Cancer/testis antigens and gametogenesis: a review and "brain-storming" session

Genes expressed both in normal testis and in malignancies (Cancer/ Testis associated genes – CTA) have become the most extensively studied antigen group in the field of tumour immunology. Despite this, many fundamentally important questions remain unanswered: what is the connection between germ-cell specific genes and tumours? Is the expression of these genes yet another proof for the importance of genome destabilisation in the process of tumorigenesis?, or maybe activation of these genes is not quite random but instead related to some programme giving tumours a survival advantage? This review collates most of the recent information available about CTAs expression, function, and regulation. The data suggests a programme related to ontogenesis, mostly to gametogenesis. In the "brain-storming" part, facts in conflict with the hypothesis of random CTA gene activation are discussed. We propose a programme borrowed from organisms phylogenetically much older than humans, which existed before the differentiation of sexes. It is a programme that has served as a life cycle with prominent ploidy changes, and from which, as we know, the germ-cell ploidy cycle – meiosis – has evolved. Further work may show whether this hypothesis can lead to a novel anti-tumour strategy

Towards no-scar cardiac surgery — minimally invasive access through umbilicus for aortic valve replacement

There is an ever-growing trend towards less-invasive procedures in all fields of medicine. We designed an animal study to prove the concept that trans-apical aortic valve replacement from an incision within the umbilicus through a single channel for instruments is feasible, which would be a major leap towards no-scar cardiac surgery. In three adult pigs, after creating a single 3-cm incision at a place where the human umbilicus would be, we introduced a 30F sheath through a tunnel created by an endoscopic vein-harvesting device up to the cardiac apex, through it and up to the left ventricle simulating the approach for trans-apical aortic valve replacement. We used a standard Amplatz nitinol occluder to seal the defect in ventricle wall later. The animals were followed up for 1h. Blood loss was minimal, and no tamponade occurred in any of the animals. In addition, we performed a test with water column static pressure to evaluate the impact of preclotting on the sealing properties of the occluders: 1min flow-through was 2860±176ml for the standard occluders and 348±56ml for preclotted occluders (p≪0.001

Lead-related infective endocarditis in latvia : A single centre experience

Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.Background and Objectives: Over the last five decades cardiac implantable electronic devices (CIED) have become established as the mainstay for the treatment of permanent bradycardias, chronic heart failure and dangerous heart rhythm disturbances. These devices improve survival and quality of life in many patients. However, infections associated with CIED implantation, particularly lead-related infective endocarditis (LRIE), can offset all benefits and make more harm than good for the patient. To date, there are no other studies in Latvia, addressing patients with lead-related infective endocarditis. The objective of this study was to identify the most common pathogens associated with LRIE and their antimicrobial resistance and to identify possible risk factors of patients who present with LRIE. Materials and Methods: The study was performed retrospectively at Pauls Stradins Clinical University Hospital (PSCUH). The study included patients who were referred to PSCUH due to LRIE for lead extraction. Patients were identified from procedural journals. Information about isolated microorganisms, patient comorbidities and visual diagnostics data was taken from patient records. Results: Forty-nine patients with CIED related infective endocarditis were included in the study, 34 (69.4%) were male, median age of all patients was 65.0 (50.5–73.0) years, median hospital stay was 15.5 (22.0–30.5) days. Successful and complete lead extraction was achieved in all patients. Thirty-two (65.3%) had received antibiotics prior to blood sample. Only in 31 (63.3%) positive culture results were seen. The most common isolated pathogens were Staphylococcus aureus (23.5%) and coagulase negative staphylococci (23.5%). Other bacteria were isolated considerably less often. The atrial lead was most common location for lead vegetations, seen in 50.0% of cases. Five (10.2%) patients have died due to the disease. Conclusions: Lead-related infective endocarditis is a major complication of cardiac implantable electronic devices with considerable morbidity and mortality, which in our study was as high as 10.2%.Peer reviewe

