Circulating MicroRNAs and Novel Proteins as Potential Biomarkers of Neurological Complications after Heart Bypass Surgery.

Postoperative recovery can be impaired by many conditions, some of which are difficult to diagnose clinically. These include type 2 neurological complications such as hypoactive subtype of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD). Hope for their timely detection may lie with novel biomarkers. Plasma concentrations of microRNA-1-3p, microRNA-21-5p, glial fibrillary acidic protein (GFAP), neuroserpin (NSP), phosphorylated axonal neurofilament subunit H (pNfH) and visinin-like protein 1 (VILIP-1) were investigated in 30 patients undergoing elective off-pump coronary artery bypass grafting. Blood samples were collected at the start and end of a surgery as well as 24 h postoperatively. Associations between the studied biomarkers' perioperative expression and type 2 neurological complications were analyzed. PD was associated with postoperative expression of GFAP; ePOCD was associated with postoperative expression of microRNA-21-5p and GFAP as well as intraoperative expression of NSP. The predictive accuracy of these molecules was found acceptable, with all their areas under the curve (AUC) values above 0.7. Multivariable regression indicated that microRNA-21-5p, GFAP and NSP were the only significant predictors of ePOCD. Evaluation of a multi-marker model including these three molecules revealed its outstanding predictive accuracy for ePOCD (AUC = 0.95). The use of microRNA-21-5p, GFAP and NSP for monitoring postoperative recovery warrants further research considering their potential to predict PD and ePOCD.

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial.

BACKGROUND: Neuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae. METHODS: In this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent "conventional" OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO2FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD). RESULTS: The incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO2FF arm, and 12.5% in the ANA arm (χ2 [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO2FF arm, and 9.5% in the ANA arm (χ2 [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001). CONCLUSIONS: Performing ANA significantly decreases the incidence of PD and ePOCD compared with "conventional" OPCAB with vein grafts, whereas CO2FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.

Novel Markers for Predicting Type 2 Neurologic Complications of Coronary Artery Bypass Grafting.

BACKGROUND: Type 2 neurologic complications of coronary artery bypass grafting (CABG) include postoperative cognitive dysfunction and delirium. Although relevant clinically, they are rarely properly recognized outside of dedicated research setting, as their identification is complex and time-consuming. The aim of this study was to examine the diagnostic potential of 4 novel brain-injury biomarkers for predicting these sequelae at the completion of off-pump CABG. METHODS: A total of 100 consecutive patients scheduled for elective isolated off-pump CABG were enrolled. Control group of patients without neurological complications (n = 48) was compared separately to study groups diagnosed with postoperative cognitive dysfunction (n = 39) and delirium (n = 26). Serum concentrations of glial fibrillary acidic protein, neuroserpin, phosphorylated axonal neurofilament subunit H, and visinin-like protein 1 were evaluated at baseline, end of surgery, as well as on postoperative day 1 and 7. RESULTS: Increased end of surgery to baseline ratio of neuroserpin predicted the occurrence of both postoperative cognitive dysfunction (area under the curve = 0.655, 95% confidence interval 0.54-0.77) and delirium (area under curve = 0.643, 95% confidence interval 0.52-0.77). Concentrations of neuroserpin were significantly higher on postoperative day 7 compared with end of surgery and postoperative day 1 in all groups. CONCLUSIONS: Among novel biochemical markers of brain damage, neuroserpin may be a promising predictor of type 2 neurological complications and may express neuroregeneration after off-pump CABG, whereas glial fibrillary acidic protein, phosphorylated axonal neurofilament subunit H, and visinin-like protein 1 may not be suitable for this clinical setting.

Three-vessel coronary artery disease may predict changes in biochemical brain injury markers after off-pump coronary artery bypass grafting.

Neurological injury is a frequent and important complication of coronary artery bypass grafting (CABG). Several risk factors for this type of sequela have been identified, among them aortic arch atherosclerosis. Our previous study indicated that atherosclerotic burden in coronary arteries may likewise predict postoperative neurological complications (Pawliszak et al., 2016b). We assessed the severity of this condition by using the SYNTAX score calculator. However, diagnosing angiographic three-vessel coronary artery disease (3VD) could be an even simpler method of achieving this goal.

Meta-analysis of uninterrupted as compared to interrupted oral anticoagulation with or without bridging in patients undergoing coronary angiography with or without percutaneous coronary intervention.

