Suitability For Transplantation Research Articles

Utility of a Model to Predict Endothelial Cell Density of Donor Corneas to Determine Suitability for Transplantation.

In Germany, approximately one-third of the harvested donor corneas are not suitable for transplantation, mostly due to insufficient endothelial cell density (ECD). The ECD can only be reliably determined after harvesting and processing of the cornea. Our group has previously developed a predictive model for corneal ECD: \( {Predicted\, ECD} = 2919-6^{\ast}\;{age}\; [{years}]-189\; [{if\, male}]\\ -7^{\ast}\;{death-to-explantation\, interval\,} [{hours}]\\ - 378\; [{if\, pseudophakic}] \;{cells/mm}^2 \). A total of 2.999 consecutive donor corneas harvested between 2017 and 2021 from the Eye Bank of Rhineland-Palatinate in Mainz, Germany, were included. An actual ECD of >2000cells/mm2 was defined as the cutoff value. To evaluate the clinical utility of the prognostic model as a screening instrument for transplant eligibility in an independent cohort, we performed a decision curve analysis. The median predicted ECD was 2061cells/mm2 (interquartile range [IQR] = 1834 to 2221), whereas the median actual ECD was 2377cells/mm2 (IQR = 1907 to 2624). There was a positive correlation between predicted and actual ECD (correlation coefficient = 0.411; P < 0.01). Our predictive model for ECD is a strong predictor for an actual ECD greater than 2000 (odds ratio = 1.374, 95% confidence interval [CI]) per 100 cells; P < 0.001, area under the curve [AUC] of 0.73). Decision curve analysis showed that the predictive model yielded a positive net benefit in clinical settings. Decision curve analysis demonstrated a positive net benefit of the ECD predictive model in clinical settings with limited eye bank resources. In possible scenarios where a choice between corneal grafts is required, or in countries with limited eye bank infrastructure and staff, the initial estimate of ECD from the formula may be beneficial.

Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes.

Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) or kidney failure, with an estimated prevalence of up to 78% in those referred for right-heart catheterization. PH is independently associated with adverse outcomes in CKD, raising the possibility that early detection and appropriate management of PH might improve outcomes in at-risk patients. Among patients with PH, the prevalence of CKD stages 3 and 4 is estimated to be as high as 36%, and CKD is also independently associated with adverse outcomes. However, the complex, heterogenous pathophysiology and clinical profile of CKD-PH requires further characterization. CKD is often associated with elevated left ventricular filling pressure and volume overload, which presumably leads to pulmonary vascular stiffening and post-capillary PH. By contrast, a distinct subgroup of patientsat high risk is characterized by elevated pulmonary vascular resistance and right ventricular dysfunction in the absence of pulmonary venous hypertension, which may represent a right-sided cardiorenal syndrome defined in principle by hypervolaemia, salt avidity, low cardiac output and normal left ventricular function. Current understanding of CKD-PH is limited, despite its potentially important ramifications for clinical decision making. In particular, whether PH should be considered when determining the suitability and timing of kidney replacement therapy or kidney transplantation is unclear. More research is urgently needed to address these knowledge gaps and improve the outcomes of patients with or at risk of CKD-PH.

Defatting of donor transplant livers during normothermic perfusion—a randomised clinical trial: study protocol for the DeFat study

BackgroundLiver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes.MethodsIn the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months).DiscussionThis study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths.Trial registrationISRCTN ISRCTN14957538. Registered in October 2022.

