Effects of conventional CPB and mini-CPB on neutrophils CD162, CD166 and CD195 expression.

OBJECTIVE: Cardiac surgery is known to trigger a systemic inflammatory response. While the use of conventional cardiopulmonary bypass (CPB) results in profound inflammation, modified mini-CPB is considered less harmful. We evaluated the impact of cardiac surgery on the expression of CD162, CD166, CD195 molecules and their association with the type of CPB used. METHODS AND RESULTS: Twenty-four patients were enrolled in our study. Twelve of them were operated using conventional CPB while the other twelve patients underwent surgery with mini-CPB. Blood samples were analysed by flow cytometry. We observed a significant increase in median fluorescence intensity of CD162 and CD195 that peaked instantly after surgery and normalized to the baseline value on the 1st day post surgery, whereas CD166 was initially down-regulated and its median fluorescence intensity (MFI) value increased to the baseline in the next few days. CONCLUSION: We observed immediate changes in the expression of CD162, CD166, and CD195 molecules on the neutrophils after surgery in both study groups of patients. The intensity of the observed changes was significantly greater in the group of patients who underwent conventional CPB compared to patients who underwent mini-CPB cardiac surgery.

Pentraxin 3 and other inflammatory biomarkers related to atrial fibrillation in cardiac surgery.

OBJECTIVES: The aim was to evaluate the association between perioperative inflammatory biomarkers and atrial fibrillation (AF) in cardiac surgical patients. METHODS: Forty-two patients undergoing cardiac surgery were divided into three groups according to the occurrence of AF: Group A (n = 22) - patients with no AF, Group B (n = 11) - patients with new onset AF postoperatively and Group C (n = 9) - patients with preoperative history of atrial fibrillation. The serum levels of PTX3, CRP, TLR2, IL-8, IL-18, sFas, MMP-7 and MMP-8 were measured at the following time points: before surgery, immediately and 6 h after surgery and on the 1st, 3rd and 7th postoperative days (POD). RESULTS: Serum levels of PTX3 showed a significant difference between Groups A and C on the 3rd POD (p<0.05) and on the 7th POD (p<0.0001). IL-8 levels were different between Groups A and C immediately after surgery (p<0.05), 6 hours after surgery (p<0.05) and on the 3rd POD (p<0.05). There was a difference between Groups B and C on the 1st POD in IL-8 levels (p<0.05). The sFas levels differed between Groups A and C on the 3rd POD (p<0.01) and the 7th POD (p<0.05). There was also a difference on the 7th POD (p<0.05) between the Groups B and C. No significant differences between the groups was seen for other biomarkers. CONCLUSION: This study demonstrates significantly different dynamics of PTX3, IL-8 and sFas levels after cardiac surgery in relation to AF.

Impact of cardiac surgery on the expression of CD40, CD80, CD86 and HLA-DR on B cells and monocytes.

OBJECTIVE: We measured and compared changes in the percentage of cells expressing CD80, CD86, CD40, HLA-DR and the expression of these molecules on B cells and monocytes of patients who underwent either on-pump, mini on-pump or off-pump cardiac surgery. METHODS: Blood samples from patients who underwent either on-pump, mini on-pump or off-pump cardiac surgery were collected before surgery, instantly after surgery and on the 1(st), 3(rd) and 7(th) days after surgery. Surface expression of CD80, CD86, CD40 and HLA-DR molecules was determined by flow cytometry. RESULTS: Our results show that all three surgical techniques altered the expression of these molecules, as well as the percentage relative number of specific cell populations. We identified statistically significant differences when comparing different surgical techniques. On-pump surgery revealed a more pronounced impact on the phenotype of immune system cells than the other techniques. Therefore, it is likely that the function of immune cells is changed the most by on-pump surgery. We found a lower decrease in the number of CD80(+) monocytes and a lower drop in the CD40 expression on monocytes in off-pump patients in comparison with on-pump patients. CONCLUSION: All the types of cardiac surgical techniques, off-pump, on-pump and modified mini-invasive on-pump, are associated with changes in CD80, CD86, CD40 and HLA-DR expression. We found several significant differences in the expression of the selected molecules when we compared all three groups of patients.

Could pentraxin 3 be a new diagnostic marker for excessive inflammatory response in cardiac surgery?

