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Objectives Surgical repair of Type A aortic dissection (TAAD) requires exclusion of the primary entry tear and reestablishment of flow into the distal true lumen. Provided that the majority of tears occur within the ascending aorta (AA), replacing only that segment seems a safe option; however, this strategy leaves the root susceptible to dilatation and need for reintervention. We aimed to review the outcomes of the two strategies: aortic root replacement (ARR) and isolated ascending aortic replacement. Methods Retrospective analysis of prospectively collected data for all consecutive patients who underwent repair of acute TAAD at our institution from 2015 to 2020 was conducted. Patients were divided into two groups: (1) ARR and (2) isolated AA replacement as index operation for TAAD repair. Primary outcomes were mortality and need for reintervention during the follow-up. Results A total of 194 patients were included in the study; 68 (35%) in the ARR group and 126 (65%) in the AA group. There were no significant differences in postoperative complications or in-hospital mortality (23%; p = 0.51) between groups. Seven patients (4.7%) died during follow-up and eight patients underwent aortic reinterventions, including proximal aortic segments (two patients) and distal procedures (six patients). Conclusion Both aortic root and AA replacement are acceptable and safe techniques. The growth of an untouched root is slow, and reintervention in this aortic segment is infrequent compared with distal aortic segments, hence preserving the root could be an option for older patients provided that there is no primary tear within the root.

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Objective In the United Kingdom, the coronavirus disease 2019 (COVID-19) pandemic has led to the cessation of elective surgery. However, there remains a need to provide urgent and emergency cardiac and thoracic surgery as well as to continue time-critical thoracic cancer surgery. This study describes our early experience of implementing a protocol to safely deliver major cardiac and thoracic surgery in the midst of the pandemic. Methods Data on all patients undergoing cardiothoracic surgery at a single tertiary referral center in London were prospectively collated during the first 7 weeks of lockdown in the United Kingdom. A comprehensive protocol was implemented to maintain a COVID-19-free environment including the preoperative screening of all patients, the use of full personal protective equipment in areas with aerosol-generating procedures, and separate treatment pathways for patients with and without the virus. Results A total of 156 patients underwent major cardiac and thoracic surgery over the study period. Operative mortality was 9% in the cardiac patients and 1.4% in thoracic patients. The preoperative COVID-19 protocol implemented resulted in 18 patients testing positive for COVID-19 infection and 13 patients having their surgery delayed. No patients who were negative for COVID-19 infection on preoperative screening tested positive postoperatively. However, 1 thoracic patient tested positive on intraoperative bronchoalveolar lavage. Conclusions Our early experience demonstrates that it is possible to perform major cardiac and thoracic surgery with low operative mortality and zero development of postoperative COVID-19 infection.

Visualization of three-dimensional (3D) elements has always played a huge role in chemistry education. At the same time, it is a challenge to teach with most representations being shown in two-dimensional (2D) media. With the recent rise of extended reality (XR) that includes virtual and augmented reality (VR/AR) technology in higher education, attempts have been made at presenting 2D representations to students in a manner that is easier to understand. However, the effectiveness of said attempts has limitations. Our AR project has developed a free-to-use mobile application “Nucleophile’s Point of View” (NuPOV) that aims to address these limitations. By allowing users to not only view chemistry concepts in an AR setting but also interact with them by hand, they are able to learn and understand at a deeper level through an individualized and self-directed learning experience. Our study has shown that such an approach proved to be relatively well-received by students.

Collaborative learning in interprofessional team care delivery across different healthcare courses and institutions is constrained by geographical locations and tedious scheduling. Three dimensional virtual environments (3D-VE) are a viable and innovative tool to bring diverse healthcare students to learn together.The aim of this study is to describe the development of a 3D-VE and to evaluate healthcare students' experiences of their collaborative learning in the environment.A mixed methods study design was employed. Participants from six healthcare courses (Medicine, Nursing, Pharmacy, Physiotherapy, Occupational Therapy, and Medical Social Work) were recruited from three institutions to form six interprofessional teams to participate in team care delivery via a 3D-VE. Pre- and post-tests were conducted to evaluate the students' attitudes toward healthcare teams and interprofessional collaboration. Four focus groups were conducted with 27 healthcare students after they completed questionnaires to evaluate their perceived usability, the sociability of computer-supported collaborative learning, and senses of presence. Interview transcripts were analyzed using thematic analysis.The students demonstrated significant improvements in their attitudes toward healthcare teams (p 0.05) and interprofessional collaboration (p 0.001) after the collaborative learning. Four themes emerged from the focus group discussions: "feeling real", whereby the students felt immersed in their own roles; the virtual environment was perceived as "less threatening" compared to face-to-face interactions; "understanding each other's roles" among different healthcare professionals; and there were some "technical hiccups" related to sound quality and navigation. The participants reported positively on the usability (mean 3.48, SD 0.64), feasibility (mean 3.39, SD 0.60) and perceived sense of presence (mean 107.24, SD 17.78) of the 3D-VE in supporting collaborative learning.Given its flexibility, practicality, and scalability, this 3D-VE serves as a promising tool for collaborative learning across different healthcare courses and institutions in preparing for future collaborative-ready workforces.

In chemistry education, the visualization of three-dimensional elements has always played an important role. However, it is challenging to teach such concepts because most of them are being done on two-dimensional media. With the recent prevalent rise of virtual reality and augmented reality (VR/AR) technologies in higher education, there have been many attempts at using these technologies to present the concept to students. However, those attempts have their limitations, and our AR project, “Nucleophile’s Point of View” (NuPOV), aims to address those limitations. By using NuPOV, users could not only view chemistry concepts from the AR interface, but they can also interact with them. These methods enable users to have an individualized and self-directed experience, which enable them to have a better understanding of the concepts. Our study has shown that such an approach proved to be relatively well received by students.

