Faculty Bibliography

BACKGROUND:Despite recent improvements in radiation safety, interventionalists are increasingly exposed to radiation during cardiac catheterization laboratory (CCL) procedures. The RADPAD was designed as a protective scatter-radiation absorbing shield with the goal of reducing scatter radiation. Early studies demonstrated between a 20 and 62 % relative reduction in scatter radiation. The purpose of this study was to examine the impact of the RADPAD through a randomized controlled trial in a large contemporary CCL. DESIGN/METHODS:The ATTENUATE (v) Trial is an investigator-initiated, prospective, randomized controlled trial which will randomize 1000 CCL procedures 1:1 to use of the RADPAD vs. no use of the RADPAD. The primary outcome of interest is the most proximal operator's dose-area product (DAP)-normalized operator dose (E) defined as E divided by DAP. Additional subgroup analysis comparing types of procedure will also be performed. Every case will utilize contemporary radiation safety equipment. SUMMARY/CONCLUSIONS:The ATTENUATE Trial is the largest randomized controlled trial to evaluate the utility of the RADPAD in reducing relative operator exposure in a contemporary CCL including coronary and structural interventions.

The interaction between sleep, circadian rhythms and cardiovascular resilience is a crucial yet underexplored research area with important public health implications. Disruptions in sleep and circadian rhythms exacerbate hypertension, diabetes mellitus and obesity, conditions that are increasingly prevalent globally and increase the risk of cardiovascular disease. A National Heart, Lung, and Blood Institute workshop examined these connections, as well as the emerging concept of cardiovascular resilience as a dynamic and multifaceted concept spanning molecular, cellular and systemic levels across an individual's lifespan. The workshop emphasized the need to expand the focus from solely understanding whether and how sleep and circadian rhythm disturbances contribute to disease, to also exploring how healthy sleep and aligned circadian rhythms can increase cardiovascular resilience. To develop a Roadmap towards this goal, workshop participants identified key knowledge gaps and research opportunities, including the need to integrate biological, behavioural, environmental and societal factors in sleep and circadian health with cardiovascular research to identify therapeutic targets. Proposed interventions encompass behavioural therapies, chronotherapy, lifestyle changes, organizational policies and public health initiatives aimed at improving sleep and circadian health for better cardiovascular outcomes. Future cross-disciplinary research and translation of discoveries into public health strategies and clinical practices could improve cardiovascular resilience across the lifespan in all populations.

The early resuscitation of patients with mild to moderate non-exsanguinating trauma has shifted from the conventional use of one to two liters of crystalloids to the use of one to two units of PRBC. This evolution assumes that the transfusion of PRBC is superior to the administration of any volume of crystalloids because of the propensity of crystalloids to migrate from the intravascular to the interstitial space leading to organ dysfunction, organ failure, and worse outcomes. However, the premise of the fluid migration relies on Starling original model of fluid exchange between the hydrostatic and oncotic pressure without considering whether the endothelial surface glycocalyx (ESG) is affected by the degree of traumatic insult and by the duration and depth of hypotension. It fails to account for the changes that occur to the PRBC during storage from the standpoint of off-loading of oxygen and the ability to negotiate the microcirculation. This review explores the impact of the burden of trauma and hemorrhage on the ESG, the changes to the RBCs that occur during storage, particularly their diminished capacity to offload oxygen and to negotiate low-shear microvascular districts, leading to failure to improve oxygen consumption despite the increase in oxygen delivery. We argue that the recent trend toward early resuscitation with one to two units of PRBC rather that low-volume crystalloids, in patients with non-exsanguinating mild to moderate trauma lacks sufficient justification.

BACKGROUND:As the incidence of frontal fibrosing alopecia (FFA) continues to rise, there is a need for an optimal treatment algorithm for FFA. OBJECTIVE:To produce an international consensus statement on the treatment modalities and prognostic indicators of FFA. METHODS:Sixty-nine hair experts from six continents were invited to participate in a three-round Delphi process. The final stage was held as a virtual meeting facilitated via Zoom. The consensus threshold was set at ≥66%. RESULTS:Of 365 questions, expert consensus was achieved in 204 (56%) questions following completion of the three rounds. Three additional questions were included at the final meeting. The category with the strongest consensus agreement was disease monitoring (9; 100%). Questions pertaining to physical therapies achieved the least category consensus (15; 40%), followed by systemic therapy (45; 43%). LIMITATIONS/CONCLUSIONS:The study lacked sufficient representation from Africa and South America. CONCLUSION/CONCLUSIONS:SOFFIA highlights areas of agreement and disagreement among experts. Robust research is warranted to provide evidence-based treatment recommendations.

