Translational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study.

BACKGROUND: Provoked anger is associated with an increased risk of cardiovascular disease events. The underlying mechanism linking provoked anger as well as other core negative emotions including anxiety and sadness to cardiovascular disease remain unknown. The study objective was to examine the acute effects of provoked anger, and secondarily, anxiety and sadness on endothelial cell health. METHODS AND RESULTS: Apparently healthy adult participants (n=280) were randomized to an 8-minute anger recall task, a depressed mood recall task, an anxiety recall task, or an emotionally neutral condition. Pre-/post-assessments of endothelial health including endothelium-dependent vasodilation (reactive hyperemia index), circulating endothelial cell-derived microparticles (CD62E+, CD31+/CD42-, and CD31+/Annexin V+) and circulating bone marrow-derived endothelial progenitor cells (CD34+/CD133+/kinase insert domain receptor+ endothelial progenitor cells and CD34+/kinase insert domain receptor+ endothelial progenitor cells) were measured. There was a group×time interaction for the anger versus neutral condition on the change in reactive hyperemia index score from baseline to 40 minutes (P=0.007) with a mean±SD change in reactive hyperemia index score of 0.20±0.67 and 0.50±0.60 in the anger and neutral conditions, respectively. For the change in reactive hyperemia index score, the anxiety versus neutral condition group by time interaction approached but did not reach statistical significance (P=0.054), and the sadness versus neutral condition group by time interaction was not statistically significant (P=0.160). There were no consistent statistically significant group×time interactions for the anger, anxiety, and sadness versus neutral condition on endothelial cell-derived microparticles and endothelial progenitor cells from baseline to 40 minutes. CONCLUSIONS: In this randomized controlled experimental study, a brief provocation of anger adversely affected endothelial cell health by impairing endothelium-dependent vasodilation.

Impact of Extracorporeal Membrane Oxygenation Bridging Duration on Lung Transplant Outcomes.

BACKGROUND: We sought to characterize the association between venovenous extracorporeal membrane oxygenation (VV-ECMO) bridging duration and outcomes in patients listed for lung transplantation. METHODS: A retrospective observational study was conducted using the Organ Procurement and Transplantation Network (OPTN) database to identify adults (aged ≥18 years) who were listed for lung transplantation between 2016 and 2020 and were bridged with VV-ECMO. Patients were then stratified into groups, determined by risk inflection points, depending on the amount of time spent on pretransplant ECMO: group 1 (≤5 days), group 2 (6-10 days), group 3 (11-20 days), and group 4 (>20 days). Waiting list survival between groups was analyzed using Fine-Gray competing risk models. Posttransplant survival was compared using Cox regression. RESULTS: Of 566 eligible VV-ECMO bridge-to-lung-transplant patients (median age, 54 years, 49% men), 174 (31%), 124 (22%), 130 (23%), and 138 (24%) were categorized as groups 1, 2, 3, and 4, respectively. Overall, median duration of VV-ECMO was 10 days (interquartile range, 1-211 days), and 178 patients (31%) died on the waiting list. In the Fine-Gray model, compared with group 1, patients bridged with longer ECMO durations in group 2 (subdistribution hazard ratio [SHR], 2.95; 95% CI, 1.63-5.35), group 3 (SHR, 3.96; 95% CI, 2.36-6.63), and group 4 (SHR, 4.33; 95% CI, 2.59-7.22, all P < .001) were more likely to die on the waiting list. Of 388 patients receiving a transplant, pretransplant ECMO duration was not associated with 1-year survival in Cox regression. CONCLUSIONS: Prolonged duration of ECMO bridging was associated with worse waiting list mortality but did not impact survival after lung transplant. Prioritization of very early transplantation may improve waiting list outcomes in this population.

Heart Allocation Change and Multiple Temporary Circulatory Support as Bridge-to-Bridge.

INTRODUCTION: We investigated how the 2018 Organ Procurement and Transplantation Network heart allocation policy change was associated with changes in characteristics and outcomes of candidates receiving multiple temporary mechanical circulatory support (mtMCS) devices. MATERIALS AND METHODS: We included adult heart transplant candidates listed October 2014-January 2018 and October 2018-January 2022 in the United Network of Organ Sharing dataset. Prepolicy and postpolicy mtMCS recipients were compared at listing, transplant, 90-days, and 1-year post-transplant. Time between first and second devices and time between first device and transplant were modeled via multivariable linear regression. Transplantation likelihood was modeled using competing risks analysis. RESULTS: Postpolicy, a higher proportion of transplant candidates received mtMCS (4% versus 1%, P < 0.001), and received their second device an adjusted 49 d sooner versus prepolicy (P = 0.001). Time to transplant was also an adjusted 35 d shorter postpolicy, with an 80% increased transplantation likelihood versus prepolicy (95% confidence interval: 1.6-1.9, P < 0.001). Postpolicy patients experienced reduced waitlist mortality (8% versus 14%, P = 0.04) with marked improvements in 90-day (93% versus 85%, P < 0.001) and 1-year (88% versus 70%, P = 0.01) post-transplant survival. CONCLUSIONS: Postpolicy mtMCS recipients are more likely to progress to transplantation sooner on the waitlist and their shorter waitlist course together with earlier change to a secondary device was associated with improved post-transplant survival versus prepolicy.

