Impact of extracorporeal blood pump gap sizes on the performance and hemocompatibility under off-design operation.

Background: Hemocompatibility remains the dominant challenge in rotary blood pumps, and more information on the relationship between individual pump design features, hemodynamics, and blood trauma in various operation conditions is necessary. The study evaluated the variation of gap sizes in extracorporeal blood pumps concerning their influence on blood compatibility, particularly during off-design conditions.

Methods: We developed a parametric generic blood pump framework for in-silico and in-vitro design feature analysis.

Collateral flow and pulsatility during large vessel occlusions: insights from a quantitative study.

Acute ischemic stroke caused by large vessel occlusions is being increasingly treated with neurovascular interventions. The hemodynamics within the collateral system of the circle of Willis (CoW) hemodynamics play a fundamental role in therapy success. However, transient data on pathological collateral flow during large vessel occlusions are not available.

Investigations of Differential Hypoxemia During Venoarterial Membrane Oxygenation with and Without Impella Support.

Purpose: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is used in patients with refractory cardiac or cardio-pulmonary failure. Native ventricular output interacts with VA ECMO flow and may hinder sufficient oxygenation to the heart and the brain. Further on, VA ECMO leads to afterload increase requiring ventricular unloading.

Evaluating the accuracy of cerebrovascular computational fluid dynamics modeling through time-resolved experimental validation.

Accurate modeling of cerebral hemodynamics is crucial for better understanding the hemodynamics of stroke, for which computational fluid dynamics (CFD) modeling is a viable tool to obtain information. However, a comprehensive study on the accuracy of cerebrovascular CFD models including both transient arterial pressures and flows does not exist. This study systematically assessed the accuracy of different outlet boundary conditions (BCs) comparing CFD modeling and an in-vitro experiment.

Systematic analysis of non-intrusive polynomial chaos expansion to determine rotary blood pump performance over the entire operating range.

This study applies non-intrusive polynomial chaos expansion (NIPCE) surrogate modeling to analyze the performance of a rotary blood pump (RBP) across its operating range. We systematically investigate key parameters, including polynomial order, training data points, and data smoothness, while comparing them to test data. Using a polynomial order of 4 and a minimum of 20 training points, we successfully train a NIPCE model that accurately predicts pressure head and axial force within the specified operating point range ([0-5000] rpm and [0-7] l/min).

Effect of TAVR commissural alignment on coronary flow: A fluid-structure interaction analysis.

Background And Objectives: Coronary obstruction is a complication that may affect patients receiving Transcatheter Aortic Valve Replacement (TAVR), with catastrophic consequences and long-term negative effects. To enable healthy coronary perfusion, it is fundamental to appropriately position the device with respect to the coronary ostia. Nonetheless, most TAVR delivery systems do not control commissural alignment to do so.

Computational modeling of hemodynamics and risk of thrombosis in the left atrial appendage using patient-specific blood viscosity and boundary conditions at the mitral valve.

Hemodynamics play a vital role for the risk of thrombosis in the left atrial appendage (LAA) and left atrium (LA) for patients with atrial fibrillation. Accurate prediction of hemodynamics in the LA can provide important guidance for assessing the risk of thrombosis in the LAA. Patient specificity is a crucial factor in representing the true hemodynamic fields.

Inflow from a Cardiopulmonary Assist System to the Pulmonary Artery and Its Implications for Local Hemodynamics-a Computational Fluid Dynamics Study.

When returning blood to the pulmonary artery (PA), the inflow jet interferes with local hemodynamics. We investigated the consequences for several connection scenarios using transient computational fluid dynamics simulations. The PA was derived from CT data.

Generic framework for quantifying the influence of the mitral valve on ventricular blood flow.

Blood flow within the left ventricle provides important information regarding cardiac function in health and disease. The mitral valve strongly influences the formation of flow structures and there exist various approaches for the representation of the valve in numerical models of left ventricular blood flow. However, a systematic comparison of the various mitral valve models is missing, making a priori decisions considering the overall model's context of use impossible.

Trends, Advantages and Disadvantages in Combined Extracorporeal Lung and Kidney Support From a Technical Point of View.

Extracorporeal membrane oxygenation (ECMO) provides pulmonary and/or cardiac support for critically ill patients. Due to their diseases, they are at high risk of developing acute kidney injury. In that case, continuous renal replacement therapy (CRRT) is applied to provide renal support and fluid management.

Flow control in the middle cerebral artery during thrombectomy: the effect of anatomy, catheter size and tip location.

Background: Catheter size, location and circle of Willis anatomy impact the flow conditions during interventional stroke therapy. The aim of the study was to systematically investigate the influence of these factors on flow control in the middle cerebral artery by means of a computational model based on 100 patients with stroke who received endovascular treatment.

Methods: The dimensions of the cervical and intracranial cerebral arteries of 100 patients who received endovascular mechanical thrombectomy for acute ischemic stroke were measured and a three-dimensional model of the circle of Willis was created based on these data.

Regulatory network-based model to simulate the biochemical regulation of chondrocytes in healthy and osteoarthritic environments.

