The latest medical research on Transplant

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about transplant gathered by our medical AI research bot.

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Useful central mechanical circulatory support system for critical biventricular heart failure associated with high pulmonary vascular resistance.

Journal of Artificial Intelligence Research

Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) is a powerful life-saving tool; however, it can sometimes induce severe pulmonary edema in patients with critical heart failure. We report favorable outcomes in critically ill patients by using a central ECMO system with an innovative blood perfusion method.

We analyzed 10 patients with severe heart failure and pulmonary edema who were treated with the central ECMO system at our institution between April 2022 and October 2023. The system consists of central cannulation with two inflows from the right atrium and left ventricle, and two outflows to the aorta and pulmonary artery, connected by two Y-connectors to a single ECMO circuit (RALV-AOPA ECMO). In this system, blood flow to the pulmonary artery is adjusted and mean pulmonary artery pressure is limited to <20 mm Hg, which reduces right ventricular afterload and prevents the worsening of pulmonary edema and hemorrhage.

Six patients were diagnosed with fulminant lymphocytic myocarditis, and four were diagnosed with coronavirus disease 2019-related myocardial injury. The ejection fraction was 6.5 ± 4.1%. The average intraoperative pulmonary vascular resistance was 4.6 ± 1.3 Wood units. After 24 h, the mean pulmonary arterial pressure was 12.8 ± 4.3 mm Hg, and pulmonary vascular resistance was 1.5 ± 0.3 Wood units. The duration of central RALV-AOPA ECMO was 3.7 ± 2.1 days. Finally, six patients were weaned, three received HeartMate3, and one received heart transplantation. At follow-up, all patients remained alive (428 ± 208 days), and two patients experienced cerebrovascular accidents without any lasting sequelae.

The central RALV-AOPA ECMO is an innovative system that achieves early improvement in pulmonary vascular resistance and is safe and feasible for patients with acute biventricular failure and pulmonary edema.

Real-time physiological environment emulation for the Istanbul heart ventricular assist device via acausal cardiovascular modeling.

Journal of Artificial Intelligence Research

The cost and complexity associated with animal testing are significantly reduced by using mock circulatory loops prior. Novel mock circulatory loops allow us to test biomedical devices preclinically due to their flexibility, scalability, and cost-effectiveness. The presented work describes the development of a hardware-in-the-loop platform to emulate human physiology for the Istanbul Heart (iHeart-II) LVAD.

A closed-loop system is developed whereby the effect of the LVAD on the heart and vice versa can be studied. An acausal model of the cardiovascular system is calibrated to emulate advanced-stage heart failure. A new prototype of the iHeart-II LVAD is connected between two air-actuated chambers emulating the left ventricle and aortic chambers with PID controllers tracking numerically modeled pressures from the in silico model. A lead-lag compensator is used to maintain fluid level. Controllers are tuned using nonlinear Hammerstein-Weiner models identified using open-loop data. The iHeart-II LVAD is operated at various speeds in its operational range, and the resulting hemodynamics are visualized in real time.

Hemodynamic variables, such as LVAD flow rate, aortic, left ventricular, and pulse pressure, demonstrate trends similar to clinical observations. The iHeart-II LVAD achieves hemodynamic normalization at ~3500 rpm for the emulated condition.

A novel evaluation methodology is adopted to study the performance of the iHeart LVAD under advanced-stage heart failure emulation. The models and controllers used in the platform are readily replicable to facilitate VAD research, pedagogy, design, and development.

IL-1 receptor antagonist anakinra downregulates inflammatory cytokines during renal normothermic machine perfusion: Preliminary results.

Journal of Artificial Intelligence Research

The interleukin 1 (IL-1) cytokine group plays a key role in sterile inflammation and may be an important target for transplant-related renal injury. This study examined the effects of anakinra, a non-specific IL-1 receptor antagonist, administered during normothermic machine perfusion (NMP) of porcine kidneys.

Paired porcine kidneys (n = 5 pairs) underwent 15 min of warm ischemia plus 2 h of static cold storage in ice. Kidneys were then perfused with autologous whole blood using an ex vivo NMP platform. Kidneys were randomly allocated to receive anakinra or vehicle administered at the start of NMP. Cortical biopsies were collected at baseline before ischemic injury and at the end of NMP. Functional parameters were recorded and calculated, and inflammatory markers were measured by qPCR and ELISA techniques.

During NMP, there were no statistically significant differences in renal blood flow, urine output, creatinine clearance or fractional excretion of sodium in the anakinra and control groups. The administration of anakinra significantly downregulated transcriptional expression of IL-6, Fas ligand and intercellular adhesion molecule 1 (p = 0.029, 0.029, 0.028, respectively).

Anakinra, an IL-1 receptor blocker, successfully attenuated the downstream inflammatory and immune-mediated response within the kidney during NMP.

Hopeful progress in artificial vision.

Journal of Artificial Intelligence Research

Visual impairment has been augmented by glasses for centuries. With the advent of newer technologies, correction of more severe visual impairment m...

Meta-analysis of in vitro methods on tracheal decellularization.