BACKGROUND: The aim of this study was to compare the dynamics of two inflammatory response biomarkers pentraxin 3 (PTX3) and C-reactive protein (CRP) after cardiac surgery with particular regard to different postoperative clinical manifestation of inflammatory response. PATIENTS AND METHODS: In this study, 42 patients undergoing open heart surgery with the use of cardiopulmonary bypass were included and divided in two groups according to the extent of clinical manifestation of inflammatory response: Group A (n=21)-patients with different severity of systemic inflammatory response syndrome (SIRS) and Group B (n=21)-patients with uneventful postoperative period (no SIRS). The serum levels of PTX3 and CRP were evaluated and compared at the following time points: before and at the end of surgery, 6 hours, 1st, 3rd, and 7th day after surgery. RESULTS: The dynamics of CRP levels were comparable between both groups and showed the classical characteristics after cardiac surgery with a peak on the 3rd postoperative day (113 vs. 132 mg/L). In contrast, the dynamics of PTX3 showed an earlier increase of serum levels with the peak on the 1st postoperative day in both groups (36.3 vs. 42.7 ng/mL). Importantly, a significant difference of PTX3 levels was found on the 3rd postoperative day (31.1 vs. 7.0 ng/mL; p<0.006) between the two groups showing significantly delayed decrease of PTX3 levels in patients with SIRS (Group A). CONCLUSION: This study demonstrates considerably different dynamics of PTX3 levels after cardiac surgery in patients with SIRS and patients without SIRS, thus it may be indicative to start the appropriate therapy.

Isolated thoracic aortitis.

Isolated thoracic aortitis is a new pathological entity. We review the histopathological features of this disease, the role of imaging, and diagnostic modalities necessary to make the diagnosis of aortitis and discuss the management of patients with an established diagnosis of isolated thoracic aortitis.

Broncho-pleural fistula following vacuum-assisted closure therapy.

We report a case of bronchopleural-cutaneous fistula following long-term vacuum-assisted closure therapy to manage a sternal dehiscence after coronary artery bypass surgery.

TLR2 in pleural fluid is modulated by talc particles during pleurodesis.

The aim of this study was to examine the role of TLR2 molecule in pleural space during thoracoscopic talc pleurodesis period in patients with malignant pleural effusion. We analyzed TLR2 molecule in soluble form as well as on membrane of granulocytes in pleural fluid. Pleural fluid examination was done at three intervals during pleurodesis procedure: 1st-before the thoracoscopic procedure, 2nd-2 hours after the terminating thoracoscopic procedure with talc insufflation, 3rd-24 hours after the thoracoscopic procedure. We reported significant increase of soluble TLR2 molecule in pleural fluid effusion during talc pleurodesis from preoperative value. This increase was approximately 8-fold in the interval of 24 hours. The changes on granulocyte population were quite different. The mean fluorescent intensity of membrane TLR2 molecule examined by flow cytometry on granulocyte population significantly decreased after talc exposure with comparison to prethoracoscopic density. To estimate the prognostic value of TLR2 expression in pleural fluid patients were retrospectively classified into either prognostically favourable or unfavourable groups. Our results proved that patients with favourable prognosis had more than 3-fold higher soluble TLR2 level in pleural fluid early, 2 hours after talc pleurodesis intervention.

The effect of conventional and mini-invasive cardiopulmonary bypass on neutrophil activation in patients undergoing coronary artery bypass grafting.

Interleukin-10 (IL-10) is considered to be a cytokine with potent anti-inflammatory properties, which have been previously linked to increased incidence of sepsis. The level of IL-10 is elevated by cardiac surgery when cardiopulmonary bypass (CPB) and methylprednisolone are used. In our study, we compare the level of IL-10, IL-10 Receptor (IL-10R), and percentage of neutrophils between two groups of cardiac surgical patients undergoing Coronary Artery Bypass Grafting, both of which were not given methylprednisolone. The first group was operated with conventional CPB, while the second group was operated with minimally invasive CPB (mini-CPB). We detected enhanced level of IL-10 during surgery and at the end of surgery in both groups of patients. While no correlation between IL-10 and IL10R was found, IL-10 was positively correlated with increased percentage of neutrophils at the time points when the level of IL-10 peaked.

Surgical treatment of primary cardiac tumors: 20-year single center experience.