BACKGROUND Epicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. However, EAT’s immune structure and cellular characterization remain incompletely described. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients. METHODS We recruited 152 patients undergoing open-chest coronary artery bypass grafting (CABG), valve repair/replacement (VR) surgery, or combined CABG/VR. Patients’ clinical and biochemical data and EAT, subcutaneous adipose tissue (SAT), and preoperative blood samples were collected. Immune cell profiling was evaluated by flow cytometry and complemented by gene expression studies of immune mediators. Bulk RNA-Seq was performed in EAT across metabolic profiles to assess whole-transcriptome changes observed in lean, obese, and diabetic groups. RESULTS Flow cytometry analysis demonstrated EAT was highly enriched in adaptive immune (T and B) cells. Although overweight/obese and diabetic patients had similar EAT cellular profiles to lean control patients, the EAT exhibited significantly (P ≤ 0.01) raised expression of immune mediators, including IL-1, IL-6, TNF-α, and IFN-γ. These changes were not observed in SAT or blood. Neither underlying coronary artery disease nor the presence of hypertension significantly altered the immune profiles observed. Bulk RNA-Seq demonstrated significant alterations in metabolic and inflammatory pathways in the EAT of overweight/obese patients compared with lean controls. CONCLUSION Adaptive immune cells are the predominant immune cell constituent in human EAT and SAT. The presence of underlying cardiometabolic conditions, specifically obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT. Obese states markedly alter EAT metabolic and inflammatory signaling genes, underlining the impact of obesity on the EAT transcriptome profile. FUNDING Barts Charity MGU0413, Abbott, Medical Research Council MR/T008059/1, and British Heart Foundation FS/13/49/30421 and PG/16/79/32419.

Background: During this SARS-CoV-2 pandemic, there has been unprecedented stress on health care systems, resulting in a change to how services are carried out. The most prominent question for healthcare professionals specialising in cardiac surgery is, should we operate during this pandemic, and to what extent ? Methods: As one of the biggest, specialised cardiac surgery centres in the UK, we researched the available published evidence surrounding this question, to formulate an answer. During this process we considered the potential risks of cardiac surgery during a pandemic on the patients, staff, the healthcare system, and the community. We also considered the immunological aspect of cardiac surgery patients and the risk it entails on them. Results We have discussed the available evidence and consequences of our findings, and we found Patients are subjected to greater risk of catching Covid-19 whilst being in hospital. Patient’s immunity is disrupted for up to 3 months post CPB, which makes them more vulnerable to catch the Covid-19 infection during admission and after discharge. Plus the burden on the whole healthcare system, by using the precious resources and occupying the necessary staff and hospital beds needed during the pandemic surge. Conclusion: Try and minimise cardiac surgery operations down to emergencies or unstable patients who have no other options apart from surgery, particularly during the surge stage of the pandemic. Strictly following structured pathways and protocols, updating relevant protocols with emerging new evidence.

Background Modern medical pedagogical strategies are shifting toward the use of virtual patient simulations. Objective This study aims to examine students' users' attitudes and experiences and clinical facilitators' perspectives on student performances in the clinical setting post-virtual patient training. Design A descriptive qualitative study design was used. Setting Nursing faculty at a local university in Singapore. Participants 24 nursing undergraduates and six clinical facilitators. Methods This study is a follow-up of an experimental study on the Virtual Counseling Application Using Artificial Intelligence (VCAAI). The study took place from the academic year 2017/2018 ended in November 2019. Focus group discussions and individual interviews were conducted. All interviews and focus group discussions were audiotaped, transcribed verbatim, and analyzed using thematic analysis. Results Two overarching themes (students' virtual patient user experience and clinical facilitators' evaluations of students' clinical communication skills) comprising six themes were generated. Themes under students' user experience included: 1) attitudes toward virtual patient training, 2) virtual patient's role in student development, and 3) enhanced features and implementation suggestions. Themes under clinical facilitators' evaluations included: 1) insights on students' communication skills and 2) approaches to improve communication skills. An overlapping theme titled ‘value of technology in teaching communication’ comprised of mutual feedback from both students and clinical facilitators. Early implementation, continued accessibility, enhancing realism and technological improvements to the VCAAI were listed as key areas for program improvement, while increased situational sensitivity and language training are recommended to further enhance students' communication skills. Conclusion The mixed attitudes toward virtual patient interactions and recognitions of the benefits of virtual patient simulations suggest the potential effectiveness of the use of virtual patients in teaching effective nursing communication skills. However, the lack of authenticity and other limitations need to be addressed before official implementations of such trainings with virtual patients to undergraduate nursing curricula.

Airway inflammation is a key aspect of diseases such as asthma. Proinflammatory cytokines such as TNFα mediate the inflammatory response. In various diseases, inflammation leads to endoplasmic reticulum (ER) stress, the accumulation of unfolded proteins, which triggers homeostatic responses to restore normal cellular function. We hypothesized that TNFα triggers ER stress through an increase in reactive oxygen species generation in human airway smooth muscle (hASM) with a downstream effect on mitofusin 2 (Mfn2). In hASM cells isolated from lung specimens incidental to patient surgery, dose- and time-dependent effects of TNFα exposure were assessed. Exposure of hASM to tunicamycin was used as a positive control. Tempol (500 μM) was used as superoxide scavenger. Activation of three ER stress pathways were evaluated by Western blotting: 1) autophosphorylation of inositol-requiring enzyme1 (IRE1α) leading to splicing of X-box binding protein 1 (XBP1); 2) autophosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) leading to phosphorylation of eukaryotic initiation factor 2α; and 3) translocation and cleavage of activating transcription factor 6 (ATF6). We found that exposure of hASM cells to tunicamycin activated all three ER stress pathways. In contrast, TNFα selectively activated the IRE1α/XBP1 pathway in a dose- and time-dependent fashion. Our results indicate that TNFα does not activate the PERK and ATF6 pathways. Exposure of hASM cells to TNFα also decreased Mfn2 protein expression. Concurrent exposure to TNFα and tempol reversed the effect of TNFα on IRE1α phosphorylation and Mfn2 protein expression. Selective activation of the IRE1α/XBP1 pathway in hASM cells after exposure to TNFα may reflect a unique homeostatic role of this pathway in the inflammatory response of hASM cells.

