Virtual reality simulation as a training tool for perfusionists in extracorporeal circulation: Establishing face and content validity.

Objective: We conducted a prospective study to assess the face and content validity of a new virtual reality (VR) extracorporeal circulation simulator (ECC) developed for perfusionists to facilitate training and practice. We evaluated the opinions of students and staff members about the feasibility of the simulation. The 2 groups consisted of experts (qualified perfusionists) and novices (trainee perfusionists).

Virtual Reality Simulator versus Conventional Advanced Life Support Training for Cardiopulmonary Resuscitation Post-Cardiac Surgery: A Randomized Controlled Trial.

External chest compressions are often ineffective for patients arresting after cardiac surgery, for whom emergency resternotomy may be required. A single-blinded randomized controlled trial (RCT) was performed, with participants being randomized to a virtual reality (VR) Cardiac Surgical Unit Advanced Life Support (CSU-ALS) simulator training arm or a conventional classroom CSU-ALS training arm. Twenty-eight cardiothoracic surgery (CTS) residents were included and subsequently assessed in a moulage scenario in groups of two, either participating as a leader or surgeon.

A Role of Circuit Clotting and Strategies to Prevent It during Blood Purification Therapy with oXiris Membrane: An Observational Multicenter Study.

Introduction: Membrane fouling is a significant complication potentially reducing clinical effects of extracorporeal blood purification (EBP) in critically ill septic patients with acute kidney injury. Although fascinating, the effect of heparin coating in preventing membrane fouling is currently unknown. This multicenter prospective study aims to preliminary describe the incidence, associated factors, and clinical consequences of premature circuit clotting in a cohort of adult critically ill septic patients treated with EBP using a high biocompatible heparin-coated hemodiafilter characterized by advanced adsorption properties.

Preoperative Left Ventricular Global Longitudinal Strain Identifies Aortic Stenosis Patients with Improved Postoperative Recovery of Left Ventricular Geometry: A Prospective Cohort Study.

Introduction: The left ventricular ejection fraction (LVEF) is commonly used as a marker of aortic stenosis (AS) disease severity and to indicate surgical intervention. However, an LVEF <50% identifies mainly advanced disease. Hence, earlier detection of subclinical LV systolic dysfunction may improve clinical decision-making.

Virtual Reality Simulation Training for Cardiopulmonary Resuscitation After Cardiac Surgery: Face and Content Validity Study.

Background: Cardiac arrest after cardiac surgery commonly has a reversible cause, where emergency resternotomy is often required for treatment, as recommended by international guidelines. We have developed a virtual reality (VR) simulation for training of cardiopulmonary resuscitation (CPR) and emergency resternotomy procedures after cardiac surgery, the Cardiopulmonary Resuscitation Virtual Reality Simulator (CPVR-sim). Two fictive clinical scenarios were used: one case of pulseless electrical activity (PEA) and a combined case of PEA and ventricular fibrillation.

Extracorporeal Blood Purification in Moderate and Severe COVID-19 Patients: A Prospective Cohort Study.

Introduction: Coronavirus disease 2019 (COVID-19) is characterized by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and with critical cases progressing to acute respiratory distress syndrome. Control of hyperinflammation has been proposed as a possible therapeutic avenue for COVID-19; extracorporeal blood purification (EBP) modalities offer an attractive mean to ameliorate maladaptive inflammation.

Aortic Valve Neocuspidization Using Xenologous Pericardium Versus Bioprosthetic Valve Replacement.

Background: Surgical aortic valve replacement (SAVR) for patients with aortic valve stenosis (AS) with small aortic root is associated with a higher rate of prosthesis-patient mismatch and suboptimal clinical outcomes. Aortic valve neocuspidization using xenologous pericardium (xAVNeo) has shown a favorable hemodynamic performance. The aim was to compare 6-year clinical outcomes of xAVNeo with SAVR.

Polyphenols and avenanthramides extracted from oat (Avena sativa L.) grains and sprouts modulate genes involved in glucose and lipid metabolisms in 3T3 L1 adipocytes.

