Quantification of Aortic Valve Fibrotic and Calcific Tissue from CTA: Prospective Comparison with Histology.

Background Quantifying the fibrotic and calcific composition of the aortic valve at CT angiography (CTA) can be useful for assessing disease severity and outcomes of patients with aortic stenosis (AS); however, it has not yet been validated against quantitative histologic findings. Purpose To compare quantification of aortic valve fibrotic and calcific tissue composition at CTA versus histologic examination. Materials and Methods This prospective study included patients who underwent CTA before either surgical aortic valve replacement for AS or orthotopic heart transplant (controls) at two centers between January 2022 and April 2023. At CTA, fibrotic and calcific tissue composition were quantified using automated Gaussian mixture modeling applied to the density of aortic valve tissue components, calculated as [(volume/total tissue volume) × 100]. For histologic evaluation, explanted valve cusps were stained with Movat pentachrome as well as hematoxylin and eosin. For each cusp, three 5-µm slices were obtained. Fibrotic and calcific tissue composition were quantified using a validated artificial intelligence tool and averaged across the aortic valve. Correlations were assessed using the Spearman rank correlation coefficient. Intermodality and interobserver variability were measured using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results Twenty-nine participants (mean age, 63 years ± 10 [SD]; 23 male) were evaluated: 19 with severe AS, five with moderate AS, and five controls. Fibrocalcific tissue composition strongly correlated with histologic findings (r = 0.92; P < .001). The agreement between CTA and histologic findings for fibrocalcific tissue quantification was excellent (ICC, 0.94; P = .001), with underestimation of fibrotic composition at CTA (bias, -4.9%; 95% limits of agreement [LoA]: -18.5%, 8.7%). Finally, there was excellent interobserver repeatability for fibrotic (ICC, 0.99) and calcific (ICC, 0.99) aortic valve tissue volume measurements, with no evidence of a difference in measurements between readers (bias, -0.04 cm3 [95% LoA: -0.27 cm3, 0.19 cm3] and 0.02 cm3 [95% LoA: -0.14 cm3, 0.19 cm3], respectively). Conclusion In a direct comparison, standardized quantitative aortic valve tissue characterization at CTA showed excellent concordance with histologic findings and demonstrated interobserver reproducibility. Clinical trial registration no. NCT06136689 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almeida in this issue.

Assessment of COVID-19 risk factors of early and long-term mortality with prediction models of clinical and laboratory variables.

BACKGROUND: Coronavirus disease (COVID-19) may lead to serious complications and increased mortality. The outcomes of patients who survive the early disease period are burdened with persistent long-term symptoms and increased long-term morbidity and mortality. The aim of our study was to determine which baseline parameters may provide the best prediction of early and long-term outcomes. METHODS: The study group comprised 141 patients hospitalized for COVID-19. Demographic data, clinical data and laboratory parameters were collected. The main study endpoints were defined as in-hospital mortality and 1-year mortality. The associations between the baseline data and the study endpoints were evaluated. Prediction models were created. RESULTS: The in-hospital mortality rate was 20.5% (n = 29). Compared with survivors, nonsurvivors were significantly older (p = 0.001) and presented comorbidities, including diabetes (0.027) and atrial fibrillation (p = 0.006). Assessment of baseline laboratory markers and time to early death revealed negative correlations between time to early death and higher IL-6 levels (p = 0.032; Spearman rho - 0.398) and lower lymphocyte counts (p = 0.018; Pearson r -0.438). The one-year mortality rate was 35.5% (n = 50). The 1-year nonsurvivor subgroup was older (p < 0.001) and had more patients with arterial hypertension (p = 0.009), diabetes (p = 0.023), atrial fibrillation (p = 0.046) and active malignancy (p = 0.024) than did the survivor subgroup. The model composed of diabetes and atrial fibrillation and IL-6 with lymphocyte count revealed the highest value for 1-year mortality risk prediction. CONCLUSIONS: Diabetes and atrial fibrillation, as clinical factors, and LDH, IL-6 and lymphocyte count, as laboratory determinants, are the best predictors of COVID-19 mortality risk.

