointestinal endoscopy revealed the presence of antral erosions in the stomach and fundal varices. A computerised tomography scan of abdomen confirmed the presence of a diaphragmatic tear and the spleen to be lying in the left hemi thorax. The appearances of the splenic vein on the scan were consistent with thrombosis.</p> <p>Conclusion</p> <p>Left sided portal hypertension as a result of isolated splenic vein thrombosis secondary to trauma is rare. The unusual presentation of our case, splenic herniation into the left hemithorax, causing fundal varices leading to upper gastrointestinal bleed 28 years after the penetrating injury, makes this case most interesting. We believe that this has not been reported in literature before.</p