BACKGROUND:handling in platelet function and thrombosis is not well understood. OBJECTIVES/OBJECTIVE:flux could attenuate platelet activation and arterial thrombosis. METHODS:levels were measured in Rhod-2- and Fura-2-loaded platelets by fluorometry, and platelet bioenergetics were analyzed using a Seahorse extracellular flux analyzer. RESULTS:platelets. CONCLUSION/CONCLUSIONS:MCU facilitates platelet activation and thrombosis by regulating calcium flux (mitochondrial and cytosolic), thereby establishing its potential as a target for antithrombotic therapeutic intervention.

Long-chain fatty acids in the blood are prevented from unfettered movement into nonfenestrated tissues or the arterial wall. During fasting, nonesterified FAs are released from adipose tissue into the circulation and bind to albumin, forming a complex >65 kDa, with limited ability to efficiently cross endothelial cell (EC) barriers without a specific receptor. For this reason, nonhepatic tissue distribution of circulating FA parallels EC expression of the FA-binding protein CD36 (cluster of differentiation 36). The deletion of CD36 in ECs reduces nonesterified FA uptake by the heart, muscle, and brown adipose tissue. The other major transport system for FAs is via lipoproteins. Circulating FAs are contained within TRLs (triglyceride-rich lipoproteins), chylomicrons during the postprandial period, and VLDL (very low-density lipoprotein) both postprandially and during fasting. LPL (lipoprotein lipase) on capillary ECs releases FAs from TRLs and likely allows their passage into tissues, in part, via a CD36-independent process. ECs can also internalize lipoprotein particles, followed by the transendothelial movement of lipids. In this review, we will discuss the pathways of EC uptake of FAs from circulation, how this process affects both EC and tissue biology, and the importance of these processes for systemic metabolism and vascular health. We will conclude with speculations on methods to modulate EC FA uptake and their implications for human health.

Neoadjuvant therapy (NAT) is the standard of care for borderline-resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC). It can be used to treat resectable PDAC. This study aimed to investigate how NAT remodels the tumor immune microenvironment (TIME) and whether this remodeling translates into survival benefits. We performed spatial and digital pathology analysis of 27 upfront resection patients (naïve group) and 39 age-, gender-, and stage-matched patients who had surgery after NAT (NAT group). AI-assisted digital pathology was used to annotate cancer cells and CD8 + T lymphocytes. Spatial correlation between CD8 + T lymphocytes and cancer cells for each case was assessed using spatial point pattern analysis, followed by generalized linear modeling (GLM) of quadrat counts of CD8 + T cells, with the quadrat counts of cancer cells as the independent variable. The regression coefficient was used to quantify the strength of their spatial correlation and then further assessed for association with patient survival. The analyses showed that the NAT group, compared with the naïve group, had increased spatial correlation of CD8 + T cells with cancer cells, suggesting enhanced effector T cell-cancer cell engagement in the NAT patients. Additionally, patients with a higher degree of spatial correlation between the two cells showed improved after-surgery survival. Through a new methodological framework that takes advantage of AI-assisted digital pathology and spatial point pattern analysis, our study has successfully captured the subtle effects of NAT-induced TIME remodeling and assessed its impact on prognosis of PDAC patients.

PURPOSE/OBJECTIVE:A critical function of public health is to monitor diseases that impede quality of life and burden affected communities. The Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network aims to advance disease monitoring for diabetes using multi-site electronic health record (EHR) data. METHODS:This work involved validating and refining case definitions for accurate identification of type 1 and type 2 diabetes cases to estimate incidence and prevalence of diabetes in children, adolescents, and young adults through age 44 years. RESULTS:In this essay, we describe the challenges experienced by the Network and lessons learned. Challenges included accessing EHR data, harmonizing EHR data from heterogeneous health systems to a common data model, and developing methods to account for bias introduced by the non-representativeness of health care utilization data. Lessons learned included approaches for data quality assessment, bias correction, and scalability. CONCLUSIONS:As the US continues to evolve its public health data systems and its approach to chronic disease monitoring, the DiCAYA Network offers guidance on factors for success as well as pitfalls to avoid.