Coronary Artery Bypass Surgery: Comparing the Long-Term Impact of Total Arterial Grafting With Multiarterial Plus Saphenous Vein Grafting.

INTRODUCTION: This study aimed to compare the long-term outcomes in a propensity matched population receiving total arterial grafting (TAG) and multiple arterial grafts (MAG) in addition to saphenous vein graft (SVG) following multivessel coronary artery bypass grafting requiring at least three distal anastomoses. METHODS: In this retrospective study, 655 patients from two centers met the inclusion criteria and were divided into two groups: TAG group (n = 231) and MAG + SVG group (n = 424). Propensity score matching was performed resulting in 231 pairs. RESULTS: No significant differences were observed between both groups in terms of early outcomes. Survival probabilities at 5, 10, and 15 y were 89.1% versus 94.2%, 76.2% versus 76.1%, and 66.7% versus 69.8% in the TAG and MAG + SVG groups, respectively (hazard ratio stratified on matched pairs: 0.90; 95% confidence interval [0.45-1.77]; P = 0.754). Freedom from major adverse cardiac and cerebral events (MACCE) in the matched cohort did not show any significant difference between both groups. Probabilities at 5, 10, and 15 y were 82.7% versus 85.6%, 62.2% versus 75.3%, and 48.8% versus 59.5% in the TAG and MAG + SVG groups, respectively (hazard ratio stratified on matched pairs: 1.12; 95% confidence interval [0.65-1.92]; P = 0.679). Subgroup analyses of the matched cohort showed no significant difference between TAR with three arterial conduits compared to TAR with two arterial conduits with sequential grafting and MAG + SVG in terms of long-term survival and freedom from MACCE. CONCLUSIONS: Multiple arterial revascularizations in addition to SVG may yield comparable long-term outcomes in terms of survival and freedom from MACCE compared to total arterial revascularization.

Impact of Second Arterial Conduit on Outcomes Following Coronary Bypass Grafting.

BACKGROUND: The aim of this study was to compare short-term outcomes and long-term survival in patients following coronary artery bypass grafting in whom second arterial conduit or saphenous vein was used as well as to find out the most optimal second arterial graft. METHODS: Between January 2006 and June 2018, 7,857 patients met the inclusion criteria and were divided into two groups: single internal thoracic artery (SITA) + Vein group (n = 7,140) and second arterial conduit group (n = 717), of these 537 patients received right internal thoracic artery (RITA) and 180 patients received radial artery (RA). We obtained 701 propensity-matched pairs for final comparison. Short-term outcomes included: 30-day mortality and major adverse cardiac and cerebral events (MACCE), reoperation for bleeding, and deep sternal wound infection (DSWI). The long-term outcome was all-cause mortality. RESULTS: No significant differences were observed between second arterial conduit versus SITA + Vein groups and between RITA versus RA groups in terms of 30-day mortality, 30-day MACCE, reoperation for bleeding, and incidence of DSWI in the matched cohort. The use of second arterial conduit was associated with a significant reduction in long-term mortality by 24% in the matched cohort (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.60-0.96; p = 0.02). RA and RITA as second arterial conduit had comparable long-term mortality (HR: 1.12; 95% CI: 0.69-1.82; p = 0.62). CONCLUSION: The use of second arterial conduit, irrespective of type, is safe and associated with improved long-term survival compared with the second venous aortocoronary graft.

Extended cardiopulmonary resuscitation: from high fidelity simulation scenario to the first clinical applications in Poznan out-of-hospital cardiac arrest program.

