The possible role of machine learning in detection of increased cardiovascular risk patients - KSC MR Study (design).

Introduction: Currently, just a few major parameters are used for cardiovascular (CV) risk quantification to identify many of the high-risk subjects; however, they leave a lot of them with an underestimated level of CV risk which does not reflect the reality. Material and methods: The submitted study design of the Kosice Selective Coronarography Multiple Risk (KSC MR) Study will use computer analysis of coronary angiography results of admitted patients along with broad patients' characteristics based on questionnaires, physical findings, laboratory and many other examinations. Results: Obtained data will undergo machine learning protocols with the aim of developing algorithms which will include all available parameters and accurately calculate the probability of coronary artery disease. Conclusions: The KSC MR study results, if positive, could establisha base for development of proper software for revealing high-risk patients, as well as patients with suggested positive coronary angiography findings, based on the principles of personalised medicine.

Non-iatrogenic left atrial wall dissection.

Non-iatrogenic left atrial wall dissection is a rare lesion defined as a gap from the mitral valve annulus to the interatrial septum or wall of the left atrium. We report the case of a 57-year-old man with symptoms of acute cardiac and renal failure. Trans-esophageal echocardiography and computed tomography showed significant mitral valve regurgitation and dissection of the posterior wall of the left atrium. On the basis of detailed trans-esophageal echocardiography, the patient underwent mitral valve replacement with closure of the dissection orifice, which appears to be the appropriate therapeutic strategy in cases of spontaneous left atrial wall dissection.

Human galectin­3: Molecular switch of gene expression in dermal fibroblasts in vitro and of skin collagen organization in open wounds and tensile strength in incisions in vivo.

Understanding the molecular and cellular processes in skin wound healing can pave the way for devising innovative concepts by turning the identified natural effectors into therapeutic tools. Based on the concept of broad­scale engagement of members of the family of galactoside­binding lectins (galectins) in pathophysiological processes, such as cancer or tissue repair/regeneration, the present study investigated the potential of galectins­1 (Gal­1) and ­3 (Gal­3) in wound healing. Human dermal fibroblasts, which are key cells involved in skin wound healing, responded to galectin exposure (Gal­1 at 300 or Gal­3 at 600 ng/ml) with selective changes in gene expression among a panel of 84 wound­healing­related genes, as well as remodeling of the extracellular matrix. In the case of Gal­3, positive expression of Ki67 and cell number increased when using a decellularized matrix produced by Gal­3­treated fibroblasts as substrate for culture of interfollicular keratinocytes. In vivo wounds were topically treated with 20 ng/ml Gal­1 or ­3, and collagen score was found to be elevated in excisional wound repair in rats treated with Gal­3. The tensile strength measured in incisions was significantly increased from 79.5±17.5 g/mm2 in controls to 103.1±21.4 g/mm2 after 21 days of healing. These data warrant further testing mixtures of galectins and other types of compounds, for example a combination of galectins and TGF­ß1.

The three-dimensional speckle tracking echocardiography in distinguishing between ischaemic and non-ischaemic aetiology of heart failure.

AIMS: The aim of this pilot study was to compare selected three-dimensional speckle tracking echocardiography (3D STE) parameters in patients with ischaemic and non-ischaemic aetiology of heart failure (HF) and to identify indices that can differentiate the two pathologies. METHODS AND RESULTS: Forty patients with left ventricular ejection fraction (LVEF) ≤ 40% were included to the study: 20 patients (age 63 ± 9.0 years, LVEF 29.0 ± 11.3%) with ischaemic cardiomyopathy and 20 patients (age 64.0 ± 11.0 years, LVEF 27.3 ± 7.5%) with non-ischaemic cardiomyopathy. All patients underwent two-dimensional (2D) and three-dimensional (3D) transthoracic echocardiography. Standard echocardiographic parameters, global longitudinal strain, and rotational parameters of left ventricle (LV) were assessed using 3D speckle tracking (3D STE). There were no differences in standard and STE parameters between the two groups. Among rotational parameters, the LV apical rotation (4.9 ± 3.5° vs. 2.3 ± 2.4°, P = 0.0022) was significantly higher in patients with ischaemic HF. Among all echocardiographic parameters, a cut-off value of 3.28° (area under the curve 0.78; 95% confidence interval, 0.62 to 0.93) was able to distinguish the ischaemic and non-ischaemic aetiology of HF with a sensitivity of 80% and specificity of 75%. CONCLUSIONS: This is the first study that compares 3D STE parameters between patients with ischaemic and non-ischaemic cardiomyopathy. It was proved that the apical rotation was significantly higher in patients with ischaemic cardiomyopathy. Our findings suggest that 3D STE might be useful in non-invasive differentiation between ischaemic and non-ischaemic aetiology of HF.

