Citations

Abstract Background Dipeptidyl peptidase 3 (DPP3) is a peptidase released from dying cells. It cleaves proteins in the renin–angiotensin pathway, which can result in hemodynamic instability. At elevated concentrations DPP3 is associated with worse outcomes, particularly in patients with shock. Herein we describe the assay performance of a DPP3 assay (4TEEN4 Pharmaceuticals GmbH) in human plasma. Methods DPP3 concentration was measured using the DPP3 immunoluminometric assay (4TEEN4 Pharmaceuticals GmbH) and the signal was read using a luminometer (Berthold Centro LB963). Analytical performance was established for precision, linearity, accuracy, detection limit, analytical specificity, reference interval, kit lot-to-lot comparison, specimen type, and sample stability. Results Limit of detection was verified at 1.6 ng/mL in EDTA plasma with a coefficient of variation (CV) of <10%. Precision studies revealed a CV ≤ 6% at 28.5 ng/mL and 59.4 ng/mL and comparability with a manufacturer performed assay was demonstrated between 7.7 and 195.2 ng/mL. An upper 97.5% limit of 22 ng/mL without age or sex associations was verified in healthy donors. The assay was not susceptible to interference from lipemia or bilirubin. However, measured DPP3 concentrations increased linearly with increasing hemolysis. DPP3 concentrations are stable in EDTA plasma for up to 24 h and at least 11 months when stored ambient or at −80°C, respectively. Conclusions DPP3 can be measured precisely in EDTA plasma using the immunoluminometric DPP3 assay. Given the potential clinical use of DPP3 in critical care patients, caution should be taken to avoid inducing pre-analytical hemolysis during sample collection.

Importance The introduction of immune checkpoint inhibitor (ICI) therapy has improved cancer outcomes but at the cost of adverse events, mainly related to the immune system. Cardiovascular (CV) toxic effects, and especially myocarditis, are of particular concern and are the subject of this position statement by the International Cardio-Oncology Society with representation of experts from oncology, hematology, and cardiology. Observations CV toxic effects of ICI therapies include inflammation-associated diseases, such as myocarditis, pericarditis, and vasculitis, as well as the aggravation of chronic inflammatory conditions, such as atherosclerosis with acute ischemic complications (myocardial infarction and stroke). Patients taking ICI therapies can also develop cardiac dysfunction, stress-induced cardiomyopathy (Takotsubo or apical ballooning syndrome), and heart failure without inflammatory cell infiltration of the myocardium. Atrial and ventricular arrhythmias can emerge in the setting of a systemic inflammatory milieu, myocarditis, or ischemia. Of all potential CV adverse effects, myocarditis remains of highest concern, although fatality rates have declined over time with a broadening spectrum of presentations ranging from troponin elevation of uncertain significance to smoldering, nonsevere, and severe or fulminant myocarditis. Conclusions and Relevance Concerns for myocarditis continue to dominate the spectrum of CV toxic effects in patients receiving ICI therapy. Recommendations for management vary according to severity. Multidisciplinary collaborations remain key for managing acute toxic effects and future cancer treatment decisions, including ICI rechallenge. Ischemic heart disease constitutes the main differential diagnosis in these patients, while pericarditis can be concomitantly present, and atrial and ventricular arrhythmias can also complicate the clinical picture. Several gaps in knowledge are identified and require further research.

A 32-fold accelerated real-time cine MRI sequence (radial sampling) demonstrated better temporal resolution and image quality than a 16-fold sequence (Cartesian sampling) in patients with cardiac implantable electronic devices and arrhythmias.

After successfully implementing an acute care telemedicine program internally, health care institutions often consider expanding and scaling services externally beyond the initial organizational network. This report outlines important considerations when expanding acute care telemedicine services externally, including cultural alignment and agility, practice context, staffing models, telemedicine technology selection, interrelated services, legal and compliance considerations, quality assurance, risk management, financing, and integration with medical education. These factors may inform program leaders of major planning considerations, potential barriers, and could influence strategic planning. Prospectively identifying and resolving challenges prior to contracting with new external sites will facilitate smooth, successful implementation and high utilization of the acute care telemedicine service.

Abstract A modified myocardium-blood composite model enables the temporal changes in instantaneous extension and contraction of in vivo myocardial fiber to be computed by using the measured blood volume fractions and wall thicknesses in the investigated left ventricular region. A 16 time-increment study of 6 dogs shows that myocardial fiber may undergo an average length change of 62% and −38% during the diastolic and systolic phases of cardiac cycle, respectively. Two comparable results had been obtained previously, but the new method is much simpler, removes the incompressibility assumption and takes into consideration the intravascular blood in the ventricular wall.

Abstract For biomechanics analysis of body organs, finite element method [1∼3] is the practical tool for dealing with the complex geometric shapes and material composition involved. Either for direct computation of the stresses and strains in the body organ or inverse determination of its material properties, the change of geometrical shapes and dimensions and the change of the loadings, both in time, must be accurately recorded. Moreover, fast imaging techniques [4] and a vast volume of computer storage memory are necessary for acquisition of such temporal data, particularly if finite-element biomedical algorithms are to be developed for routine use. This paper reports a chronological development of finite-element inverse determination of global and regional material properties, passive diastolic stiffness and active systolic contractile strength of the in vivo heart wall. A collection of computer algorithms has been accumulated as a result of continuing collaborative research on cardiopulmonary dynamics by the authors and their co-workers since 1973.

ABSTRACT Background and hypothesis End-stage renal disease patients require peritoneal dialysis (PD) as a life-saving therapy; however, they continue to experience systemic inflammation and increased cardiovascular pathology. These complications can be exacerbated by exposure to PD solutions (PDS) containing glucose. This highlights the clinical unmet need for novel osmotic agents to replace glucose. Here, we tested troxerutin, a Food and Drug Administration–approved drug, as a potential osmotic agent. Methods To evaluate troxerutin osmotic and non-toxic effects, in vitro and in vivo experiments were carried out using artificial membranes, mice and cultured human mesothelial cells (MCs). The local and systemic consequences of chronic peritoneal exposure to PDS associated to renal insufficiency were investigated in a preclinical model. 5/6 nephrectomized C57BL/6J mice were daily exposed to glucose- or troxerutin-PDS for 60 days, then evaluating tissue damage, proinflammatory markers and cardiac damage. Results In vitro and in vivo studies revealed that troxerutin exhibits similar osmotic and ultrafiltration capacities to glucose, but with colloidal properties. Moreover, only glucose, but not troxerutin, reduced MC viability, induced mesothelial-to-mesenchymal transition, and increased damage markers (such as interleukin-6 and vascular endothelial growth factor A). In the preclinical model, long-term treatment with glucose-PDS, but not troxerutin-PDS, significantly increased peritoneal membrane thickening, tissue proinflammatory markers (evaluated in peritoneum, kidney, heart and aorta) and cardiovascular damage (cardiac hypertrophy and fibrosis) in mice. These preclinical data clearly demonstrate the wide deleterious effects of chronic peritoneal exposure to glucose-containing PDS in mice with kidney insufficiency and that the replacement of glucose with troxerutin notably reduces these effects. Conclusion Troxerutin emerges as a more biocompatible alternative to glucose as an osmotic agent for PD therapy, exhibiting no adverse local or systemic side effects in preclinical studies. This research presents a novel approach to reduce cardiovascular complications of PD in end-stage kidney disease.