Objectives The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. Background AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. Methods This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro–brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Results In 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro–brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001). Conclusions CMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471), Graphical abstract

Thoracic aortic aneurysm (TAA) represents a major cause of mortality and morbidity in Western countries. The natural history of TAA is indolent, with patients usually being asymptomatic until a catastrophic event such as rupture or dissection ensues. As such, early diagnosis is crucial and the search is ongoing for a biomarker that can indicate the presence of TAA with sufficient accuracy to act as a screening tool. To date, no such marker has been developed for the diagnosis of non-familial or 'sporadic' TAA. However, our increased understanding of the pathogenesis of both familial and sporadic TAA has suggested potential candidates for diagnostic biomarkers. Many markers/pathways have been shown to have differential activity levels or expression in the aortic tissue of TAA. However, priority is given to markers that have shown differential levels in blood plasma, as blood tests represent the easiest route for mass screening for TAA. This review aims to evaluate the efficacy of clinical tests already in use in diagnosing TAA, explore novel proposed biomarkers and identify key areas of future interest.

Purpose Assess angioedema risk with exposure to angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) compared with beta-blockers, by race/ethnicity. Methods New-user cohorts of Medicare beneficiaries 65 years or older initiating ACEI, ARB, or beta-blocker treatment from March 2007 to March 2014 were constructed. Angioedema incidence rates by drug and race/ethnicity were computed for 1-30 and 31-365 days of treatment. Cox proportional hazards regression was used to examine angioedema risk between cohorts. Results Angioedema incidence rates (per 1000 person years) in beta-blocker users were 1.80 (whites), 4.11 (blacks), 1.89 (Asians), and 2.10 (Hispanics); in ACEI users, 4.03, 23.77, 2.94, and 4.27; and in ARB users, 1.73, 3.11, 1.10, and 1.90, respectively. Incidence rates were significantly higher in the first 30 days of exposure for all drug × race/ethnic groups. Overall, angioedema risk increased among ACEI users (hazard ratio, 2.91; 95% confidence interval, 2.75-3.07) but not ARB users (0.93, 0.85-1.02) versus beta-blocker users. Angioedema risk with ACEIs versus beta-blockers increased more in blacks (6.28, 5.44-7.24) than whites (2.33, 2.19-2.48), Hispanics (2.04, 1.36-3.07), and Asians (1.48, 0.94-2.35). Compared with white beta-blocker users, angioedema risk was increased 2.9-fold in whites, 20.2-fold in blacks, and 2.3-fold in other race/ethnic groups combined during the first 30 days of ACEI exposure. Conclusions There was significant effect modification of angioedema risk by race and ACEI use for blacks, but not for other race/ethnicity groups. Angioedema risk was significantly greater in the first 30 days of exposure for all, and highest among blacks.

The ability of nursing undergraduates to communicate effectively with health care providers, patients, and their family members is crucial to their nursing professions as these can affect patient outcomes. However, the traditional use of didactic lectures for communication skills training is ineffective, and the use of standardized patients is not time- or cost-effective. Given the abilities of virtual patients (VPs) to simulate interactive and authentic clinical scenarios in secured environments with unlimited training attempts, a virtual counseling application is an ideal platform for nursing students to hone their communication skills before their clinical postings.The aim of this study was to develop and test the use of VPs to better prepare nursing undergraduates for communicating with real-life patients, their family members, and other health care professionals during their clinical postings.The stages of the creation of VPs included preparation, design, and development, followed by a testing phase before the official implementation. An initial voice chatbot was trained using a natural language processing engine, Google Cloud's Dialogflow, and was later visualized into a three-dimensional (3D) avatar form using Unity 3D.The VPs included four case scenarios that were congruent with the nursing undergraduates' semesters' learning objectives: (1) assessing the pain experienced by a pregnant woman, (2) taking the history of a depressed patient, (3) escalating a bleeding episode of a postoperative patient to a physician, and (4) showing empathy to a stressed-out fellow final-year nursing student. Challenges arose in terms of content development, technological limitations, and expectations management, which can be resolved by contingency planning, open communication, constant program updates, refinement, and training.The creation of VPs to assist in nursing students' communication skills training may provide authentic learning environments that enhance students' perceived self-efficacy and confidence in effective communication skills. However, given the infancy stage of this project, further refinement and constant enhancements are needed to train the VPs to simulate real-life conversations before the official implementation.

BackgroundAn in-house three-dimensional (3D) multiplayer online role-playing game was developed for professional skills training of pharmacy students. Students play the game in a post-apocalyptic world to save humankind from zombies. They solve virtual patient encounters through visual and motion-capture technologies. Their gaming perceptions and experiences were investigated.MethodA self-administered questionnaire obtained participants’ demographics, gaming interests, perceptions of game effectiveness, preferences on gaming elements and gameplay experience through the Game Engagement Questionnaire (GEQ). Pre-gameplay and post-gameplay assessments were tracked to assess student learning. Descriptive statistics and paired sample t-tests were used for analysis.ResultsFifty-five students were recruited. Two-thirds of the gameplay group (67.9%) liked the post-apocalyptic fantasy settings and heroic storyline (66.0%). Three quarters liked the modern setting (73.1%), authentic plots (73.5%) and plot animations (72.3%). Participants felt the game was effective in training health communication and patient history-taking skills (81.8%). Participants’ test scores for counselling increased from 66.1%±7.6% (pre-gameplay) to 70.3%±8.0% (post-gameplay, p=0.004). The highest scoring GEQ dimension was sensory and imaginative immersion (2.92±0.74).ConclusionStudents found the game useful for pharmacy professional skills training. With proper implementation, this game can become a useful tool to enhance student learning and gear them towards clinical practices.