Introduction: Primary cardiac tumors are a rare condition presenting with a variety of symptoms. The outcomes of their surgical treatment in the modern era from central Europe have not been recently reported. Aim: To evaluate the short- and long-term outcomes of the cardiac tumor operations at our department throughout the last 20 years. Material and methods: This was a retrospective analysis of all primary cardiac tumor operations performed at our institution between 2000 and 2020. Perioperative data were extracted from patient records. Long-term data were provided by the National Registry of Cardiac Surgery. Results: Sixty procedures for primary cardiac tumor were performed throughout the study period. The most common type of tumor was myxoma (88%), followed by fibroelastoma (8%), lipoma (2%) and sarcoma (2%). There were 2 perioperative deaths (3%). The most common perioperative complication was atrial fibrillation (47%). One (2%) patient underwent reoperation 6 years later because of myxoma recurrence. We recorded 13 long-term deaths, but only 1 patient died as a consequence of cardiac tumor (sarcoma) 15 months after the surgery. Long-term survival of the cohort was comparable with the age- and sex-matched general population up to 15 years postoperatively (relative survival 0.91, CI 0.68-1.23). Rich histopathological illustrations are provided in the online supplementary material. Conclusions: Surgical resection is the standard treatment of primary cardiac tumors. The outcomes of benign tumors are excellent and the long-term postoperative survival is comparable with the general population. The prognosis of malignant tumors remains poor.

Expression of urokinase plasminogen activator receptor on monocytes and granulocytes is modulated by cardiac surgery.

AIMS: Coronary artery bypass grafting (CABG) is linked to the induction of the blood coagulation/fibrinolysis cascade, which is an integral component of inflammation induced by cardiac surgery. We followed the modulation of urokinase plasminogen activator receptor uPAR (CD87) separately for monocytes and granulocytes in blood of cardiac surgery patients. METHODS: Expression of uPAR, analyzed as Median Fluorescence Intensity (MFI), on blood monocytes and granulocytes was determined by flow cytometry. Changes in uPAR expression in patients undergoing CABG using standard cardiopulmonary bypass ("on-pump") were compared to the changes in uPAR expression in patients undergoing CABG using mini-invasive cardiopulmonary bypass ("mini on-pump"). RESULTS: In "on-pump" patients, the median of uPAR expression on granulocytes before surgery was 18.1 (InterQuartile Range (IQR): 15.6-20.4). uPAR expression was significantly decreased after surgery (p<0.001), on the first postoperative day (p<0.001), and on the third postoperative day (p<0.05). In "mini on-pump" patients, the median of uPAR expression on granulocytes before surgery was 15.2 (IRQ: 13.8-19.4). The significantly decreased uPAR expression was found only at the end of surgery (p<0.05). The similar pattern of uPAR expression was also found for monocytes. The preoperative level in "on-pump" patients was 23.3 (IRQ: 18.9-30.2). There was significantly decreased uPAR expression at the end of surgery (p<0.01) and at the first postoperative day (p<0.05). In "mini on-pump" patients, the preoperative uPAR expression was 16.9 (IQR: 14.5-20.2). Expression of uPAR was significantly decreased only after surgery (p<0.05). When comparing "onpump" patients to "mini on-pump" patients, no significant differences in the expression of uPAR were found. CONCLUSION: uPAR expression on granulocytes and monocytes is significantly modulated by cardiac surgery.

Solitary metastasis of clear cell renal cell carcinoma in sternum diagnosed unexpectedly during cardiac surgery - A rare but potentially fatal trap.

We present a very rare case of fatal complication during the cardiac surgery caused by unrecognized solitary metastasis of clear cell renal cell carcinoma in the sternum.

Lung Collapse during Mini-Thoracotomy Reduces Penetration of Cefuroxime to the Tissue: Interstitial Microdialysis Study in Animal Models.