Journal of Artificial Intelligence Research

Tracheal decellularization is one of the main processes to provide tracheal substitutes for tracheal replacement. Recently, studies have been held for agents and combinations of processes for tracheal decellularization with different outcomes. This study aimed to evaluate the efficacy of tracheal decellularization by the immunogenic cellular elements using residual deoxyribonucleic acid (DNA) contents (ng/mg) and the preservation of biomechanical integrity by glycosaminoglycan (GAG) content (μg/mg), modulus tensile strength (MPa), ultimate tensile strength (MPa), and stress loading of 50% deformation (N).

We conducted a meta-analysis based on PRISMA criteria. Data from experimental studies in MEDLINE, Scopus, and ScienceDirect from inception to August 21, 2023, were sought and computed using RevMan 5.4. The outcomes of tracheal decellularization were evaluated through effect size estimates based on pooled Standardized Mean Difference (SMD) with 95% CI.

Tracheal decellularization has significantly reduced the DNA and GAG content after the process (SMD: -11.77, 95% CI [-13.92, -8.62], p < 0.00001; SMD: -6.70, 95% CI [-9.55, -3.85], p < 0.00001). No significant outcomes were observed in modulus and ultimate tensile strength result (SMD: -0.14, 95% CI [-0.64, 0.36], p = 0.58; SMD: 0.11, 95% CI [-0.57, 0.80], p = 0.75). The stress loading of 50% deformation was observed to significantly lower (SMD: -1.61, 95% CI [-2.49, -0.72], p = 0.0004).

Tracheal decellularization has been proven to effectively remove immunogenic cells. However, extracellular matrix integrity and biomechanical properties vary among different decellularization techniques, indicating a need for further refinement to achieve better preservation.

Circulating cell-free DNA in liver transplantation: A pre- and post-transplant biomarker of graft dysfunction.

Journal of Artificial Intelligence Research

Liver transplantation (LT) is still limited by organ shortage and post-transplant monitoring issues. While machine perfusion techniques allow for improving organ preservation, biomarkers like donor-derived cell-free DNA (dd-cfDNA) and mitochondrial cfDNA (mt-cfDNA) may provide insights into graft injury and viability pre- and post-LT.

A prospective observational cohort study was conducted on LT recipients (n = 45) to evaluate dd-cfDNA as a biomarker of graft dysfunction during the first 6 months after LT. Dd-cfDNA was quantified on blood samples collected pre-LT and post-LT using droplet digital PCR. In livers undergoing dual hypothermic oxygenated machine perfusion (D-HOPE), total cfDNA and mt-cfDNA levels were measured on perfusate samples collected at 30-min intervals. Correlations with graft function and clinical outcomes were assessed.

Dd-cfDNA levels peaked post-LT and correlated with transaminase levels and histological injury severity. The longitudinal assessment showed that postoperative complications and rejection were associated with an increase in dd-cfDNA levels. Mt-cfDNA levels in D-HOPE perfusate correlated with graft function parameters post-LT and were higher in patients with early allograft dysfunction and severe complications.

This study confirms dd-cfDNA as a marker of graft injury after LT and suggests that perfusate mt-cfDNA levels during D-HOPE correlate with graft function and post-transplant clinical outcome. Integration of these tests into clinical practice may improve transplant management and viability assessment during hypothermic perfusion.

Donor-Specific Blood Transfusion in Lung Transplantation.

Transplant International

Lung transplantation is still hindered by a high rate of chronic rejection necessitating profound immunosuppression with its associated complicatio...

ECG Features in Orthotopic Cardiac Xenotransplantation: Comparisons With Published Literature.

Xenotransplantation

Although there is a plethora of literature on electrocardiographic changes following cardiac allotransplantation, there is little in the field of cardiac xenotransplantation. The only published literature to date is that of the first pig-to-human cardiac xenotransplantation. Here we take a close look at the electrocardiographic parameters in four non-human primate recipients of orthotopic cardiac xenotransplantation to develop baseline metrics for comparison.

Orthotopic cardiac xenotransplantion was carried out in four non-human primate recipients. Electrocardiographic parameters were followed at various intervals using an internal hemodynamic monitoring system (DSI) as well as a standard 12-lead electrocardiogram (ECG). ECG intervals were then compared to published literature on porcine ECG intervals and pig-to-human cardiac xenotransplantation.

There were no significant differences observed between timepoints for HR, PR, QRS, QT, or QTc after cardiac xenotransplantation for each animal subject. ECG parameters were statistically similar to those of in situ mini-pig hearts in the literature. ECG parameters from the DSI on average were shorter than those from a traditional ECG, however, DSI parameters were consistent over time.

These results demonstrate the possibility of conduction health for genetically engineered porcine donor hearts following cardiac xenotransplantation. Ongoing work to compare the results of an ECG in a porcine donor heart before and after implantation into a NHP is necessary to better characterize variables that may be at play in the function of the conduction system.

Ultrasound Assessment of Pleural Effusions After Orthotopic Pig-to-Baboon Cardiac Xenotransplantation.