BACKGROUND: The outcomes of out-of-hospital cardiac arrest (OHCA) patients are poor. In some OHCA cases, the reason is potentially reversible cardiac or aortic disease. It was suggested previously that high-quality cardiopulmonary resuscitation (CPR) followed by extracorporeal membrane oxygenation (ECMO) support may improve the grave prognosis of OHCA. However, extended CPR (ECPR) with ECMO application is an extremely invasive and cutting-edge procedure. The purpose of this article is to describe how high-fidelity medical simulation as a safe tool enabled implementation of the complex, multi-stage ECPR procedure. METHOD: A high fidelity simulation of OHCA in street conditions was prepared and carried out as part of a ECPR procedure implemented in an in-hospital area. The simulation tested communication and collaboration of several medical teams from the pre-hospital to in-hospital phases along with optimal use of equipment in management of a sudden cardiac arrest (SCA) patient. RESULTS: The critical and weak points of an earlier created scenario were collected into a simulation scenario checklist of ECPR algorithm architecture. A few days later, two ECPR procedures followed by cardiologic interventions for OHCA patients (one pulmonary artery embolectomy for acute pulmonary thrombosis and one percutaneous coronary artery angioplasty with drug eluting stent implantation for acute occlusion of the left anterior descending artery), were performed for the first time in Poland. The protocol was activated five times in the first 2 months of the POHCA Program. CONCLUSION: High fidelity medical simulation in real-life conditions was confirmed to be a safe, useful tool to test and then implement the novel and complex medical procedures. It enabled to find, analyze and solve the weakest points of the earlier developed theoretical protocol and eventually succeed in clinical application of complete ECPR procedure.

Proteomic Profiling of Leukocytes Reveals Dysregulation of Adhesion and Integrin Proteins in Chronic Kidney Disease-Related Atherosclerosis.

A progressive loss of functional nephrons defines chronic kidney disease (CKD). Complications related to cardiovascular disease (CVD) are the principal causes of mortality in CKD; however, the acceleration of CVD in CKD remains unresolved. Our study used a complementary proteomic approach to assess mild and advanced CKD patients with different atherosclerosis stages and two groups of patients with different classical CVD progression but without renal dysfunction. We utilized a label-free approach based on LC-MS/MS and functional bioinformatic analyses to profile CKD and CVD leukocyte proteins. We revealed dysregulation of proteins involved in different phases of leukocytes' diapedesis process that is very pronounced in CKD's advanced stage. We also showed an upregulation of apoptosis-related proteins in CKD as compared to CVD. The differential abundance of selected proteins was validated by multiple reaction monitoring, ELISA, Western blotting, and at the mRNA level by ddPCR. An increased rate of apoptosis was then functionally confirmed on the cellular level. Hence, we suggest that the disturbances in leukocyte extravasation proteins may alter cell integrity and trigger cell death, as demonstrated by flow cytometry and microscopy analyses. Our proteomics data set has been deposited to the ProteomeXchange Consortium via the PRIDE repository with the data set identifier PXD018596.

Exceptional life-threatening complication 19 years after Ravitch correction of pectus excavatum.

BACKGROUND: Ravitch technique of chest correction has been considered, although invasive, as a safe and efficacious surgical method. CASE: We describe a case of a 35-year-old woman with cardiac tamponade and in cardiogenic shock due to exceptional late complication after pectus excavatum reconstruction by means of classic Ravitch technique 19 years earlier. This very late adverse event was caused by a broken metal sternal wire that injured the wall of the ascending aorta. The patient underwent salvage repair of this segment of the aorta in cardiopulmonary bypass. Postoperative course and postdischarge 3-year follow-up have been uneventful. CONCLUSION: Therefore, life-threatening cardiovascular complications may occur even many years after reconstructive surgery for chest deformity.

Expression Profile of Genes Encoding Proteins Involved in Regulation of Vasculature Development and Heart Muscle Morphogenesis-A Transcriptomic Approach Based on a Porcine Model.

Despite significant advances in treatment of acute coronary syndromes (ACS) many subjects still develop heart failure due to significantly reduced ejection fraction. Currently, there are no commonly available treatment strategies that replace the infarcted/dysfunctional myocardium. Therefore, understanding the mechanisms that control the regeneration of the heart muscle is important. The development of new coronary vessels plays a pivotal role in cardiac regeneration. Employing microarray expression assays and RT-qPCR validation expression pattern of genes in long-term primary cultured cells isolated form the right atrial appendage (RAA) and right atrium (RA) was evaluated. After using DAVID software, it indicated the analysis expression profiles of genes involved in ontological groups such as: "angiogenesis", "blood vessel morphogenesis", "circulatory system development", "regulation of vasculature development", and "vasculature development" associated with the process of creation new blood vessels. The performed transcriptomic comparative analysis between two different compartments of the heart muscle allowed us to indicate the presence of differences in the expression of key transcripts depending on the cell source. Increases in culture intervals significantly increased expression of SFRP2, PRRX1 genes and some other genes involved in inflammatory process, such as: CCL2, IL6, and ROBO1. Moreover, the right atrial appendage gene encoding lysyl oxidase (LOX) showed much higher expression compared to the pre-cultivation state.

