A "NIRS" death experience: a reduction in cortical oxygenation by time-resolved near-infrared spectroscopy preceding cardiac arrest

Near-infrared spectroscopy (NIRS) has been used effectively post-cardiac-arrest to gauge adequacy of resuscitation and predict the likelihood of achieving a return of spontaneous circulation. However, preempting hemodynamic collapse is preferable to achieving ROSC through advanced cardiac life support. Minimizing "time down" without end-organ perfusion has always been a central pillar of ACLS. In many critically ill patients there is a prolonged phase of end-organ hypoperfusion preceding loss of palpable pulses and initiation of ACLS. Due to the relative infrequency of in-hospital cardiac arrest, NIRS has not previously evaluated the period immediately prior to hemodynamic collapse. Here we report a young man who suffered a pulseless electrical activity (PEA) arrest while cortical oxygenation was monitored using time-resolved near-infrared spectroscopy. The onset of cortical deoxygenation preceded the loss of palpable pulses by 15 min, suggesting that TRS-NIRS monitoring might provide a means of preempting PEA arrest. Our experience with this patient represents a promising new direction for continuous NIRS monitoring and has the potential to not only predict clinical outcomes, but affect them to the patient's benefit as well

mTOR Is Essential for the Proteotoxic Stress Response, HSF1 Activation and Heat Shock Protein Synthesis

The target of rapamycin (TOR) is a high molecular weight protein kinase that regulates many processes in cells in response to mitogens and variations in nutrient availability. Here we have shown that mTOR in human tissue culture cells plays a key role in responses to proteotoxic stress and that reduction in mTOR levels by RNA interference leads to increase sensitivity to heat shock. This effect was accompanied by a drastic reduction in ability to synthesize heat shock proteins (HSP), including Hsp70, Hsp90 and Hsp110. As HSP transcription is regulated by heat shock transcription factor 1 (HSF1), we examined whether mTOR could directly phosphorylate this factor. Indeed, we determined that mTOR could directly phosphorylate HSF1 on serine 326, a key residue in transcriptional activation. HSF1 was phosphorylated on S326 immediately after heat shock and was triggered by other cell stressors including proteasome inhibitors and sodium arsenite. Null mutation of S326 to alanine led to loss of ability to activate an HSF1-regulated promoter-reporter construct, indicating a direct role for mTOR and S326 in transcriptional regulation of HSP genes during stress. As mTOR is known to exist in at least two intracellular complexes, mTORC1 and mTOR2 we examined which complex might interact with HSF1. Indeed mTORC1 inhibitor rapamycin prevented HSF1-S326 phosphorylation, suggesting that this complex is involved in HSF1 regulation in stress. Our experiments therefore suggest a key role for mTORC1 in transcriptional responses to proteotoxic stress

Journal of Clinical Monitoring and Computing 2017/2018 end of year summary:monitoringand provocationof the microcirculation and tissue oxygenation

The microcirculation is the ultimate goal of hemodynamic optimization in the perioperative and critical care setting. In this fourth end-of-year summary of the Journal of Clinical Monitoring and Computing on this topic, we take a closer look at papers published in the last 2years that focus on this important aspect. The majority of these papers investigated the use of either cerebral or peripheral tissue oxygen saturation, derived non-invasively using near infrared spectroscopy (NIRS). In some of these studies, the microcirculation was provocated by inducing short-term tissue hypoxia, allowing the assessment of functional microvascular reserve. Additionally, studies on technical differences between NIRS monitors are summarized, as well as studies investigating the feasibility of NIRS monitoring, mainly in the pediatric patient population. Last but not least, novel monitoring tools allow assessing oxygenation at a (sub)cellular level, and those papers incorporating these techniques are also reviewed here