Transplant Evaluation Research Articles

Frailty assessments and changes in frailty over time in elderly veteran Kidney Transplant candidates: Effects on transplant evaluations

Background and hypothesisFrailty has emerged as an important factor in the pre-transplant evaluation process as studies have shown that it is associated with increased waitlist mortality, lower rates of transplant listing, and higher rates of delisting. There have not been many studies on frailty in elderly pre-transplant patients. In this study, we determined the common frailty phenotypes in an elderly population, and its effects on transplant success. MethodsOver a 3-year period, frailty was determined for all patients evaluated at our center. Patient characteristics were summarized using descriptive statistics, overall and by level of frailty. Differences in patient characteristics by level of frailty were assessed for statistical significance using analysis of variance for age and chi-square or Fisher's exact test. Transplant outcomes such as listing success, transplant rates and post-transplant outcomes were tied to initial frailty assessments as well as the changes in frailty over time. ResultsA total of 375 patients were evaluated over the study period. The mean age was 64±9 years. African American patients were less likely to be frail. After adjusting for age and race, the most significant predictors of listing were the walk test (aOR: 0.42, 95 % CI: 0.22–0.79) and physical activity (aOR: 0.45, 95 % CI: 0.28–0.74). A total of 30 patients (8 %) with a pre-listing frailty evaluation died prior to transplantation. Frail walk test and physical activity assessment led to a 2-fold increase in pre-transplant mortality (7 % vs 17 %; 6 % vs 13 %). ConclusionOur study is the first to focus on a purely geriatric population and shows the importance of frailty on listing success, transplant rates and mortality prior to listing. These data point to the need for the development of tools to target frailty as a guide for improving transplant success in elderly patients.

Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

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.

Race, substance use, and evaluation for heart transplantation: Insights from a large urban medical center

It is unknown whether racial disparities in access to heart transplantation (HT) are amplified when coupled with substance use. We examined patients evaluated for HT over eight years at an urban transplant center. We evaluated substance use and race/ethnicity as independent and interactive predictors of HT and left ventricular assist device (LVAD) implantation. Of 1148 patients evaluated for HT, substance use was cited as an ineligibility factor in 151 (13%) patients, 16 (11%) of whom ultimately received HT. Significantly more non-Hispanic Black patients were deemed ineligible due to substance use (n=59, 19%) compared to other races/ethnicities (non-Hispanic white: n=68, 12%; other race/ethnicity: n=24, p=0.002). No racial differences were observed in likelihood of HT among patients initially excluded for substances, but more non-Hispanic Black patients ultimately received LVAD than the other racial groups. This study encourages greater awareness of the role of substance use and race in the HT evaluation.

Flexible bronchoscopy in pediatric lung transplantation.

Pediatric lung transplantation represents a treatment option for children with advanced lung disease or pulmonary vascular disorders who are deemed an appropriate candidate. Pediatric flexible bronchoscopy is an important and evolving field that is highly relevant in the pediatric lung transplant population. It is thus important to advance our knowledge to better understand how care for children after lung transplant can be maximally optimized using pediatric bronchoscopy. Our goals are to continually improve procedural skills when performing bronchoscopy and to decrease the complication rate while acquiring adequate samples for diagnostic evaluation. Attainment of these goals is critical since allograft assessment by bronchoscopic biopsy is required for histological diagnosis of acute cellular rejection and is an important contributor to establishing chronic lung allograft dysfunction, a common complication after lung transplant. Flexible bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy plays a key role in lung transplant graft assessment. In this article, we discuss the application of bronchoscopy in pediatric lung transplant evaluation including historical approaches, our experience, and future directions not only in bronchoscopy but also in the evolving pediatric lung transplantation field. Pediatric flexible bronchoscopy has become a vital modality for diagnosing lung transplant complications in children as well as assessing therapeutic responses. Herein, we review the value of flexible bronchoscopy in the management of children after lung transplant and discuss the application of novel techniques to improve care for this complex pediatric patient population and we provide a brief update about new diagnostic techniques applied in the growing lung transplantation field.

