Vera Maravic-Stojkovic

Background/Aim. A protection of heart and other organs from ischemic-reperfusion injuries can be provided by remote ischemic preconditioning (RIPC) by brief episodes of ischemia and reperfusion in distant tissues. The aim of this study was to assess effects of RIPC on early outcomes in patients underwent coronary bypass surgery (CABG) following acute coronary syndrome without persistent ST segment elevation (NSTEMI ACS). Methods. This trial included 42 patients randomized into two groups: the group 1 received RIPC and the group 2 was without RIPC (control group). Pre-, intra- and postoperative parameters were compared but primary endpoint was myocardial injury reflected as value of troponin I measured preoperatively and 1, 6, 12, 24, 48 and 72 h postoperatively. The secondary endpoints were hemodynamic parameters, blood loss, intensive care unit stay, mortality etc. Results. The groups 1 and 2 were similar in preoperative characteristics including age, New York Heart Association (NYHA) class, EuroSCORE II, left ventricular ejection fraction. The only significant difference between groups was for triple vessel coronary disease with dominance in the RIPC group [20 (100%) vs. 17 (77.3%),p = 0.049]. Cardiopulmonary bypass time [mean (+/- standard deviation): 83.0 (22.9) vs. 67.0 (17.4) minutes, p = 0.015], cross clamp time [57.9 (15.4) vs. 44.3 (14.3) minutes, p = 0.005] and number of conduits [median (25-75th percentile): 23.5(34 vs. 3(2-3), p = 0.002] were different. Other intra- and postoperative variables did not differ between groups. There were no differences in C reactive protein levels and postoperative hemodynamic parameters. Average troponin values in all time points revealed no significant differences between groups (p(0h) = 0.740,p(1h) = 0.212,p(6h)= 0.504,p(12h)= 0.597, p(24h) = 0.562, p(48h) = 0.465 and p(72h) = 0.715, respectively). Furthermore, there were no significant differences in adverse events, hospital stay and mortality between groups. Conclusion. Treatment with RIPC during CABG following NSTEMI ACS did not provide better myocardial protection and hemodynamics characteristics but further larger randomized studies are needed t. prove its real value.

Objective: We evaluated the utility of preoperative midregional (MR) pro-adrenomedullin (proADM) and cardiac troponin T (TnT) for improved detection of patients at high risk for perioperative cardiac events and mortality after major noncardiac surgery. Subjects and Methods: This prospective, single-center, observational study enrolled 79 patients undergoing major noncardiac surgery. After initial clinical assessment (clinical history, physical examination, echocardiogram, blood tests, and chest X-ray), MR-proADM and high-sensitivity TnT (hsTnT) were measured within 48 h prior to surgery by immunoluminometric and electrochemiluminescence immunoassay. Patients were followed by the consulting physician until discharge or up to 14 days in the hospital after surgery. Perioperative cardiac events included myocardial infarction and development or aggravation of congestive heart failure. Data were compared between patients who developed target events and event-free patients. Results: Within 14 days of monitoring, 14 patients (17.72%) developed target events: 9 (11.39%) died and 5 (6.33%) developed cardiovascular events. The average age of the patients was 71.29 ± 6.62 years (range: 55–87). Sex, age, and hsTnT did not significantly differ between groups. MR- proADM concentration was higher in deceased patients (p = 0.01). The upper quartile of MR-proADM was associated with a fatal outcome (66.7 vs. 20.0%, p < 0.01) and with cardiovascular events (64.3 vs. 16.9%, p < 0.01). MR-proADM above the cutoff value (≥0.85) was associated with a fatal outcome (88.9 vs. 20.0%, p < 0.01) and cardiovascular events (71.4 vs. 28.6%, p < 0.01); this association was not observed for hsTnT. Conclusion: Preoperative measurement of MR-proADM provides useful information for perioperative cardiac events in high-risk patients scheduled for noncardiac surgery.

Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship. The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017. We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment. Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis. From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects. Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidance was associated with a 2.4-day reduction in antibiotic exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay were similar in both groups. A sensitivity aggregate-data analysis based on all 32 eligible trials showed similar results. This updated meta-analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects. Results were similar for different clinical settings and types of ARIs, thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs. Future high-quality research is needed to confirm the results in immunosuppressed patients and patients with non-respiratory infections.

Copeptin is a sensitive and more stable surrogate marker for arginine vasopressin. In this study, we evaluated copeptin levels in carotid endarterectomy (CEA) patients, perioperatively, to determine whether copeptin levels can be related to carotid artery cross clamping (CC) time and to postoperative neurological outcomes. Copeptin, interleukin 6, C-reactive protein, cortisol, and brain natriuretic peptide were measured preoperatively (T1) and 3 hours postoperatively (T3) as well as intraoperatively (T2). We recruited 77 patients. Values of copeptin rose gradually over the observed times: T1 = 7.9 (6.4-9.6), T2 = 12.6 (9.3-16.8), and T3 = 72.3 (49.1-111.2) pmol/L. There was a significant difference for repeated measurement (P = .000, P = .000, and P = .000). Duration of carotid artery CC during CEA does not affect postoperative copeptin level (CC ≤ 13 minutes: 106.8 ± 93.6 pmol/L, CC > 13 minutes: 96.7 ± 89.1 pmol/L; P = .634). Preoperative copeptin level was significantly higher in patients with ulcerated plaque morphology. Activation of the stress axis in patients undergoing CEA results in copeptin elevation. Duration of CC during CEA does not affect postoperative copeptin levels.

We evaluated the prognostic value of copeptin levels in a cohort of surgical patients after elective carotid endarterectomy (CEA). Twenty-one patients with perioperative stroke were prospectively recruited. The diagnosis of cerebrovascular event (CVE) was confirmed by computed tomography. Additionally, 21 patients with CEA without any complications (control patients) were enrolled. Blood samples were taken within 3 hours of the symptom onset. Circulating copeptin level was significantly higher in patients with CVE when compared to controls (P = .025), and significantly higher in nonsurvivors than in survivors (P = .030) after CVE. Plasma concentrations of interleukin 6 (IL-6) and C-reactive protein (CRP) were also elevated in patients with CVE (IL-6: P = .043; CRP: P = .002). We conclude that the activation of the stress axis in patients with CEA results with copeptin elevation, but more so in patients with perioperative stroke. Copeptin may be a helpful biomarker for stroke risk assessment in patients after CEA.

Biomarkers are indicators of normal biological processes, pathogenic processes or pharmacologic responses to therapeutic interventions. Interleukin-6 (IL - 6) is a biomarker whose synthesis could be activated by various stimuli, such as interferon-g (IFN - g), tumor necrosis factor (TNF) and/or interleukin - 1 (IL - 1). IL - 6 achieves its effects through the IL-6 receptor (IL - 6R). It has been shown that transgenic mice, which have induced expression of IL - 6 and IL - 6R develop myocardial hypertrophy. In myocardial hypertrophy, an important role is played by a newly discovered cardiotrophin-1, a member of the IL - 6 family. The activity of IL - 6 is associated with the development of abdominal aortic aneurysm (AAA); in fact, it has been shown that the concentration of IL - 6 positively correlates with AAA diameters. C-reactive protein (CRP) is one of the biomarkers of cardiovascular diseases. Local production of CRP by the smooth muscular and endothelial cells of the vessel leads to the development of atherosclerosis to a large extent. Oxidized low-density lipoprotein (ox - LDL) also has an important role in the development of atherosclerosis. After penetrating the intima of the vessel, ox - LDL induces monocyte collection, i.e. monocytes are translated into macrophages that bind ox - LDL. Having filled the macrophages with ox - LDL, the signals of cell death are activated, which leads to the creation of foamy cells that make up the initial part of the atherosclerotic plaque. New knowledge about the mechanism of action and the role of biomarkers in the development of cardiovascular diseases will certainly provide an opportunity to prevent the onset of these disorders, as well as an adequate therapy in the treatment of cardiovascular diseases, which is one of the main goals of intensive research in the field of biomarkers.