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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). Methods:Perfusionists (n = 12 experts and n = 11 trainees) received instructions on how to use the VR simulator and then proceeded to perform the start of cardiopulmonary bypass in the VR environment. Participants then completed a Usefulness, Satisfaction, and Ease of Use Questionnaire. The questions were rated on a 5-point Likert scale, ranging from 1 (fully disagree) to 5 (fully agree), to assess the face validity and content validity of this simulator. Results: Participants reported a predominantly positive experience with the VR-ECC simulator, with 96% (n = 22) agreeing that the simulator was a useful way of training ECC scenarios. All participants found it easy to interact with the software (100%, n = 23), and 82% of students (n = 9) believed it helped them remember the steps involved with initiating ECC. Finally, (87% [n = 20]) of participants believed the image quality and depth perception were good. Conclusions: Our next-generation simulator was valid for face and content constructs, and almost all participants found it to be a useful way of training for ECC scenarios. This simulator represents a first step toward truly blended digital learning and a new interactive, flexible, and innovative modality for perfusion training.

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. The primary binary outcomes were two time targets: (1) delivering three stacked shocks within 1 min and (2) resternotomy within 5 min. Secondary outcomes were the number of protocol mistakes made and a questionnaire after the VR simulator. The conventional training group administered stacked shocks within 1 min in 43% (n = 6) of cases, and none in the VR group reached this target, missing it by an average of 25 s. The resternotomy time target was reached in 100% of the cases (n = 14) in the conventional training group and in 83% of the cases (n = 10) in the VR group. The VR group made 11 mistakes in total versus 15 for those who underwent conventional training. Participants reported that the VR simulator was useful and easy to use. The results show that the VR simulator can provide adequate CSU-ALS training. Moreover, VR training results in fewer mistakes suggesting that repetitive practice in an immersive environment improves skills.

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. In this prospective study, we researched the face validity and content validity of the CPVR-sim. Objective: We designed a prospective study to assess the feasibility and to establish the face and content validity of two clinical scenarios (shockable and nonshockable cardiac arrest) of the CPVR-sim partly divided into a group of novices and experts in performing CPR and emergency resternotomies in patients after cardiac surgery. Methods: Clinicians (staff cardiothoracic surgeons, physicians, surgical residents, nurse practitioners, and medical students) participated in this study and performed two different scenarios, either PEA or combined PEA and ventricular fibrillation. All participants (N=41) performed a simulation and completed the questionnaire rating the simulator's usefulness, satisfaction, ease of use, effectiveness, and immersiveness to assess face validity and content validity. Results: Responses toward face validity and content validity were predominantly positive in both groups. Most participants in the PEA scenario (n=26, 87%) felt actively involved in the simulation, and 23 (77%) participants felt in charge of the situation. The participants thought it was easy to learn how to interact with the software (n=24, 80%) and thought that the software responded adequately (n=21, 70%). All 15 (100%) expert participants preferred VR training as an addition to conventional training. Moreover, 13 (

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. Administration of IL-2 to humans within a clinical trial and of IL-2 receptor (IL-2R)-biased IL-2 to mice resulted in pronounced expansion of type 1 DCs, including migratory and cross-presenting subsets, and type 2 DCs, although neither DC precursors nor mature DCs had functional IL-2Rs. In mechanistic studies, IL-2 signals stimulated innate lymphoid cells, natural killer cells, and T cells to synthesize the cytokines FLT3L, CSF-2, and TNF. These cytokines redundantly caused DC expansion and activation, which resulted in improved antigen processing and correlated with favorable anticancer responses in mice and patients. Thus, IL-2 immunotherapy-mediated stimulation of DCs contributes to anticancer immunity by rendering tumors more immunogenic.

Aleksandra Kapedanovska-Nestorovska,1 Aleksandar J Dimovski,1,2 Zoran Sterjev,1 Nadica Matevska Geskovska,1 Ljubica Suturkova,1 Petar Ugurov,3 Zan Mitrev,4 Rodney Rosalia5 1Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje, Republic of North Macedonia; 2Research Center for Genetic Engineering and Biotechnology “Georgi D.Efremov”, Macedonian Academy of Sciences and Arts, Skopje, Republic of North Macedonia; 3Semi Intensive Care Unit, Zan Mitrev Clinic, Skopje, Republic of North Macedonia; 4Department of Cardiovascular Surgery, Zan Mitrev Clinic, Skopje, Republic of North Macedonia; 5Department of Clinical Research, Zan Mitrev Clinic, Skopje, Republic of North MacedoniaCorrespondence: Rodney RosaliaZan Mitrev Clinic, Bledski Dogovor #8, Skopje 1000, Republic of MacedoniaTel +389 71305957Email rodney.rosalia@zmc.mk Aleksandra Kapedanovska-NestorovskaFaculty of Pharmacy, University Ss Cyril and Methodius, Mother Theresa 47, Skopje 1000, Republic of MacedoniaTel +389 72228998Email alka@ff.ukim.edu.mkAims: The present observational cohort study evaluated the association between the AKR1D1*36 (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.Results: The median follow up time was 38.5 (IQR 24–48) months; Kaplan-Meier/Log-rank analysis showed that patients carrying the AKR1D1*36 allelic variant have a shorter event-free-survival compared to wild type patients, hazard ratio = 2.193 (95% CI, 1.091 to 4.406); p = 0.0155. Multivariable Cox regression analysis confirmed the AKR1D1*36 allele as a

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. In this review we summarize and discuss the features and biological relevance of several enhanced IL-2 formulations, compare these to IL-15-based therapeutics, and try to foreshadow their potential in immunological research and immunotherapy.