Invasive Cardiac Hemodynamics in Apical Hypertrophic Cardiomyopathy.

Symptomatic limitations in apical hypertrophic cardiomyopathy may occur because of diastolic dysfunction with resultant elevated left ventricular filling pressures, cardiac output limitation to exercise, pulmonary hypertension (PH), valvular abnormalities, and/or arrhythmias. In this study, the authors aimed to describe invasive cardiac hemodynamics in a cohort of patients with apical hypertrophic cardiomyopathy. Patients presenting to a comprehensive hypertrophic cardiomyopathy center with apical hypertrophic cardiomyopathy were identified (n=542) and those who underwent invasive hemodynamic catheterization (n=47) were included in the study. Of these, 10 were excluded due to postmyectomy status or incomplete hemodynamic data. The mean age was 56±18 years, 16 (43%) were women, and ejection fraction was preserved (≥50%) in 32 (91%) patients. The most common indication for catheterization was dyspnea (48%) followed by suspected PH (13%), and preheart transplant evaluation (10%). Elevated left ventricular filling pressures at rest or exercise were present in 32 (86%) patients. PH was present in 30 (81%) patients, with 6 (20%) also having right-sided heart failure. Cardiac index was available in 25 (86%) patients with elevated resting filling pressures. Of these, 19 (76%) had reduced cardiac index and all 6 with right-sided heart failure had reduced cardiac index. Resting hemodynamics were normal in 8 of 37 (22%) patients, with 5 during exercise; 3 of 5 (60%) patients had exercise-induced elevation in left ventricular filling pressures. In patients with apical hypertrophic cardiomyopathy undergoing invasive hemodynamic cardiac catheterization, 86% had elevated left ventricular filling pressures at rest or with exercise, 81% had PH, and 20% of those with PH had concomitant right-sided heart failure.

Impact of delayed listing after initiating kidney transplant evaluation on transplant outcomes.

Longer end-stage renal disease time has been associated with inferior kidney transplant outcomes. However, the contribution of transplant evaluation is uncertain. We explored the relationship between time from evaluation to listing (ELT) and transplant outcomes. This retrospective study included 2535 adult kidney transplants from 2000 to 2015. Kaplan-Meier survival curves, log-rank tests, and Cox regression models were used to compare transplant outcomes. Patient survival for both deceased donor (DD) recipients (p<.001) and living donor (LD) recipients (p<.0001) was significantly higher when ELT was less than 3 months. The risks of ELT appeared to be mediated by other risks in DD recipients, as adjusted models showed no associated risk of graft loss or death in DD recipients. For LD recipients, ELT remained a risk factor for patient death after covariate adjustment. Each month of ELT was associated with an increased risk of death (HR=1.021, p=.04) but not graft loss in LD recipients in adjusted models. Kidney transplant recipients with longer ELT times had higher rates of death after transplant, and ELT was independently associated with an increased risk of death for LD recipients. Investigations on the impact of pretransplant evaluation on post-transplant outcomes can inform transplant policy and practice.

Longitudinal analysis of liver transplant candidates for hepatocellular carcinoma in a single center.