Background: Single-lung ventilation facilitates surgical exposure during minimally invasive cardiac surgery. However, a deeper knowledge of antibiotic distribution within a collapsed lung is necessary for effective antibiotic prophylaxis of pneumonia. Patients and Methods: The pharmacokinetics/pharmacodynamics (PK/PD) of cefuroxime were compared between the plasma and interstitial fluid (ISF) of collapsed and ventilated lungs in 10 anesthetized pigs, which were ventilated through a double-lumen endotracheal cannula. Cefuroxime (20 mg/kg) was administered in single 30-minute intravenous infusion. Samples of blood and lung microdialysate were collected until six hours post-dose. Ultrafiltration, in vivo retrodialysis, and high-performance liquid chromatography-tandem mass spectrometry were used to determine plasma and ISF concentrations of free drug. The concentrations were examined with non-compartmental analysis and compartmental modeling. Results: The concentration of free cefuroxime in ISF was lower in the non-ventilated lung than the ventilated one, evidenced by a lung penetration factor of 47% versus 63% (p < 0.05), the ratio between maximum concentrations (65%, p < 0.05), and the ratio between the areas under the concentration-time curve (78%, p = 0.12). The time needed to reach a minimum inhibitory concentration (MIC) was 30%-40% longer for a collapsed lung than for a ventilated one. In addition, a delay of 10-40 minutes was observed for lung ISF compared with plasma. The mean residence time values (ISF collapsed lung > ISF ventilated lung > plasma) could explain the absence of practically important differences in the time interval with the concentration of cefuroxime exceeding the MICs of sensitive strains (≤4 mg/L). Conclusion: The concentration of cefuroxime in the ISF of a collapsed porcine lung is lower than in a ventilated one; furthermore, its equilibration with plasma is delayed. Administration of the first cefuroxime dose earlier or at a higher rate may be warranted, as well as dose intensification of the perioperative prophylaxis of pneumonia caused by pathogens with higher MICs.

Up-regulation of the Apo/Fas (CD95) complex on neutrophils harvested during cardiac surgery: distinct findings in patients operated on with or without the use of cardiopulmonary bypass.

AIMS: In a group of patients undergoing cardiac surgery performed both with ("on-pump") and without the use ("offpump") of cardiopulmonary bypass (CPB), we studied the changes of neutrophil membrane apoptosis-inducing complex Apo/Fas. METHODS: Expression of Apo/Fas (CD95) on leukocytes was evaluated by flow cytometry. RESULTS: In "on-pump" patients, we found an increase in the expression of CD95 median intensity fluorescence (MFI) on granulocytes from a baseline level median=56, (Q( 1)=45.5, Q(3)=64) to a median=88, (Q(1)=62, Q( 3)=109.5; p<0.01) at the 3(rd) postoperative day and median=74, (Q(1)=63, Q(3)=84.5; p<0.01) at the 7(th) postoperative day. In "off-pump" patients, granulocyte CD95 MFI was median=55, (Q(1)=51, Q(3)=84) before surgery. The significant increase was found on the 3(rd) postoperative day only; median=90, (Q( 1)=66; Q(3)=98; p<0.05). A similar pattern in the CD95 expression was also found if percentage changes of granulocyte CD95 MFI were followed. Moreover, the significantly increased Apo/Fas expression expressed as a percentage change of CD95 MFI was found in "on-pump" patients compared to "off-pump" patients, both at the 3(rd) postoperative day (p<0.05) and at the 7(th) postoperative day (p<0.01). CONCLUSIONS: This is the first direct evidence of increasing densities of the Apo/Fas complex on neutrophils in cardiac surgical patients.

Expression of CD200/CD200R regulatory molecules on granulocytes and monocytes is modulated by cardiac surgical operation.

AIMS: Cardiac surgical operation is inseparably linked to the induction of an inflammatory response. Both humoral and cellular regulatory mechanisms are operating to maintain body homeostasis. We followed the changes in the expression of CD200/CD200R regulatory molecules on monocytes and granulocyte of cardiac surgical patients operated on using either standard (OP) or modified "mini-invasive" cardiopulmonary bypass (MOP). METHODS: Expression of CD200/CD200R regulatory molecules was determined by flow cytometry. RESULTS: The expression of CD200R on granulocytes was increased after surgery in both groups of patients, but the increase was statistically significant only in OP patients (p<0.01). At this time point, there was a significant difference in CD200R expression on granulocytes when comparing OP to MOP patients, being higher in the former group (p<0.01). The expression of CD200R on monocytes was diminished after surgery and during an early postoperative period in both groups of patients. The expression of CD200 on monocytes was significantly diminished after surgery in both groups (p<0.01). Nonetheless, we observed an increase in CD200 expression in OP patients at the 3rd postoperative day. There was a statistically significantly increased CD200 expression on monocytes of OP patients (p<0.001) at the 3rd postoperative day when we compared OP and MOP groups. The expression of CD200 on granulocytes was significantly higher after surgery and at the 3rd postoperative day in OP when compared to MOP patients. CONCLUSIONS: CD200R expression on granulocytes was significantly increased, while CD200 and CD200R expression on monocytes was decreased after cardiac surgery.