Thymic Stromal Lymphopoietin Induction Suppresses Lung Cancer Development.

Lung cancer is the leading cause of cancer deaths in the United States and across the world. Immunotherapies, which activate tumor-infiltrating cytotoxic T lymphocytes, have demonstrated efficacy for the treatment of advanced-stage lung cancer. However, the potential for harnessing the immune system against the early stages of lung carcinogenesis to prevent cancer development and recurrence remains unexplored. Using a mouse model of lung adenocarcinoma, we investigated the effects of thymic stromal lymphopoietin (TSLP) induction on early cancer development in the lungs. Herein, we demonstrate that systemic TSLP induction suppressed spontaneous lung cancer development in KrasG12D mice. TSLP drove a significant CD4+ T cell response to block lung cancer progression from atypical alveolar hyperplasia to adenocarcinoma. Our findings suggest that TSLP can be used in the early stages of lung cancer development to trigger a lasting immunity in the tissue and prevent the development of advanced disease.

The stress, salt excretion, and nighttime blood pressure (SABRE) study: Rationale and study design.

Background: Abnormal diurnal patterns of blood pressure (BP) on ambulatory BP monitoring (ABPM), defined by reduced BP dipping or elevated nighttime BP, are associated with increased risk for adverse cardiovascular events. Psychological stress is associated with abnormal diurnal patterns of BP. Exposure to an acute stressor (e.g., mental stress task) normally increases urinary sodium excretion. However, some individuals have sodium retention after stress provocation, revealing substantial between-person variability in the degree of stress-induced sodium excretion. Prior research suggests urinary sodium excretion that does not occur during the daytime may shift toward the nighttime, accompanied by an increase in nighttime BP. Associations between psychological stress and the diurnal patterns of sodium excretion and BP are not yet fully understood. Design: The study is conducted in both the laboratory and naturalistic environment with a multi-racial/ethnic sample of 211 healthy adults. In the laboratory, change in urinary sodium excretion in response to mental stress tasks is examined with pre-/post-stress assessments of sodium excretion. Changes in angiotensin-II, catecholamines, BP, heart rate, endothelin-1, and cortisol are also assessed. In the 24-hour naturalistic environment, the diurnal patterns of sodium excretion and systolic BP are assessed as daytime-to-nighttime ratio of sodium excretion and ABPM, respectively. Ecological momentary assessments of perceived stress are also collected. Summary: The SABRE study investigates previously unexplored associations between stress-induced urinary excretion in the laboratory, diurnal patterns of sodium excretion and BP in the naturalistic environment, and ecological stress. It has high potential to advance our understanding of the role of psychological stress in hypertension.

Improving contemporary outcomes following heart transplantation for cardiac amyloidosis.

BACKGROUND: The incidence of systemic amyloidosis is rising, and there is a concomitant rise in heart transplant for an indication of cardiac amyloidosis. METHODS: We utilized the Organ Procurement and Transplantation Network (OPTN) database to retrospectively assess survival and outcomes in adult patients undergoing heart transplant for cardiac amyloidosis from 1999 to 2019. We also compared survival among four distinct time periods: 1999-2001, 2002-2008, 2008-2015, 2016-2019. RESULTS: Of 41,103 patients, 425 (1.03%) were transplanted for an indication of restrictive cardiomyopathy due to cardiac amyloidosis (RCM-Amyloidosis). The percent of all transplants occurring for RCM-Amyloidosis increased from 0.25% in the 1999-2001 era to 1.74% in the 2015-2019 era (p < .001). Across eras, Kaplan-Meier survival functions were comparable between RCM-Amyloidosis and non-RCM patients at 1 year (88% vs. 89%, p = .56) and at 5 years (72% vs. 77%, p = .092), but worse for RCM-Amyloidosis patients at 10 years (44% vs. 59%, p = .002). With adjustment for other clinical variables in multivariable Cox regression model, RCM-Amyloidosis was not associated with increased risk of death at 1 year (hazard ratio [HR] = 1.11, p = .56) or at 5 years (HR = 1.20, p = .18), but it was associated with increased risk of death at 10 years (HR = 1.35, p = .01). Cardiac amyloidosis was not associated with any morbidity outcomes following transplant, including graft failure, acute rejection, or hospitalization for infection or rejection. CONCLUSIONS: Our data suggest a trend of improving survival among RCM-Amyloidosis patients compared with non-RCM patients across transplant eras, with current similarities in 1- and 5-year survival but a persistent, increased risk of mortality at 10 years.