Wailitst lost is an critical issue and we investigated the long-term effect of insufficient liver functional reserve at liver transplantation evaluation on waitlist outcomes in patients with hepatocellular carcinoma (HCC). Clinical data of patients with HCC waitlisted for liver transplantation were retrospectively collected from a single hospital cohort during the period from 2014 to 2021. Parameters of liver reserve, including cirrhosis, Child-Pugh grade, and Model for End-Stage Liver Disease (MELD) scores, were analyzed for patient survival, after adjustment for tumor factors. Of 292 eligible patients, 94.2% had cirrhosis, 55.8% had Child-Pugh grade B or C, and the median MELD score was 13.2. The median follow-up time was 2.2years, with a dropout rate of 62.7%. Eighty-nine candidates (30.5%) eventually received liver transplant, including 67 from live donors. The estimated 1-year mortality rate reached 40.6% in 203 patients who remained on the waitlist without receiving a transplant, of whom 143 died. Most deaths were attributed to liver failure (37.1%) and cancer death (35.7%). After we adjusted for tumor confounders, including alpha fetoprotein, primary HCC stage, tumor number at evaluation, and sequential cancer treatment before and while waiting, hazard ratios (HRs) for patient survival were 1.69 (95% confidence interval, 1.18-2.41) for cirrhotic stage B or C, 1.07 (1.04-1.10) for MELD scores, and 1.14 (1.04-1.25) for tumor size at transplant evaluation. Transplantation was a protective disease modifier with adjusted HR 0.22 (0.14-0.33). Insufficient liver functional reserve poses more risk than expected to liver transplant waitlist outcomes with HCC.

Referral and Beyond: Restructuring the Kidney Transplant Process to Support Greater Access in the United States

Advocates for improved equity in kidney transplant in the US have recently focused efforts on initiatives to increase referral for transplant evaluation. However, because donor kidneys remain scarce, increased referrals are likely to result in an increasing number of patients proceeding through the evaluation process without ultimately receiving a kidney. Unfortunately, the process of referral and evaluation can be highly resource-intensive for patients, families, transplant programs, and payers. Patients and families may incur out-of-pocket expenses and be required to complete testing and treatments that they might not have chosen in the course of routine clinical care. Kidney transplant programs may struggle with insufficient capacity, inefficient workflow, and challenging programmatic finances and payers will need to absorb the increased expenses of upfront pretransplant costs. Increased referral in isolation may risk simply transmitting system stress and resulting disparities to downstream processes in this complex system. We argue that success in efforts to improve access through increased referrals hinges on adaptations to the pretransplant process more broadly. We call for an urgent reevaluation and redesign at multiple levels of the pretransplant system in order to achieve the aim of equitable access to kidney transplantation for all patients with kidney failure.

Disparities in Access to Liver Transplant Referral and Evaluation among Patients with Hepatocellular Carcinoma in Georgia.

Among patients with early-stage HCC in Georgia, age and insurance type were associated with referral to liver transplant, race, and poverty with evaluation initiation, and insurance type with evaluation completion. Opportunities to improve transplant access include informing referring providers about insurance requirements, addressing barriers to evaluation initiation, and streamlining the evaluation process.

The Association Between Preoperative Pectoralis Muscle Quantity and Outcomes After Cardiac Transplantation

Background: Sarcopenia is underappreciated in advanced heart failure and is not routinely assessed. In patients receiving a left ventricular assist device (LVAD), preoperative sarcopenia, defined using CT-derived pectoralis muscle area index (muscle area indexed to body surface area), is an independent predictor of post-operative mortality. The association between preoperative sarcopenia and outcomes after heart transplant (HT) is unknown. Objectives: The primary aim was to determine if preoperative sarcopenia, diagnosed using pectoralis muscle area index, is an independent predictor of days alive and out of the hospital (DAOH) post-transplant. Methods: Patients who underwent HT from January 2018 to June 2022 with available preoperative chest CT scans were included. Sarcopenia was diagnosed as pectoralis muscle area index in the lowest sex-specific tertile. The primary endpoint was DAOH at 1-year post-transplant. Results: 169 patients were included. Patients with sarcopenia (n=55) had fewer DAOH compared to those without, with a median difference of 17 days (320 vs. 337 days, p=0.004). Patients with sarcopenia had a longer index hospitalization and were also more likely to be discharged to a facility other than home. In a Poisson regression model, sarcopenia was a significant univariable and the strongest multivariable predictor of DAOH at 1-year (Parameter estimate = -0.17, 95% CI -0.19 to -14, p = <0.0001). Conclusions: Preoperative sarcopenia, diagnosed using pectoralis muscle area index, is an independent predictor of poor outcomes after HT. This parameter is easily measurable from commonly obtained preoperative CT scans and may be considered in the transplant evaluation.

