Pretransplant Characteristics Research Articles

Impact of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplant Outcomes.

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are acute, significant respiratory deteriorations in patients with IPF and can lead to increased morbidity and mortality. It remains unclear how AE-IPF impacts lung transplant (LTX) outcomes. All adult patients who were listed for LTX between July 2005 and October 2020 at the Loyola University Medical Center with a diagnosis of IPF were included. Pretransplant characteristics and posttransplant outcomes were gathered via retrospective chart review. The primary outcome was short- and long-term survival for patients transplanted during stable IPF versus those with AE-IPF. One hundred fifty-nine patients were included in this study, 17.6% of whom were transplanted during AE-IPF. AE-IPF patients were more likely to have higher oxygen needs pretransplant, have higher lung allocation score, and were more likely to be intubated or be on extracorporeal membrane oxygenation as compared with stable IPF patients. Survival by AE status at transplant did not differ at 90 d or 1 y posttransplantation. There were also no significant differences in rates of severe primary graft dysfunction or acute rejection within 1 y. Patients with AE-IPF were more likely to have higher oxygenation requirements and higher lung allocation score at the time of LTX than those with stable IPF. Despite this, there were no differences in survival at 90 d, 1 y, or 3 y, or differences in incidence of severe primary graft dysfunction or acute cellular rejection. Transplantation of patients with AE-IPF has clinical outcomes comparable with transplantation of patients with stable IPF. This contrasts with previous studies examining LTX in patients with AE-IPF.

Analysis of IL-17A, IL-17F, and miR-146a-5p Prior to Transplantation and Their Role in Kidney Transplant Recipients

Background/Objectives: The balance between regulatory and Th17 cells plays an important role in maintaining the immune tolerance after kidney transplantation (KTx) which is essential for transplantation success, defined as a long graft survival and an absence of organ rejection. The present study aimed to assess whether the pretransplant characteristics of IL-17A and IL-17F, their receptors, as well as miR-146a-5p, an miRNA associated with IL-17A/F regulation, can predict KTx outcomes. Methods: A group of 108 pre-KTx dialysis patients and 125 healthy controls were investigated for single nucleotide substitutions within genes coding for IL-17A, IL-17F, their IL-17RA/RC receptors, and miR-146a-5p. Genotyping was performed using LightSNiP assays. In addition, IL17-A/F serum concentrations were determined using ELISA while miR-146a-5p expression was analyzed by RT-PCR. Results: The IL-17F (rs763780) G allele prevailed in KTx recipients as compared to healthy individuals (OR = 23.59, p < 0.0001) and was associated with a higher IL-17F serum level (p = 0.0381) prior to transplantation. Higher miR-146a-5p expression before KTx was more frequently detected in recipients with an increased IL-17A serum concentration (p = 0.0177). Moreover, IL-17A (rs2275913) GG homozygosity was found to be associated with an increased incidence of deaths before KTx (OR = 4.17, p = 0.0307). T-cell or acute rejection episodes were more frequently observed among patients with the C allele of miR-146a-5p (rs2910164) (OR = 5.38, p = 0.0531). IL17-RA/-RC genetic variants (p < 0.05) seem to be associated with eGFR values. Conclusions: These results imply that IL-17F (rs763780) polymorphism is associated with the serum level of this cytokine and may be related to the risk of renal disease and transplant rejection together with miR-146a-5p (rs2910164), while the IL-17A (rs2275913) genotype may affect patients’ survival before KTx.

Influence of cardiac diagnosis on outcomes of pediatric heart-lung transplantation.