Association of psychosocial risk factors and liver transplant evaluation outcomes in metabolic dysfunction-associated steatotic liver disease.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a standardized psychosocial assessment tool used in liver transplantation (LT) evaluation and has been primarily studied in patients with alcohol-associated liver disease. We aimed to evaluate the relationship between SIPAT score and metabolic syndrome severity and LT waitlist outcomes in a large cohort of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We performed a single-center retrospective cohort study of patients with MASLD evaluated for LT from 2014-2021. The utility of the previously defined total SIPAT cut-off (<21 [excellent/good candidates] vs ≥21 [minimally acceptable/high risk candidates]) was studied. Multivariable logistic regression analyses examined associations between continuous SIPAT score and LT waitlisting outcomes. Youden's J statistic was used to identify the optimal SIPAT cut-off for MASLD patients. A total of 480 patients evaluated for transplant with MASLD were included. Only 9.4% of patients had SIPAT score ≥21. Patients with SIPAT score ≥21 had higher hemoglobin A1c compared to patients with lower psychosocial risk (median (IQR): 7.8 (6.0-9.7) vs 6.6 (5.8, 7.9); p=0.04). There were no other differences in metabolic comorbidities between SIPAT groups. Increasing SIPAT score was associated with decreased odds of listing (OR: 0.82 per five-point increase; p=0.003) in multivariable models. A SIPAT of ≥12 was identified as the optimal cut-off in this population, resulting in an adjusted OR for listing of 0.53 vs SIPAT <12 (p=0.001). In this large cohort of MASLD patients evaluated for LT, few patients met the previously defined high SIPAT cut-off for transplant suitability. Nevertheless, increasing SIPAT score was associated with waitlist outcome. Our suggested SIPAT cut-off of ≥12 for MASLD patients warrants further external validation using data from other centers.

Introduction of ex vivo perfusion of extended-criteria donor hearts in a single center in Asia.

The shortage of organs for heart transplantation has created a need to explore the use of extended-criteria organs. We report the preliminary use of normothermic TransMedics Organ Care System-an ex vivo approach to preserve extended-criteria brain-dead donor hearts. This System maintains a normal temperature, provides continuous perfusion and oxygenation, reduces ischemic time, and enables additional viability assessment options. In a retrospective single-centre study conducted from April 2020 to March 2023, four extended criteria brain-dead donor hearts were perfused and monitored using the Organ Care System. Suitability for transplantation was assessed based on stable or decreasing lactate levels, along with appropriate perfusion parameters. The Organ Care for use of the Organ Care System were coronary artery disease, left ventricular hypertrophy, high-dose inotrope use in the donor, a downtime exceeding 20min, and a left ventricular ejection fraction of 40-50%. Three out of the four donor hearts were transplanted, while one was discarded due to rising lactate concentration. The three recipients had a higher surgical risk profile for heart transplant. All showed normal cardiac function and no primary graft dysfunction postoperatively. At 2-3years post-transplant, all recipients have a ventricular function of > 60%, with only one showing evidence of mild rejection. The Organ Care System enables the successful transplantation of marginal donor organs in high-risk recipients, showcasing the feasibility of recruiting donors with extended criteria. This technique is safe and promising, expanding the donor pool and addressing the organ shortage in heart transplantation in Hong Kong.

#165 Substantial variation in the evaluation of kidney transplant recipient candidates prior to waitlisting: a worldwide scoping review

Abstract Background and Aims Before patients with end stage kidney disease can undergo kidney transplantation, their suitability is assessed through a transplantation work-up. Several international guidelines have outlined the most important factors in determining patient suitability for kidney transplantation, but there is little agreement among them and it is unclear whether their recommendations have been adopted into clinical practice. Variation in the evaluation of kidney transplant recipient candidates could contribute to inefficiency and inequality in accessing the transplant waiting list and kidney transplantation. Therefore, the standardization of pre-waitlisting practice patterns is desirable and in line with recommendations from Europe [1] and the US [2]. An overview of publications on pre-waitlisting practices for kidney transplantation is needed to increase the transparency of kidney transplant recipient candidacy evaluation and is a first step towards the standardization of pre-waitlisting procedures. To date, such an overview has not been performed. Therefore, our aim was to conduct a scoping review on the evaluation of kidney transplant recipient candidates prior to waitlisting, investigating: (a) the content of the transplantation work-up; (b) contraindications to waitlisting; and (c) the organization of the transplantation work-up. Method A systematic search was conducted in Ovid Medline and Ovid EMBASE in collaboration with a medical information specialist. Studies reporting practice patterns on the evaluation of adults receiving their first kidney graft from a deceased donor were included. Studies were excluded if they only reported: on pediatric patients; from the perspective of the patients; practice patterns following waitlisting; COVID-19-related changes to practice patterns; and results from novelty screening methods used to evaluate kidney transplant recipient candidates without evidence that these methods were also used in clinical practice. Results Results from 40 studies were summarized, of which a majority were conducted in Europe (n = 11) and the US (n = 21). The content of the transplantation work-up varied widely between studied centers. Results show that the presence of a written transplantation work-up was common in the US, UK, and Norway, while in other countries, the presence of a written transplantation work-up protocol was not reported. Common domains within the transplantation work-up included screening for infections, heart disease, peripheral artery disease, and malignancy. A wide range of contraindications to waitlisting were reported. The criteria for contraindications related to obesity and age/frailty varied between studied centers and appear to have changed over time. In general, the organization of the transplantation work-up (e.g. the referral process, the transplant care team, and the use of multidisciplinary meetings) was comparable across studied centers, but differences were observed in the way the transplantation work-up was carried out. Conclusion This is the first review summarizing practice patterns related to the evaluation of kidney transplant recipient candidates prior to waitlisting. Results showed substantial variation in the evaluation of kidney transplant recipient candidates and pre-waitlisting practice patterns globally. These findings contribute to increasing the transparency of pre-waitlisting practice patterns, as was endorse by EU and US recommendations. In turn, this may aid in standardizing criteria used to evaluate kidney transplant recipient candidates prior to waitlisting, which could improve kidney transplantation access and outcomes.