Characteristics and Outcomes of a Single-Centre Cohort of Adult Congenital Heart Disease Patients Referred for Heart Transplant

Adult congenital heart disease (ACHD) services increasingly encounter heart failure (HF) in the ageing ACHD population. Optimal timing of referral for heart transplant (HTx) evaluation in this heterogeneous population is complex and ill-defined. We aim to outline the characteristics and outcomes of ACHD patients referred for HTx from a large Australian ACHD centre. Retrospective review of ACHD patients referred for HTx from a primary ACHD centre (1992-2021). Database analysis of patient demographics, characteristics, wait-listing, and transplantation outcomes was performed. A total of 45 patients (mean age 37±9.9 years old; 69% male) were referred for HTx with a mean follow-up of 5.9±6.3 years. Of these, 22 of 45 (49%) were listed and transplanted, including one heart-lung transplant. The commonest diagnosis was dextro-transposition of the great arteries (13/45, 29%). Most patients, 33 of 45 (73.3%) had undergone at least one cardiac surgery in childhood. Indications for HTx referral included HF in 34 of 45 (75%), followed by pulmonary hypertension in 7 of 45 (11%). Median transplant wait-list time was 145 days (interquartile range, 112-256). Of the 23 patients not wait-listed, the reasons included clinical stability in 13 of 45 (29%), psychosocial factors in 2 of 45 (4.4%) and prohibitive surgical risk, including multiorgan dysfunction, in 8 of 45 (17.7%). Transplant was of a single organ in most, 21 of 22 (95.5%). Overall mortality was 5 of 22 (22.7%) in those after HTx, and 14 of 23 (60.9%) in those not listed (p=0.0156). Increasingly, ACHD patients demonstrate the need for advanced HF treatments. HTx decision-making is complex, and increased mortality is seen in those not wait-listed. Ultimately, the referral of ACHD patients for HTx is underpinned by local decision-making and experience, wait-list times and outcomes.

Abstract CT278: [DREAM] Double lung transplant registry aimed for lung-limited malignancies - a prospective registry study for medically refractory cancers

Abstract BackgroundAdenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are listed as ‘special circumstances’ for lung transplantation according to a consensus document from the International Society for Heart and Lung Transplantation (ISHLT) (Weill D et al., 2015). Five studies have reported on lung transplantation in carefully selected subsets of patients with multifocal lung adenocarcinoma (Raemdonck DV et al., 2016; Glanville AR et al., 2018). The 5-year survival rate of bilateral sequential lung transplantation was estimated at over 50% in patients with multifocal BAC, invasive adenocarcinoma, and NSCLC (Ahmad U et al., 2012; Paloyan EB et al., 2000; Zorn GL et al., 2003; de Perrot M et al., 2004). Another a case series reported a post-transplant recurrence-free survival of 23 to 56 months in three patients (Garver RI et al., 1999). Moreover, there is an unmet need for patients who have lung-limited metastasis after successful treatment for primary tumors such as sarcomas or colorectal cancer (CRC). As with liver transplantation for CRC patients who have liver-confined metastases (Dueland S et at., 2020; Hernandez-Alejandro R et al., 2022), the applicability of lung transplantation in lung-limited metastatic patients should be explored. There is also an unmet need for patients with respiratory failure with a history of cancer in the last 5 years. MethodsThis is a prospective registration trial to evaluate outcomes of patients who undergo double lung transplantation for the treatment of the select groups of medically refractory cancers (primary lung cancers or metastatic cancers in lungs). Overall survival (OS), disease-free survival (DFS), allograft rejection (AR) and allograft survival (AS) as well as molecular and genetic biomarkers will be monitored to investigate the correlation with prognosis.The study duration will be 10 years including surveillance. Recruitment is to occur during the first 5 years of the study. The goal is to enroll 125 participants through the Northwestern Medicine Clinical Programs.Essential Criteria:1.The tumor should be without any extrapulmonary metastasis as determined by standard of care diagnostic and staging workup.2.All standard of care or experimental oncological treatments known to improve survival should have failed or deemed infeasible 3.Patients should meet the general criteria for lung transplant evaluation and listing Study cohorts:•Cohort A: Primary lung cancers - Examples include, but not limited to, invasive mucinous/non-mucinous non-small cell lung cancers and multifocal carcinomas.•Cohort B: Metastatic cancers to the lung only - Examples include, but not limited to, germ cell tumors, head &amp; neck tumors, colorectal tumors, renal cell tumors, testicular cancers.•Cohort C: Respiratory failure with a history of cancer in the last 5 years- Examples include, but not limited to interstitial lung disease (ILD), pulmonary fibrosis (idiopathic or secondary), advanced chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, cystic fibrosis (CF), emphysema due to alpha-1 antitrypsin deficiency, and pulmonary arterial hypertension (PAH) Clinical trial registry number : NCT05671887.Enrollment began November 16, 2022. Trial is open and continues to enroll participants as of Jan 8, 2024. Citation Format: Young Kwang Chae, Liam Il-Young Chung, Rade Tomic, Ankit Bharat. [DREAM] Double lung transplant registry aimed for lung-limited malignancies - a prospective registry study for medically refractory cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT278.

