Novel Drug Targets for Ischemic Stroke Identified Through Mendelian Randomization Analysis of the Blood Proteome.

Background: Novel, effective, and safe drugs are warranted for treatment of ischemic stroke. Circulating protein biomarkers with causal genetic evidence represent promising drug targets, but no systematic screen of the proteome has been performed.

Methods: First, using Mendelian randomization (MR) analyses, we assessed 653 circulating proteins as possible causal mediators for 3 different subtypes of ischemic stroke: large artery atherosclerosis, cardioembolic stroke, and small artery occlusion.

Improvement in staff behavior during surgical procedures to prevent post-operative complications (ARIBO): study protocol for a cluster randomised trial.

Background: Inappropriate staff behaviour during surgical procedures may disrupt the surgical performance and compromise patient safety. We developed an innovative monitoring and feedback system combined with an adaptive approach to optimise staff behaviour intraoperatively and prevent post-operative complications (POC) in orthopaedic surgery.

Methods/design: This protocol describes a parallel-group, cluster randomised, controlled trial with orthopaedic centre as the unit of randomisation.

The PROTROPIC feasibility study: prognostic value of elevated troponins in critical illness.

Purpose: Elevated cardiac troponin concentrations in people with critical illness are associated with an increased risk of death. We aimed to assess the feasibility of a larger study to ascertain the utility of cardiac troponin as a prognostic tool for mortality in critically ill patients.

Methods: Patients admitted to participating intensive care units during the one-month enrolment period were eligible.

Direct Oral Anticoagulants Versus Vitamin K Antagonists in Patients Undergoing Cardioversion for Atrial Fibrillation: a Systematic Review and Meta-analysis.

Background: Clinical guidelines recommend peri-cardioversion anticoagulation in patients with atrial fibrillation (AF). We performed a systematic review and meta-analysis to compare the safety and efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with AF undergoing cardioversion.

Methods: We searched CENTRAL, MEDLINE, and EMBASE for randomized controlled trials (RCTs) and observational studies comparing DOACs to VKAs in patients undergoing cardioversion for AF.

Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) study: Results of a pilot study.

Background: Cardiac surgery patients are at high risk for postoperative bleeding. Intravenous (IV) tranexamic acid (TxA) is a commonly used antifibrinolytic drug, but is associated with postoperative seizures. We conducted this pilot randomized controlled trial (RCT) to determine the feasibility of a larger trial that will be designed to investigate the impact of TxA administration route, intrapericardial (IP) vs IV, on postoperative bleeding and seizures.

Atrial Fibrillation and Cognitive Function: JACC Review Topic of the Week.

Numerous vascular risk factors and vascular diseases contribute to cognitive impairment and dementia. Many studies and registries show an association of atrial fibrillation (AF) with cognitive impairment, cognitive decline, and dementia. This is true for vascular dementia and Alzheimer's disease.

Pre-hospital mechanical ventilation in septic shock patients.

Background: Mechanical ventilation can cause deleterious effects on the lung and thus alter patient's prognosis. The aim of this study was to describe the characteristics of prehospital mechanical ventilation in patients with septic shock requiring mechanical ventilation in the prehospital setting.

Methods: Patients with septic shock subjected to pre-hospital intubation and mechanical ventilation by a mobile intensive care unit were consecutively included and retrospectively analysed.

Steroids in cardiac surgery trial: a substudy of surgical site infections.

Purpose: Postoperative infection, particularly in cardiac surgery, results in significant morbidity, mortality, and healthcare cost. Identification of novel predictors of postoperative infection can target high-risk populations for prophylactic intervention.

Methods: Steroids in cardiac surgery (SIRS) was a multi-centre randomized-controlled trial assessing intraoperative administration of methylprednisone during cardiac surgery, which enrolled 7,507 patients across 80 centres in 18 countries.

The ASOS Surgical Risk Calculator: development and validation of a tool for identifying African surgical patients at risk of severe postoperative complications.

Background: The African Surgical Outcomes Study (ASOS) showed that surgical patients in Africa have a mortality twice the global average. Existing risk assessment tools are not valid for use in this population because the pattern of risk for poor outcomes differs from high-income countries. The objective of this study was to derive and validate a simple, preoperative risk stratification tool to identify African surgical patients at risk for in-hospital postoperative mortality and severe complications.

Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis.

Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating both acute myocardial infarction (AMI) and ischemic heart failure (IHF). However, the safety profile and efficacy of MSC therapy is not well-known. We conducted a systematic review of clinical trials that evaluated the safety or efficacy of MSCs for AMI or IHF.

Restrictive compared with liberal red cell transfusion strategies in cardiac surgery: a meta-analysis.

Aims: To determine whether a restrictive strategy of red blood cell (RBC) transfusion at lower haemoglobin concentrations is inferior to a liberal strategy of RBC transfusion at higher haemoglobin concentrations in patients undergoing cardiac surgery.

Methods And Results: We conducted a systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials of the effect of restrictive and liberal RBC transfusion strategies on mortality within 30 days of surgery as the primary outcome. Secondary outcomes were those potentially resulting from anaemia-induced tissue hypoxia and transfusion outcomes.

Blood CSF1 and CXCL12 as Causal Mediators of Coronary Artery Disease.

Background: Identification of biomarkers that cause coronary artery disease (CAD) has led to important advances in prevention and treatment. Epidemiological analyses have identified many biomarker-CAD relationships; however, these associations may arise from reverse causation and/or confounding and therefore may not represent true causal associations. Mendelian randomization (MR) analyses overcome these limitations.

Skin mottling score and capillary refill time to assess mortality of septic shock since pre-hospital setting.

Objectives: The early identification of septic shock patients at high risk of poor outcome is essential to early initiate optimal treatments and to decide on hospital admission. Biomarkers are often used to evaluate the severity. In prehospital settings, the availability of biomarkers, such as lactate, is restricted.

Correction to: Advances in anesthesia technology are improving patient care, but many challenges remain.

Unfortunately, after publication of this article [1], it was noticed that the name of Ashraf A. Dahaba is incorrectly displayed as Ashraf Dahaba. The full, corrected author list can be seen here.

Advances in anesthesia technology are improving patient care, but many challenges remain.

Although significant advances in clinical monitoring technology and clinical practice development have taken place in the last several decades, in this editorial we argue that much more still needs to be done. We begin by identifying many of the improvements in perioperative technology that have become available in recent years; these include electroencephalographic depth of anesthesia monitoring, bedside ultrasonography, advanced neuromuscular transmission monitoring systems, and other developments. We then discuss some of the perioperative technical challenges that remain to be satisfactorily addressed, such as products that incorporate poor software design or offer a confusing user interface.

Blood HER2 and Uromodulin as Causal Mediators of CKD.

Many biomarkers have been epidemiologically linked with CKD; however, the possibility that such associations are due to reverse causation or confounding limits the utility of these biomarkers. To overcome this limitation, we used a Mendelian randomization (MR) approach to identify causal mediators of CKD. We performed MR by first identifying genetic determinants of 227 serum protein biomarkers assayed in 4147 participants of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial who had early or prediabetes, and assessing the effects of these biomarkers on CKD in the CKD genetics consortium (=117,165; 12,385 cases) using the inverse-variance weighted (fixed-effects) method.

Perioperative patient outcomes in the African Surgical Outcomes Study: a 7-day prospective observational cohort study.

Background: There is a need to increase access to surgical treatments in African countries, but perioperative complications represent a major global health-care burden. There are few studies describing surgical outcomes in Africa.

Methods: We did a 7-day, international, prospective, observational cohort study of patients aged 18 years and older undergoing any inpatient surgery in 25 countries in Africa (the African Surgical Outcomes Study).

Transfusion Requirements in Cardiac Surgery III (TRICS III): Study Design of a Randomized Controlled Trial.

Objectives: To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity.

Design: Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design (ClinicalTrials.gov number, NCT02042898).

Relationships of kidney injury molecule-1 with renal function and cardiovascular risk factors in the general population.

Background: Kidney injury molecule-1 (KIM-1) has been associated with kidney damage in patients with preexisting renal disease. However, little is known about the relationships of KIM-1 with renal function and cardiovascular risk factors in healthy individuals from the general population.

Methods: Healthy individuals aged 25-41years were enrolled in a population-based study.

Assessment of safety and efficacy of mesenchymal stromal cell therapy in preclinical models of acute myocardial infarction: a systematic review protocol.

Background: Despite advances in treatment, acute myocardial infarction (MI) is still associated with significant morbidity and mortality, especially in patients with extensive damage and scar formation. Based on some promising preclinical studies, there is interest in the use of mesenchymal stromal cells (MSCs) to promote cardiac repair after acute MI. However, there is a need for a systematic review of this evidence to summarize the efficacy and safety of MSCs in preclinical models of MI.