No clear clinical benefit of using mini-invasive extracorporeal circulation in coronary artery bypass grafting in low-risk patients.

BACKGROUND: Current research is engaged in innovative technologies of extracorporeal circulation (ECC) systems in an effort to eliminate negative effects. Some studies have shown that, due to the complexity of technical settings of mini-ECC, they invoke a weaker immune response compared to classic ECC. The clinical benefits of using these systems have not been clearly proven yet. METHODS: A group of 54 patients who were indicated for elective coronary surgery were randomised into two groups - Group A (patients operated on using classic ECC - open modification) and Group B (patients operated on using mini-ECC). The concentrations of IL-6, PMN elastase and MCP-1 in both groups were monitored per- and postoperatively, along with the postoperative clinical course. RESULTS: The groups did not differ in the basic pre- and peroperative characteristics. We recorded a lower priming for mini-ECC (p < 0.001) and significantly reduced hemodilution during ECC. There were no differences in the clinical outcome in either group. Serum concentrations of monitored markers of immune reaction towards ECC showed higher activity during standard ECC. CONCLUSION: New technologies used in mini-systems have proven to lower activation of the immune system, which can be monitored using kinetics of proinflammatory mediators. In spite of these comparable laboratory results, we did not find differences in short-term clinical results when comparing both these groups of low-risk patients.

Serum level of sCD163, a soluble receptor for hemoglobin, is influenced by cardiac surgery.

BACKGROUND: The scavenger receptor for complexes hemoglobin-haptoglobin (CD163), which is expressed on monocytes/ macrophages, is shed to the body fluids in a soluble form (sCD163). OBJECTIVES: To evaluate the dynamics of sCD163 in the blood of patients undergoing cardiac surgery. PATIENTS AND METHODS: Sixty-one adult patients who underwent coronary artery bypass grafting (CABG) were enrolled in the study. They were assigned to undergo CABG using either cardiopulmonary bypass (CPB), "on-pump", (22 patients), modified CPB, mini "on-pump", (17 patients) or without CPB, "off-pump", (22 patients) surgery. Serum levels of sCD163 in venous blood samples taken before and after surgery, and during an early postoperative period, were evaluated by Macro 163(TM) diagnostic kit (IQ Products, Groningen, NL). RESULTS: Compared to the preoperative levels ("on-pump"; 344 ng/mL, "off-pump"; 314.5 ng/mL, mini-invasive "on-pump"; 336.5 ng/mL) serum levels were elevated at the finish of surgery, reaching maximum at the 1(st) postoperative day ("onpump"; 658 ng/mL; p<0.05, "off-pump"; 810.5 ng/mL; p<0.01; mini-invasive "on-pump"; 663 ng/mL; non-significant).No significant differences regarding the serum levels of sCD163 between different surgical approaches were found. CONCLUSION: Serum level of sCD163 scavenger molecule for hemoglobin is elevated at the end of surgery and at the 1(st) postoperative day, being little influenced by cardiopulmonary bypass.

RANK/RANKL expression is induced by cardiac surgical operation.

BACKGROUND: Cardiac surgery provokes a systemic inflammatory response in any patient. This complex body reaction involves also RANK/RANKL molecules which have been recently identified as principal regulators of bone metabolism. AIMS: To follow the changes in the expression of RANK/RANKL molecules on innate immune cells of cardiac surgical patients. PATIENTS AND METHODS: Twenty-six patients undergoing cardiac surgical were assigned to undergo coronary artery bypass grafting using either cardiopulmonary bypass ("on-pump") or modified "miniinvasive on-pump". The expression of RANK/RANKL was performed by flow cytometry. RESULTS: Significantly increased expression of RANK on monocytes of "miniinvasive on-pump" patients was found at the 1st, the 3nd, and 7th postoperative days. The similar pattern was found also for monocyte RANKL expression. In addition, RANKL expression was significantly increased at the 3rd postoperative day in "on-pump" patient. No significant differences between "miniinvasive on-pump" and "on-pump" cardiac surgical patients were found. CONCLUSION: The expression of both RANK and RANKL molecules is significantly enhanced on monocytes of "miniinvasive on-pump" cardiac surgical patients.