Role of Uncertainty in Illness and Coping Strategies in Advance Directive Completion in Patients With End-stage Liver Disease.

We examined the associations among advance directives (ADs) completion, coping, uncertainty in illness, and optimism and pessimism in patients with end-stage liver disease (ESLD). Although associations among ADs, coping, and uncertainty have been studied in patients with other life-limiting illnesses, these concepts have not been studied together in patients with ESLD. Patients were recruited at 2 health care institutions as part of a larger prospective study. They were enrolled if they had a diagnosis of nonhepatocellular carcinoma ESLD, Sodium Model for End-Stage Liver Disease ≥15, and no prior history of liver transplantation. Uncertainty, coping, optimism, and pessimism were assessed using the Uncertainty in Illness Scale for Adults, Revised Ways of Coping Checklist, and Life Orientation Test-revised. AD documentation at the time of study enrollment was retrospectively extracted from patient medical records. In the sample [N = 181; median age = 57 y, 115 (64%) males], male sex [odds ratio (OR) = 4.66; 95% CI: 1.53, 14.17], being listed or under evaluation for liver transplantation (OR = 3.09; 95% CI: 1.10, 8.67), greater Sodium Model for End-Stage Liver Disease scores (OR = 1.10; 95% CI: 1.01, 1.20), and greater uncertainty (OR = 1.04; 95% CI: 1.01, 1.07) were positively associated with AD documentation. Higher coping avoidance was negatively associated with AD documentation (OR = 0.915; 95% CI: 0.840, 0.997). Clinicians should consider the role of uncertainty and coping measures to improve patient-specific advance care planning conversations and expand opportunities for all patients with ESLD to file an AD, especially women and patients not listed or under evaluation for transplantation.

(1303) - 1 Year Experience with Routine Abdominal-Pelvic CT Scan Screening in Patients Under Evaluation for Heart Transplantation

(1303) - 1 Year Experience with Routine Abdominal-Pelvic CT Scan Screening in Patients Under Evaluation for Heart Transplantation

Echocardiographic evaluation of myocardial structural and functional changes in patients with stage 5 chronic kidney disease before and after kidney transplantation

