Geospatial epidemiology of coronary artery disease treated with percutaneous coronary intervention in Crete, Greece

Coronary artery disease (CAD) constitutes a leading cause of morbidity and mortality worldwide. Percutaneous coronary intervention (PCI) is indicated in a significant proportion of CAD patients, either to improve prognosis or to relieve symptoms not responding to optimal medical therapy. Thus the annual number of patients undergoing PCI in a given geographical area could serve as a surrogate marker of the total CAD burden there. The aim of this study was to analyze the potential, spatial patterns of PCItreated CAD patients in Crete. We evaluated data from all patients subjected to PCI at the island's sole reference centre for cardiac catheterization within a 4-year study period (2013-2016). The analysis focused on regional variations of yearly PCI rates, as well as on the effect of several clinical parameters on the severity of the coronary artery stenosis treated with PCI across Crete. A spatial database within the ArcGIS environment was created and an analysis carried out based on global and local regression using ordinary least squares (OLS) and geographically weighted regression (GWR), respectively. The results revealed significant inter-municipality variation in PCI rates and thus potentially CAD burden, while the degree and direction of correlation between key clinical factors to coronary stenosis severity demonstrated specific geographical patterns. These preliminary results could set the basis for future research, with the ultimate aim to facilitate efficient healthcare strategies planning.

Erratum: [Corrigendum] CD271+ stem cell treatment of patients with chronic stroke: A retrospective case series report.

[This corrects the article DOI: 10.3892/etm.2020.8948.].

Significant unfavorable geometrical changes in ascending aorta despite stable diameter at follow-up.

OBJECTIVE: The clinical importance of following up on the ascending aortic diameter lies in the fundamental presumption that wall pathology eventually manifests as a change in shape. However, the diameter describes the vessel locally, and the 55 mm criterion fails to prevent most dissections. We hypothesized that geometric changes across the ascending aorta are not necessarily imprinted on its diameter; i.e. the maximum diameter correlates weakly and insignificantly with elongation, surface stretching, engorgement, and tortuosity. METHODS: Two databases were interrogated for patients who had undergone at least 2 ECG-gated CT scans. The absence of motion artifacts permitted the generation of exact copies of the ascending aorta which then underwent three-dimensional analysis producing objective and accurate measurements of the centreline length, surface, volume, and tortuosity. The correlations of these global variables with the diameter were explored. RESULTS: Twenty-two patients, 13 male and 9 female, were included. The mean age at the first and last scan was 63.7 and 67.1 y, respectively. The mean diameter increase was approximately 1 mm/y. There were no dissections, while 7 patients underwent preemptive surgery. The yearly change rate of the global variables, normalized to height if applicable, showed statistically insignificant, weak, or negligible correlation with diameter increments at follow-up. Most characteristically, a patient's aorta maintained its diameter, while undergoing 1 mm/y elongation, 151 mm2/(y·m) stretching, 2366 mm3/(y·m) engorgement, and 0.02/y tortuosity. CONCLUSION: Maximum diameter provides a local description of the ascending aorta and cannot fully portray the pathological process across this vessel. Following up the diameter is not suggestive of length, surface, volume, and tortuosity changes.

Injecting a ventricular tachycardia into the heart-Α unique case report.

INTRODUCTION: A 52-year-old woman presented with a complex ventricular arrhythmia in an intraoperative context, during kyphoplasty for an osteoporotic fracture of a lumbar vertebra. The subject showed no indications of a previous cardiovascular condition. METHODS AND RESULTS: Causes of arrhythmias associated with the procedure were excluded. Due to her positive family history for dilated cardiomyopathy, upcoming thoughts were made for unmasking a previous asymptomatic cardiomyopathy. Nevertheless, an intracardiac cement embolism was diagnosed and, finally, the patient underwent an open-heart surgery with successful removal of the cardiac cement. Νo new arrhythmia recorded during follow up. CONCLUSION: To the best of our knowledge, this is the first reported case of ventricular arrhythmogenic presentation of a cardiac cement embolus after a KP procedure.