EQ-5D-5L questionnaire as suitable assessment of quality of life after epiduroscopy : Multicenter randomized double-blind pilot study.

BACKGROUND: Epiduroscopy is a well-established diagnostic and to certain level therapeutic tool in complex situations, where conventional methods such as magnetic resonance imaging (MRI) lack power or resolution to detect pathological changes. Such a situation is primarily failed back surgery syndrome (FBSS) but also radicular pain without surgery. The aim of this study was to determine the effectiveness of epiduroscopic treatment in patients with FBSS. METHODS: A total of 79 patients with FBSS were randomized into 2 groups. The first group underwent epiduroscopy and received mechanical lysis of adhesions only, the second group received also medication into the epidural space (methylprednisolone and hyaluronidase). Patients were subsequently followed for 12 months, with evaluation also after 6 months post-epiduroscopy. Patients were checked in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression as defined in the 5­dimensional EQ-5D-5L questionnaire and to asses suitability of this questionnaire in chronic pain states. Data were collected using EQ-5D-5L questionnaire and also quality of life (QoL) questionnaire. RESULTS: In the terms of ability to walk (dimension mobility) and also ability to do housework, study or leisure activities (dimension usual activity) patients improved in both groups after 6 and 12 months after epiduroscopy. In pain dimension there was improvement mainly after 6 months which correlated also with self-care dimension and quality of life self-assessment. Results in anxiety/depression dimension were mixed. CONCLUSION: Epiduroscopy appears to be a beneficial procedure for both patient groups, especially after 6 months, with some benefit remaining after 12 months. The EQ-5D-5L questionnaire seems to be a suitable and comprehensive way to assess patient health in chronic pain states.

Right aortic arch with an aberrant left subclavian artery and aortic coarctation including a descending aortic aneurysm.

BACKROUND: The right aortic arch and aortic coarctation are rare congenital anomalies with the incidence of 0.1% and 0.03-0.04%. We present a case report of a 51-year-old woman with the right aortic arch with aberrant left subclavian artery and coarctation of the aorta with post-stenotic aneurysm. CASE PRESENTATION: Resection of the coarctation and aneurysm with replacement by tubular prosthesis was performed on partial cardiopulmonary bypass via femoral vessels. CONCLUSION: Partial cardiopulmonary bypass is an applicable method for ensuring the perfusion of the distal part of the body and an aberrant left subclavian artery is not a contraindication of this technique.

Left atrial appendage strain rate is associated with documented thromboembolism in nonvalvular atrial fibrillation.

BACKGROUND: The left atrial appendage (LAA) strain and strain rate have not yet been studied in the prediction of cardiac thromboembolism. Therefore, this study aimed to evaluate the significance of LAA strain and strain rate as assessed by speckle-tracking imaging in relation to documented thromboembolic events. METHODS: A group of 80 patients with a mean age of 65 years who were referred for electrical cardioversion of nonvalvular atrial fibrillation was retrospectively analyzed. Each patient underwent 2D transesophageal echocardiography (TEE). Velocity vector imaging (VVI)-derived LAA strain and strain rate in parallel with other conventional TEE predictors were analyzed in terms of their association with previous embolic stroke and peripheral embolization. RESULTS: By comparing the two groups of patients with (22/80) and without embolic events (58/80), patients with embolic events were older, had higher CHA2DS2-VASc scores, higher incidence of coronary artery disease and LAA thrombi, and worse LAA strain and strain rate. Moreover, patients without embolization more often used anticoagulants than patients with embolic events. After adjusting for the abovementioned embolic risk factors, only the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years [double weight], diabetes mellitus, stroke [double weight], vascular disease, age from 65 to 74 years, sex category) score and the LAA strain rate remained as significant predictors of embolic events. CONCLUSION: The results of the study show that the VVI-derived LAA strain rate is a significant predictor of documented ischemic stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. Its predictive power is similar to the predictive power of the CHA2DS2-VASc score.

Genistein Improves Skin Flap Viability in Rats: A Preliminary In Vivo and In Vitro Investigation.