In osteoarthritis (OA), chondrocyte metabolism dysregulation increases relative catabolic activity, which leads to cartilage degradation. To enable the semiquantitative interpretation of the intricate mechanisms of OA progression, we propose a network-based model at the chondrocyte level that incorporates the complex ways in which inflammatory factors affect structural protein and protease expression and nociceptive signals. Understanding such interactions will leverage the identification of new potential therapeutic targets that could improve current pharmacological treatments.

An Accelerated Thrombosis Model for Computational Fluid Dynamics Simulations in Rotary Blood Pumps.

Purpose: Thrombosis ranks among the major complications in blood-carrying medical devices and a better understanding to influence the design related contribution to thrombosis is desirable. Over the past years many computational models of thrombosis have been developed. However, numerically cheap models able to predict localized thrombus risk in complex geometries are still lacking.

Intraventricular Flow Simulations in Singular Right Ventricles Reveal Deteriorated Washout and Low Vortex Formation.

Purpose: Patients with a functionally univentricular heart represent one of the most common severe cardiac lesions with a prevalence of 3 per 10,000 live births. Hemodynamics of the singular ventricle is a major research topic in cardiology and there exists a relationship between fluid dynamical features and cardiac behavior in health and disease. The aim of the present work was to compare intraventricular flow in single right ventricle (SRV) patients and subjects with healthy left hearts (LV) through patient-specific CFD simulations.

Possible Contexts of Use for In Silico Trials Methodologies: A Consensus-Based Review.

The term "In Silico Trial" indicates the use of computer modelling and simulation to evaluate the safety and efficacy of a medical product, whether a drug, a medical device, a diagnostic product or an advanced therapy medicinal product. Predictive models are positioned as new methodologies for the development and the regulatory evaluation of medical products. New methodologies are qualified by regulators such as FDA and EMA through formal processes, where a first step is the definition of the Context of Use (CoU), which is a concise description of how the new methodology is intended to be used in the development and regulatory assessment process.

Understanding the influence of left ventricular assist device inflow cannula alignment and the risk of intraventricular thrombosis.

Background: Adverse neurological events associated with left ventricular assist devices (LVADs) have been suspected to be related to thrombosis. This study aimed to understand the risks of thrombosis with variations in the implanted device orientation. A severely dilated pulsatile patient-specific left ventricle, modelled with computational fluid dynamics, was utilised to identify the risk of thrombosis for five cannulation angles.

Tipless transseptal cannula concept combines improved hemodynamic properties and risk-reduced placement: An in silico proof-of-concept.

As a leading cause of death worldwide, heart failure is a serious medical condition in which many critically ill patients require temporary mechanical circulatory support (MCS) as a bridge-to-recovery or bridge-to-decision. In many cases, the TandemHeart system is used to unload the left heart by draining blood from the left atrium (LA) to the femoral artery via a transseptal multistage cannula. However, even though the correct positioning of the cannula is crucial for a safe treatment, the long cannula tip currently used in transseptal cannulas complicates positioning, making the cannula vulnerable to displacement during MCS.

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research.

Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals.

Estimation of left ventricular stroke work based on a large cohort of healthy children.

Left ventricular stroke work is an important prognostic marker to analyze cardiac function. Standard values for children are, however, missing. For clinicians, standards can help to improve the treatment decision of heart failures.

A Novel Multiplex Based Platform for Osteoarthritis Drug Candidate Evaluation.

Osteoarthritis (OA) is characterized by irreversible cartilage degradation with very limited therapeutic interventions. Drug candidates targeted at prototypic players had limited success until now and systems based approaches might be necessary. Consequently, drug evaluation platforms should consider the biological complexity looking beyond well-known contributors of OA.

COMBSecretomics: A pragmatic methodological framework for higher-order drug combination analysis using secretomics.

Multi drug treatments are increasingly used in the clinic to combat complex and co-occurring diseases. However, most drug combination discovery efforts today are mainly focused on anticancer therapy and rarely examine the potential of using more than two drugs simultaneously. Moreover, there is currently no reported methodology for performing second- and higher-order drug combination analysis of secretomic patterns, meaning protein concentration profiles released by the cells.

Multi-tissue network analysis for drug prioritization in knee osteoarthritis.

Knee osteoarthritis (OA) is a joint disease that affects several tissues: cartilage, synovium, meniscus and subchondral bone. The pathophysiology of this complex disease is still not completely understood and existing pharmaceutical strategies are limited to pain relief treatments. Therefore, a computational method was developed considering the diverse mechanisms and the multi-tissue nature of OA in order to suggest pharmaceutical compounds.

An ex vivo tissue model of cartilage degradation suggests that cartilage state can be determined from secreted key protein patterns.

The pathophysiology of osteoarthritis (OA) involves dysregulation of anabolic and catabolic processes associated with a broad panel of proteins that ultimately lead to cartilage degradation. An increased understanding about these protein interactions with systematic in vitro analyses may give new ideas regarding candidates for treatment of OA related cartilage degradation. Therefore, an ex vivo tissue model of cartilage degradation was established by culturing tissue explants with bacterial collagenase II.