Background The ability of nursing undergraduates to communicate effectively with health care providers, patients, and their family members is crucial to their nursing professions as these can affect patient outcomes. However, the traditional use of didactic lectures for communication skills training is ineffective, and the use of standardized patients is not time- or cost-effective. Given the abilities of virtual patients (VPs) to simulate interactive and authentic clinical scenarios in secured environments with unlimited training attempts, a virtual counseling application is an ideal platform for nursing students to hone their communication skills before their clinical postings. Objective The aim of this study was to develop and test the use of VPs to better prepare nursing undergraduates for communicating with real-life patients, their family members, and other health care professionals during their clinical postings. Methods The stages of the creation of VPs included preparation, design, and development, followed by a testing phase before the official implementation. An initial voice chatbot was trained using a natural language processing engine, Google Cloud’s Dialogflow, and was later visualized into a three-dimensional (3D) avatar form using Unity 3D. Results The VPs included four case scenarios that were congruent with the nursing undergraduates’ semesters’ learning objectives: (1) assessing the pain experienced by a pregnant woman, (2) taking the history of a depressed patient, (3) escalating a bleeding episode of a postoperative patient to a physician, and (4) showing empathy to a stressed-out fellow final-year nursing student. Challenges arose in terms of content development, technological limitations, and expectations management, which can be resolved by contingency planning, open communication, constant program updates, refinement, and training. Conclusions The creation of VPs to assist in nursing students’ communication skills training may provide authentic learning environments that enhance students’ perceived self-efficacy and confidence in effective communication skills. However, given the infancy stage of this project, further refinement and constant enhancements are needed to train the VPs to simulate real-life conversations before the official implementation.

BACKGROUND The ability of nursing undergraduates to communicate effectively with health care providers, patients, and their family members is crucial to their nursing professions as these can affect patient outcomes. However, the traditional use of didactic lectures for communication skills training is ineffective, and the use of standardized patients is not time- or cost-effective. Given the abilities of virtual patients (VPs) to simulate interactive and authentic clinical scenarios in secured environments with unlimited training attempts, a virtual counseling application is an ideal platform for nursing students to hone their communication skills before their clinical postings. OBJECTIVE The aim of this study was to develop and test the use of VPs to better prepare nursing undergraduates for communicating with real-life patients, their family members, and other health care professionals during their clinical postings. METHODS The stages of the creation of VPs included preparation, design, and development, followed by a testing phase before the official implementation. An initial voice chatbot was trained using a natural language processing engine, Google Cloud’s Dialogflow, and was later visualized into a three-dimensional (3D) avatar form using Unity 3D. RESULTS The VPs included four case scenarios that were congruent with the nursing undergraduates’ semesters’ learning objectives: (1) assessing the pain experienced by a pregnant woman, (2) taking the history of a depressed patient, (3) escalating a bleeding episode of a postoperative patient to a physician, and (4) showing empathy to a stressed-out fellow final-year nursing student. Challenges arose in terms of content development, technological limitations, and expectations management, which can be resolved by contingency planning, open communication, constant program updates, refinement, and training. CONCLUSIONS The creation of VPs to assist in nursing students’ communication skills training may provide authentic learning environments that enhance students’ perceived self-efficacy and confidence in effective communication skills. However, given the infancy stage of this project, further refinement and constant enhancements are needed to train the VPs to simulate real-life conversations before the official implementation.

Background This study aimed to evaluate short-term and long-term mortalities in a cohort of unselected hospitalized patients with serum sodium concentration ([Na+]) variations within and outside of reference range. Methods All adult patients admitted to the Mayo Clinic, Rochester, MN, USA from January 2011 to December 2013 (n = 147358) were retrospectively screened. Unique patients admitted during the study period were examined. The main exposure was serum [Na+] variation. Outcome measures were hospital and 1-year all-cause mortalities. Results A total of 60944 patients, mean age 63 ± 17 years, were studied. On admission, 17% (n = 10066) and 1.4% (n = 852) had hypo- and hypernatremia, respectively. During the hospital stay, 11044 and 4128 developed hypo- and hypernatremia, respectively, accounting for 52.3 and 82.9% of the total hypo- and hypernatremic patients. Serum [Na+] variations of ≥6 mEq/L occurred in 40.6% (n = 24 740) of the 60 944 patients and were significantly associated with hospital and 1-year mortalities after adjusting potential confounders (including demographics, comorbidities, estimated glomerular filtration rate, admission serum [Na+], number of [Na+] measurements and length of hospital stay). Adjusted odds ratios for hospital and 1-year mortalities increased with increasing [Na+] variations in a dose-dependent manner, from 1.47 to 5.48 (all 95% confidence intervals >1.0). Moreover, in fully adjusted models, [Na+] variations (≥6 mEq/L) within the reference range (135–145 mEq/L) or borderline hypo- or hypernatremia (133–137 and 143–147 mEq/L, respectively) compared with 138–142 mEq/L were associated with increased hospital and 1-year mortalities. Conclusion In hospitalized adults, [Na+] fluctuation (≥6 mEq/L) irrespective of admission [Na+] and borderline hypo- or hypernatremia are independent predictors of progressively increasing short- and long-term mortality burdens.

