Subnormothermic Machine Perfusion of Neonatal and Small-Sized Pediatric Donor Hearts.

Donor heart machine perfusion enables avoidance of prolonged cold ischemia, however the optimal temperature is yet to be elucidated. Given that maintenance of temperature beyond ambient levels demands significant energy, we sought to determine the suitability of room-temperature perfusion preservation of neonatal/pediatric-sized (5-20 kg) piglet donor hearts. A custom device was fabricated suitable for this purpose, with continuous readout of perfusion pressure, flow rate, temperature, and oxygen saturation.

Mild Permissive Alkalosis Improves Outcomes in Porcine Negative Pressure Ventilation Ex-Situ Lung Perfusion.

Background: Ex-Situ Lung Perfusion (ESLP) employs a membrane deoxygenator and mixed (N/O/CO) or pure sweep gas (CO) to target venous blood gas composition with physiologic pCO and pH. Clinically, mild permissive alkalosis counteracts elevated pulmonary vascular resistance (PVR) to improve perfusion. Increased PVR and pulmonary artery pressure (PAP) during ESLP mirrors rising pro-inflammatory cytokines.

Mitral Valve Repair in Patients with Chronic Kidney Disease: Long-Term Outcomes and Cardiac Remodeling.

Objectives: Literature examining mitral valve repair (MVr) outcomes in patients with chronic kidney disease (CKD) is largely limited to short-term outcomes and percutaneous approaches. This study is the first to present long-term outcomes of mortality and morbidity with paired cardiac remodeling data from patients with CKD undergoing surgical MVr.

Design: A retrospective, observational, comparative study.

Risk factors for thromboembolic events in pediatric patients with ventricular assist devices.

Objective: Pediatric patients on ventricular assist devices (VAD) are at risk of thromboembolic (TE) complications. Our objective was to identify factors associated with TE events, including the role of initial anticoagulation strategy and device type in the pediatric VAD population.

Methods: This was a retrospective, single-center review (2005-2022) of children who were implanted with paracorporeal pulsatile (PP), paracorporeal continuous (PC), or a combination of devices.

Moderate-Flow Perfusion is Superior to Low-Flow Perfusion in Ex Situ Lung Perfusion.

Background: Full-flow perfusion during prolonged ex situ lung perfusion (ESLP) results in unacceptable pulmonary edema formation. Clinical ESLP at 30% to 50% predicted cardiac output (CO) supports acceptable physiologic outcomes; however, progressive pulmonary edema still develops. Lower flow rates may provide equivalent physiologic preservation with less edema formation due to reduced hydrostatic pressures.

First North American experience with the Berlin Heart EXCOR Active driver.

For smaller pediatric patients on ventricular assist devices, the Berlin Heart EXCOR remains the main form of durable support. It requires a connection to the external IKUS, which has limited portability and battery life. The new EXCOR Active mobile driving unit has a battery life of up to 13 hours.

Normothermic Perfusion is Superior to Cold Perfusion in Porcine Ex Situ Lung Perfusion.

Background: Cold ex situ lung perfusion (ESLP) has demonstrated improved preservation in small animal ESLP compared to normothermic ESLP and cold static preservation. We hypothesized that cold negative pressure ventilation (NPV)-ESLP would improve graft function in a porcine transplantation model.

Methods: Four perfusate temperatures were examined with 12 hours NPV-ESLP in a large animal transplantation model.

Optimizing Resuscitation of the Donation after Circulatory Death Heart by Mitochondrial Protection in a Female Porcine Model.

Background: Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death [DCD]). Using a translational porcine model of DCD, this study developed and evaluated a protocol based on cardioprotection by multidrug postconditioning to optimize resuscitation of DCD hearts during ex situ heart perfusion (ESHP).

Methods: Hearts of female pigs (45.

Relation of body mass index to long-term survival and cardiac remodelling for patients undergoing mitral valve replacement surgery.

Background And Aims: Studies have demonstrated that obesity is paradoxically associated with reduced mortality following cardiac surgery. However, these studies have treated various types of cardiac surgery as a single entity. With mitral valve (MV) surgeries being the fastest-growing cardiac surgical interventions in North America, the purpose of this study was to identify the impact of body mass index (BMI) on long-term survival and cardiac remodelling of patients undergoing MV replacement (MVR).

The Effects of Oxygen-Derived Free-Radical Scavengers During Normothermic Ex-Situ Heart Perfusion.

Oxidative stress occurs during ex-situ heart perfusion (ESHP) and may negatively affect functional preservation of the heart. We sought to assess the status of key antioxidant enzymes during ESHP, and the effects of augmenting these antioxidants on the attenuation of oxidative stress and improvement of myocardial and endothelial preservation in ESHP. Porcine hearts were perfused for 6 hours with oxygen-derived free-radical scavengers polyethylene glycol (PEG)-catalase or PEG-superoxide dismutase (SOD) or with naive perfusate (control).

Cyclosporine A Does Not Mitigate Liver Ischemia/Reperfusion Injury in an Ex Vivo Porcine Model of Donation After Circulatory Death.