Differences in MicroRNA Expression in Pericoronary Adipose Tissue in Coronary Artery Disease Compared to Severe Valve Dysfunction.

Pericoronary adipose tissue (PCAT) is a source of microRNAs (miRs) that act as messengers for intercellular communication. We investigated whether the PCAT surrounding significant coronary atherosclerotic lesions shows specific miR expression patterns compared with PCAT surrounding plaque-free segments. We included 49 patients with 3-vessel coronary artery disease (CAD) and 19 patients with severe valvular disease but no CAD, who underwent elective cardiac surgery. The PCAT was harvested from two sites: adjacent to a significant atherosclerotic coronary lesion and from plaque-free segments. miR-133a, miR-21, miR-26b, miR-9, and miR-143 levels in PCAT cells were quantified by real-time reverse transcription polymerase chain reaction (data expressed as arbitrary units). Expression of miR-133, miR-21, and miR-26b in adipose tissue at a site without atherosclerotic lesion was much lower in patients with CAD than in those without CAD (0.82 ± 1.37 vs 1.86 ± 0.52, P < .001, 0.45 ± 1.3 vs 1.51 ± 1.11, P < .001, 0.3 ± 1.25 vs 1.2 ± 0.73, P = .02, respectively). In addition, miR-133, miR-21, and miR-143 in CAD patients showed significantly greater expression in PCAT from atherosclerotic lesion compared with plaque-free segments (1.32 ± 0.96 vs 0.82 ± 0.37 (P = .011), 0.91 ± 1.7 vs 0.3 ± 1.25 (P = .012), 1.2 ± 1.59 vs 0.43 ± 0.54 (P < .001), respectively). Our findings open new perspectives for the role of PCAT in the pathophysiology of atherosclerosis and should be further investigated.

Use of Cytokine Filters During Cardiopulmonary Bypass: Systematic Review and Meta-Analysis.

INTRODUCTION: Cardiac surgery involving cardiopulmonary bypass (CPB) activates an inflammatory response releasing cytokines that are associated with less favourable outcomes. This study aims to compare i) CPB during cardiac surgery (control) versus ii) CPB with haemoadsorption therapy; and assess the effect of adding this therapy in reducing the inflammatory cytokines burden. METHODS: A systematic literature review with meta-analysis was conducted regarding the main outcomes (operative mortality, ventilation duration, intensive care unit [ICU] and hospital stays) and day-1 inflammatory markers levels post-surgery. Fifteen (15) studies were included for final analysis (eight randomised controlled trials, seven observational studies) with no evidence of publication bias. RESULTS: Subgroup analysis of non-elective surgeries across observational studies (emergency and infective endocarditis) significantly favoured cytokine filters in terms of 30-day mortality (OR 0.40, 95% CI 0.20, 0.83; p=0.01) and shorter ICU stay (MD -42.36, 95% CI -68.07, -16.65; p=0.001). At day-1 post-surgery, there was a significant difference favouring the cytokine filter group in c-reactive protein (CRP) (MD -0.71, 95% CI -0.84, -0.59; p<0.001) with no differences in white blood count (WBC), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-α), IL-6, IL-8 and lactate. When comparing cytokine filters and control across all studies there was no significant difference in operative mortality, ventilation duration, hospital stay and ICU length of stay. Also, there were no statistical differences in randomised controlled trials (RCTs) using haemadsorption filters. CONCLUSIONS: A significant reduction in 30-day mortality and ICU stay could be obtained by using haemadsorption therapy during non-elective cardiac surgery, especially emergency surgery and in patients with higher inflammatory burden such as infective endocarditis.

Machine learning and artificial intelligence in cardiac transplantation: A systematic review.

