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OBJECTIVE Obesity has a complex impact on acute respiratory distress syndrome patients, being associated with increased likelihood of developing the syndrome but reduced likelihood of dying. We propose that such observations are potentially explained by a model in which obesity influences the iatrogenic injury that occurs subsequent to intensive care admission. This study therefore investigated whether fat feeding protected mice from ventilator-induced lung injury. DESIGN In vivo study. SETTING University research laboratory. SUBJECTS Wild-type C57Bl/6 mice or tumor necrosis factor receptor 2 knockout mice, either fed a high-fat diet for 12-14 weeks, or age-matched lean controls. INTERVENTIONS Anesthetized mice were ventilated with injurious high tidal volume ventilation for periods up to 180 minutes. MEASUREMENTS AND MAIN RESULTS Fat-fed mice showed clear attenuation of ventilator-induced lung injury in terms of respiratory mechanics, blood gases, and pulmonary edema. Leukocyte recruitment and activation within the lungs were not significantly attenuated nor were a host of circulating or intra-alveolar inflammatory cytokines. However, intra-alveolar matrix metalloproteinase activity and levels of the matrix metalloproteinase cleavage product soluble receptor for advanced glycation end products were significantly attenuated in fat-fed mice. This was associated with reduced stretch-induced CD147 expression on lung epithelial cells. CONCLUSIONS Consumption of a high-fat diet protects mice from ventilator-induced lung injury in a manner independent of neutrophil recruitment, which we postulate instead arises through blunted up-regulation of CD147 expression and subsequent activation of intra-alveolar matrix metalloproteinases. These findings may open avenues for therapeutic manipulation in acute respiratory distress syndrome and could have implications for understanding the pathogenesis of lung disease in obese patients.

The replicative life span of human fibroblasts is heterogeneous, with a fraction of cells senescing at every population doubling. To find out whether this heterogeneity is due to premature senescence, i.e. driven by a nontelomeric mechanism, fibroblasts with a senescent phenotype were isolated from growing cultures and clones by flow cytometry. These senescent cells had shorter telomeres than their cycling counterparts at all population doubling levels and both in mass cultures and in individual subclones, indicating heterogeneity in the rate of telomere shortening. Ectopic expression of telomerase stabilized telomere length in the majority of cells and rescued them from early senescence, suggesting a causal role of telomere shortening. Under standard cell culture conditions, there was a minor fraction of cells that showed a senescent phenotype and short telomeres despite active telomerase. This fraction increased under chronic mild oxidative stress, which is known to accelerate telomere shortening. It is possible that even high telomerase activity cannot fully compensate for telomere shortening in all cells. The data show that heterogeneity of the human fibroblast replicative life span can be caused by significant stochastic cell-to-cell variation in telomere shortening.

Objectives There is a scarcity of literature reporting hospital costs for treating out of hospital cardiac arrest (OOHCA) survivors, especially within the UK. This is essential for assessment of cost-effectiveness of interventions necessary to allow just allocation of resources within the National Health Service. We set out primarily to calculate costs stratified against hospital survival and neurological outcomes. Secondarily, we estimated cost effectiveness based on estimates of survival and utility from previous studies to calculate costs per quality adjusted life year (QALY). Setting We performed a single centre (London) retrospective review of in-hospital costs of patients admitted to the intensive care unit (ICU) following return of spontaneous circulation (ROSC) after OOHCA over 18 months from January 2011 (following widespread introduction of targeted temperature management and primary percutaneous intervention). Participants Of 69 successive patients admitted over an 18-month period, survival and cerebral performance category (CPC) outcomes were obtained from review of databases and clinical notes. The Trust finance department supplied ICU and hospital costs using the Payment by Results UK system. Results Of those patients with ROSC admitted to ICU, survival to hospital discharge (any CPC) was 33/69 (48%) with 26/33 survivors in CPC 1–2 at hospital discharge. Cost per survivor to hospital discharge (including total cost of survivors and non-survivors) was £50 000, cost per CPC 1–2 survivor was £65 000. Cost and length of stay of CPC 1–2 patients was considerably lower than CPC 3–4 patients. The majority of the costs (69%) related to intensive care. Estimated cost per CPC 1–2 survivor per QALY was £16 000. Conclusions The costs of in-hospital patient care for ICU admissions following ROSC after OOHCA are considerable but within a reasonable threshold when assessed from a QALY perspective.

The authors report the case of a previously well 34-year-old woman presenting with a hypertensive crises and a grand-mal seizure following elective caesarean section. Initial treatment of extreme hypertension, of a presumed eclamptic aetiology, with magnesium and labetalol was complicated by intermittent profound hypotensive episodes. This was accompanied by severe biventricular failure and fluctuating systemic vascular resistance. Abdominal ultrasound revealed a left suprarenal mass. A diagnosis of phaeochromocytoma was confirmed on abdominal CT and urinary assays. The patient was stabilised with α and β blockade, was successfully extubated and subsequently had the tumour surgically excised. The cardiac function returned to normal on echocardiography and she has made a complete recovery.

Out-of-hospital cardiac arrest (OOHCA) causes 60,000 UK and 300,000 US deaths each year. Survival to hospital discharge in the developed world has historically been 7 to 10% with obvious cognitive impairment in 10% of survivors. Primary percutaneous coronary intervention (PPCI) and targeted temperature management (TTM) (or at least hyperthermia avoidance) have been shown to improve survival in comatose patients post OOHCA. There is no reliable method to predict poor outcome on presentation. We aimed to identify factors associated with poor outcome in our single-centre regional referral OOHCA population.

Before the introduction of primary percutaneous coronary intervention (PCI) and therapeutic hypothermia (TH) to out-of-hospital cardiac arrest (OOHCA) management, survival to hospital discharge with intact neurological function was poor [1,2]. We aimed to quantify the survival and degree of neurological impairment in OOHCA patients admitted to our ICU since the adoption of post-OOHCA bundles.