Managing patients on extracorporeal membrane oxygenation support during the COVID-19 pandemic - a proposal for a nursing standard operating procedure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is effective in a selected critically ill patient population with promising results in refractory hypoxemia related to the novel coronavirus disease (COVID-19). However, it requires specialized clinicians and resources in advanced technology. Moreover, the COVID-19 remains an ongoing global emergency, and there is no evidence-based practice in preparedness. This article proposes an innovative and optimized nursing care protocol, the Standard Operating Procedure (SOP), that regulates safety and efficiency in using personal protective equipment (PPE) during ECMO-relevant procedures while providing ECMO therapy for patients with COVID-19. METHODS: After performing a narrative literature search, we developed a high-fidelity translational simulation scenario. It included practicing appropriate donning and doffing PPE during work organization, ECMO-related procedures, and routine daily nursing care and management of ECMO over nine hours. In addition, we held supplementary constructive debrief meetings to consult international expert in the field. RESULTS: A proposal for nursing standardized operating procedures was created, divided into categories. They included work organization, workload references, competences, infrastructural conditions, cannulation equipment, daily routine nursing care, and procedures during ECMO. CONCLUSIONS: High-fidelity medical simulation can play an important role in staff training, improvement in previously gained proficiency, and development of optimal SOP for nursing care and management during ECMO in patients with COVID-19. Optimal SOPs may further guide multidisciplinary teams, including intensive care units and interventional departments.

Cardioprotective Effect of Low Level of LDL Cholesterol on Perioperative Myocardial Injury in Off-Pump Coronary Artery Bypass Grafting.

Background and Objectives: Coronary artery disease is still a major cause of death in developed countries. Low-density lipoprotein cholesterol (LDL-C) lowering with statin therapy is a key strategy in major acute coronary events' prevention. The aim of the study was to establish if there is a cardioprotective effect of pre-operative LDL lowering therapy on perioperative myocaridal injury in patients undergoing off-pump coronary artery bypass grafting (CABG). Moreover, the impact of pre-operative LDL level on long term outcome was analysed. Materials and Methods: The retrospective single center analysis included 662 consecutive patients (431 (65%) males and 231 (35%) female, mean age of 65 ± 8) referred for cardiac surgery due to stable chronic coronary syndrome between 2012-2018. The follow up was 9 years. Results: A statistically significant difference was found in postoperative serum Troponin-I for LDL thresholds of 1.8 mmol/L (p = 0.009), 2.6 mmol/L (p = 0.03) and 3.0 mmol/L (p = 0.001). The results indicate that cardioprotective role of LDL is achieved within LDL concentration rate below 1.8 mmol/L (<70 mg/dL). Five patients died perioperatively, whereas 1-year and 9-year overall mortality rates were 4% (n = 28) and 18.6% (n = 123), respectively. Comparing the survival group with diseased, Mann-Whitney U test showed a statistically significant difference in HDL-C (p = 0.007), Troponin (p = 0.009), Castelli index (p = 0.001) and atherogenic index (p = 0.004). Preoperative levels of total cholesterol, LDL-C and HDL-C did not significantly differ between survivors and diseased. The 9-year mortality risk did not differ significantly between subgroups divided according to LDL-C thresholds of 1.4 mmol/L (55 mg/dL), 1.8 mmol/L (70 mg/dL), 2.6 mmol/L (100 mg/dL) and 3.0 mmol/L (116 mg/dL). Conclusions: Preoperative low level of LDL-C cholesterol (below 1.83 mmol/L, 70 mg/dL) has a cardioprotective effect on perioperative myocardial injury in off-pump coronary artery bypass grafting.