BACKGROUND: This review aims to systematically evaluate the currently available evidence investigating the use of artificial intelligence (AI) and machine learning (ML) in the field of cardiac transplantation. Furthermore, based on the challenges identified we aim to provide a series of recommendations and a knowledge base for future research in the field of ML and heart transplantation. METHODS: A systematic database search was conducted of original articles that explored the use of ML and/or AI in heart transplantation in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to November 2021. RESULTS: Our search yielded 237 articles, of which 13 studies were included in this review, featuring 463 850 patients. Three main areas of application were identified: (1) ML for predictive modeling of heart transplantation mortality outcomes; (2) ML in graft failure outcomes; (3) ML to aid imaging in heart transplantation. The results of the included studies suggest that AI and ML are more accurate in predicting graft failure and mortality than traditional scoring systems and conventional regression analysis. Major predictors of graft failure and mortality identified in ML models were: length of hospital stay, immunosuppressive regimen, recipient's age, congenital heart disease, and organ ischemia time. Other potential benefits include analyzing initial lab investigations and imaging, assisting a patient with medication adherence, and creating positive behavioral changes to minimize further cardiovascular risk. CONCLUSION: ML demonstrated promising applications for improving heart transplantation outcomes and patient-centered care, nevertheless, there remain important limitations relating to implementing AI into everyday surgical practices.

Automated ascending aorta delineation from ECG-gated computed tomography images.

The instrumental role of comprehensive geometrical quantification in contemporary, effective descriptions of aortic growth and disease is well established. General or specific purpose algorithms are being developed to provide automatic landmark detection and high accuracy measurements. In the present study, an objective method for automated delineation of the ascending aorta is introduced, based on geometrical properties of the aortic wall. In the proximal ascending aorta, the method identifies the sinotubular junction by tracing the mean surface curvature transition region from the origins of the coronary arteries to the location where the aorta acquires its tubular shape. In the distal ascending aorta, the brachiocephalic artery origin is defined by a split centreline cross section within the brachiocephalic artery-aortic arch bifurcation region. The method's accuracy of detection was quantified against the manual border identification performed by two experienced observers on 3D aortic reconstructions of 44 computed tomography examinations. Median (method, observer) distance and inclination measurements ranged from 0.89 [1.02] mm and 4.66 [5.07]°, respectively, in the proximal border, to 2.18 [2.39] mm and 7.13 [4.77]° in the distal. Accuracy of border detection was found to be high compared to interobserver variability and relevant automatic and manual methodology results previously reported in literature. Delineation of the ascending aorta on a three-dimensional aortic reconstruction with automated identification of the sinotubular junction (proximal border) and of the origin of the brachiocephalic artery (distal border).

Prolonged complete atrioventricular block due to neostigmine and amiodarone interaction in an amyloidosis patient with left main dissection and postoperative intestinal pseudo-obstruction.

Cardiac amyloidosis has been strongly associated with postoperative intractable circulatory failure, and intestinal amyloidosis could lead to intestinal pseudo-obstruction. The latter can be treated with neostigmine, which is notorious for its brief bradyarrhythmic complications. The amyloidosis patient presented herein, suffered an iatrogenic left main dissection, failure of bailout stenting and finally underwent urgent surgery. Meticulous fluid and drug management was key to keeping this patient stable. Postoperative atrial fibrillation was treated with amiodarone. The postoperative course was complicated with intestinal pseudo-obstruction, which was ultimately resolved with neostigmine. This short-lived cholinesterase inhibitor interacted with amiodarone and caused a previously undocumented prolonged complete atrioventricular block that resolved 48 hours after both drugs' discontinuation. The neostigmine amiodarone interaction warrants clinical vigilance and is speculated to be due to their partially shared second messenger pathway involving cyclic adenosine monophosphate. Patients with cardiac amyloidosis could maintain hemodynamic stability perioperatively.

Evidence That HFE H63D Variant Is a Potential Disease Modifier in Cluster Headache.