OBJECTIVES: To assess safety and effectiveness of different periprocedural antithrombotic strategies in patients receiving long-term oral anticoagulation and undergoing coronary angiography with or without percutaneous coronary intervention (PCI). METHODS: Studies comparing uninterrupted oral anticoagulation (UAC) with vit. K antagonists vs interrupted oral anticoagulation (IAC) with or without bridging anticoagulation before coronary procedures were eligible for inclusion in the current meta-analysis. Endpoints selected were 30-day composite of major adverse cardiovascular or cerebrovascular and thromboembolic events (MACCE) and major bleeding. RESULTS: Eight studies (7 observational and 1 randomized controlled trial [N=2325pts.]) were included in the analysis. There was no difference in MACCE between UAC and IAC; RR (95%CIs): 0.74 (0.34-1.64); p=0.46 but there was a statistically significant MACCE risk reduction with UAC as compared to IAC with bridging: 0.52 (0.29-0.95); p=0.03. Likewise, there were no statistically significant differences between UAC vs IAC in regard to major bleeding: 0.62 (0.16-2.43); p=0.49; but as compared to IAC with bridging, UAC was associated with statistically significant 65% lower risk of major bleeding: 0.35 (0.13-0.92); p=0.03. Additionally, meta-regression analysis revealed significant linear correlation between log RR of MACCE (ß=-4.617; p<0.001) and major bleeding (ß=6.665; p=0.022) and mean value of target INR suggestive of higher thrombotic and secondary haemorrhagic risk below estimated INR cut-off of 2.17-2.27 within 30days. CONCLUSIONS: Uninterrupted OAC is at least as safe as interrupted OAC, and seems to be much safer than interrupted OAC with bridging anticoagulation in patients undergoing coronary angiography with or without PCI.

Cerebrovascular Events After No-Touch Off-Pump Coronary Artery Bypass Grafting, Conventional Side-Clamp Off-Pump Coronary Artery Bypass, and Proximal Anastomotic Devices: A Meta-Analysis.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) has been shown to reduce the risk of neurologic complications as compared to coronary artery bypass grafting performed with cardiopulmonary bypass. Side-clamping of the aorta while constructing proximal anastomoses, however, still carries substantial risk of cerebral embolization. We aimed to perform a comprehensive meta-analysis of studies assessing 2 clampless techniques: aortic "no-touch" and proximal anastomosis devices (PAD) for OPCAB. METHODS AND RESULTS: PubMed, CINAHL, CENTRAL, and Google Scholar databases were screened for randomized controlled trials and observational studies comparing "no-touch" and/or PAD with side-clamp OPCAB and reporting short-term (≤30 days) outcomes: cerebrovascular accident and all-cause mortality. A total of 18 studies (3 randomized controlled trials) enrolling 25 163 patients were included. Aortic "no-touch" was associated with statistically lower risk of cerebrovascular accident as compared to side-clamp OPCAB: risk ratio 95% CI: 0.41 (0.27-0.61); P<0.01; I(2)=0%. Event rates were 0.36% and 1.28% for "no-touch" and side-clamp OPCAB, respectively. No difference was seen between PAD and side-clamp OPCAB: 0.71 (0.33-1.55); P=0.39; I(2)=39%. A trend towards increased 30-day all-cause mortality with PAD and no difference with "no-touch" were observed when compared to side-clamp OPCAB. In a subset analysis, "no-touch" consistently reduced the risk of cerebrovascular accident regardless of patients' baseline risk characteristics. A benefit with PAD was observed in low-risk patients. CONCLUSIONS: Aortic "no-touch" technique was associated with nearly 60% lower risk of postoperative cerebrovascular events as compared to conventional side-clamp OPCAB with effect consistent across patients at different risk.

Gentamicin-collagen sponge reduces the risk of sternal wound infections after heart surgery: Meta-analysis.

OBJECTIVES: Sternal wound infections are serious postoperative complications that increase the length of hospital stay and healthcare costs. The benefit of implantable gentamicin-collagen sponges in reducing sternal wound infections has been questioned in a recent multicenter trial. We aimed to perform a comprehensive meta-analysis of studies assessing the efficacy of implantable gentamicin-collagen sponges in sternal wound infection prevention. METHODS: Multiple databases were screened for studies assessing the efficacy of implantable gentamicin-collagen sponges after heart surgery. The primary end point was sternal wound infection, and secondary end points were the occurrence of deep sternal wound infection, superficial sternal wound infection, mediastinitis, and mortality. Randomized controlled trials and observational studies were analyzed separately. By means of meta-regression, we examined the correlation between sternal wound infection and extent to which the bilateral internal thoracic artery was harvested. RESULTS: A total of 14 studies (N = 22,135, among them 4 randomized controlled trials [N = 4672]) were included in the analysis. Implantable gentamicin-collagen sponges significantly reduced the risk of sternal wound infection by approximately 40% when compared with control (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.39-0.98; P = .04 for randomized controlled trials and RR, 0.61; 95% CI, 0.42-0.89; P = .01 for observational studies). A similar, significant benefit was demonstrated for deep sternal wound infection (RR, 0.60; 95% CI, 0.42-0.88; P = .008) and superficial sternal wound infection (RR, 0.60; 95% CI, 0.43-0.83; P = .002). The overall analysis revealed a reduced risk of mediastinitis (RR, 0.64; 95% CI, 0.45-0.91; P = .01). The risk of death was unchanged. A significant positive linear correlation (P = .05) was found between the log RR of sternal wound infection and the percentage of patients receiving bilateral internal thoracic artery grafts. CONCLUSIONS: Implantable gentamicin-collagen sponges significantly reduce the risk of sternal wound infection after cardiac surgery, with evidence consistent in randomized and observational-level data. However, the extent of this benefit might be attenuated in patients receiving bilateral internal thoracic artery grafts.