This study aimed to evaluate the effect of polyphenol (PE) and avenanthramide (AE) extracts from oat grains (OG) and sprouts (OS) on genes related to glucose and lipid metabolisms in 3T3 L1 adipocytes. The AE-OS exerted the greatest effect on genes involved in glucose metabolism, increasing Glut4, Irs1, and Pi3k expression by 3.0- to 3.

Perspectives on Repurposed Drugs Based on Globally Accepted Therapeutic Guidelines to Combat SARS-CoV-2 Infection.

A beta coronavirus was identified in Wuhan, China, in December 2019 and was named severe acute respiratory syndrome coronavirus-2. It spread globally at a rapid rate and killed innumerable people. The SARS-CoV-2 infection, also called coronavirus disease 2019, was declared a pandemic by WHO on March 11, 2020.

Minimally Invasive Surgical Repair of Vertebral Artery Ostium Stenosis in Patients with Ischemic Stroke: A Single-Center Case Series.

Background: Ischemic stroke is the second leading cause of death in North Macedonia. Posterior circulation disease, caused by vertebral artery (VA) ostium (VAo) stenosis, is a common cause of ischemic stroke. We established a treatment approach using surgical revascularization of posterior circulation disease.

Early Initiation of Extracorporeal Blood Purification Using the AN69ST (oXiris) Hemofilter as a Treatment Modality for COVID-19 Patients: a Single-Centre Case Series.

Introduction: Severe coronavirus disease 2019 (COVID-19) is characterised by hyperinflammatory state, systemic coagulopathies, and multiorgan involvement, especially acute respiratory distress syndrome (ARDS). We here describe our preliminary clinical experience with COVID-19 patients treated via an early initiation of extracorporeal blood purification combined with systemic heparinisation and respiratory support.

Methods: Fifteen patients were included; several biomarkers associated with COVID-19 severity were monitored.

Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines.

Coronavirus disease 2019 (COVID-19) has swept the world, unlike any other pandemic in the last 50 years. Our understanding of the disease has evolved rapidly since the outbreak; disease prognosis is influenced mainly by multi-organ involvement. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure are strongly associated with morbidity and mortality.

Interleukin-2 signals converge in a lymphoid-dendritic cell pathway that promotes anticancer immunity.

Tumor-infiltrating dendritic cells (DCs) correlate with effective anticancer immunity and improved responsiveness to anti-PD-1 checkpoint immunotherapy. However, the drivers of DC expansion and intratumoral accumulation are ill-defined. We found that interleukin-2 (IL-2) stimulated DC formation through innate and adaptive lymphoid cells in mice and humans, and this increase in DCs improved anticancer immunity.

Outcomes with Ventricular Assist Device Therapy for Advanced Heart Failure in North Macedonia: First Annual Report.

Introduction: Mechanical circulatory support by a continuous-flow ventricular assist device (VAD) improves survival and quality of life in selected patients with advanced heart failure. Developing countries have been struggling to construct a contemporary and effective health care system to manage advanced heart failure. This observation represents the first annual report on clinical outcomes with VAD for patients with advanced heart failure in the Republic of North Macedonia.

Workflow for the Implementation of Precision Genomics in Healthcare.

To enable the implementation of precise genomics in a local healthcare system, we devised a pipeline for filtering and reporting of relevant genetic information to healthy individuals based on exome or genome data. In our analytical pipeline, the first tier of filtering is variant-centric, and it is based on the selection of annotated pathogenic, protective, risk factor, and drug response variants, and their one-by-one detailed evaluation. This is followed by a second-tier gene-centric deconstruction and filtering of virtual gene lists associated with diseases, and VUS-centric filtering according to ACMG pathogenicity criteria and pre-defined deleteriousness criteria.

A Pediatric Case of Glioblastoma Multiforme Associated With a Novel Germline p.His112CysfsTer9 Mutation in the Gene Accompanied by a p.Arg283Cys Mutation in the Gene: A Case Report.

Targeted gene panel testing has the power to interrogate hundreds of genes and evaluate the genetic risk for many types of hereditary cancers simultaneously. We screened a 13-year-old male patient diagnosed with glioblastoma multiforme with the aim to get further insights into the biology of his condition. Herein, we applied gene panel sequencing and identified a heterozygous frameshift mutation c.

The () Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome.

Aims: The present observational cohort study evaluated the association between the (rs1872930) allele and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in clopidogrel treated patients.

Methods: We screened 198 consecutive cardiovascular patients on clopidogrel therapy admitted in October to November 2010 with cardiovascular or cerebrovascular symptoms; of these 118 met the study protocol entry criteria; the median age of the cohort was 62.5 years (IQR 57-66 years), and 55% were females.

Continuous venovenous hemodiafiltration using cytokine-adsorbing hemofilters as adjuvant therapy for anaerobic descending necrotizing mediastinitis: a case report.

Background: We describe a combinatorial intensive care approach and discuss the critical factors that allowed us to successfully manage a life-threatening case of acute anaerobic septic shock triggered by descending necrotizing mediastinitis.

Case Presentation: We admitted a 38-year-old critically ill Kosovar Albanian man to our intensive care unit because of clinical manifestations of severe sepsis. His condition had worsened in the previous 2 weeks following unsuccessful antibiotic therapy for tonsillitis complicated by retropharyngeal abscesses.

Cardiac autotransplantation and ex vivo surgical repair of giant left atrium: a case presentation.

Background: Chronic Mitral Valve disease is strongly associated with Left atrial enlargement; the condition has a high mortality risk. Clinical manifestations include atrial fibrillation, pulmonary hypertension, thromboembolic events, and in cases of Giant Left Atrium (GLA) and a distorted cardiac silhouette. Full sternotomy, conventional open-heart surgery, reductive atrioplasty and atrioventricular valve repair are required to resolve symptoms.

Fibroma of the breast: a rare tumour in the spectrum of the benign spindle cell tumours of the mammary stroma.

Benign spindle cell tumours of the mammary stroma comprises different lesions that show a variable degree of fibroblastic/myofibroblastic differentiation. We herein report a previously under-recognised hypocellular fibrocollagenous tumour of the breast, for which the term "fibroma" is proposed. The tumour was composed of CD34-positive bland-looking spindle cells embedded in an abundant hyalinised stroma.

The Histone Methyltransferase Ezh2 Controls Mechanisms of Adaptive Resistance to Tumor Immunotherapy.

Immunotherapy and particularly immune checkpoint inhibitors have resulted in remarkable clinical responses in patients with immunogenic tumors, although most cancers develop resistance to immunotherapy. The molecular mechanisms of tumor resistance to immunotherapy remain poorly understood. We now show that induction of the histone methyltransferase Ezh2 controls several tumor cell-intrinsic and extrinsic resistance mechanisms.

Poly-(lactic-co-glycolic-acid)-based particulate vaccines: particle uptake by dendritic cells is a key parameter for immune activation.

Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects the type and magnitude of the immune response in comparison to sustained release from a local depot. PLGA microparticles (MP, volume mean diameter≈112 μm) and nanoparticles (NP, Z-average diameter≈350 nm) co-encapsulating ovalbumin (OVA) and poly(I:C), with comparable antigen (Ag) release characteristics, were prepared and characterized.

CD40-targeted dendritic cell delivery of PLGA-nanoparticle vaccines induce potent anti-tumor responses.

Dendritic cells (DC) play a prominent role in the priming of CD8(+) T cells. Vaccination is a promising treatment to boost tumor-specific CD8(+) T cells which is crucially dependent on adequate delivery of the vaccine to DC. Upon subcutaneous (s.

Use of enhanced interleukin-2 formulations for improved immunotherapy against cancer.

The use of interleukin-2 (IL-2) for the stimulation of an effector immune response against metastatic cancer dates back to the early 1980s. Administration of unmodified IL-2, either alone or together with antigen-specific approaches, has resulted in remarkably long-term survival of some patients suffering from metastatic melanoma. However, such treatment is usually hampered by the appearance of toxic adverse effects, which has motivated the engineering of modified IL-2 formulations showing reduced toxicity while being more potent at stimulating anti-tumor effector immune cells.