Long-term survival after heart transplantation for cardiac sarcoidosis.

BACKGROUND: Cardiac sarcoidosis is an increasingly common indication for a heart transplant, but there is a paucity of knowledge with regard to long-term outcomes following transplant. METHODS: We utilized the Organ Procurement and Transplantation Network database to retrospectively analyze adult patients undergoing first-time, single-organ heart transplant between January 1999 and March 2020. RESULTS: Of the 41,447 patients that underwent heart transplant during the study period, 289 (0.7%) were transplanted for a primary diagnosis of restrictive cardiomyopathy due to cardiac sarcoidosis (RCM-Sarcoidosis). RCM-Sarcoidosis was associated with 33% reduced risk of mortality over 10 years compared to non-RCM indications in a multivariable Cox proportional hazards model (p = .03). Ten-year survival functions were improved among RCM-Sarcoidosis compared to this reference group (73.4% [64.2%-80.6%] vs. 59.5% [58.8%-60.1%], p = .002). Among patients transplanted after 1999 who had at least 10 years of follow-up (n = 19,489), median survival of RCM-Sarcoidosis patients was 11.9 [8.3-14.6] years while that of non-RCM patients was 9.9 [4.0-13.1] years. RCM-Sarcoidosis was not associated with an increased risk of secondary outcomes such as graft failure, rejection, or infection. The incidence of retransplant was comparable between RCM-Sarcoidosis and non-RCM patients (1.38% vs. 1.50%, p = .93). CONCLUSIONS: These data suggest that long-term outcomes following transplant for cardiac sarcoidosis are favorable compared to heart transplant for other indications.

Scaled Anatomical Model Creation of Biomedical Tomographic Imaging Data and Associated Labels for Subsequent Sub-surface Laser Engraving (SSLE) of Glass Crystals.

Biomedical imaging modalities like computed tomography (CT) and magnetic resonance (MR) provide excellent platforms for collecting three-dimensional data sets of patient or specimen anatomy in clinical or preclinical settings. However, the use of a virtual, on-screen display limits the ability of these tomographic images to fully convey the anatomical information embedded within. One solution is to interface a biomedical imaging data set with 3D printing technology to generate a physical replica. Here we detail a complementary method to visualize tomographic imaging data with a hand-held model: Sub Surface Laser Engraving (SSLE) of crystal glass. SSLE offers several unique benefits including: the facile ability to include anatomical labels, as well as a scale bar; streamlined multipart assembly of complex structures in one medium; high resolution in the X, Y, and Z planes; and semi-transparent shells for visualization of internal anatomical substructures. Here we demonstrate the process of SSLE with CT data sets derived from pre-clinical and clinical sources. This protocol will serve as a powerful and inexpensive new tool with which to visualize complex anatomical structures for scientists and students in a number of educational and research settings.

Three-dimensional printing of X-ray computed tomography datasets with multiple materials using open-source data processing.

Advances in three-dimensional (3D) printing allow for digital files to be turned into a "printed" physical product. For example, complex anatomical models derived from clinical or pre-clinical X-ray computed tomography (CT) data of patients or research specimens can be constructed using various printable materials. Although 3D printing has the potential to advance learning, many academic programs have been slow to adopt its use in the classroom despite increased availability of the equipment and digital databases already established for educational use. Herein, a protocol is reported for the production of enlarged bone core and accurate representation of human sinus passages in a 3D printed format using entirely consumer-grade printers and a combination of free-software platforms. The comparative resolutions of three surface rendering programs were also determined using the sinuses, a human body, and a human wrist data files to compare the abilities of different software available for surface map generation of biomedical data. Data shows that 3D Slicer provided highest compatibility and surface resolution for anatomical 3D printing. Generated surface maps were then 3D printed via fused deposition modeling (FDM printing). In conclusion, a methodological approach that explains the production of anatomical models using entirely consumer-grade, fused deposition modeling machines, and a combination of free software platforms is presented in this report. The methods outlined will facilitate the incorporation of 3D printed anatomical models in the classroom. Anat Sci Educ 10: 383-391. © 2017 American Association of Anatomists.