Using the brain to heal the heart: A case discussion and review of panhypopituitarism-induced chronic heart and kidney failure

In this paper, we present a detailed case study from our transplant evaluation clinic, focusing on a postpartum patient with end-stage heart and kidney failure being considered for heart transplantation. The evaluation revealed pituitary dysfunction, correlating with Sheehan syndrome, a condition arising from significant blood loss that leads to pituitary gland hypoperfusion and necrosis. This diagnosis is particularly noteworthy considering the pituitary gland's vital role in hormonal regulation, which impacts multiple organ systems. The gland's vulnerability to ischemia, especially due to its enlargement during pregnancy, is a critical factor. Our case highlights the necessity of thorough pre-transplant evaluations to identify reversible endocrine factors contributing to organ failure, emphasizing the complex interplay between endocrine health and organ transplant suitability. This study serves as an important reminder for clinicians to consider endocrine causes in transplant candidates, especially in postpartum patients.

Use of Levosimendan in patients with INTERMACS 3 profile: weaning from inotropic support and short- to medium-term evolution

Abstract Funding Acknowledgements None. Introduction Patients with advanced heart failure (HF) in cardiogenic shock (CS) present a markedly high mortality rate. For CS patients dependent on inotropes, management is difficult with few therapeutic options available, especially in the absence of a suitability for heart transplantation (HTX) or left ventricular assist device implantation (LVAD), thus associating an even worse prognosis. Purpose With our study we aim to analyse the rate of weaning from inotropic support when Levosimendan, a calcium sensitizer with positive inotropic effects, is used in INTERMACS 3 CS patients and their short to medium-term evolution. We then evaluate if the absence of right ventricular dysfunction, of renal dysfunction, non-ischemic aetiology and QRS width could be predicting factors of a successful weaning from inotropes. Materials and methods We conducted a monocentric retrospective analysis of patients from a tertiary cardiac intensive care unit that have received a 24 hours Levosimendan infusion in the context of INTERMACS 3 cardiogenic shock between August 2015 – April 2023. Results Of the 137 subjects included in the analysis, 62 patients received Levosimendan for INTERMACS 3 CS. The median age was 59±15.3 and 91.9% (n=57) were male. Baseline LVEF was 19±6%, cardiac index 1.67±0.4L/min/m2, median NTproBNP 13 378 ± 11 126ng/L. 51.6% (n=32) had ischemic heart disease and 40.3% (n=25) had dilated cardiomyopathy. After Heart Team discussion, only 37% (n=23) were considered eligible for HTX or LVAD. Successful inotrope weaning was experienced in 68% (n=42). Amongst patients with weaning failure, most outcomes resulted in either death (45%), ambulatory continuous Dobutamine infusion (30%), or benefited from a HTX if eligible (15%). The weaning failure rates were similar amongst patients eligible and non-eligible to HTX or LVAD with different outcomes after weaning failure as shown in Figure 1. The overall survival rates at 1 month and 6 months were of 83.8% and 53.2% respectively, with a significant difference between survival rates according to inotrope weaning success or failure as shown in Figure 2. We found no clinical, biological, or echocardiographic parameter to be significantly associated with an increased probability of weaning. Conclusion Levosimendan use in INTERMACS 3 CS patients provides a good rate of success in weaning from inotropic support and could be a useful tool in allowing treatment optimization and stabilization in non HTX or LVAD eligible patients, as well as being a "bridge to transplantation" alternative. No predicting factors for successful weaning have been identified.