Objectives To assess the necessity for balloon aortic valvuloplasty (BAV) during transfemoral transcatheter aortic valve implantation (TAVI) when using balloon-expandable valves. Background BAV is a usual part of TAVI procedures, prior to valve implantation. However, the benefits and necessity of this are unknown and recent evidence in self-expanding valves suggests it may not be necessary. Methods Retrospective single-center study of 154 patients undergoing first-time, transfemoral TAVI for native aortic valve stenosis, with (N = 76), and without (N = 78), BAV as part of the procedure. Data collected included demographic, procedural, and outcome data. Results BAV did not alter VARC-2 defined procedural success or early safety compared to not performing a BAV, including mortality, degree of aortic regurgitation, or need for post-TAVI balloon dilatation, although there was a strong trend to reduced stroke when not performing a BAV. There was a significantly reduced procedural time (P = 0.01) and fluoroscopic time (P

Objectives The aim of this study was to assess the 1-year outcome after transcatheter aortic valve replacement (TAVR) of the Direct Flow Medical (DFM) valve in patients with severe symptomatic aortic stenosis who were contraindicated or high risk for surgery. Background The DFM transcatheter heart valve is a new-generation, nonmetallic aortic valve with a pressurized support structure and conformable double-ring annular sealing delivered through an 18-F sheath. The device allows repositioning, retrieval, and assessment of valve performance before permanent implantation. Methods A prospective multicenter European registry was set up to determine the safety and performance of the valve in 100 consecutive patients (10 centers). Echocardiographic and angiographic data were evaluated by an independent core laboratory, and adverse events were adjudicated by a clinical events committee using Valve Academic Research Consortium criteria. Results Patients were 83.1 ± 5.9 years of age and had a logistic EuroSCORE of 22.5 ± 11.3% and a Society of Thoracic Surgeons score of 9.7 ± 8.7%. Correct valve positioning was obtained in 99% of cases with a combined 30-day safety endpoint at 10%, including major stroke in 5.0%, major vascular complications in 2.0%, and death in 1%. At 12 months, 95% of patients were in New York Heart Association functional class I or II. Freedom from any death was 90%, and freedom from any death or major stroke was 85%. Echocardiography demonstrated none/trace to mild aortic regurgitation in 100% of patients and an unchanged mean aortic gradient of 12.2 ± 6.6 mm Hg and effective orifice area of 1.6 ± 0.4 cm 2 . Conclusions At 1 year, the DFM transcatheter heart valve had durable hemodynamics. This study demonstrates that the low rate of early complications and the low risk of significant aortic regurgitation translated into midterm clinical benefit.

Acute kidney injury (AKI) is a common clinical syndrome directly related to patient short-term and long-term morbidity and mortality. Over the last decade, the occurrence rate of AKI has been increasing, and there has also been a growing epidemic of chronic kidney diseases (CKD) and end-stage kidney disease (ESRD) linked to severe and repeated episodes of AKIs. The detection and management of AKI are currently far from satisfactory. A large proportion of AKI patients, especially those with preexisting CKD, are at an increased risk of non-resolving AKI and progressing to CKD and ESRD. Proposed pathological processes that contribute to the transition of AKI to CKD and ESRD include severity and frequency of kidney injury, alterations of tubular cell phenotype with cells predominantly in the G2/M phase, interstitial fibrosis and microvascular rarification related to loss of endothelial-pericyte interactions and pericyte dedifferentiation. Innate immune responses, especially dendritic cell responses related to inadequate adenosine receptor (2a)-mediated signals, autophagic insufficiency and renin-angiotensin system activation have also been implicated in the progression of AKI and transitions from AKI to CKD and ESRD. Although promising advances have been made in understanding the pathophysiology of AKI and AKI consequences, much more work needs to be done in developing biomarkers for detecting early kidney injury, prognosticating kidney disease progression and developing strategies to effectively treat AKI and to minimize AKI progression to CKD and ESRD.

BACKGROUND With the availability and capabilities of varied technologically enhanced learning activities, the blended learning approach has become increasingly popular in interprofessional education. The combined use of different technologically enhanced learning activities has not been fully examined, particularly to determine the effects of instructional sequences for effective learning outcomes. OBJECTIVE The objective of this study was to investigate whether the instructional sequences of a blended learning approach can improve students’ learning outcomes on interprofessional competencies. METHODS A randomized controlled study was conducted with 40 interprofessional health care teams. These teams undertook three technologically enhanced learning activities—Web-based instruction (WI), virtual reality (VR), and simulation exercise (SE)—after random assignment to three groups based on three different instructional sequences (WI-VR-SE, WI-SE-VR, and SE-WI-VR). Pretests and posttests were conducted to evaluate the students’ learning outcomes on interprofessional competencies. RESULTS A total of 198 participants from the three groups completed the questionnaires. All three groups reported significant improvement in their levels of self-efficacy (P CONCLUSIONS This study shows that the instructional sequence of a blended learning approach can have a significant impact on students’ learning outcomes. The learning of concepts from WI followed by problem-solving activity in the SE was found to be a more effective learning sequence than the reverse sequence. We recommend that future studies focus on scaffolding students’ learning when planning instructional sequences for technologically enhanced learning activities within blended learning environments.

An aneurysm of an aberrant subclavian artery is un usual prevalence of anomalies of aortic arch, with a literature reported prevalence of 2%. Timely elective intervention is of paramount. The advancement in stenting techniques has promoted this practice to be an alternative to conventional open surgical repair which is associated with high rates of perioperative complications including mortality outcomes. However, new faces of this old disease are emerging as we move to novelty and innovation era. We discuss in this review the advancements in this disease entity highlighting and collecting the world experiences.