Neutrophile-to-Lymphocyte Ratio as a Predictor of Mortality and Response to Treatment in Invasive Aspergillosis among Heart Transplant Recipients-Exploratory Study.

Background and objective: Aspergillus pulmonary infections are potentially life-threatening complications that can occur after heart transplantation. The aim of the study was to find an easily available mortality predictor during Aspergillosis infection therapy following heart transplantation. Materials and methods: This study involved 15 heart recipients with the mean age of 55 ± 6 years who were diagnosed with invasive aspergillosis (IA) in a mean time of 80 ± 53 (19-209) days after orthotropic heart transplantation. Results: Out of fifteen patients diagnosed with IA, five died. The mean time from diagnosis to death in the deceased group was 28 ± 18 days. They were diagnosed with IA in a mean time of 80 ± 53 (19-209) days after orthotropic heart transplantation. During the initial seven days of therapy, the neutrophil to lymphocyte ratio (NLR) significantly differed between the two groups on day three and day seven, with median values of 10.8 [4.3-17.0] vs. 20.2 [17.4-116.8] (p = 0.0373) and 5.2 [3.2-8.1] vs. 32.2 [13.5-49.9] (p = 0.0101) in the survivor and the deceased group, respectively. The NLR was a significant predictor of death both on day three (cut-off point 17.2) and day seven (cut-off point 12.08) of therapy. Conclusions: Findings in our study indicate that NLR may be of predictive value in the estimation of mortality risk or response to treatment among patients with invasive aspergillosis following heart transplantation.

Monocyte-to-Lymphocyte Ratio as a Predictor of Worse Long-Term Survival after Off-Pump Surgical Revascularization-Initial Report.

Background and objective: Coronary artery disease is one of the leading causes of deaths nowadays and the trends in diagnosis and revascularization are still in plateau despite well-known factors. Simple whole blood count parameters may be used to measure inflammatory reactions that are involved in processes of atherosclerosis progression. The aim of our study was to analyse the association between simply available hematologic indices and long-term mortality following off-pump coronary artery bypass grafting (OPCAB). Material and Methods: The study group comprised 129 consecutive patients (16 females and 113 males, mean age 66 ± 6 years) who underwent surgical revascularization with off-pump technique between January 2014 and September 2019. The mean follow-up was 4.7 +/-1.9 years. A receiver operating characteristics curve was applied to estimate demographical and perioperative parameters including MLR for mortality. Results: Cox regression analysis revealed chronic pulmonary obstructive disease (HR = 2.86, 95%CI 1.05-7.78), MLR (HR = 3.81, 95%CI 1.45-10.06) and right coronary artery blood flow (HR = 1.06, 95%CI 1.00-1.10) as significant factors predicting increased mortality risk. In the presented model, the MLR > 1.44 on 1st postoperative day was a significant predictor of late mortality after the OPCAB procedure (HR = 3.82, 95%CI 1.45-10.06). Conclusions: Pronounced inflammatory reaction after off-pump surgery measured by MLR > 1.44 can be regarded as a worse long-term prognostic factor.

The Proliferation and Differentiation of Adipose-Derived Stem Cells in Neovascularization and Angiogenesis.

Neovascularization and angiogenesis are vital processes in the repair of damaged tissue, creating new blood vessel networks and increasing oxygen and nutrient supply for regeneration. The importance of Adipose-derived Mesenchymal Stem Cells (ASCs) contained in the adipose tissue surrounding blood vessel networks to these processes remains unknown and the exact mechanisms responsible for directing adipogenic cell fate remain to be discovered. As adipose tissue contains a heterogenous population of partially differentiated cells of adipocyte lineage; tissue repair, angiogenesis and neovascularization may be closely linked to the function of ASCs in a complex relationship. This review aims to investigate the link between ASCs and angiogenesis/neovascularization, with references to current studies. The molecular mechanisms of these processes, as well as ASC differentiation and proliferation are described in detail. ASCs may differentiate into endothelial cells during neovascularization; however, recent clinical trials have suggested that ASCs may also stimulate angiogenesis and neovascularization indirectly through the release of paracrine factors.