Xenotransplantation

Pleural effusions develop frequently after cardiac surgery in humans. Lung ultrasound is an essential non-invasive tool in the diagnosis and treatment of these effusions. Pleural effusions also develop regularly after preclinical cardiac xenotransplantation experiments. Unlike in the human setting, modern ultrasound devices lack pre-installed tools for calculating the volume of pleural effusions in baboons. The aim of this study was to analyze ultrasound examinations of pleural effusions after orthotopic pig-to-baboon cardiac xenotransplantation experiments in order to develop a formula for calculating the effusion volume based on ultrasound measurements.

Hearts from seven genetically modified (GGTA1-KO, hCD46/hTBM transgenic) juvenile pigs were orthotopically transplanted into male baboons. Postoperatively, the baboons were tested regularly for the development of pleural effusions using ultrasound. When thoracocentesis was required, the drained effusion volume (EV) was compared to ultrasound-derived calculations using various formulas. These calculations were based on measuring the distance between lung and diaphragm at the effusions' maximum height (Hmax). Subsequently, the most promising formula was used to describe the interobserver variability between trained and untrained staff members to predict effusion volumes based on ultrasound measurements.

Ultrasound measurement correlated very strongly with the absolute EV (r = 0.9156, p < 0.0001), with EV indexed to total body weight (r = 0.9344, p < 0.0001) and with EV indexed to body surface area (BSA) (r = 0.9394, p < 0.0001). The ratio between Hmax and EV increased with total body weight and BSA and also depended on the baboon species. The sonographic measurements taken by an experienced and an inexperienced observer showed only low interobserver variability. A Bland-Altman plot of both observers' measurements showed an overall bias of -2.39%.

Ultrasound imaging provides a simple and non-invasive tool for measuring pleural effusion quantity in baboons. This facilitates simple and efficient monitoring even in the hands of untrained personnel and may guide the decision-making to perform thoracocentesis.

The Outcomes of Adenovirus Infection in Kidney Transplant Recipients.

Transplant Infectious Disease

Adenovirus (ADV) infection can lead to significant morbidity and mortality in immunocompromised patients, particularly in those with hematopoietic stem cells or solid organ transplants. The incidence of ADV infection in kidney transplant (KT) is not well-defined as ADV is often asymptomatic and not routinely checked.

This retrospective case-series study included KT and simultaneous pancreas-KT (SPKT) recipients from January 1, 2008, to January 31, 2024, across three Mayo Clinic sites (Arizona, Florida, and Minnesota) with symptomatic adenovirus polymerase chain reaction cases. The primary outcomes were allograft function at various intervals post-ADV infection, allograft, and patient survival.

We report one of the largest multi-site case series regarding outcomes of ADV in KT with 17 patients. The median time to ADV infection was 30 weeks (5-74). Five patients (29%) developed disseminated infection. Nine patients (53%) of the entire cohort experienced graft loss within a median of 35 (4-168) weeks, with four (44%) of graft loss attributed to ADV. Nine patients (53%) developed rejections post-ADV infection with a median of 4 (2-8) weeks after resolution. One patient died from acute hypoxic respiratory failure from ADV infection.

ADV should be considered in KT/SPKT patients with renal dysfunction, hematuria, and with or without fever. Despite the low mortality rate, there is a significant risk of graft loss and rejection after ADV infection. It is crucial to screen for ADV and develop intervention strategies for treatment. Further multicenter studies are needed to better define, stage, and manage ADV infection.

Impact of Bebtelovimab Treatment Timing on COVID-19 Outcomes in Ambulatory Solid Organ Transplant Recipients.

Transplant Infectious Disease

Outcomes after bebtelovimab treatment for COVID-19 were favorable for most but not all solid organ transplant recipients (SOTRs) during the era of Omicron BA.2 to BA.5, but effects of timing of bebtelovimab administration on these outcomes are unknown. We sought to compare outcomes of SOTR who received early bebtelovimab ("EBT", given ≤ 2 days from diagnosis) versus late bebtelovimab ("LBT", given between Days 3 and 7), versus no bebtelovimab (NBT).

This was a retrospective cohort study of SOTRs with mild-to-moderate COVID-19, with endpoint of 30-day COVID-19-related hospitalization. Multivariable logistic regression was performed to determine variables associated with receiving EBT, and to assess impact of EBT on hospitalization. A propensity score (PS) was calculated for EBT versus NBT.

Of 297 SOTRs, 162 (58.1%) received EBT, 46 (16.5%) LBT, and 71 (25.4%) NBT. Early bebtelovimab treatment was associated with a lower risk of 30-day COVID-19-related hospitalization compared to NBT (OR, 0.112 [95% CI, 0.018-0.686]; p = 0.018). There was no significant difference in hospitalization risk between LBT and NBT, suggesting that delayed administration may not confer additional benefits over no treatment.

Early bebtelovimab treatment in outpatient SOTRs was associated with a lower risk of hospitalization compared to no treatment, while late administration did not show a significant advantage over no treatment. Although bebtelovimab is no longer authorized, these findings suggest that the timing of COVID therapies for SOTRs may be important to optimize outcomes.