Expression of Toll-like receptors 2 and 4 on innate immunity cells modulated by cardiac surgical operation.

OBJECTIVE: This study aimed to follow-up on the changes in the expression of Toll-like receptors (TLRs) on monocytes and granulocytes in venous blood of patients undergoing cardiac surgical operation. MATERIAL AND METHODS: TLR2 and TLR4 expression on blood cells was determined by flow cytometry in 40 patients undergoing cardiac surgery performed either with cardiopulmonary bypass (CPB) ("on-pump") or without it ("off-pump"). RESULTS: Intensity of the expression of TLR2 on both monocytes and granulocytes, expressed as median fluorescence intensity, is significantly reduced during CPB, being lower in both groups at the finish of surgery. These changes are not so remarkable in the case of TLR4 expression. Compared to "on-pump" patients, there is a higher relative number of TLR2(+) granulocytes in "off-pump" patients at the finish of surgery and of TLR4(+) granulocytes on the first postoperative day. CONCLUSIONS: We found characteristic patterns in the expression of TLR2 and TLR4 on monocytes and granulocytes in venous blood of patients undergoing cardiac surgery with or without CPB.

Early expression of FcgammaRI (CD64) on monocytes of cardiac surgical patients and higher density of monocyte anti-inflammatory scavenger CD163 receptor in "on-pump" patients.

OBJECTIVE: Activation of innate immunity cells is inseparably linked to cardiac surgical operation. The aim of this study was to assess the kinetics in the expression of receptor for Fc part of IgG, FcgammaRI (CD64), and scavenger receptor CD163 on peripheral blood cells of cardiac surgical patients and to examine the effect of cardiac bypass as a separable influence on the systemic acute inflammatory response. METHODS: Forty patients, twenty in each group, were randomly assigned to CABG surgery performed either with "on-pump" or without "off-pump" cardiopulmonary bypass. Standardized quantitative flow cytometry method was used to determine the expression of surface markers. RESULTS: The density of CD64 molecule on monocytes reached maximum on the 1st postoperative day (P<.001) whereas the peak for CD64 molecule expression on granulocytes was postponed to the 3rd postoperative day (P<.001). The expression of CD163 scavenger molecule on monocytes reached maximum on the 1st postoperative day (P<.001). The density of CD163 molecule on monocytes on the 1st postoperative day is significantly higher in "on-pump" patients in comparison with "off-pump" patients (P<.001). CONCLUSION: In cardiac surgical patients the expression of activation marker FcgammaR1 (CD64) on monocytes is increased earlier in comparison with granulocytes in both "on-pump" and "off-pump" patients. The expression of scavenger molecule CD163 on monocytes is significantly higher in "on-pump" patients.

Lipopolysaccharide binding protein and sCD14 are not produced as acute phase proteins in cardiac surgery.

OBJECTIVES: The changes in the serum levels of lipopolysaccharide binding protein (LBP) and sCD14 during cardiac surgery were followed in this study. DESIGN: Thirty-four patients, 17 in each group, were randomly assigned to coronary artery bypass grafting surgery performed either with ("on-pump") or without ("off-pump") cardiopulmonary bypass. LBP and sCD14 were evaluated by ELISA. RESULTS: The serum levels of LBP were gradually increased from the 1st postoperative day and reached their maximum on the 3rd postoperative day in both "on-pump" and "off-pump" patients (30.33+/-9.96 microg/mL; 37.99+/-16.58 microg/mL), respectively. There were no significant differences between "on-pump" and "off-pump" patients regarding LBP. The significantly increased levels of sCD14 from the 1st up to the 7th postoperative day in both "on-pump" and "off-pump" patients were found with no significant differences between these groups. No correlations between LBP and sCD14 and IL-6, CRP and long pentraxin PTX3 levels were found. CONCLUSIONS: The levels of LBP and sCD14 are elevated in cardiac surgical patients being similar in both groups. These molecules are not produced as acute phase proteins in these patients.