Short-term outcome of attention and executive functions from aorta no-touch and traditional off-pump coronary artery bypass surgery.

OBJECTIVES: Postoperative cognitive dysfunction (POCD) is an important neuropsychiatric complication of coronary artery bypass grafting (CABG). It is most likely caused by microembolic brain damage and affects domains of attention, memory, executive functions and dexterity. In order to achieve better neuroprotection, surgeons introduced some advantageous operating procedures. Noteworthy among them is a state-of-the-art off-pump CABG aorta no-touch technique ("no touch" OPCABG). The aim of this study was to investigate the short-term effect of "no touch" OPCABG on patients' attention and executive functions. METHODS: In this prospective, observational, single-surgeon trial, 74 patients scheduled for elective CABG were studied. Thirty-five patients underwent "no-touch" OPCABG and were compared to 39 patients who underwent "traditional" OPCABG. Subjects underwent neurological and neuropsychological evaluation at the time of admission (7 ± 2 days preoperatively) and discharge (7 days postoperatively). RESULTS: Patients who underwent "traditional" OPCABG showed a significant decline in postoperative performance on 4 neuropsychological tests, while patients treated with "no touch" OPCABG showed a significant decline on 1 test. Twenty patients from "traditional" OPCABG group and ten patients from "no touch" OPCABG group were diagnosed with POCD. CONCLUSIONS: Use of "no touch" OPCABG was associated with better attention and executive functions 1 week after surgery compared with "traditional" OPCABG.

[Cognitive dysfunction after cardiac surgery]. / Zaburzenia funkcjonowania poznawczego po zabiegach kardiochirurgicznych.

In spite of the progress in medicine post operative cognitive deficiency (POCD) remains an important clinical problem. Since the introduction of cardiac surgery there have been frequent reports of its adverse neurological outcomes. Recent technological advances have contributed to a lesser occurrence of clinically evident complications such as coma, stroke, epilepsy or blindness. This brought to attention a more common yet occult disorder--POCD. The above malady mostly concerns memory and executive functions. POCD has a negative impact on the quality of life and labor market attachment, however it's relation to mortality seems to be most disturbing. Prevalence of POCD is mainly associated with microembolisms, hipoperfusion and inflammatory reaction of the central nervous system following cardiac surgery. In addition many studies have shown the importance ofbiochemical disorders, cerebral oedema and the influence of comorbidities in the development of POCD. In the light of available evidence, there is no substantial difference between the cognitive outcomes of various types of cardiac surgery. Recent studies show that POCD in this clinical setting is mostly mild and transient. There are, however, patients who suffer from persisting POCD. Modern medicine has not developed standards for treatment of this complication. Setting up methods for prevention, detection and treatment of POCD should be the concern of both physicians and researchers in the following years.

Does Toxoplasma gondii infection affect cognitive function? A case control study.

According to studies, latent Toxoplasma gondii infection may affect several functions of the human brain. Here we search for the association between latent toxoplasmosis and cognitive performance. We tested 70 individuals for latent T. gondii infection. There were 26 Toxoplasma-infected subjects and 44 Toxoplasma-free subjects. Within these two groups we assessed cognitive performance using a set of standardized, widely recognized neuropsychological tests: Trail Making Test, Stroop Test, Verbal Fluency Test, Digit Span Test and N-back test. The relationship between chronic toxoplasmosis and cognitive performance was assessed, with adjustment for age and sex. Patients with latent toxoplasmosis performed worse on one neuropsychological test, N-back Test--percentage of correct answers (beta -8.08; 95% CI - 15.64 to -0.53; p < 0.05) compared to seronegative patients. However, after adjustment for age and sex, no statistically significant associations between latent toxoplasmosis and the scores on any cognitive tests were noticed. As statistically significant relationship was not observed, this study does not confirm that chronic latent T. gondii infection affects cognition.