Integrated transcriptomics and histopathology approach identifies a subset of rejected donor livers with potential suitability for transplantation

BackgroundLiver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation).ResultsWe identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers.ConclusionsOur integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.

Psychosocial readiness assessment for heart transplant candidates

BackgroundPsychosocial evaluation for transplant suitability is required by the Centers for Medicare and Medicaid Services (CMS) as a condition of participation for transplant programs. There are no regulations regarding follow-up reassessment for transplant readiness after waitlisting. ObjectivesAn evidence-based pilot project was developed and implemented to evaluate the feasibility of psychosocial readiness assessments for waitlisted heart transplantation candidates. The primary aim was to test the feasibility of these assessments in practice from a patient and programmatic perspective. MethodsDuring a 12-week period, waitlisted outpatients underwent one assessment each. Socioeconomic elements of caregiver support, housing, transportation, and insurance coverage status were assessed by simple using “yes/no” questions. To assess mental health needs, the General Anxiety Disorder-7 questionnaire (GAD-7) and the Patient Health Questionnaire-8 (PHQ-8) tools were utilized. Rescheduled readiness visits and no-show rates were measured. A post-implementation Qualtrics survey was administered to measure team member perceptions of feasibility. ResultsA total of 57 patients were assessed during the 12-week period. The primary aim of feasibility was achieved with 93 % of visits performed with freedom from rescheduling or patient no-show to the visit. Additionally, 75 % of team members reported the readiness assessments were feasible to complete in practice. ConclusionsAddressing the non-medical and mental health needs of waitlisted heart transplant patients allows transplant programs to maintain candidates with necessary resources and care. The readiness assessments are feasible in practice and may serve to reduce untoward outcomes in the post-transplant phase by providing targeted care prior to the time of transplant.

An Unexpected Partnership: Alexis Carrel, Charles Lindbergh, and Normothermic Machine Perfusion.

Organ transplantation is a triumph of modern medicine which represents a culmination of science and imagination, saving thousands of lives a year. However, transplantation is severely limited by suitable donor allografts. To expand the donor pool and make transplantation achievable for all, normothermic machine perfusion (NMP) is being employed more frequently. Normothermic machine perfusion involves the utilization of a device to approximate the physiology of the human body, preserve organs outside of the donor, and provide a dynamic assessment platform to determine organ suitability for transplantation. As NMP technology advances, it will soon be possible to genetically modify and actively repair these organs. Although its application to the field of transplantation is relatively new, the concept, foundation, and development of NMP can be traced back to the pioneering work of the surgeon-scientist, Alexis Carrel and the famous aviator, Charles Lindbergh in the 1930s. Their collaboration resulted in the Carrel-Lindbergh Perfusion device, an early perfusion device that was able to keep organs alive ex vivo for weeks and is most appropriately viewed as a precursor to modern machine perfusion technologies. As NMP technology becomes more advanced and refined, it is important to acknowledge the historical context in which these technologies emerged.

The stuck haemodialysis catheter—a case report of a rare but dreaded complication following kidney transplantation

BackgroundTunnelled cuffed haemodialysis catheters are at increased risk of incarceration or becoming ‘stuck’ via fibrotic adhesion to the central veins when left in situ for prolonged periods of time. Stuck catheters cannot be removed using standard techniques such as bedside dissection of the cuff. Whilst there are several strategies published for the removal of these incarcerated lines, there is no consensus on the best approach. Here we present a challenging case of a stuck haemodialysis catheter in the acute post transplantation period.Case PresentationA 66-year-old female on haemodialysis presented for kidney transplantation with a tunnelled-cuffed haemodialysis catheter in situ for five years. Following transplantation, removal of the line was unsuccessful despite dissection of the cuff, with traction causing a choking sensation with tracheal movement. Eventually, the line was removed without complications utilising sequential balloon dilatation by interventional radiology and the patient was discharged without complications.ConclusionsThis case serves as a timely reminder of the risks of long-term tunnelled haemodialysis catheters and as a caution towards proceeding with kidney transplantation in those with long-term haemodialysis catheters in situ. Greater nephrologist awareness of interventional radiology techniques for this challenging situation will help to avoid more invasive strategies. The risks of a stuck catheter should be included in the discussions about the optimal vascular access and transplantation suitability for a given patient.