Aortic prosthesis choice is controversial in young adults because robust comparative outcome data are lacking. We therefore compared mortality and morbidity in young adults after bioprosthetic versus mechanical aortic valve replacement.This was a retrospective analysis of 5111 patients aged 18 to 50 years undergoing primary aortic valve replacement in California and New York State from 1997 to 2006. Median follow-up time was 11.8 years (maximum 18.9 years). The primary endpoint was mortality; secondary endpoints were stroke, bleeding, and reoperation. Propensity score matching yielded 1175 patient pairs.Bioprosthetic valves increased from 14% to 47% of aortic valve replacements between 1997 and 2014 (P .001). There was no survival difference with bioprosthetic versus mechanical aortic valves in the propensity score-matched cohort: actuarial 15-year survival was 79.0% (95% confidence interval [CI], 75.8%-81.8%) versus 81.5% (95% CI, 78.5%-84.2%) respectively (hazard ratio [HR], 1.14; 95% CI, 0.93-1.40, P = .20). No interaction was found between age and prosthesis choice on survival (PAlthough lifetime risks are represented incompletely, these findings suggest that in adults aged 18-50 years, bioprostheses are a reasonable alternative to mechanical valves for aortic valve replacement.

BACKGROUND There has been a dearth of collaborative learning across tertiary institutions due to challenges in scheduling and geographical locations. Three-dimensional virtual environments are a viable and innovative tool to bring diverse healthcare students to learn together. OBJECTIVE The purpose of this study is to describe the development of a multiuser virtual environment and to evaluate healthcare students’ experiences of their collaborative learning in the environment. METHODS A mixed method study design was employed. Participants from six healthcare courses (Medicine, Nursing, Pharmacy, Physiotherapy, Occupational Therapy, and Medical Social Work) were recruited from three institutions to form six interprofessional healthcare teams who participated in interdisciplinary team care via a virtual environment. Four focus groups were conducted with 27 healthcare students after they completed questionnaires to evaluate their perceived usability, the sociability of computer-supported collaborative learning, and senses of presence. Interview transcripts were analyzed using thematic analysis. RESULTS Four themes emerged from the students’ experiences: “Bringing everyone together” to learn in the virtual platform was perceived as a valuable experience; “Feeling real”, whereby the students felt immersed in their own healthcare profession’s roles; learning in the virtual environment was perceived as “less threatening” compared to face-to-face interactions; and there were some “technical hiccups” related to sound quality and navigation. The participants reported positively on the usability (mean 3.48, SD 0.64) and feasibility (mean 3.39, SD 0.60) of the virtual environment in supporting collaborative learning. With a maximum score of 168, they also perceived a moderately strong sense of presence (mean 107.24, SD 17.78) in the environment. CONCLUSIONS This study provides evidence for the acceptance of a virtual platform for collaborative learning in team care delivery. Given its flexibility, practicality, and scalability, this virtual platform serves as a promising tool for collaborative learning across different healthcare courses and institutions.

Background Sulfonamide antibacterials are widely used in pregnancy, but evidence about their safety is mixed. The objective of this study was to assess the association between first-trimester sulfonamide exposure and risk of specific congenital malformations. Methods Mother–infant pairs were selected from a cohort of 1.2 million live-born deliveries (2001–2008) at 11 US health plans comprising the Medication Exposure in Pregnancy Risk Evaluation Program. Mothers with first-trimester trimethoprim–sulfonamide (TMP-SUL) exposures were randomly matched 1:1 to (i) a primary comparison group (mothers exposed to penicillins and/or cephalosporins) and (ii) a secondary comparison group (mothers with no dispensing of an antibacterial, antiprotozoal, or antimalarial medication during the same time period). The outcomes were cardiovascular abnormalities, cleft palate/lip, clubfoot, and urinary tract abnormalities. Results We first identified 7615 infants in the TMP-SUL exposure group, of which 7595 (99%) were exposed to a combination of TMP-SUL and the remaining 1% to sulfonamides alone. After matching (1:1) to the comparator groups and only including those with complete data on covariates, there were 20 064 (n = 6688 per group) in the primary analyses. Overall, cardiovascular defects (1.52%) were the most common and cleft lip/palate (0.10%) the least common that were evaluated. Compared with penicillin/cephalosporin exposure, and no antibacterial exposure, TMP-SUL exposure was not associated with statistically significant elevated risks for cardiovascular, cleft lip/palate, clubfoot, or urinary system defects. Conclusions First-trimester TMP-SUL exposure was not associated with a higher risk of the congenital anomalies studied, compared with exposure to penicillins and/or cephalosporins, or no exposure to antibacterials. Copyright © 2015 John Wiley & Sons, Ltd.

Management of aortic valve disease and, in particular, aortic valve stenosis has evolved through the course of time from medical management and balloon valvuloplasty to the presumed gold-standard surgical intervention. However, with the advent of surgical innovation, intra- and postoperative patients monitoring, understanding of hemodynamic dysfunction, and choices of prosthesis, conventional surgical aortic valve replacements are currently being challenged in particular in moderate- and high-risk patients. Although the long-term results and survival are not robustly available, the durability of the new prosthesis, repair, and the freedom from reoperation remain debatable. In this review, we aim to highlight the surgical innovation attained, choices of aortic valve prosthesis, and also dwell on the current evidence, practice, and trend steered to managing patients with aortic valve stenosis.

