Although heat shock proteins have been studied for decades, new intracellular and extracellular functions in a variety of diseases continue to be discovered. Heat shock proteins function within networks of interacting proteins; they can alter cellular physiology rapidly in response to stress without requiring new protein synthesis. This review will focus on the heat shock protein 70 family and consider especially the functions of the inducible member, heat shock protein 72, in the setting of cerebral ischemia. In general, inhibiting apoptotic signalling at multiple points and upregulating survival signaling, heat shock protein 70 has a net pro-survival effect. Heat shock protein 70 has both anti-inflammatory and pro-inflammatory effects depending on the cell type, context, and intracellular or extracellular location. Intracellular effects are often anti-inflammatory with inhibition of Nuclear Factor κB signaling. Extracellular effects can lead to inflammatory cytokine production or induction of regulatory immune cells and reduced inflammation. Brief Summary Heat shock protein 70 is induced in cells by stress, but is also released from cells. Intracellular and extracellular heat shock protein 70 have distinct roles as survival proteins and modulators of the immune response.

Cerebral blood flow (CBF) is rigorously regulated by various powerful mechanisms to safeguard the match between cerebral metabolic demand and supply. The question of how a change in cardiac output (CO) affects CBF is fundamental, because CBF is dependent on constantly receiving a significant proportion of CO. The authors reviewed the studies that investigated the association between CO and CBF in healthy volunteers and patients with chronic heart failure. The overall evidence shows that an alteration in CO, either acutely or chronically, leads to a change in CBF that is independent of other CBF-regulating parameters including blood pressure and carbon dioxide. However, studies on the association between CO and CBF in patients with varying neurologic, medical, and surgical conditions were confounded by methodologic limitations. Given that CBF regulation is multifactorial but the various processes must exert their effects on the cerebral circulation simultaneously, the authors propose a conceptual framework that integrates the various CBF-regulating processes at the level of cerebral arteries/arterioles while still maintaining autoregulation. The clinical implications pertinent to the effect of CO on CBF are discussed. Outcome research relating to the management of CO and CBF in high-risk patients or during high-risk surgeries is needed.

Background: Postoperative delirium is a serious complication of surgery associated with prolonged hospitalisation, longterm cognitive decline, and mortality. This study aimed to determine whether targeting bispectral index (BIS) readings of 50 (light anaesthesia) was associated with a lower incidence of POD than targeting BIS readings of 35 (deep anaesthesia). Methods: This multicentre randomised clinical trial of 655 at-risk patients undergoing major surgery from eight centres in three countries assessed delirium for 5 days postoperatively using the 3 min confusion assessment method (3D-CAM) or CAM-ICU, and cognitive screening using the Mini-Mental State Examination at baseline and discharge and the Abbreviated Mental Test score (AMTS) at 30 days and 1 yr. Patients were assigned to light or deep anaesthesia. The primary outcome was the presence of postoperative delirium on any of the first 5 postoperative days. Secondary outcomes included mortality at 1 yr, cognitive decline at discharge, cognitive impairment at 30 days and 1 yr, unplanned ICU admission, length of stay, and time in electroencephalographic burst suppression. Results: The incidence of postoperative delirium in the BIS 50 group was 19% and in the BIS 35 group was 28% (odds ratio 0.58 [95% confidence interval: 0.38e0.88]; P¼0.010). At 1 yr, those in the BIS 50 group demonstrated significantly better cognitive function than those in the BIS 35 group (9% with AMTS 6 vs 20%; P<0.001).