Development of regional extracorporeal life support system: The importance of innovative simulation training.

BACKGROUND: Despite advances in mechanical ventilation, severe acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality rates ranging from 30% to 60%. Extracorporeal Membrane Oxygenation (ECMO) can be used as a "bridge to recovery". ECMO is a complex network that provides oxygenation and ventilation and allows the lungs to rest and recover from respiratory failure, while minimizing iatrogenic ventilator-induced lung injury. In the critical care settings, ECMO is shown to improve survival rates and outcomes in patients with severe ARDS. The primary objective was to present an innovative approach for using high-fidelity medical simulation before setting ECMO program for reversible respiratory failure (RRF) in Poland's first unique regional program "ECMO for Greater Poland", covering a total population of 3.5 million inhabitants in the Greater Poland region (Wielkopolska). AIM AND METHODS: Because this organizational model is complex and expensive, we use advanced high-fidelity medical simulation to prepare for the real-life implementation. The algorithm was proposed for respiratory treatment by veno-venous (VV) Extracorporeal Membrane Oxygenation (ECMO). The scenario includes all critical stages: hospital identification (Regional Department of Intensive Care) - inclusion and exclusion criteria matching using an authorship protocol; ECMO team transport; therapy confirmation; veno-venous cannulation of mannequin's artificial vessels and implementation of perfusion therapy and transport with ECMO to another hospital in a provincial city (Clinical Department of Intensive Care), where the VV ECMO therapy was performed in the next 48 h, as training platform. RESULTS: The total time, by definition, means the time from the first contact with the mannequin to the cannulation of artificial vessels and starting VV perfusion on ECMO, did not exceed 3 h - including 75 min of transport (the total time of simulation with first call from provincial hospital to admission to the Clinical Intensive Care department was 5 h). The next 48 h for perfusion simulation "in situ" generated a specific learning platform for intensive care personnel. Shortly after this simulation, we performed, the first in the region: ECMO used for RRF treatment. The transport was successful and exceeded 120 km. During first year of Program duration we performed 6 successful ECMO transports (5 adult and 1 paediatric) with 60% of adult patient survival of ECMO therapies. Three patients in good condition were discharged to home. Two years old patient was successfully disconnected from ECMO and in stabile condition is treated in Paediatric Department. CONCLUSIONS: We discovered the important role of medical simulation, not only as an examination for testing the medical professional's skills, but also as a mechanism for creating non-existent procedures. During debriefing, it was found that the previous simulation-based training allowed to build a successful procedural chain, to eliminate errors at the stage of identification, notification, transportation and providing ECMO perfusion therapy.

Severe structural deterioration of small aortic bioprostheses treated with valve-in-valve transcatheter aortic valve implantation.

OBJECTIVES: The aim of this study was to evaluate outcomes of valve-in-valve transcatheter aortic valve implantation (VIV-TAVI) in patients with degenerated small bioprostheses. METHODS: Outcomes of consecutive 27 high-risk patients (logistic EuroSCORE 35.5 ± 18.5%) with a mean age of 81.0 ± 5.9 years who underwent VIV-TAVI for degenerated small bioprostheses (19 mm-11.1%; 20 mm-11.1%; 21 mm-77.8%) were analyzed. Medtronic CoreValve (n = 11) or CoreValve Evolut-R prostheses (n = 16) were implanted. Follow-up was 3.2 ± 2.0 years. RESULTS: Early mortality was 11.1%. One patient died intraoperatively due to left ventricle perforation, two others during the in-hospital period as a result of sudden cardiac death and pulmonary embolism. VIV-TAVI was completed in 26 cases (96.3%-success rate). Two patients required pacemaker implantation. Acute kidney injury occurred in two other patients. At discharge, mean transvalvular gradient was 19.2 ± 9.5 mmHg and in 25.9% of patients mean gradient exceeded 20 mmHg. Overall mortality was 25.9% and mortality from cardiac or unknown causes at 18.5%. Ninety percent of survivors were in New York Heart Association (NYHA) class I or II. CONCLUSIONS: Transfemoral VIV-TAVI in patients with small, degenerated bioprostheses appears to be a promising alternative to surgery. Although the vast majority of patients have significant improvement in their NYHA class, the rate of persistent, residual gradients is relatively high and will need to be followed closely with serial echocardiograms.