BACKGROUND Ischemia/reperfusion injury (IRI) is an inherent problem in organ transplantation, owing to the obligate period of ischemia that organs must endure. Cyclosporine A (CsA), though better know as an immunosuppressant, has been shown to mitigate warm IRI in a variety of organ types, including the liver. However, there is little evidence for CsA in preventing hepatic IRI in the transplant setting.

A Novel Rotavirus Reverse Genetics Platform Supports Flexible Insertion of Exogenous Genes and Enables Rapid Development of a High-Throughput Neutralization Assay.

Despite the success of rotavirus vaccines, rotaviruses remain one of the leading causes of diarrheal diseases, resulting in significant childhood morbidity and mortality, especially in low- and middle-income countries. The reverse genetics system enables the manipulation of the rotavirus genome and opens the possibility of using rotavirus as an expression vector for heterologous proteins, such as vaccine antigens and therapeutic payloads. Here, we demonstrate that three positions in rotavirus genome-the C terminus of NSP1, NSP3 and NSP5-can tolerate the insertion of reporter genes.

Vaccination with a replication-defective cytomegalovirus vaccine elicits a glycoprotein B-specific monoclonal antibody repertoire distinct from natural infection.

Human Cytomegalovirus (HCMV) is the leading infectious congenital infection globally and the most common viral infection in transplant recipients, therefore identifying a vaccine for HCMV is a top priority. Humoral immunity is a correlate of protection for HCMV infection. The most effective vaccine tested to date, which achieved 50% reduction in acquisition of HCMV, was comprised of the glycoprotein B protein given with an oil-in-water emulsion adjuvant MF59.

Family perspectives of ex situ heart perfusion.

Background: Pediatric patients awaiting a heart transplant have high waitlist mortality. Several strategies have been utilized to decrease waiting times, but a mortality risk still exists. New medical technologies may improve waiting times and associated mortality.

Predicting outcomes following short-term ventricular assist device implant with the MELD-XI score.

Background: Short-term continuous flow (STCF) ventricular assist devices (VADs) are utilized in adults with cardiogenic shock; however, mortality remains high. Previous studies have found that high pre-operative MELD-XI scores in durable VAD patients are associated with mortality. The use of the MELD-XI score to predict outcomes in STCF-VAD patients has not been explored.

Infants less than or equal to 2.5 kg have increased mortality and worse motor neurodevelopmental outcomes at 2 years of age after Norwood-Sano palliation.

Objectives: In infants with single-ventricle congenital heart disease, prematurity and low weight at the time of the Norwood operation are risk factors for mortality. Reports assessing outcomes (including neurodevelopment) post Norwood palliation in infants ≤2.5 kg are limited.

The Impact of Ex Situ Heart Perfusion in Pediatric Transplantation: An Analysis of the OPTN Database.

Ex situ heart perfusion (ESHP) has increased the pool of donors in adults. However, this is not true in pediatrics due to lack of devices. Therefore, we sought to understand organ refusal in pediatrics and estimate donor heart usage with ESHP.

Activity of pemetrexed in pre-clinical chordoma models and humans.

Chordomas are rare slow growing tumors, arising from embryonic remnants of notochord with a close predilection for the axial skeleton. Recurrence is common and no effective standard medical therapy exists. Thymidylate synthase (TS), an intracellular enzyme, is a key rate-limiting enzyme of DNA biosynthesis and repair which is primarily active in proliferating and metabolically active cells.

Mapping the landscape of genetic dependencies in chordoma.

Identifying the spectrum of genes required for cancer cell survival can reveal essential cancer circuitry and therapeutic targets, but such a map remains incomplete for many cancer types. We apply genome-scale CRISPR-Cas9 loss-of-function screens to map the landscape of selectively essential genes in chordoma, a bone cancer with few validated targets. This approach confirms a known chordoma dependency, TBXT (T; brachyury), and identifies a range of additional dependencies, including PTPN11, ADAR, PRKRA, LUC7L2, SRRM2, SLC2A1, SLC7A5, FANCM, and THAP1.

Thoracic organ machine perfusion: A review of concepts with a focus on reconditioning therapies.

Thoracic organ transplantation, including lung, heart, and heart-lung transplants are highly regarded as gold standard treatments for patients suffering from heart failure or chronic end stage lung conditions. The relatively high prevalence of conditions necessitating thoracic organ transplants combined with the lack of available organs has resulted in many either dying or becoming too ill to receive a transplant while on the waiting list. There is a dire need to increase both the number of organs available and the utilization of such organs.

Ex situ heart perfusion for optimization of pediatric donor organ utilization: Attitudes and perceptions.

Background: Children with heart failure have the highest mortality while awaiting transplantation. Ex situ heart perfusion (ESHP), a method for continuous perfusion of the donor heart, has the potential to improve access to transplant by increasing travel distance between donor and recipient. An adult ESHP device is currently available, but as of yet there is no pediatric device.

Percutaneous Treatment of Ascending Aortic Obstruction in a Young Child After Orthotopic Heart Transplantation.

We report a case of a 14-month-old child with ascending aortic obstruction (AAO) post cardiac transplantation, who underwent successful percutaneous ascending aortic stent angioplasty. Congenital or acquired AAO is typically treated with surgical augmentation. The experience with percutaneous techniques is limited and often avoided due to challenges with equipment stability and proximity to coronary arteries and aortic valve leaflets.