Selective estrogen receptor modulators (SERMs) have been developed to achieve beneficial effects of estrogens while minimizing their side effects. In this context, we decided to evaluate the protective effect of genistein, a natural SERM, on skin flap viability in rats and in a series of in vitro experiments on endothelial cells (migration, proliferation, antioxidant properties, and gene expression profiling following genistein treatment). Our results showed that administration of genistein increased skin flap viability, but importantly, the difference is only significant when treatment is started 3 days prior the flap surgery. Based on our in vitro experiments, it may be hypothesized that the underlying mechanism may rather by mediated by increasing SOD activity and Bcl-2 expression. The gene expression profiling further revealed 9 up-regulated genes (angiogenesis/inflammation promoting: CTGF, CXCL5, IL-6, ITGB3, MMP-14, and VEGF-A; angiogenesis inhibiting: COL18A1, TIMP-2, and TIMP-3). In conclusion, we observed a protective effect of genistein on skin flap viability which could be potentially applied in plastic surgery to women undergoing a reconstructive and/or plastic intervention. Nevertheless, further research is needed to explain the exact underlying mechanism and to find the optimal treatment protocol.

Should open excisions and sutured incisions be treated differently? A review and meta-analysis of animal wound models following low-level laser therapy.

Although low-level laser therapy (LLLT) was discovered already in the 1960s of the twentieth century, it took almost 40 years to be widely used in clinical dermatology/surgery. It has been demonstrated that LLLT is able to increase collagen production/wound stiffness and/or improve wound contraction. In this review, we investigated whether open and sutured wounds should be treated with different LLLT parameters. A PubMed search was performed to identify controlled studies with LLLT applied to wounded animals (sutured incisions-tensile strength measurement and open excisions-area measurement). Final score random effects meta-analyses were conducted. Nineteen studies were included. The overall result of the tensile strength analysis (eight studies) was significantly in favor of LLLT (SMD = 1.06, 95% CI 0.66-1.46), and better results were seen with 30-79 mW/cm2 infrared laser (SMD = 1.44, 95% CI 0.67-2.21) and 139-281 mW/cm2 red laser (SMD = 1.52, 95% CI 0.54-2.49). The overall result of the wound contraction analysis (11 studies) was significantly in favor of LLLT (SMD = 0.99, 95% CI 0.38-1.59), and the best results were seen with 53-300 mW/cm2 infrared laser (SMD = 1.18, 95% CI 0.41-1.94) and 25-90 mW/cm2 red laser (SMD = 1.6, 95% CI 0.27-2.93). Whereas 1-15 mW/cm2 red laser had a moderately positive effect on sutured wounds, 2-4 mW/cm2 red laser did not accelerate healing of open wounds. LLLT appears effective in the treatment of sutured and open wounds. Statistical heterogeneity indicates that the tensile strength development of sutured wounds is more dependent on laser power density compared to the contraction rate of open wounds.

Aortic Valve Repair of a Stenotic Unicuspid Aortic Valve in Young Patients.

BACKGROUND: The unicuspid aortic valve (UAV) is a well-described pediatric congenital abnormality, with incidence of 0.02% in the general population. Bicuspidization has been described as a potential surgical option to repair this defect. METHODS: Seventeen symptomatic young patients with a unicuspid valve combined with either valve insufficiency or valve stenosis underwent aortic valve (AV) bicuspidization procedure by using an equine pericardium. In addition to bicuspidization, 8 patients underwent aortic ring implantation and 5 patients underwent supracoronary replacement of the aorta. RESULTS: Our results show safety of the bicuspidization procedure. No deaths occurred during our average follow-up period of 26 months. Freedom from reoperation for any valve-related reason was 100% during this follow-up period. We observed a statistically significant increase in the AV area from 0.8 ± 0.1 cm2 to 2.8 ± 0.7 cm2 (p < 0.01), a statistically significant decrease in the mean systolic pressure gradient from 36 ± 13.3 mm Hg to 9 ± 4 mm Hg (p < 0.001), a statistically significant decrease in aortic insufficiency grade from 2.1 ± 1.0 to 0.6 ± 0.7 (p < 0.01) before and after bicuspidization, respectively, and a statistically significant decrease in the left ventricular end-diastolic diameter from 49.88 ± 5.11 mm to 40.46 ± 7.20 mm (p < 0.0005) and a statistically significant increase of the left ventricular ejection fraction from 56% ± 8.20% to 64% ± 7.83% at the time of follow-up. CONCLUSIONS: From our study, bicuspidization is an attractive surgical option to repair UAV, particularly in young patients who do not want to be subjected to long-term anticoagulation therapy or who refuse a more traditional surgical approach, such as Ross procedure, for reasons described previously.