Impact of demographic factors on corneal donor recovery.

Death-to-preservation time (DTP) is a commonly reported, but infrequently studied, measure of efficiency for the corneal tissue procurement process and is a key screening component for corneal tissue suitability for transplantation. It is unknown whether demographic factors such as race, age, or gender may affect DTP. This retrospective cross-sectional study included all deceased-donor eye tissue collected by CorneaGen Eye Banks between June 1, 2012 and June 30, 2016. Exposure variables of race, age, and gender were independently analyzed with the outcome variable, DTP, using three simple linear regression analyzes.Associations were then confirmed by a multiple linear regression analysis within a single model. A total of 24,138 unique donors were identified from 48,207 donor eyes. Simple linear regression analysis showed that relative to White donors, Black and Hispanic donors were associated with a 2.40h (95% CI 2.07-2.74h, p < 0.001) and 2.48h (95% CI 2.15-2.80h, p < 0.001) longer mean DTP, respectively. DTP decreased with increasing age, at a rate of 30min per every 10years (95% CI 27-33min, p < 0.001).Male donors were associated with a 35min (95% CI 26-44min, p < 0.001) longer DTP relative to female donors. A multiple linear regression confirmed the results of the three simple linear regressions. In a large cohort of corneal donors, non-White race, younger age, and male gender were associated with longer DTP.

Changing the liver transplant assessment process from inpatient to a day-case and outpatient approach to reduce inpatient bed utlisation

The liver transplant assessment process involves a complex set of tests and clinical reviews to determine suitability for liver transplantation. We had an assessment process involving a 3-day inpatient stay...

Kidney Transplantation Contraindications: Variation in Nephrologist Practice and Training Vintage

IntroHealth system leaders aim to increase access to kidney transplantation in part by encouraging nephrologists to refer more patients for transplant evaluation. Little is known about nephrologists’ referral decisions and whether nephrologists with older training vintage weigh patient criteria differently (e.g., more restrictively). MethodsUsing a novel, iteratively validated survey of U.S.-based nephrologists, we examined how nephrologists assess adult patients’ suitability for transplant, focusing on established, important criteria: seven clinical (e.g., overweight) and seven psychosocial (e.g., insurance). We quantified variation in nephrologist restrictiveness—proportion of criteria interpreted as absolute or partial contraindications versus minor or negligible concerns—and tested associations between restrictiveness and nephrologist age (proxy for training vintage) in logistic regression models, controlling for nephrologist- and practice-level factors. ResultsOf nephrologists invited (n=144), 42 survey respondents (29% response rate) were 85% male and 54% non-Hispanic white, with mean age 52 years, and 67% spent ≥1 day/week in outpatient dialysis facilities. Nephrologists interpreted patient criteria inconsistently; consistency was lower for psychosocial criteria (intraclass correlation coefficient [ICC] 0.28) than for clinical criteria (ICC 0.43; p<0.01). With each additional 10 years of age, nephrologists’ odds of interpreting criteria restrictively (top tertile) doubled (adjusted odds ratio [aOR] 1.96, 95% CI 0.95-4.07), with marginal statistical significance. This relationship was significant when interpreting psychosocial criteria (aOR 3.18, 95% CI 1.16-8.71) but not when interpreting clinical criteria (aOR 1.12, 95% CI 0.52-2.38). ConclusionNephrologists interpret evaluation criteria variably when assessing patient suitability for transplant. Guideline-based educational interventions could influence nephrologists’ referral decision-making differentially by age.