A new self-expanding aortic stent valve with annular fixation: in vitro haemodynamic assessment

Objective: Balloon-expandable stent valves require flow reduction during implantation (rapid pacing). The present study was designed to compare a self-expanding stent valve with annular fixation versus a balloon-expandable stent valve. Methods: Implantation of a new self-expanding stent valve with annular fixation (Symetis®, Lausanne, Switzerland) was assessed versus balloon-expandable stent valve, in a modified Dynatek Dalta® pulse duplicator (sealed port access to the ventricle for transapical route simulation), interfaced with a computer for digital readout, carrying a 25 mm porcine aortic valve. The cardiovascular simulator was programmed to mimic an elderly woman with aortic stenosis: 120/85 mmHg aortic pressure, 60 strokes/min (66.5 ml), 35% systole (2.8 l/min). Results: A total of 450 cardiac cycles was analysed. Stepwise expansion of the self-expanding stent valve with annular fixation (balloon-expandable stent valve) resulted in systolic ventricular increase from 120 to 121 mmHg (126 to 830 ± 76 mmHg)*, and left ventricular outflow obstruction with mean transvalvular gradient of 11 ± 1.5 mmHg (366 ± 202 mmHg)*, systolic aortic pressure dropped distal to the valve from 121 to 64.5 ± 2 mmHg (123 to 55 ± 30 mmHg) N.S., and output collapsed to 1.9 ± 0.06 l/min (0.71 ± 0.37 l/min* (before complete obstruction)). No valve migration occurred in either group. (* = p < 0.05). Conclusions: Implantation of this new self-expanding stent valve with annular fixation has little impact on haemodynamics and has the potential for working heart implantation in vivo. Flow reduction (rapid pacing) is not necessar

Four-Year Outcomes of Left Main Percutaneous Coronary Intervention with a Bioresorbable Scaffold in the Circumflex Ostium

Publisher Copyright: © 2022 Andrejs Erglis et al.Objectives. The study aimed to investigate the long-term outcomes of a double stent scaffold strategy in patients with left main (LM) bifurcation lesions involving the ostium of the left circumflex artery (LCX), utilizing a drug-eluting stent (DES) in the LM extending into the left anterior descending artery (LAD) and a bioresorbable vascular scaffold (BVS) in the LCX ostium. Background. The high occurrence of in-stent restenosis of the LCX ostium is the major limitation of percutaneous coronary intervention (PCI) for LM lesions with a two-stent strategy. Methods. This was a single-center, prospective, single-arm study of 46 consecutively enrolled patients with a stable coronary artery disease and significant unprotected LM distal bifurcation disease. Patients underwent imaging-guided PCI using DES in the LM-LAD and BVS in the LCX using a T-stent or mini-crush technique. The primary outcome at four years was the composite of death, myocardial infarction, stroke, and target lesion revascularization (TLR). Results. At four years, the primary outcome was identified in 9 patients (19.6%). All events were TLRs except one myocardial infarction due to BVS thrombosis. Seven of the eight TLRs were a result of side branch BVS restenosis. Univariate predictors of the 4-year outcome were higher LDL cholesterol and BVS size ≤2.5 mm. On multivariate analysis, LCX lesion preparation with a cutting balloon and post-procedure use of intravascular ultrasound for optimization were found to be independent protective factors of MACE. Conclusions. In selected patients with LM distal bifurcation disease, an imaging-guided double stent scaffold strategy with DES in the LM and BVS in the LCX ostium was technically successful in all patients and was reasonably safe and effective for four years.Peer reviewe

Comparison of outcome between blood culture positive and negative infective endocarditis patients undergoing cardiac surgery