Detection of Pathological Changes in the Aorta during Thoracic Aortic Aneurysm Progression on Molecular Level.

The progression of thoracic aortic aneurysm depends on regulation of aortic wall homeostasis and on changes in the structural components of the extracellular matrix, which are affected by multiple molecular signalling pathways. We decided to correlate the diameter of ascending thoracic aneurysm with gene expression of inflammation markers (IL-6, CRP), cytokine receptors (IL-6R, TNFR1, and TNFR2), and extracellular matrix components (Emilin-1, MMP9, and TIMP) for detection of the degree of pathological process of TAA formation. The experimental group was divided into three groups according to the diameter of the aortic aneurysm. Whole blood and tissue samples were properly collected and used for nucleic acid, chromatin, and protein isolation. The mRNA levels were detected by qRT-PCR. For the detection of protein levels a Cytokine Array IV assay kit was used in combination with a biochip analyzer. In aortic tissue, significant positive correlations were found between increased mRNA levels of inflammatory cytokines (CRP and IL-6) on both mRNA levels in tissue and protein from the blood with maximum in stage 3. Changes of gene expression of selected genes can be used for the experimental study of the inflammatory receptor inhibitors during trials targeted on slowing down the progress of aortic wall aneurysm.

Surgical Treatment of a Catheter-Induced Iatrogenic Dissection of the Right Coronary Artery following Cardiac Catheterization.

Iatrogenic dissections of the ascending aorta are an uncommon and severe complication during cardiac catheterization. A 68-year-old female patient underwent diagnostic cardiac catheterization due to non-ST-elevation myocardial infarction. During the procedure, a catheter-induced 360(°) Class I dissection of the right coronary artery occurred. The patient developed severe bradycardia, which was treated with a temporary pacemaker. She underwent an emergency operation with ligation and a saphenous vein graft in the right coronary artery. The postoperative course was uneventful; and on postoperative day 6, she was discharged home.

Pharmacological activation of estrogen receptors-α and -ß differentially modulates keratinocyte differentiation with functional impact on wound healing.

Estrogen deprivation is considered responsible for many age-related processes, including poor wound healing. Guided by previous observations that estradiol accelerates re­epithelialization through estrogen receptor (ER)­ß, in the present study, we examined whether selective ER agonists [4,4',4''-(4-propyl [1H] pyrazole-1,3,5-triyl)­trisphenol (PPT), ER­α agonist; 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), ER­ß agonist] affect the expression of basic proliferation and differentiation markers (Ki­67, keratin­10, ­14 and ­19, galectin­1 and Sox­2) of keratinocytes using HaCaT cells. In parallel, ovariectomized rats were treated daily with an ER modulator, and wound tissue was removed 21 days after wounding and routinely processed for basic histological analysis. Our results revealed that the HaCaT keratinocytes expressed both ER­α and ­ß, and thus are well-suited for studying the effects of ER agonists on epidermal regeneration. The activation of ER­α produced a protein expression pattern similar to that observed in the control culture, with a moderate expression of Ki­67 being observed. However, the activation of ER­ß led to an increase in cell proliferation and keratin­19 expression, as well as a decrease in galectin­1 expression. Fittingly, in rat wounds treated with the ER­ß agonist (DPN), epidermal regeneration was accelerated. In the present study, we provide information on the mechanisms through which estrogens affect the expression patterns of selected markers, thus modulating keratinocyte proliferation and differentiation; in addition, we demonstrate that the pharmacological activation of ER-α and -ß has a direct impact on wound healing.

Follow-up after the Ross procedure, how significant it is, case reports of three patients.

BACKGROUND: Dilatation of the pulmonary autograft is a major drawback of the Ross procedure and it is the leading cause for reoperation in these patients. CASE PRESENTATION: In this report we describe 3 cases reports, each one with a different outcome, of patients that underwent the Ross procedure. CONCLUSIONS: In order to prevent any lethal or non-lethal complications of the pulmonary autograft these patients need a close and life- long systematic follow-up.

Melatonin treatment in the prevention of postoperative delirium in cardiac surgery patients.

