Background-Inflammation in adipose tissue has been implicated in vascular dysfunction, but the local mechanisms by which this occurs are unknown. Methods and Results-Small arteries with and without perivascular adipose tissue were taken from subcutaneous gluteal fat biopsy samples and studied with wire myography and immunohistochemistry. We established that healthy adipose tissue around human small arteries secretes factors that influence vasodilation by increasing nitric oxide bioavailability. However, in perivascular fat from obese subjects with metabolic syndrome (waist circumference 111Ϯ2.8 versus 91.1Ϯ3.5 cm in control subjects, PϽ0.001; insulin sensitivity 41Ϯ5.9% versus 121Ϯ18.6% in control subjects, PϽ0.001), the loss of this dilator effect was accompanied by an increase in adipocyte area (1786Ϯ346 versus 673Ϯ60 m 2 , PϽ0.01) and immunohistochemical evidence of inflammation (tumor necrosis factor receptor 1 12.4Ϯ1.1% versus 6.7Ϯ1%, PϽ0.001). Application of the cytokines tumor necrosis factor receptor-␣ and interleukin-6 to perivascular fat around healthy blood vessels reduced dilator activity, resulting in the obese phenotype. These effects could be reversed with free radical scavengers or cytokine antagonists. Similarly, induction of hypoxia stimulated inflammation and resulted in loss of anticontractile capacity, which could be rescued by catalase and superoxide dismutase or cytokine antagonists. Incubation with a soluble fragment of adiponectin type 1 receptor or inhibition of nitric oxide synthase blocked the vasodilator effect of healthy perivascular adipose tissue. Conclusions-We conclude that adipocytes secrete adiponectin and provide the first functional evidence that it is a physiological modulator of local vascular tone by increasing nitric oxide bioavailability. This capacity is lost in obesity by the development of adipocyte hypertrophy, leading to hypoxia, inflammation, and oxidative stress. Key Words: hypoxia Ⅲ inflammation Ⅲ obesity Ⅲ microcirculation Ⅲ nitric oxide synthase M etabolic syndrome is a precursor to type 2 diabetes mellitus and cardiovascular disease, with a prevalence of almost 40% in the adult population. 1 Central obesity is believed to be the main cause of metabolic syndrome, and this is reflected in newer definitions of the condition with large waist circumference as a prerequisite. 2 Although associations of obesity with hypertension, 3 insulin resistance, 4 and cardiovascular disease 5 are well described, the underlying mechanisms are poorly understood. Two areas of research that may provide insight into these are the vasoactive properties of perivascular adipose tissue (PVAT) and the inflammatory changes that occur in fat as obesity develops. Demonstrated in 1991, 6 it is now accepted that healthy PVAT has an anticontractile effect. [7][8][9][10] The mechanism appears to be both endothelium dependent via release of nitric oxide 8,10 and endothelium-independent via generation of hydrogen peroxide. 8 In obesity and metabolic syndrome, there is also a conformational chang...

Objectives: To identify the implementation strategies used in World Health Organization Surgical Safety Checklist (SSC) uptake in low-and middleincome countries (LMICs); examine any association of implementation strategies with implementation effectiveness; and to assess the clinical impact. Background: The SSC is associated with improved surgical outcomes but effective implementation strategies are poorly understood. Methods: We searched the Cochrane library, MEDLINE, EMBASE and PsycINFO from June 2008 to February 2019 and included primary studies on SSC use in LMICs. Coprimary objectives were identification of implementation strategies used and evaluation of associations between strategies and implementation effectiveness. To assess the clinical impact of the SSC, we estimated overall pooled relative risks for mortality and morbidity. The study was registered on PROSPERO (CRD42018100034). Results: We screened 1562 citations and included 47 papers. Median number of discrete implementation strategies used per study was 4 (IQR: 1-14, range 0-28). No strategies were identified in 12 studies. SSC implementation occurred with high penetration (81%, SD 20%) and fidelity (85%, SD 13%), but we did not detect an association between implementation strategies and implementation outcomes. SSC use was associated with a reduction in mortality (RR 0.77; 95% CI 0.67-0.89), all complications (RR 0.56; 95% CI 0.45-0.71) and infectious complications (RR 0.44; 95% CI 0.37-0.52). Conclusions:The SSC is used with high fidelity and penetration is associated with improved clinical outcomes in LMICs. Implementation appears well supported by a small number of tailored strategies. Further application of implementation science methodology is required among the global surgical community.

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Mortality rates alone are no longer a sufficient guide to quality of care. Due to medical advances, patients are surviving for longer following critical illness and major surgery; therefore, functional outcomes and long-term quality of life are of increasing consequence. Post-operative cognitive dysfunction has been acknowledged as a complication following anaesthesia for many years, and interest in persistent cognitive dysfunction following a critical illness is growing. Psychological and neurocognitive sequelae following discharge from intensive care are acknowledged to occur with sufficient significance to have recently coined the term 'the post-intensive care syndrome'. Rehabilitation following critical illness has been highlighted as an important goal in recently published national UK guidelines, including the need to focus on both physical and non-physical recovery. Neuropsychological and cognitive consequences following anaesthesia and critical illness are significant. The exact pathophysiological mechanisms linking delirium, cognitive dysfunction and neuropsychological symptoms following critical illness are not fully elucidated but have been studied elsewhere and are outside the scope of this article. There is limited evidence as yet for specific peri-operative preventative strategies, but early management and rehabilitation strategies following intensive care discharge are now emerging. This article aims to summarise the issues and appraise current options for management, including both neuroprotective and neurorehabilitative strategies in intensive care. KeywordsIntensive care, critical illness, rehabilitation, cognitive dysfunction, delirium, post-traumatic stress disorder Over the last decade, there has been an increase in the complexity of patients presenting to intensive care, due in part to the severity of co-morbidities at presentation and an increasingly elderly population. Despite this, mortality rates are improving; the long-term consequences of critical illness are thus becoming ever more relevant. The risk factors and pathogenesis of delirium and post-cognitive dysfunction have been reviewed thoroughly elsewhere. This article summarises the relevant findings in these areas and deliberately focuses on the psychological and neurocognitive sequelae following critical illness including depression, anxiety, post-traumatic stress disorder and cognitive dysfunction; reviewing the evidence for incidence, pathophysiology and management. Psychological and neurocognitive consequences of critical illnessThe neuropsychological sequelae that occur following a critical care admission are numerous and can be highly distressing for patients and their families. Symptoms that occur include intrusive memories, delusions, delirium, panic episodes and nightmares. Conditions such as depression, anxiety, post-traumatic stress disorder (PTSD) and cognitive dysfunction are increasingly recognised among patients who survive an intensive care admission and are described collectively as the 'post-intensive care...

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Both intraoperative peak inspiratory pressure and FiO are independent factors significantly associated with development of a postoperative pulmonary complication in emergency laparotomy patients. Further studies are required to identify causality and to demonstrate if their manipulation could lead to better clinical outcomes.

Severe burns injuries are associated with a significant, global, cognitive deficit. Patients also report worse QoL, depression and post-traumatic stress. Perceived QoL from cognitive impairment was more closely associated with depression than cognitive impairment.

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