Perioperative Cardiovascular Risk Stratification and Modification

Worldwide, annually approximately 100 million people undergo some form of non-cardiac surgery. Cardiac events, such as myocardial infarction are a major cause of perioperative morbidity and mortality in these patients. Though the true incidence of perioperative cardiac complications is difficult to assess, it is estimated that approximately 2.0–3.5% of patients undergoing major non-cardiac surgery experience a major adverse cardiac event. Furthermore an estimated 0.5–1.5% of patients die within 30 days after the surgical procedure due to a cardiovascular cause. The pathophysiology of perioperative cardiac events is complex. Similar to the non-operative setting it is thought that approximately half of all perioperative myocardial infarctions are attributable to a sustained coronary oxygen demand/supply mismatch. Coronary plaque rupture, leading to thrombus formation and subsequent vessel occlusion, is thought to be the other important cause of acute perioperative coronary syndromes

Identification of a novel protein containing two C2 domains selectively expressed in the rat brain and kidney

AbstractWe have isolated and characterized a rat brain cDNA clone which encodes a new protein of 474 amino acids in length which contains two C2 domains structurally homologous to those present in synaptotagmins. The overall amino acid identity in C2 domains between this protein and the synaptotagmins is 36–44%. This protein also contains 3 putative consensus sequences for phosphorylation by cAMP-dependent protein kinase. RNA blot hybridization revealed a 3.0 kb transcript abundantly expressed only in the rat brain and the kidney. Thus, we called this brain/kidney protein (B/K). In situ hybridization and Northern blot analyses showed that the B/K transcript was found in forebrain including the olfactory bulb, cerebral cortex, hippocampus, and hypothalamus. In the kidney, high levels of B/K transcript were expressed in the papillary region of the inner medulla, the inner stripe of the outer medulla and the cortex. The selective expression in forebrain and kidney suggests that B/K may be involved in similar cAMP-dependent processes at these very different sites

Correlated changes in perceptions of the gender and orientation of ambiguous biological motion figures

SummaryThe sensitivity of the mammalian visual system to biological motion cues has been shown to be general and acute [1–3]. Human observers, in particular, can deduce higher-order information, such as the orientation of a figure (which way it is facing), its gender, emotional state, and even personality traits, on the basis only of sparse motion cues. Even when the stimulus information is confined to point lights attached to the major joints of an actor (so-called point-light figures), observers can use information about the way the actor is moving to tell what they are doing, whether they are a male or female, and how they are feeling [4–6]. Here we report the novel finding that stimulus manipulations that made such walkers appear more female also had the effect of making the walkers appear more often as if they were walking away from rather than towards observers. Using frontal-view (or rear-view) point-light displays of human walkers, we asked observers to judge whether they seemed to be walking towards or away from the viewing position. Independent of their own gender, observers reliably reported those figures they perceived to be male as looking like they were approaching (as reported in [7]), but those they perceived to be female as walking away. Furthermore, figures perceived to be gender-neutral also appeared more often, although not exclusively, to be walking towards observers

Non-coronary atherosclerosis

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosi

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570