INTRODUCTION: Post-cardiac surgery delirium is a severe complication. The circadian rhythm of melatonin secretion has been shown to be altered postoperatively. AIM OF THE STUDY: It was hypothesized that restoring normal sleeping patterns with a substance that is capable of resynchronizing circadian rhythm such as exogenous administration of melatonin may possibly reduce the incidence of postoperative delirium. MATERIAL AND METHODS: This paper represents a prospective clinical observational study. Two consecutive groups of 250 consecutive patients took part in the study. Group A was the control group and group B was the melatonin group. In group B, the patients received prophylactic melatonin treatment. The main objectives were to observe the incidence of delirium, to identify any predictors of delirium, and to compare the two groups based on the delirium incidence. RESULTS: The incidence of delirium was 8.4% in the melatonin group vs. 20.8% in the control group (p = 0.001). Predictors of delirium in the melatonin group were age (p = 0.001) and higher EuroSCORE II value (p = 0.001). In multivariate analysis, age and EuroSCORE II value (p = 0.014) were predictors of postoperative delirium. Comparing the groups, the main predictors of delirium were age (p = 0.001), EuroSCORE II value (p = 0.001), cardio-pulmonary bypass (CPB) time (p = 0.001), aortic cross-clamping (ACC) time (p = 0.008), sufentanil dose (p = 0.001) and mechanical ventilation (p = 0.033). CONCLUSIONS: Administration of melatonin significantly decreases the incidence of postoperative delirium after cardiac surgery. Prophylactic treatment with melatonin should be considered in every patient scheduled for cardiac surgery.

"V" aortoplasty of the proximal descending aorta in the elephant trunk procedure.

Complex pathology of the aorta, especially in patients presenting an aneurysm involving the entire aortic arch and proximal descending aorta has been approached in one or two stages. Surgical management of those with an extremely wide diameter of the proximal descending aorta is not yet well defined. The patient in this case was an asymptomatic 47-year-old female with systemic lupus erythematosus (SLE) associated with aneurysm of the ascending aorta, whose aortic arch and descending aorta had presented only overall weakness (examination by inspection and palpation without histological verification). The imaging identified a giant aorta arising at the level of the sinotubular junction (STJ), ending up immediately below the diaphragm. In the first stage she underwent surgical replacement of the entire ascending aorta, aortic arch and proximal part of the descending aorta by combining the elephant trunk with a new type of aortoplasty. In the second stage an endovascular stent graft was inserted into the elephant trunk in the descending aorta. The patient continues to do well 20 months following the repair. In this manuscript type we describe a novel technique of "V" aortoplasty of the proximal descending aorta in order to facilitate the performing of anastomosis between the Dacron graft and aortic aneurysm.

Plantago lanceolata†L. water extract induces transition of fibroblasts into myofibroblasts and increases tensile strength of healing skin wounds.

OBJECTIVES: Although the exact underlying mechanisms are still unknown, Plantago lanceolata L. (PL) water extracts are frequently used to stimulate wound healing and to drain abscesses. Therefore, in this experimental study the effect of PL water extract on skin wound healing was studied in Sprague-Dawley rats. METHODS: Two excisional and one incisional skin wounds were performed on the back of each rat. Wounds were treated for three consecutive days with two different concentrations of the aqueous extract of PL. Rats were sacrificed 7, 14, and 21 days after surgery. Samples of wounds were processed for macroscopic (excisions - wound contraction measurement), biomechanical (incisions - wound tensile strength (TS) measurement) and histological examination (excisions). KEY FINDINGS: It was shown that open wounds treated with PL extract contained myofibroblasts and demonstrated significantly higher contraction rates. Furthermore, significantly increased wound TSs were recorded in treated rats as a consequence of increased organization of extracellular matrix proteins, such as the collagen type 1. CONCLUSIONS: We demonstrated that PL aqueous extract improves skin wound healing in rats. However, further research need to be performed to find optimal therapeutic concentration, and exact underlying mechanism prior obtained results may be introduced into the clinical practice.

Surgical management of a hypoplastic distal aortic arch and coarctation of aorta in a patient with Klippel-Feil syndrome, ascending aortic aneurysm and bicuspid aortic valve.

Klippel-Feil syndrome has been associated with cardiovascular malformations, but only 3 cases have been reported to be associated with aortic coarctation and surgical management is not defined. A 51-year old woman with Klippel-Feil syndrome associated with an aneurysm of the ascending aorta, hypoplastic aortic arch and aortic coarctation at the level of the left subclavian artery presented with shortness of breath 2 years after diagnosis. Imaging identified interim development of a 7.2-cm aneurysm at the level of the aortic coarctation. She underwent surgical repair with a Dacron interposition graft under hypothermic circulatory arrest. She continues to do well 18 months following repair.