Objectives Remote ischaemic preconditioning (RIPC), using brief cycles of limb ischaemia/reperfusion, is a non-invasive, low-cost intervention that may reduce perioperative myocardial injury (PMI) in patients undergoing cardiac surgery. We investigated whether RIPC can also improve short-term clinical outcomes. Methods One hundred and eighty patients undergoing elective coronary artery bypass graft (CABG) surgery and/or valve surgery were randomised to receive either RIPC (2–5 min cycles of simultaneous upper arm and thigh cuff inflation/deflation; N=90) or control (uninflated cuffs placed on the upper arm and thigh; N=90). The study primary end point was PMI, measured by 72 h area under the curve (AUC) serum high-sensitive troponin-T (hsTnT); secondary end point included short-term clinical outcomes. Results RIPC reduced PMI magnitude by 26% (−9.303 difference (CI −15.618 to −2.987) 72 h hsTnT-AUC; p=0.003) compared with control. There was also evidence that RIPC reduced the incidence of postoperative atrial fibrillation by 54% (11% RIPC vs 24% control; p=0.031) and decreased the incidence of acute kidney injury by 48% (10.0% RIPC vs 21.0% control; p=0.063), and intensive care unit stay by 1 day (2.0 days RIPC (CI 1.0 to 4.0) vs 3.0 days control (CI 2.0 to 4.5); p=0.043). In a post hoc analysis, we found that control patients administered intravenous glyceryl trinitrate (GTN) intraoperatively sustained 39% less PMI compared with those not receiving GTN, and RIPC did not appear to reduce PMI in patients given GTN. Conclusions RIPC reduced the extent of PMI in patients undergoing CABG and/or valve surgery. RIPC may also have beneficial effects on short-term clinical outcomes, although this will need to be confirmed in future studies. Trial registration number ClinicalTrials.gov ID: NCT00397163.

ObjectivesThe study sought a prospective multicenter nonrandomized evaluation of the Direct Flow Medical (DFM) system for the treatment of severe aortic stenosis.BackgroundThe DFM transcatheter aortic valve system is a nonmetallic design with a pressurized support structure that allows precise positioning, retrieval, and assessment of valve performance prior to permanent implantation.MethodsOne hundred high surgical risk patients with severe aortic stenosis were evaluated for the primary endpoint. There were 75 patients in the group evaluable for the secondary endpoints and 25 in the pre-specified roll-in training phase. Echocardiographic and angiographic data were evaluated by an independent core laboratory and adverse events adjudicated by clinical event committee and classified according to Valve Academic Research Consortium (VARC) criteria.ResultsThere was 99% freedom from all cause mortality at 30 days (primary endpoint). VARC criteria defined 30 day combined freedom from patient safety event rate was 91% and overall device success was 93%. The post-implantation echocardiography results demonstrated mild or no aortic regurgitation in 99% (73 of 74) with a mean gradient of 12.6 ± 7.1 mm Hg (n = 72) and effective orifice area of 1.50 ± 0.56 cm2 and New York Heart Association functional class was I or II in 92% of cases.ConclusionsThe present study demonstrates the safety and efficacy of the DFM system in surgical high risk patients with severe aortic stenosis and complex anatomy aortic regurgitation was less than moderate in 99% of patients.

Objective: This study aimed to investigate the predictive value of circumferential iliofemoral calcifications and current manufacturer recommendations, which are not evidence-based, in transfemoral (TF) transcatheter aortic valve implantation (TAVI) Methods: A patient cohort with a broad range of iliofemoral anatomies undergoing TF TAVI (n=132) were retrospectively divided as “suitable” (n=76, 58%) and “unsuitable” (n=56, 42%) candidates according to current recommendations. Iliofemoral angiography and reconstructed mul- tislice CT (MSCT) images were used for access screening in the majority of patients. Results: Vessel properties were significantly worse in the “unsuitable group.” The sheath-to-iliofemoral artery ratio (SIFAR) and calcium score were 1.35±0.2 and 1.7±0.8 in the unsuitable group, compared to 1.0±0.12 (p

Background: With the availability and capabilities of varied technologically enhanced learning activities, the blended learning approach has become increasingly popular in interprofessional education. The combined use of different technologically enhanced learning activities has not been fully examined, particularly to determine the effects of instructional sequences for effective learning outcomes. Objective: The objective of this study was to investigate whether the instructional sequences of a blended learning approach can improve students’ learning outcomes on interprofessional competencies. Methods: A randomized controlled study was conducted with 40 interprofessional health care teams. These teams undertook three technologically enhanced learning activities—Web-based instruction (WI), virtual reality (VR), and simulation exercise (SE)—after random assignment to three groups based on three different instructional sequences (WI-VR-SE, WI-SE-VR, and SE-WI-VR). Pretests and posttests were conducted to evaluate the students’ learning outcomes on interprofessional competencies. Results: A total of 198 participants from the three groups completed the questionnaires. All three groups reported significant improvement in their levels of self-efficacy (P

AIMS: The aim of this study was to introduce and demonstrate the feasibility in an acute preclinical model of a new transcatheter heart valve concept with a self-expanding wire frame, polymeric leaflets and a sealing component. METHODS AND RESULTS: The TRISKELE valve was developed based on a previously validated polymeric leaflet design, an adaptive sealing cuff and a novel nitinol wire frame which reduces stress on the leaflets and radial pressure on the surrounding tissue. A valve prototype of 26 mm nominal diameter was manufactured by automated dip coating of a biostable polymer. The prototype was implanted via brachiocephalic approach in orthotopic position in an acute ovine model through a highly controllable multistage deployment process. The atraumatic retrievability of the valve after full expansion was verified in situ before final release in the optimal position. Observation indicated secure valve anchoring, adequate leaflet motion, and no interference of coronary flow or mitral valve function. CONCLUSIONS: The TRISKELE valve system has the potential to mitigate complications related to imprecise valve positioning, and may offer a safer and more economical TAVI solution to a broad range of patients. The valve is currently under preclinical investigation for its long-term function and durability.