Cluster headache (CH) is a primary headache disorder with a complex genetic background. Several studies indicate a potential link between iron homeostasis and the pathophysiology of primary headaches. The HFE gene encodes for a protein involved in iron metabolism, while genetic variants in HFE have been associated with hereditary hemochromatosis (HH), an iron overload disorder. The objective of the current study was to examine the association of the more common HFE H63D variant, with the susceptibility to develop CH and diverse clinical phenotypes in a population of Southeastern European Caucasian (SEC) origin. Genomic DNA samples from 128 CH patients and 294 neurologically healthy controls were genotyped for the HFE rs1799945 (H63D) variant. H63D genotypic and allelic frequency distribution did not differ significantly between patients and controls (p > 0.05). Subgroup analysis revealed a significantly more frequent occurrence of the variant G allele in chronic compared to episodic CH patients, indicative for a possible correlation of the HFE gene with the susceptibility for disease chronification. Although homozygosity for the less prevalent H63D variant G allele was minimal in the CH cohort, the results of the present study are in accordance with previous studies in CH and migraine patients, suggesting that HFE H63D variant modifies the disease clinical characteristics. Hence, despite the absence of a per se association with CH susceptibility in the current SEC cohort, variability in HFE gene may be potentially regarded as a disease modifier genetic factor in CH.

Prevalence and Clinical Significance of Drug-Drug and Drug-Dietary Supplement Interactions among Patients Admitted for Cardiothoracic Surgery in Greece.

BACKGROUND: Drug interactions represent a major issue in clinical settings, especially for critically ill patients such as those with cardiovascular disease (CVD) who require cardiothoracic surgery (CTS) and receive a high number of different medications. METHODS: A cross-sectional study aimed at evaluating the exposure and clinical significance of drug-drug (DDIs) and drug-dietary supplement interactions (DDSIs) in patients admitted for CTS in the University Hospital of Crete Greece. DDIs were evaluated regarding underlying pharmacological mechanisms upon admission, preoperation, postoperation, and discharge from CTS clinic. Additionally, upon admission, the use of dietary supplements (DSs) and if patients had informed their treating physician that they were using these were recorded with subsequent analysis of potential DDSIs with prescribed medications. RESULTS: The study employed 76 patients who were admitted for CTS and accepted to participate. Overall, 166 unique DDIs were identified, with 32% of them being related to pharmacokinetic (PK) processes and the rest (68%) were related to possible alterations of pharmacodynamic (PD) action. CVD medications and drugs for central nervous system disorders were the most frequently interacting medications. In total, 12% of the identified DDIs were of serious clinical significance. The frequency of PK-DDIs was higher during admission and discharge, whereas PD-DDIs were mainly recorded during pre- and postoperation periods. Regarding DS usage, 60% of patients were using DSs and perceived them as safe, and the majority had not informed their treating physician of this or sought out medical advice. Analysis of medical records showed 30 potential combinations with prescribed medications that could lead in DDSIs due to modulation of PK or PD processes, and grapefruit juice consumption was involved in 38% of them. CONCLUSIONS: An increased burden of DDIs and DDSIs was identified mostly upon admission for patients in CTS clinics in Greece. Healthcare providers, especially prescribing physicians in Greece, should always take into consideration the possibility of DDIs and the likely use of DS products by patients to promote their well-being; this should only be undertaken after receiving medical advice and an evidenced-based evaluation.

Thinking outside the Ischemia Box: Advancements in the Use of Multiple Sclerosis Drugs in Ischemic Stroke.

Ischemic stroke (IS) is a major cause of death and disability, despite early intervention. Thrombo-inflammation, the inflammatory process triggered by ischemia, is a concept that ties IS with multiple sclerosis (MS), under the wider 'umbrella' of neuroinflammation, i.e., the inflammation of the nervous tissue. Drawing from this, numerous studies have explored the potential of MS disease-modifying drugs in the setting of IS. In this review, we present the available studies and discuss their potential in ameliorating IS outcomes. Based on our search, the vast majority of the studies have been conducted on animals, yielding mostly positive results. Two clinical trials involving natalizumab showed that it does not confer any benefits, but four human studies regarding fingolimod have showcased its potential in improving recovery prospects. However, concerns on safety and other issues are raised, and basic questions still need to be answered.

Thrombosis and Haemostasis challenges in COVID-19 - Therapeutic perspectives of heparin and tissue-type plasminogen activator and potential toxicological reactions-a mini review.