Artificial Intelligence in the Detection of Fatty Liver Disease

Background: The current gold standard for quantification of the fat content of the liver (i.e., nonalcoholic fatty liver disease, NAFLD) is the visual microscopic inspection of liver biopsies by pathologists. Percentage of macrosteatosis (%MaS), used in determining NAFLD diagnosis, is vital in determining the transplant suitability of a donor liver. A major limitation of this method is inevitable human error which causes interobserver variability and overestimation of %MaS which could cause a potential discard of donor livers. We hypothesize that artificial intelligence (AI) can assist pathologists in providing a more objective and accurate measure of %MaS.&#x0D; Methods: Our literature review identified HALO (image analysis) and U-Net (deep-learning) as AI programs currently available for high-accuracy %MaS calculation in liver biopsies. We compared the pathologist-reported %MaS from de-novo liver transplant (LT) biopsy samples taken 2h post-reperfusion to the %MaS calculated by HALO and/or U-Net (Fig. 1). 250 patients had undergone de novo LT at Indiana University between 2019-2020, and 211 of these patients had sufficient data (liver enzyme tests, biopsy results) to be included. Each biopsy sample was digitized into 5 random non-overlapping tiles at 20x magnification using a Leica microscope. Early allograft dysfunction (EAD) is defined by the presence of at least one of the following: (i) INR &gt;1.6 on postoperative day (POD) 7, (ii) total bilirubin &gt;10 mg/dL on POD7, or (iii) AST/ALT &gt;2000 IU/L within the first 7 days following LT.&#x0D; Results: Our literature review identified that both HALO and U-Net estimated the %MaS in liver allograft biopsies significantly lower than pathologists' estimation (Fig.1). Of 211 included patients, 46 (21.8%) had EAD. In this ongoing project, we found U-Net to have a 97.3% training accuracy with eight epochs (2000 biopsy images each). Tiles from the first ten patients are being analyzed by HALO and/or U-Net to calculate an average %MaS for each patient. These calculations will be compared to the %MaS estimation made by pathologists.&#x0D; Conclusions: The rapidly evolving field of AI is emerging as a promising method in the quantification of the fat content of the liver with increased accuracy. AI will therefore help pathologists and transplant surgeons to determine liver transplant viability and better predict EAD in transplant patients.

A radiographic score for human donor lungs on ex vivo lung perfusion predicts transplant outcomes

BackgroundEx vivo lung perfusion (EVLP) is an advanced platform for isolated lung assessment and treatment. Radiographs acquired during EVLP provide a unique opportunity to assess lung injury. The purpose of our study was to define and evaluate EVLP radiographic findings and their association with lung transplant outcomes. MethodsWe retrospectively evaluated 113 EVLP cases from 2020-21. Radiographs were scored by a thoracic radiologist blinded to outcome. Six lung regions were scored for five radiographic features (consolidation, infiltrates, atelectasis, nodules, and interstitial lines) on a scale of 0 to 3 to derive a score. Spearman’s correlation was used to correlate radiographic scores to biomarkers of lung injury. Machine learning models were developed using radiographic features and EVLP functional data. Predictive performance was assessed using the area under the curve. ResultsConsolidation and infiltrates were the most frequent findings at 1h EVLP (radiographic lung score 2.6 (3.3) and 4.6 (4.3)). Consolidation (r=-0.536 and -0.608, p<0.0001) and infiltrates (r=-0.492 and -0.616, p<0.0001) were inversely correlated with oxygenation (∆pO2) at 1h and 3h of EVLP. First-hour consolidation and infiltrate lung scores predicted transplant suitability with an area under the curve of 87% and 88%, respectively. Prediction of transplant outcomes using a machine learning model yielded an area under the curve of 80% in the validation set. ConclusionsEVLP radiographs provide valuable insight into donor lungs being assessed for transplantation. Consolidation and infiltrates were the most common abnormalities observed in EVLP lungs, and radiographic lung scores predicted the suitability of donor lungs for transplant.

NADPH oxidase overexpression and mitochondrial OxPhos impairment are more profound in human hearts donated after circulatory death than brain death.