A Control-Theoretic Model of Atherosclerosis.

We propose a control-theoretic aggregate model of the progression of atherosclerosis plaque, a chronic inflammatory disease of the arterial wall, to study the basic features of this disease. In the model, we exploit the role of inflammation in the disease progression, and use statins-drugs commonly recommended in atherosclerosis-to control this progression. We use a logistic function to allow for constrained growth of plaque. In the model, both the patient's age and overall health impact the plaque growth and its sensitivity to statins. The model parameters are estimated using original data, or calibrated using published research as well as our own clinical and laboratory studies. We contend that our model helps to gauge the statins' impact on a patient's plaque thickness, hence the disease's progression and cardiovascular risk, without requiring artery scans.

Differences in Expression of Genes Involved in Bone Development and Morphogenesis in the Walls of Internal Thoracic Artery and Saphenous Vein Conduits May Provide Markers Useful for Evaluation Graft Patency.

Coronary artery bypass grafting (CABG) is one of the most efficient procedures for patients with advanced coronary artery disease. From all the blood vessels with the potential to be used in this procedure, the internal thoracic artery (ITA) and the saphenous vein (SV) are the most commonly applied as aortocoronary conduits. Nevertheless, in order to evaluate the graft patency and efficiency effectively, basic knowledge should be constantly expanding at the molecular level as well, as the understanding of predictive factors is still limited. In this study, we have employed the expressive microarray approach, validated with Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), to analyze the transcriptome of both venous and arterial grafts. Searching for potential molecular factors, we analyzed differentially expressed gene ontologies involved in bone development and morphogenesis, for the possibility of discovery of new markers for the evaluation of ITA and SV segment quality. Among three ontological groups of interest-"endochondral bone morphogenesis", "ossification", and "skeletal system development"-we found six genes common to all of them. BMP6, SHOX2, COL13A1, CSGALNACT1, RUNX2, and STC1 showed differential expression patterns in both analyzed vessels. STC1 and COL13A1 were upregulated in ITA samples, whereas others were upregulated in SV. With regard to the Runx2 protein function in osteogenic phenotype regulation, the RUNX2 gene seems to be of paramount importance in assessing the potential of ITA, SV, and other vessels used in the CABG procedure. Overall, the presented study provided valuable insight into the molecular background of conduit characterization, and thus indicated genes that may be the target of subsequent studies, also at the protein level. Moreover, it has been suggested that RUNX2 may be recognized as a molecular marker of osteogenic changes in human blood vessels.

Vascular restenosis in coronary artery bypass grafting might be associated with VEGF-C/VEGFR-3 signaling pathway.

The vascular endothelial growth factor (VEGF) family of peptides and caveolins (CAVs) are reported to contribute, in early graft failure in patients, a coronary artery bypass grafting (CABG). To investigate the possible association of ultimate luminal occlusion to VEGFs and CAVs expression, a functional analysis (based on the molecular biology, bioinformatics, histology, and clinical studies) was performed. Twenty-four hundred and sixty-eight CABG patients diagnosed with multivessel stable coronary artery disease (CAD) were enrolled into prospective study and assigned to two subgroups: double- and triple-vessel CAD subjects. Distal parts of all the harvested saphenous vein (SV) and internal thoracic artery (ITA) segments were used for further tests. ITA graft failure did not differ between double-vessel and triple-vessel CAD patients. The number of SV occlusions was significantly higher in triple-vessel CAD subjects. The microarray analysis performed on SV and ITA samples obtained exclusively from triple-vessel CAD patients who developed early graft occlusion revealed 383 genes with increased and 301 genes with decreased expression in ITA samples as compared to SV grafts. This was followed by functional analysis of 'blood vessel development' group of genes. Average VEGF-C expression in ITA grafts was higher than in corresponding SV grafts; FLT4 expression was significantly higher in SV than in ITA transplants. VEGFR-3 and CAV3 expression demonstrated immunohistochemically in SMCs of the tunica media of SV grafts predicted their early restenosis in triple-vessel CAD patients. CAV2 protein expression in SMCs of ITA grafts indicated the risk of early graft failure both in double-vessel and triple-vessel CAD subjects.