Pediatric Heart-lung transplant (HLTX) is performed for endstage congenital heart disease (CHD) with irreversible pulmonary hypertension or non-congenital heart disease (NCHD) with end-stage heart and lung disease. CHD could influence the outcomes of HTLX due to increased complexity of the operation as compared to NCHD. In this study we evaluated the influence of cardiac diagnosis on outcomes of pediatric HTLX. The UNOS database (1987-2022) was queried for primary HTLX in patients <18years. The data were extracted for demographics, pretransplant characteristics, post-transplant outcomes, and analyzed for the impact of cardiac diagnosis on post-transplant outcomes. Standard statistical tests were used. Survival was compared using the Kaplan-Meier method. Ninety of the 213 patients who underwent HLTX had CHD. There were no demographic differences. Heart listing status was similar but with a higher LAS score for NCHD. NCHD had higher pre-operative life support use (mechanical ventilation, inotropes or dialysis) but the use of ECMO as a bridge to transplantation was similar. Wait-list times were longer for CHD. The ischemic times were similar. Post-transplant dialysis, stroke, prolonged mechanical ventilation, and rejection were similar. Survival at 30-days, 1-year, and long-term survival at 17years was similar. Non-survivors at 30-days post-transplant were on life support, used ECMO as a bridge, had lower wait-list times, longer ischemic times and had strokes. Non-survivors at 1-year had similar factors in addition to a higher dialysis use. Cardiac diagnosis had no impact on outcomes after Pediatric HLTX. Patients on life support or ECMO before transplantation were transplanted faster but with lower survival.

(162) - Pre-Transplant Psychosocial Evaluation Characteristics and Associations with Pediatric Heart Transplant Outcomes

(162) - Pre-Transplant Psychosocial Evaluation Characteristics and Associations with Pediatric Heart Transplant Outcomes

Open-Label Randomized Controlled Study of Ciprofloxacin vs Rifaximin as Neutropenia Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation

Loss of microbiota diversity has been clearly associated with poor outcomes in the allogeneic hematopoietic stem cell transplantation setting. However, the choice of the optimal antibiotic prophylaxis during the pre-engraftment phase remains unclear. We designed a prospective randomized study to compare our standard-of-care neutropenia prophylaxis (ciprofloxacin) with rifaximin. We enrolled 38 consecutive adult patients who underwent allogeneic hematopoietic stem cell transplantation setting and were randomly assigned to receive ciprofloxacin (20 patients) or rifaximin (18 patients) at day -1. Pretransplant and transplant characteristics did not differ between groups. Cumulative incidence (CI) of acute graft-vs-host disease grade II to IV and moderate/severe chronic graft-vs-host disease was similar in both groups. With a median follow-up of 13.2 months (range, 6.8-30.2) in surviving patients, the 1-year CI of relapse was 20.8% in ciprofloxacin vs 17.8% in rifaximin (P = .616). Importantly, the 1-year CI of treatment-related mortality was significantly reduced in the ciprofloxacin group (10.2% vs 27.8%, P = .032), leading to higher 1-year overall survival (88.9% vs 74.6%, P = .038). In Cox-regression multivariate analysis, antibiotic prophylaxis remained the only predictor of overall survival, independently of donor type, disease risk index, and moderate/severe chronic graft-vs-host disease. Further studies are needed to assess the effects on microbiota diversity and confirm these outcomes.

Sex differences in clinical characteristics and outcomes in patients undergoing heart transplantation.

Whether sex affects selection for and outcomes after heart transplantation (HTx) remains unclear. We aimed to show sex differences in pre-transplant characteristics and outcomes after HTx. From 1995 to 2019, 49200 HTx recipients were prospectively enrolled in the Organ Procurement and Transplantation Network. Logistic regression models were used to evaluate clinical characteristics by sex. Multivariable Cox regression models were fitted to assess sex differences in all-cause mortality, cardiovascular mortality, graft failure, cardiac allograft vasculopathy (CAV), and malignancy. In 49200 patients (median age 55years, interquartile range 46-62; 24.6% women), 49732 events occurred during a median follow-up of 8.1years. Men were older than women, had more often ischaemic cardiomyopathy (odds ratio [OR] 3.26, 95% confidence interval [CI] 3.11-3.42; P<0.001), and a higher burden of cardiovascular risk factors, whereas women had less malignancies (OR 0.47, CI 0.44-0.51; P<0.001). Men were more often treated in intensive care unit (OR 1.24, CI 1.12-1.37; P<0.001) with a higher need for ventilatory (OR 1.24, CI 1.17-1.32; P<0.001) or VAD (OR 1.53, CI 1.45-1.63; P<0.001) support. After multivariable adjustment, men had a higher risk for CAV (hazard ratio [HR] 1.21, CI 1.13-1.29; P<0.001) and malignancy (HR 1.80, CI 1.62-2.00; P<0.001). There were no differences in all-cause mortality, cardiovascular mortality, and graft failure between sexes. In this US transplant registry, men and women differed in pre-transplant characteristics. Male sex was independently associated with incident CAV and malignancy even after multivariable adjustment. Our results underline the need for better personalized post-HTx management and care.