Intestinal failure-associated liver disease (IFALD) is complex and diagnosed by concurrent use of parenteral nutrition, clinical presentation, and alterations in hepatic biomarkers exclusive of other causes of liver disease. In comparison with individual measures, composite biomarkers may provide a more effective means for assessing disease progression and response to treatment than single parameters. Since IFALD is considered by some to be a type of drug-induced liver injury (DILI), those diagnostic criteria could potentially be used in this population. Using a preexisting database of children treated for IFALD, our aim was to determine if a similar composite biomarker could be applied to this population.Adult DILI criteria were applied at baseline, when treatment for IFALD (ie, direct bilirubin ≥2.0 mg/dL) was initiated.A total of 214 patients with IFALD treated at Boston Children's Hospital were identified; 168 patients were eligible for analysis. Most patients analyzed were male (61%) and preterm (87%). Alkaline phosphatase (ALP) ≥2× upper limit of normal (ULN) captured the least amount of DILI (11%), while γ-glutamyltransferase (GGT) ≥1× ULN accounted for the most (62%). Using adult DILI criteria, 60 (39%) patients with IFALD were found to have DILI. Substituting GGT ≥1× ULN for ALP ≥2× ULN improved the sensitivity, with 105 (69%) of patients meeting at least 1 criterion for DILI.Numerous challenges made it difficult to apply the DILI criteria to children with IFALD. Direct bilirubin, fractionated ALP, and perhaps GGT may be more suitable. Given its complex etiology and the age-based differences due to hepatic immaturity and growth, a more suitable composite marker needs to be developed to assess IFALD in this population.

To assess the necessity for balloon aortic valvuloplasty (BAV) during transfemoral transcatheter aortic valve implantation (TAVI) when using balloon-expandable valves.BAV is a usual part of TAVI procedures, prior to valve implantation. However, the benefits and necessity of this are unknown and recent evidence in self-expanding valves suggests it may not be necessary.Retrospective single-center study of 154 patients undergoing first-time, transfemoral TAVI for native aortic valve stenosis, with (N = 76), and without (N = 78), BAV as part of the procedure. Data collected included demographic, procedural, and outcome data.BAV did not alter VARC-2 defined procedural success or early safety compared to not performing a BAV, including mortality, degree of aortic regurgitation, or need for post-TAVI balloon dilatation, although there was a strong trend to reduced stroke when not performing a BAV. There was a significantly reduced procedural time (P = 0.01) and fluoroscopic time (P 0.001) without performing a BAV. There were no differences in cerebral embolization (solid, gaseous, or total emboli) noted between the 2 groups, as measured on transcranial doppler (TCD).TAVI can be effectively and safely performed without a BAV and this results in reduced procedural and fluoroscopic times, although embolization to the brain is not reduced. There is a trend toward reduced stroke risk. (J Interven Cardiol 2016;29:319-324).

The purpose of this review is to objectively evaluate the biochemical and pathophysiological properties of 0.9% saline (henceforth: saline) and to discuss the impact of saline infusion, specifically on systemic acid-base balance and renal hemodynamics. Studies have shown that electrolyte balance, including effects of saline infusion on serum electrolytes, is often poorly understood among practicing physicians and inappropriate saline prescribing can cause increased morbidity and mortality. Large-volume (>2 L) saline infusion in healthy adults induces hyperchloremia which is associated with metabolic acidosis, hyperkalemia, and negative protein balance. Saline overload (80 ml/kg) in rodents can cause intestinal edema and contractile dysfunction associated with activation of sodium-proton exchanger (NHE) and decrease in myosin light chain phosphorylation. Saline infusion can also adversely affect renal hemodynamics. Microperfusion experiments and real-time imaging studies have demonstrated a reduction in renal perfusion and an expansion in kidney volume, compromising O2 delivery to the renal parenchyma following saline infusion. Clinically, saline infusion for patients post abdominal and cardiovascular surgery is associated with a greater number of adverse effects including more frequent blood product transfusion and bicarbonate therapy, reduced gastric blood flow, delayed recovery of gut function, impaired cardiac contractility in response to inotropes, prolonged hospital stay, and possibly increased mortality. In critically ill patients, saline infusion, compared to balanced fluid infusions, increases the occurrence of acute kidney injury. In summary, saline is a highly acidic fluid. With the exception of saline infusion for patients with hypochloremic metabolic alkalosis and volume depletion due to vomiting or upper gastrointestinal suction, indiscriminate use, especially for acutely ill patients, may cause unnecessary complications and should be avoided. More education regarding saline-related effects and adequate electrolyte management is needed.

Aims Haemodynamics alone do not fully explain symptoms and prognosis in clinically severe aortic stenosis (AS). Myocardial disease, specifically diffuse myocardial fibrosis (DMF), may contribute. We used equilibrium contrast cardiovascular magnetic resonance (EQ-CMR) and sought to non-invasively measure DMF in severe AS and determine its clinical significance before and after valve replacement. Methods and results Patients with severe AS underwent echocardiography, brain natriuretic peptide (BNP), 6 min walk test (6MWT), and EQ-CMR pre- ( n = 63) at baseline and at 6 months post- ( n = 42) aortic valve replacement (AVR). EQ-CMR was also performed in 30 normal controls. Baseline : patients with AS had more DMF than controls (18 vs. 13%, P = 0.007) with a wide range (5–38%) that overlapped controls. The extent of diffuse fibrosis correlated inversely with the 6MWT performance ( r 2 = 0.22, P = 0.001). Those with severe diastolic dysfunction had more DMF ( P = 0.01). On multivariable analysis, the predictors of performance at 6MWT were diffuse fibrosis and BNP ( P = 0.003 and 0.02, respectively). Post-op: following valve replacement, morphological and functional parameters improved [6 MWT, LA area, BNP, left ventricular (LV) hypertrophy, and volumes]. LV hypertrophy regression was shown to be cell volume reduction ( P < 0.001) and not fibrosis regression ( P = 0.54). Of the five deaths over six-month follow-up, four occurred in patients in the highest tertile of DMF. Conclusion DMF as measured by EQ-CMR is elevated in severe AS vs. normal controls but with a considerable overlap. It correlates with functional capacity at baseline. LV hypertrophy regression 6 months after AVR is cellular rather than fibrosis resolution.

Airway inflammation plays a key role in asthma. In various diseases, inflammation leads to an increase in reactive oxygen species (ROS) generation and is associated with accumulation of unfolded pr...