Introduction. Chronic kidney disease, stage 5, leads to structural remodeling of the myocardium, and heart failure. Kidney transplantation promotes normalization of structural and functional parameters of the myocardium through reverse remodeling with an improvement of its systolic function.Aim. To evaluate structural and functional changes of the myocardium in patients before and after kidney transplantation, using echocardiography.Material and methods. A retrospective cross-sectional study included 111 individuals of whom 36 patients underwent evaluation for kidney transplant waiting list placement program (Group I), and 51 patients received kidney transplants from deceased donors (Group II). Group III consisted of 24 individuals without kidney pathology. All patients underwent transthoracic two-dimensional echocardiography using the Phillips Epiq 7 device to determine the structural and functional parameters of the heart, including the use of speckle-tracking technique to assess longitudinal and circumferential myocardial deformation of the left ventricle.Results. There were no statistically significant differences in transthoracic echocardiography results between patients in Group I and Group II. When compared to the parameters of patients in Group III, statistically significant differences were found in the following parameters: volume and volume index of the left atrium, end-diastolic volume index, left ventricular mass index, interventricular septum thickness and posterior wall thickness of the left ventricle, as well as diastolic function parameters (E/A). Patients in Group I and Group II had significantly higher values of left atrium diameter: 32 (26.0;38.0) mmHg and 31.0 (27.3;40.0) mmHg, respectively, (p1-2=0.949), while in Group III this parameter value was 22.5 (20.8;25.3) mmHg (p1-3&lt;0.001, p2-3&lt;0.001). Correlation analysis revealed statistically significant correlations between left ventricular mass index and global circumferential strain (r=0.41, p=0.0027), as well as between E/e' ratio and left ventricular mass index (r=0.323, p=0.00197). It was found that after 3 months post kidney transplantation, there was a decrease in the left atrium diameter, volume, and volume index. The values of left atrium diameter immediately after kidney transplantation and after 3 months were 40 (32.5;45) mmHg and 35 (25.5;41.0) mmHg (p=0.049); those of the left atrium volume were 62.5 (50.0;77.3) and 51.5 (47.5;64.5) ml (p=0.03); and those of the left atrium volume index were 33.4 (29.3;40.2) and 28.3 (25.5;33.6) ml/m2 (p=0.01) respectively.Conclusions. Patients with chronic kidney disease stage 5 have a high incidence of functional and structural abnormalities of the left heart chambers; left ventricular mass index positively correlates with E/e' and global circumferential strain. At 3 months after kidney transplantation, there was a slight positive trend manifested in the form of a decrease in left atrium diameter and a decrease in left ventricle volume. Further dynamic study of this group of patients in the long term after kidney transplantation is planned.

Programmatic Palliative Care Consultations in Pediatric Heart Transplant Evaluations.

Guidelines advocate for integrating palliative care into the management of heart failure (HF) and of children with life-limiting disease. The potential impact of palliative care integration into pediatric HF on patient-centered outcomes is poorly understood. The present study sought to assess the association of programmatic implementation of palliative care into the heart transplant evaluation process with hospital-free days (HFD) and end of life (EOL) treatment choices. The study included patients less than 19 years of age who underwent a heart transplant evaluation between February 2012 and April 2020 at a single center. Patients evaluated in the programmatic palliative care (PPC) era (January 2016-April 2020) were compared to patients evaluated in the pre-PPC era (February 2012-December 2015). The study included 188 patients, with 91 (48%) in the PPC era and 97 (52%) in the pre-PCC era. Children < 1 year of age at the time of the evaluation represented 32% of the cohort. 52% of patients had single ventricle physiology. PPC was not significantly associated with increased HFD (IRR 0.94 [95% CI 0.79-1.2]). PPC was however associated with intensity of EOL care with decreased mechanical ventilation (OR 0.12 [95% CI 0.02-0.789], p = 0.03) and decreased use of ionotropic support (OR 0.13 [95% CI 0.02-0.85], p =0.03). PPC in pediatric heart transplant evaluations may be associated with less invasive interventions at EOL.

The impact of socioeconomic deprivation on liver transplantation.