The coronavirus disease (COVID)-19 pandemic is a major challenge for the health systems worldwide. Acute respiratory distress syndrome (ARDS), is one of the most common complications of the COVID-19 infection. The activation of the coagulation system plays an important role in the pathogenesis of ARDS. The development of lung coagulopathy involves thrombin generation and fibrinolysis inhibition. Unfractionated heparin and its recently introduced counterpart low molecular weight heparin (LMWH), are widely used anticoagulants with a variety of clinical indications allowing for limited and manageable physio-toxicologic side effects while the use of protamine sulfate, heparin's effective antidote, has made their use even safer. Tissue-type plasminogen activator (tPA) is approved as intravenous thrombolytic treatment. The present narrative review discusses the use of heparin and tPA in the treatment of COVID-19-induced ARDS and their related potential physio-toxicologic side effects. The article is a quick review of articles on anticoagulation in COVID infection and the potential toxicologic reactions associated with these drugs.

Does the clinical effectiveness of Mitraclip compare with surgical repair for mitral regurgitation?

BACKGROUND: Surgical repair of the mitral valve has long been the established therapy for degenerative mitral regurgitation (MR). Newer transcatheter methods over the last decade, such as the MitraClip, serve to restore mitral function with reduced procedural burden and enhanced recovery. This study aims to compare the shortterm and midterm outcomes of MitraClip insertion with surgical repair for MR. METHODS: A systematic review of the literature was conducted for studies comparing outcomes between surgical repair and MitraClip. The initial search returned 1850 titles, from which 12 studies satisfied the inclusion criteria (one randomized controlled trial and 11 retrospective studies). RESULTS: The final analysis comprised 4219 patients (MitraClip 1210; surgery 3009). Operative mortality was not different between the groups (odds ratio [OR] = 1.63, 95% confidence interval [CI]: [0.63-4.23]; p = .317). Length of hospital stay was significantly shorter in the MitraClip group (standardized mean difference [SMD] = 0.882, 95% CI: [0.77-0.99]; p < .001) with considerable heterogeneity (I2 > 90%; p < .001). The rate of reoperation on the mitral valve was lower in the surgical group (OR = 0.392; 95% CI: [0.188-0.817]; p = .012) as was the rate of MR recurrence grade moderate or above (OR = 0.29; 95% CI: [0.19-0.46]; p < .001) during midterm follow up. Long term survival (4-5 years) was also similar between both groups (hazard ratio = 0.70; 95% CI: [0.35-1.41]; p = .323). CONCLUSIONS: This study highlights the superior midterm durability of surgical valve repair for MR compared with the MitraClip.

Improved strategies to counter the COVID-19 pandemic: Lockdowns vs. primary and community healthcare.

COVID-19 pandemic mitigation strategies are mainly based on social distancing measures and healthcare system reinforcement. However, many countries in Europe and elsewhere implemented strict, horizontal lockdowns because of extensive viral spread in the community which challenges the capacity of the healthcare systems. However, strict lockdowns have various untintended adverse social, economic and health effects, which have yet to be fully elucidated, and have not been considered in models examining the effects of various mitigation measures. Unlike commonly suggested, the dilemma is not about health vs wealth because the economic devastation of long-lasting lockdowns will definitely have adverse health effects in the population. Furthermore, they cannot provide a lasting solution in pandemic containment, potentially resulting in a vicious cycle of consecutive lockdowns with in-between breaks. Hospital preparedness has been the main strategy used by governments. However, a major characteristic of the COVID-19 pandemic is the rapid viral transmission in populations with no immunity. Thus, even the best hospital system could not cope with the demand. Primary, community and home care are the only viable strategies that could achieve the goal of pandemic mitigation. We present the case example of Greece, a country which followed a strategy focused on hospital preparedness but failed to reinforce primary and community care. This, along with strategic mistakes in epidemiological surveillance, resulted in Greece implementing a second strict, horizontal lockdown and having one of the highest COVID-19 death rates in Europe during the second wave. We provide recommendations for measures that will reinstate primary and community care at the forefront in managing the current public health crisis by protecting hospitals from unnecessary admissions, providing primary and secondary prevention services in relation to COVID-19 and maintaining population health through treatment of non-COVID-19 conditions. This, together with more selective social distancing measures (instead of horizontal lockdowns), represents the only viable and realistic long-term strategy for COVID-19 pandemic mitigation.