Publisher Copyright: © 2021, The Author(s).Background: Up to 30% or even more of all infective endocarditis (IE) cases are recognized as blood culture negative, meaning that the causative agent is left unidentified. The prompt diagnosis together with the identification of causative microorganism and targeted antibiotic treatment can significantly impact the prognosis of the disease and further patient’s health status. In some studies, blood culture negative endocarditis has been shown to be associated with delayed diagnosis, worse outcome and course of the disease, and a greater number of intra and postoperative complications. Methods: We retrospectively analysed the medical records of all patients who underwent cardiac surgery for endocarditis between years 2016 and 2019. The aim of this study was to analyse short and long-term mortality and differences of laboratory, clinical and echocardiography parameters in patients with blood culture positive endocarditis (BCPE) and blood culture negative endocarditis (BCNE) and its possible impact on the clinical outcome. Results: In our study population were 114 (55.1%) blood culture positive and 93 (44.9%) blood culture negative cases of infectious endocarditis. The most common pathogens in the blood culture positive IE group were S.aureus in 36 cases (31.6%), Streptococcus spp. in 27 (23.7%), E.faecalis in 24 (21.1%), and other microorganisms in 27 (23.7%). Embolic events were seen in 60 patients (28.9%). In univariate analyses, detection of microorganism, elevated levels of procalcitonin were found to be significantly associated with intrahospital death, however it did not reach statistical significance in multivariate analyses. Among microorganisms, S.aureus was significantly associated with intrahospital death in both univariate and multivariate analyses. Conclusions: There are no statistically significant differences between groups of BCPE and BCNE in terms of intrahospital mortality, hospital and ICU stay or 3-year mortality. There were higher levels of procalcitonin in BCPE group, however procalcitonin failed to show independent association with mortality in multivariate analysis. The most common microorganism in the BCPE group was S.aureus. It was associated with independently higher intrahospital mortality when compared to other causative microorganisms.publishersversionPeer reviewe

The fusion of tissue spheroids attached to pre-stretched electrospun polyurethane scaffolds

Publisher Copyright: © 2014, © The Author(s) 2014. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.Effective cell invasion into thick electrospun biomimetic scaffolds is an unsolved problem. One possible strategy to biofabricate tissue constructs of desirable thickness and material properties without the need for cell invasion is to use thin (<2 µm) porous electrospun meshes and self-assembling (capable of tissue fusion) tissue spheroids as building blocks. Pre-stretched electrospun meshes remained taut in cell culture and were able to support tissue spheroids with minimal deformation. We hypothesize that elastic electrospun scaffolds could be used as temporal support templates for rapid self-assembly of cell spheroids into higher order tissue structures, such as engineered vascular tissue. The aim of this study was to investigate how the attachment of tissue spheroids to pre-stretched polyurethane scaffolds may interfere with the tissue fusion process. Tissue spheroids attached, spread, and fused after being placed on pre-stretched polyurethane electrospun matrices and formed tissue constructs. Efforts to eliminate hole defects with fibrogenic tissue growth factor-β resulted in the increased synthesis of collagen and periostin and a dramatic reduction in hole size and number. In control experiments, tissue spheroids fuse on a non-adhesive hydrogel and form continuous tissue constructs without holes. Our data demonstrate that tissue spheroids attached to thin stretched elastic electrospun scaffolds have an interrupted tissue fusion process. The resulting tissue-engineered construct phenotype is a direct outcome of the delicate balance of the competing physical forces operating during the tissue fusion process at the interface of the pre-stretched elastic scaffold and the attached tissue spheroids. We have shown that with appropriate treatments, this process can be modulated, and thus, a thin pre-stretched elastic polyurethane electrospun scaffold could serve as a supporting template for rapid biofabrication of thick tissue-engineered constructs without the need for cell invasion.publishersversionPeer reviewe

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p&nbsp;&lt;.001. Over 24&nbsp;months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10&nbsp;ml/min/1.73&nbsp;m2 decrease), that was most notable in patients with eGFR &lt;30&nbsp;ml/min/1.73&nbsp;m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90&nbsp;ml/min/1.73&nbsp;m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P &lt;.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes