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IntroductionIncreased inflammatory processes after non-cardiac surgery are very common. The association between postoperative inflammation and the occurrence of cardiovascular complications after non-cardiac surgery are still not entirely clear. Therefore, we will evaluate the association between postoperative inflammation and the occurrence of major cardiovascular complications in patients at-risk for cardiovascular complications undergoing non-cardiac surgery. We will further evaluate the association of postoperative inflammation and days-at-home within 30 days after surgery (DAH30), the incidence of acute kidney injury, postoperative N-terminal probrain natriuretic peptide (NT-proBNP) concentrations and neurocognitive decline.Methods and analysisIn this multicentre study, we will include 1400 patients at-risk for cardiovascular complications undergoing non-cardiac surgery. Our primary aim is to evaluate the association of postoperative maximum C-reactive protein concentration and the occurrence of a composite of five major cardiovascular complications (myocardial infarction, myocardial injury after non-cardiac surgery, new onset of atrial fibrillation, stroke and death) within 30 days after surgery using a Mann-Whitney-U test as well as a logistic regression model. As our secondary aim, we will evaluate the association of a composite of three inflammatory biomarkers (interleukin 6, procalcitonin and copeptin) on the occurrence of our composite of five cardiovascular complications within 30 days and 1 year after surgery, acute kidney injury, DAH30 and NT-proBNP concentrations using linear or logistic regression models. We will measure inflammatory biomarkers before surgery, and on the first, second, third and fifth postoperative day. We will check medical records and conduct a telephone survey 30 days and 1 year after surgery. We evaluate neurocognitive function, using a Montreal Cognitive Assessment, before and 1 year after surgery.Ethics and disseminationThis study was approved by the ethics committees at the Medical University of Vienna (2458/2020) and at the Medical University of Graz (33-274 ex 20/21).Trial registration numberNCT04753307.

IntroductionThe effect of different anaesthetics on the incidence of postoperative delirium is still not entirely clear. Therefore, we will evaluate the effect of desflurane versus sevoflurane versus propofol for the maintenance of anaesthesia on the incidence of postoperative delirium in older adults undergoing moderate- to high-risk major non-cardiac surgery. We will further compare the incidences of delayed neurocognitive recovery, long-term postoperative neurocognitive disorder, postoperative nausea and vomiting between the groups.Methods and analysisIn this multicentre, prospective, observer-blinded, randomised controlled clinical trial, we will include 1332 patients ≥65 years of age undergoing moderate- to high-risk major non-cardiac surgery lasting at least 2 hours. Patients will be randomly 1:1:1 assigned to receive desflurane, sevoflurane or propofol for anaesthesia. Maintenance of anaesthesia will be performed in a goal-directed manner using processed electroencephalography with an intraoperative goal of bispectral index 40–60. Our primary outcome will be the incidence of postoperative delirium within the first five postoperative days. Postoperative delirium will be assessed using the three-dimensional-confusion assessment method (3D-CAM) or CAM-intensive care unit (ICU) in the morning and evening of the first five postoperative days by blinded study personnel. The primary outcome, the incidence of postoperative delirium, will be compared between the three study groups using a χ2 test. Furthermore, a logistic regression model for the incidence of postoperative delirium will be performed, accounting for randomised groups as well as other predefined confounding factors.Ethics and disseminationThis clinical trial has been approved by the ethics committee and the Federal Office for Safety in Healthcare as the competent authority for clinical trials in Austria. The results of this trial will be published in a peer-reviewed journal.Trial registration numberClinicalTrials.gov NCT05990790.

Efficient and precise detection techniques, along with extensive repertoires of specific binding reagents, will be needed to meet the challenges of proteome analyses. The recently established proximity ligation mechanism enables sensitive high-capacity protein measurements by converting the detection of specific proteins to the analysis of DNA sequences. Proximity probes containing oligonucleotide extensions are designed to bind pairwise to target proteins and to form amplifiable tag sequences by ligation when brought in proximity. In our previous report, both the ligatable arms and the protein binders were DNA molecules. We now generalize the method by providing simple and convenient protocols to convert any polyclonal antibodies or matched pair of monoclonal antibodies to proximity probe sets through the attachment of oligonucleotide sequences. Sufficient reagent for >100,000 proximity ligation assays can be prepared from 1 μg of antibody. The technique is applied to measure cytokines in a homogenous test format with femtomolar detection sensitivities in 1-μI samples, and we exemplify its utility in situations when only minute sample amounts are available.

Background: Nucleic acid amplification allows the detection of single infectious agents. Protein-based assays, although they provide information on ongoing infections, have substantially less detection sensitivity. Methods: We used proximity ligation reactions to detect proteins on bacteria and virus particles via nucleic acid amplification. Antibodies recognizing viral or bacterial surface proteins were equipped with DNA strands that could be joined by ligation when several antibodies were bound in proximity to surface proteins of individual infectious agents. Results: Detection sensitivities similar to those of nucleic acid-based detection reactions were achieved directly in infected samples for a parvovirus and an intracellular bacterium. Conclusions: This method enables detection of ligated DNA strands with good sensitivity by real-time PCR and could be of value for early diagnosis of infectious disease and in biodefense.

Background: Improved methods are required to screen drug candidates for their influences on protein interactions. There is also a compelling need for miniaturization of screening assays, with attendant reductions in reagent consumption and assay costs. Methods: We used sensitive, miniaturized proximity ligation assays (PLAs) to monitor binding of vascular endothelial growth factor A (VEGF-A) to 2 of its receptors, VEGFR-1 and VEGFR-2. We measured the effects of proteins and low molecular weight compounds capable of disrupting these interactions and compared the results with those obtained by immunoblot analysis. We analyzed 6 different inhibitors: a DNA aptamer, a mixed DNA/RNA aptamer, a monoclonal VEGF-A neutralizing antibody, a monoclonal antibody directed against VEGFR-2, a recombinant competitive protein, and a low molecular weight synthetic molecule. Results: The PLAs were successful for monitoring the formation and inhibition of VEGF-A–receptor complexes, and the results correlated well with those obtained by measuring receptor phosphorylation. The total PLA time is just 3 hours, with minimal manual work and reagent additions. The method allows evaluation of the apparent affinity [half-maximal inhibitory concentration (IC50)] from a dose–response curve. Conclusions: The PLA may offer significant advantages over conventional methods for screening the interactions of ligands with their receptors. The assay may prove useful for parallel analyses of large numbers of samples in the screening of inhibitor libraries for promising agents. The technique provides dose–response curves, allowing IC50 values to be calculated.