The role of MiRNA-21 in gliomas: Hope for a novel therapeutic intervention?

Gliomas are the most common primary brain tumors in adults. They are generally very resistant to treatment and are therefore associated with negative outcomes. MicroRNAs (miRNAs) are small, non-coding RNA molecules that affect many cellular processes by regulating gene expression and, post-transcriptionally, the translation of mRNAs. MiRNA-21 has been consistently shown to be upregulated in glioma and research has shown that it is involved in a wide variety of biological pathways, promoting tumor cell survival and invasiveness. Furthermore, it has been implicated in resistance to treatment, both against chemotherapy and radiotherapy. In this review, we gathered the existent data on miRNA-21 and gliomas, in terms of its expression levels, association with grade and prognosis, the pathways it involves and its targets in glioma, and finally how it leads to treatment resistance. Furthermore, we discuss how this knowledge could be applied in clinical practice in the years to come. To our knowledge, this is the first review to assess in extent and depth the role of miRNA-21 in gliomas.

The flavoring and not the nicotine content is a decisive factor for the effects of refill liquids of electronic cigarette on the redox status of endothelial cells.

Electronic cigarettes are constantly gaining ground as they are considered less harmful than conventional cigarettes, and there is also the perception that they may serve as a potential smoking cessation tool. Although the acute effects of electronic cigarette use have been extensively studied, the long-term potential adverse effects on human health remain largely unknown. It has been well-established that oxidative stress is involved in the development of various pathological conditions. So far, most studies on e-cigarettes concern the effects on the respiratory system while fewer have focused on the vascular system. In the present study, we attempted to reveal the effects of electronic cigarette refill liquids on the redox state of human endothelial cells (EA.hy926 cell line). For this purpose, the cytotoxic effect of three e-liquids with different flavors (tobacco, vanilla, apple/mint) and nicotine concentrations (0, 6, 12, 18 mg/ml) were initially examined for their impact on cell viability of EA.hy926 cells. Then, five redox biomarkers [reduced form of glutathione (GSH), reactive oxygen species (ROS), total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyls (CARBS)] were measured. The results showed a disturbance in the redox balance in favor of free radicals in tobacco flavored e-liquids while vanilla flavored e-liquids exhibited a more complex profile depending on the nicotine content. The most interesting finding of the present study concerns the apple/mint flavored e-liquids that seemed to activate the cellular antioxidant defense and, thus, to protect the cells from the adverse effects of free radicals. Conclusively, it appears that the flavorings and not the nicotine content play a key role in the oxidative stress-induced toxicity of the e-liquids.

Targeting vulnerable atherosclerotic plaque via PET-tracers aiming at cell-surface overexpression of somatostatin receptors.

Cardiovascular disease (CD) is the leading cause of death in the developed world, with major atherothrombotic events, being mainly attributed to the rupture of unstable, vulnerable atherosclerotic lesions, leading to blood flow obstruction. Since unstable atherosclerotic plaques frequently do not cause hemodynamically significant blood flow restriction, conventional stress imaging tests cannot depict the vulnerable, high-risk for rupture atherosclerotic lesions. Therefore, molecular imaging techniques targeting specific pathophysiologic features related to atherosclerotic plaque rupture mechanism, hold promise for precise and individualized treatment strategies of CD. In the current report, we describe in a patient diagnosed with pancreatic neuroendocrine tumor, the selective uptake of 68Ga-DOATATE by an atherosclerotic lesion in the thoracic aorta. This data indicates that 68Ga-DOTATATE, which is a positron emitting tomography tracer, targeting the recruitment of macrophages taking place in the vulnerable plaque, could potentially serve as an imaging probe for the detection of high-risk, prone to rupture plaques.