Despite global expansion, social disparities impact all phases of liver transplantation, from patient referral to post-transplant care. In pediatric populations, socioeconomic deprivation is associated with delayed referral, higher waitlist mortality, and reduced access to living donor transplantation. Children from socially deprived communities are twice as much less adherent to immunosuppression and have up to a 32% increased incidence of graft failure. Similarly, adult patients from deprived areas and racial minorities have a higher risk of not initiating the transplant evaluation, lower rates of waitlisting, and a 6% higher risk of not being transplanted. Social deprivation is racially segregated, and Black recipients have an increased risk of post-transplant mortality by up to 21%. The mechanisms linking social deprivation to inferior outcomes are not entirely elucidated, and powered studies are still lacking. We offer a review of the most recent evidence linking social deprivation and post-liver transplant outcomes in pediatric and adult populations, as well as a literature-derived theoretical background model for future research on this topic.

Biofabrication of biomimetic undulating microtopography at the dermal-epidermal junction and its effects on the growth and differentiation of epidermal cells.

The undulating microtopography located at the junction of the dermis and epidermis of the native skin is called rete ridges (RRs), which plays an important role in enhancing keratinocyte function, improving skin structure and stability, and providing three-dimensional (3D) microenvironment for skin cells. Despite some progress in recent years, most currently designed and manufactured tissue-engineered skin models still cannot replicate the RRs, resulting in a lack of biological signals in the manufactured skin models. In this study, a composite manufacturing method including electrospinning, 3D printing, and functional coating was developed to produce the epidermal models with RRs. Polycaprolactone (PCL) nanofibers were firstly electrospun to mimic the extracellular matrix environment and be responsible for cell attachment. PCL microfibers were then printed onto top of the PCL nanofibers layer by 3D printing to quickly prepare undulating microtopography and finally the entire structures were dip-coated with gelatin hydrogel to form a functional coating layer. The morphology, chemical composition, and structural properties of the fabricated models were studied. The results proved that the multi-process composite fabricated models were suitable for skin tissue engineering. Live and dead staining, cell counting kit-8 (CCK-8) as well as histology (haematoxylin and eosin (HE) methodology) and immunofluorescence (primary and secondary antibodies combination assay) were used to investigate the viability, metabolic activity, and differentiation of skin cells forin vitroculturing.In vitroresults showed that each model had high cell viability, good proliferation, and the expression of differentiation marker. It was worth noting that the sizes of the RRs affected the cell growth status of the epidermal models. In addition, the unique undulation characteristics of the epidermal-dermal junction can be reproduced in the developed epidermal models. Overall, thesein vitrohuman epidermal models can provide valuable reference for skin transplantation, screening and safety evaluation of drugs and cosmetics.

Survival of Infants With Severe Congenital Kidney Disease After ECMO and Kidney Support Therapy.

Congenital kidney failure not only affects the homeostatic functions of the kidney, but also affects neonatal respiratory integrity. Until recently, extracorporeal membrane oxygenation (ECMO) support was not used in this population because the need for ECMO clearly established nonviability. Since 2016, 31 neonates have been admitted to the NICU at Children's of Alabama with congenital kidney failure. Five patients were placed on ECMO for severe respiratory distress unresponsive to conventional interventions. We evaluated neonates with congenital kidney failure and pulmonary hypoplasia/hypertension refractory to conventional therapies who received ECMO support within the first 9 postnatal days. We describe the pre and postnatal diagnoses, ECMO course details, dialysis modalities, complications, procedures, and long-term outcomes of these patients. All 5 patients received kidney support therapy by postnatal day 7. Diagnoses included posterior urethral valves, bilateral renal dysplasia, and autosomal recessive polycystic kidney disease. Gestational age ranged from 35.6 to 37.1 weeks. Birth weight ranged from 2740 to 3140 g. Days on ECMO ranged from 4 to 23. Four survived and are living today. Pulmonary hypertension resolved in surviving patients. Three surviving patients require no oxygen support, and 1 patient requires nocturnal oxygen. Three survivors received a kidney transplant, and 1 awaits transplant evaluation. Patients with congenital kidney failure with severe pulmonary hypoplasia/pulmonary hypertension no longer warrant a reflexive assignment of nonviability. Meticulous ECMO, respiratory, nutritional, and kidney support therapies may achieve a favorable long-term outcome. Further investigation of strategies for optimal outcome is needed.