This study investigated cardiac stress and mitochondrial oxidative phosphorylation (OxPhos) in human donation after circulatory death (DCD) hearts regarding warm ischemic time (WIT) and subsequent cold storage and compared them with that of human brain death donor (DBD) hearts. A total of 24 human hearts were procured for the research study-6 in the DBD group and 18 in the DCD group. DCD group was divided into three groups (n = 6) based on different WITs (20, 40, and 60 min). All hearts received del Nido cardioplegia before being placed in normal saline cold storage for 6 h. Left ventricular biopsies were performed at hours 0, 2, 4, and 6. Cardiac stress [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits: 47-kDa protein of phagocyte oxidase (p47phox), 91-kDa glycoprotein of phagocyte oxidase (gp91phox)] and mitochondrial oxidative phosphorylation [OxPhos, complex I (NADH dehydrogenase) subunit of ETC (CI)-complex V (ATP synthase) subunit of ETC (CV)] proteins were measured in cardiac tissue and mitochondria respectively. Modulation of cardiac stress and mitochondrial dysfunction were observed in both DCD and DBD hearts. However, DCD hearts suffered more cardiac stress (overexpressed NADPH oxidase subunits) and diminished mitochondrial OxPhos than DBD hearts. The severity of cardiac stress and impaired oxidative phosphorylation in DCD hearts correlated with the longer WIT and subsequent cold storage time. More drastic changes were evident in DCD hearts with a WIT of 60 min or more. Activation of NADPH oxidase via overproduction of p47phox and gp91phox proteins in cardiac tissue may be responsible for cardiac stress leading to diminished mitochondrial oxidative phosphorylation. These protein changes can be used as biomarkers for myocardium damage and might help assess DCD and DBD heart transplant suitability.NEW & NOTEWORTHY First human DCD heart research studied cardiac stress and mitochondrial dysfunction concerning WIT and the efficacy of del Nido cardioplegia as an organ procurement solution and subsequent cold storage. Mild to moderate cardiac stress and mitochondrial dysfunction were noticed in DCD hearts with WIT 20 and 40 min and cold storage for 4 and 2 h, respectively. These changes can serve as biomarkers, allowing interventions to preserve mitochondria and extend WIT in DCD hearts.

Detailed cause of donor ineligibility in living donor kidney transplants: a retrospective, single-center cohort study

BackgroundLiving kidney donors are evaluated to determine their physical and psychological suitability for transplantation and ensure their safety. During this process, we frequently encounter cases where a donor is found to be ineligible. In this study, we surveyed donors who are ineligible for transplantation at our hospital to educate patients, their families, and medical staff regarding transplantation in the future. MethodsWe examined the proportion of ineligible donors among 237 potential donors who visited our hospital between January 2002 and March 2022. Data were collected retrospectively from electronic medical records and evaluated from various aspects such as age, body mass index, medical history, medications, and renal function. ResultsThe mean age at presentation was 55.5 years, the male-to-female ratio was 1:1.6, and no significant difference was found between the ineligible and eligible donor groups. The transplant ineligibility rate was 23.6%, and the categories were for medical, backout, immunologic, and recipient-related reasons, in descending order. Furthermore, a low glomerular filtration rate (GFR) was the most common cause of medical cases. ConclusionMany patients were judged ineligible because of lifestyle-related diseases such as low GFR, diabetes mellitus, and obesity. Therefore, thorough patient education should be conducted using these data as a reference to reduce the number of donors ineligible because of lifestyle-related diseases.

Where, when, how and what seagrass to transplant for long lasting results in transitional water systems: the cases of Cymodocea nodosa, Zostera marina, Zostera noltei and Ruppia cirrhosa

Seagrasses play a vital role in marine ecosystems worldwide. However, until recently these ecosystems were experiencing declines due to various global and local threats. In response to this issue, initiatives have been launched to combat seagrass loss by addressing local and regional major stressors and actively engaging in restoration efforts by transplantation. Although seagrass restoration has progressed significantly with the development of numerous transplant techniques, these are not always crowned with success. This is often due to the fact that the environmental parameters of water, sediment and biota of the recipient sites are not carefully considered in their suitability for transplantation. In this study, the multi-year experiences and data from numerous environmental surveys in transitional water systems have been condensed to define limit values for the ideal growth conditions and the extreme values in which the survival of four aquatic angiosperm species is possible: Cymodocea nodosa, Zostera marina, Zostera noltei and Ruppia cirrhosa. Approaches to transplants, seasonality and critical issues have been explored. The identified limits and parameters of water, sediment and biota will help to define the suitability of a recipient site for the rooting of seagrasses, increasing the chances of success for transplant operations.