Quantifying the influence of combined lung and kidney support using a cardiovascular model and sensitivity analysis-informed parameter identification.

The combination of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) pose complex hemodynamic challenges in intensive care. In this study, a comprehensive lumped parameter model (LPM) is developed to simulate the cardiovascular system, incorporating ECMO and CRRT circuit dynamics. A parameter identification framework based on global sensitivity analysis (GSA) and multi-start gradient-based optimization was developed and tested on 30 clinical data points from eight veno-arterial ECMO patients.

Technical evaluation of the InBios Strongy Detect IgG ELISA assay for the diagnosis of Strongyloides stercoralis infection.

Background: Strongyloidiasis is a neglected tropical disease (NTD) caused by the soil-transmitted helminth Strongyloides stercoralis, recently included in the 2030 targets of the World Health Organization for the control of STHs. Assessment of infection prevalence is fundamental for decision-making about the implementation of control programs, but diagnostic assays to be applied in such context require evaluation. Seroassays based on recombinant antigens, which could be produced in a standardized and scalable manner, are particularly appealing for use in control programs.

Citrate-Coated Iron Oxide Nanoparticles Facilitate Endothelialization of Left Ventricular Assist Device Impeller for Improved Antithrombogenicity.

Although left ventricular assist devices (LVADs) are an alternative to heart transplantation, their artificial surfaces often lead to serious thrombotic complications requiring high-risk device replacement. Coating blood-contacting surfaces with antithrombogenic endothelial cells is considered an effective strategy for preventing thrombus formation. However, this concept has not yet been successfully implemented in LVADs, as severe cell loss is to be expected, especially on the impeller surface with high prothrombogenic supraphysiological shear stress.

Human-Sized Organ Machine Perfusion: A Systematic Review on the Added Value of Medical Imaging for Organ Condition Assessment.

Machine perfused organs offer an excellent experimental platform, e.g., for studying organ physiology and for conducting pre-clinical trials for drug delivery.

Three-Dimensional Heart Modeling of Hypertrophic Obstructive Cardiomyopathy for In Situ Patient-Specific Simulation to Optimize Septal Myectomy.

Objective: Hypertrophic obstructive cardiomyopathy (HOCM) develops in at least 1 out of 715 young adults. Patients who are refractory to medical therapy qualify for septal myectomy. Due to anatomy, serious complications such as ventricular septal defect and heart block may occur.

A Volume-Adjustable Artificial Womb for Extremely Preterm Infants.

More than 13 million children are born preterm annually. Prematurity-related mortality accounts for 0.9 million deaths worldwide.

ECMOve: A Mobilization Device for Extracorporeal Membrane Oxygenation Patients.

Extracorporeal membrane oxygenation (ECMO) is a temporary lifesaving treatment for critically ill patients with severe respiratory or cardiac failure. Studies demonstrated the feasibility of in-hospital mobilizing during and after ECMO treatment preventing neuromuscular weakness and impaired physical functioning. Despite more compact mobile ECMO devices, implementation of ambulatory ECMO remains labor-intensive, complex, and challenging.

Safety Findings of Dosing Gene Therapy Vectors in NHP With Pre-existing or Treatment-Emergent Anti-capsid Antibodies.

Replication-incompetent adeno-associated virus (AAV)-based vectors are nonpathogenic viral particles used to deliver therapeutic genes to treat multiple monogenic disorders. AAVs can elicit immune responses; thus, one challenge in AAV-based gene therapy is the presence of neutralizing antibodies against vector capsids that may prevent transduction of target cells or elicit adverse findings. We present safety findings from two 12-week studies in nonhuman primates (NHPs) with pre-existing or treatment-emergent antibodies.

Novel Size-Variable Dedicated Rodent Oxygenator for ECLS Animal Models-Introduction of the "RatOx" Oxygenator and Preliminary In Vitro Results.

The overall survival rate of extracorporeal life support (ECLS) remains at 60%. Research and development has been slow, in part due to the lack of sophisticated experimental models. This publication introduces a dedicated rodent oxygenator ("RatOx") and presents preliminary in vitro classification tests.

Refurbishment of Extracorporeal Life Support Oxygenators in the Context of In Vitro Testing.

Refurbishing single use extracorporeal membrane oxygenation (ECMO) oxygenators for in vitro research applications is common. However, the refurbishment protocols that are established in respective laboratories have never been evaluated. In the present study, we aim at proving the relevance of a well-designed refurbishing protocol by quantifying the burden of repeatedly reused oxygenators.

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.

Development and evaluation of a variable, miniaturized oxygenator for various test methods.

Background: Extracorporeal membrane oxygenation (ECMO) became an accepted therapy for the treatment of severe acute respiratory distress syndrome and chronic obstructive pulmonary disease. However, ECMO systems are still prone to thrombus formation and decrease of gas exchange over time. Therefore, it is necessary to conduct qualified studies to identify parameters for optimization of ECMO systems, and especially the oxygenator.

Young mice administered adult doses of AAV5-hFVIII-SQ achieve therapeutic factor VIII expression into adulthood.

Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) gene transfer provided reduced bleeding for adult clinical trial participants with severe hemophilia A. However, pediatric outcomes are unknown. Using a mouse model of hemophilia A, we investigated the effect of vector dose and age at treatment on transgene production and persistence.

thrombogenicity evaluation of rotary blood pumps by thromboelastometry.

thrombogenicity tests for rotary blood pumps (RBPs) could benefit from assessing coagulation kinematics, as RBP design improves. In this feasibility study, we investigated if the method of thromboelastometry (TEM) is able to assess coagulation kinematics under the conditions of RBP tests. We conducted thrombogenicity tests (n=4) by placing Deltastream DP3 pumps into test loops that were filled with 150 mL of slightly anti-coagulated porcine blood, adjusted to an activated clotting time (ACT) well below clinically recommended levels.

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.

TPMS-based membrane lung with locally-modified permeabilities for optimal flow distribution.

Membrane lungs consist of thousands of hollow fiber membranes packed together as a bundle. The devices often suffer from complications because of non-uniform flow through the membrane bundle, including regions of both excessively high flow and stagnant flow. Here, we present a proof-of-concept design for a membrane lung containing a membrane module based on triply periodic minimal surfaces (TPMS).

In Vitro and In Vivo Feasibility Study for a Portable VV-ECMO and ECCOR System.

Extracorporeal membrane oxygenation (ECMO) is an established rescue therapy for patients with chronic respiratory failure waiting for lung transplantation (LTx). The therapy inherent immobilization may result in fatigue, consecutive deteriorated prognosis, and even lost eligibility for transplantation. We conducted a feasibility study on a novel system designed for the deployment of a portable ECMO device, enabling the physical exercise of awake patients prior to LTx.

Lack of germline transmission in male mice following a single intravenous administration of AAV5-hFVIII-SQ gene therapy.

Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is an adeno-associated virus serotype five gene therapy under investigation for the treatment of hemophilia A. Herein, we assessed the potential for germline transmission of AAV5-hFVIII-SQ in mice. Male B6.

Extracorporeal Hyperoxygenation Therapy (EHT) for Carbon Monoxide Poisoning: In-Vitro Proof of Principle.

Carbon monoxide (CO) poisoning is the leading cause of poisoning-related deaths globally. The currently available therapy options are normobaric oxygen (NBO) and hyperbaric oxygen (HBO). While NBO lacks in efficacy, HBO is not available in all areas and countries.

The porcine abattoir blood model-Evaluation of platelet function for in-vitro hemocompatibility investigations.

Background: The major obstacle of blood-contacting medical devices is insufficient hemocompatibility, particularly thrombogenicity and platelet activation. Pre-clinical in-vitro testing allows for the evaluation of adverse thrombogenicity-related events, but is limited, among others, by the availability and quantity of human blood donations. The use of animal blood is an accepted alternative for several tests; however, animal and particularly abattoir blood might present species-specific differences to human blood as well as elevated blood values, and pre-activated platelets due to stressed animals and non-standardized blood collection.

Three-dimensional membranes for artificial lungs: Comparison of flow-induced hemolysis.

Background: Membranes based on triply periodic minimal surfaces (TPMS) have proven a superior gas transfer compared to the contemporary hollow fiber membrane (HFM) design in artificial lungs. The improved oxygen transfer is attributed to disrupting the laminar boundary layer adjacent to the membrane surface known as main limiting factor to mass transport. However, it requires experimental proof that this improvement is not at the expense of greater damage to the blood.

In-Vitro Visualization of Thrombus Growth in Artificial Lungs Using Real-Time X-Ray Imaging: A Feasibility Study.

Purpose: Extracorporeal membrane oxygenation has gained increasing attention in the treatment of patients with acute and chronic cardiopulmonary and respiratory failure. However, clotting within the oxygenators or other components of the extracorporeal circuit remains a major complication that necessitates at least a device exchange and bears risks of adverse events for the patients. In order to better predict thrombus growth within oxygenators, we present an approach for in-vitro visualization of thrombus growth using real-time X-ray imaging.

New Trends, Advantages and Disadvantages in Anticoagulation and Coating Methods Used in Extracorporeal Life Support Devices.

The use of extracorporeal life support (ECLS) devices has significantly increased in the last decades. Despite medical and technological advancements, a main challenge in the ECLS field remains the complex interaction between the human body, blood, and artificial materials. Indeed, blood exposure to artificial surfaces generates an unbalanced activation of the coagulation cascade, leading to hemorrhagic and thrombotic events.

Veno-venous extracorporeal blood phototherapy increases the rate of carbon monoxide (CO) elimination in CO-poisoned pigs.

Background And Objectives: Carbon monoxide (CO) inhalation is the leading cause of poison-related deaths in the United States. CO binds to hemoglobin (Hb), displaces oxygen, and reduces oxygen delivery to tissues. The optimal treatment for CO poisoning in patients with normal lung function is the administration of hyperbaric oxygen (HBO).