BEST Life-"Bringing ECMO Simulation To Life"-How Medical Simulation Improved a Regional ECMO Program.

The implemented "ECMO for Greater Poland" program takes full advantage of the ECMO (extracorporeal membrane oxygenation) perfusion therapy to promote health for 3.5 million inhabitants in the region. The predominant subjects of implementation are patients with hypothermia, with severe reversible respiratory failure (RRF), and treatment of other critical states leading to heart failure such as sudden cardiac arrest, cardiogenic shock or acute intoxication. Finally, it promotes donation after circulatory death (DCD) strategy in selected organ donor cases. ECMO enables recovery of organs' function after unsuccessful lifesaving treatment. Because this organizational model is complex and expensive, we use advanced high-fidelity medical simulation to prepare for real-life implementation. During the first four months, we performed scenarios mimicking "ECMO for DCD," "ECMO for ECPR (extended cardiopulmonary resuscitation)," "ECMO for RRF" and "ECMO in hypothermia." It helped to create algorithms for aforementioned program arms. In the following months, three ECMO courses for five departments in Poznan (capitol city of Greater Poland) were organized and standardized operating procedures for road ECMO transportation within Medical Emergency System were created. Soon after simulation program, 38 procedures with ECMO perfusion therapy including five road transportations on ECMO were performed. The Maastricht category II DCD procedures were done four times on real patients and in two cases double successful kidney transplantations were carried out for the first time in Poland. ECMO was applied in two patients with hypothermia, nine adult patients with heart failure, and five with RRF, for the first time in the region. In the pediatric group, ECMO was applied in four patients with RRF and 14 with heart failure after cardiac surgery procedures. Additionally, one child was treated successfully following 200 km-long road transport on ECMO. We achieved good and promising results especially in VV ECMO therapy. Simulation-based training enabled us to build a successful procedural chain, and to eliminate errors at the stage of identification, notification, transportation, and providing ECMO perfusion therapy. We discovered the important role of medical simulation, not only to test the medical professional's skills, but also to promote ECMO therapy in patients with critical/life-threatening states. Moreover, it also resulted in increase of the potential organ pool from DCD in the Greater Poland region.

Preoperative factors predicting saphenous vein graft occlusion in coronary artery bypass grafting: a multivariate analysis.

Saphenous vein segments are frequently used as aortocoronary bypass grafts, particularly in patients over 65 years of age. In the majority of patients, venous grafts maintain their patency for 5-6 years; however, some become occluded within 12 months after surgery. There are some defined predictive biological factors used to assess saphenous vein graft long-term patency rates, but little is known about molecular parameters for estimating the risk of early vein occlusion. The pathogenesis of this process involves the proliferation of stem cells, as well as progenitor cells, in the graft wall. Histologically, this is reflected by CD34 and CD133 expression in endothelial and smooth muscle cells. Thus, the aim of present work was to perform a multivariate analysis of stem cell and progenitor cell markers in saphenous vein graft walls before transplantation to arterial circulation and correlate these results with early graft occlusion. A total of 718 patients, who underwent coronary artery bypass grafting using a saphenous vein graft, were enrolled in this prospective study. CD34, CD133 and von Willebrand factor expression was evaluated via immunohistochemistry. A multivariate analysis revealed that strong CD133 expression in smooth muscle cells can be considered a risk factor for early graft failure. Our findings suggest that CD133 expression in smooth muscle cells of the tunica media in saphenous vein grafts obtained from coronary artery bypass graft patients before graft transplantation to coronary circulation might predict the possibility of early graft occlusion.