Treatment results of children with the diagnosis of acute myeloid leukemia. Is trisomy 21 an important cause of mortality?

Background: Acute myeloid leukemia (AML) is the second most common leukemia accounts for 20% of childhood leukemia. Intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) improve outcomes. In this study, it was aimed to present the clinical features and treatment results of patients diagnosed with pediatric AML in the last three years. Methods: It is an observational clinical study, patients who received chemotherapy and HSCT with the diagnosis of AML between 2018 and 2020 were retrospectively evaluated. Age, gender, AML subtype, genetic characteristics, laboratory findings, treatment responses, febrile neutropenia and fungal infection frequencies of the patients were evaluated. HSCT indications, pre-transplant bone marrow aspiration results, transplant type, donor characteristics, and post-transplant complications of patients who underwent HSCT were recorded. Post-treatment status and treatment success rates of the patients were evaluated. Results: Of the 46 patients included in the study, 26 were female and 20 were male. The mean age was 8.2 ± 5.75 years. The most common subtypes were AML M4 and M5 with 9 patients. Total of 201 febrile neutropenia attacks were observed. Suspicious or definite proven Aspergillus infection was detected in 20 of the patients. HSCT was applied to 27 of the patients. Four patients were Down syndrome-myeloid leukemia (DS-ML) and FLT3-ITD mutation was detecetd in 5 patients. Conclusions: FLT3-ITD mutation, relapse disease, and pre-HSCT M2 bone marrow were found to be highly correlated with progressive disease and mortality. In addition, patients with Down syndrome had a high mortality due to additional comorbidity and drug adverse effects.

A model for calculating the long-term estimated post-transplant survival of deceased donor liver transplant patients.

The estimated long-term survival (EPTS) score is used for kidney allocation. A comparable prognostic tool to accurately quantify EPTS benefit in deceased donor liver transplant (DDLT) candidates is nonexistent. Using the Scientific Registry of Transplant Recipients (SRTR) database, we developed, calibrated, and validated a nonlinear regression equation to calculate liver-EPTS (L-EPTS) for 5- and 10-year outcomes in adult DDLT recipients. The population was randomly split (70:30) into two discovery (N=26,372 and N=46,329) and validation cohorts (N=11,288 and N=19,859) for 5- and 10-year post-transplant outcomes, respectively. Discovery cohorts were used for variable selection, Cox proportional hazard regression modeling, and nonlinear curve fitting. Eight clinical variables were selected to construct the L-EPTS formula, and a five-tiered ranking system was created. Tier thresholds were defined and the L-EPTS model was calibrated (R2=0.96 [5-year] and 0.99 [10-year]). Patients' median survival probabilities in the discovery cohorts for 5- and 10-year outcomes ranged from 27.94% to 89.22% and 16.27% to 87.97%, respectively. The L-EPTS model was validated via calculation of receiver operating characteristic (ROC) curves using validation cohorts. Area under the ROC curve was 82.4% (5-year) and 86.5% (10-year). L-EPTS has high applicability and clinical utility because it uses easily obtained pre-transplant patients characteristics to accurately discriminate between those who are likely to receive a prolonged survival benefit and those who are not. It is important to evaluate medical urgency alongside survival benefit and placement efficiency when considering the allocation of a scarce resource. There are no funding sources related to this project.

Assessing the impact of transplant case management on clinical outcomes.

Case management is commonly used by health plans to attempt to improve the care received by their members who have complex needs, such as those who undergo transplantation. There are few observational studies evaluating the effects that transplant case management programs have on clinical outcomes following a solid organ transplant. This limits the understanding of the quantitative effectiveness of such programs. This retrospective cohort study of solid organ transplant recipients with access to a transplant case management program used a case-control study design. Propensity score 1:1 matching was used to balance the comparison groups on demographic and pretransplant clinical characteristics. Health care claims data were used to determine whether program participation affected clinical outcomes following the transplant. A cohort of 1756 adults 18 years and older (878 cases and 878 controls) who had a solid organ transplant between 2018 and 2020 was followed beginning at the time of referral to transplant until 90 days following the transplant procedure. Transplant recipients who participated in the case management program had significantly lower 30-day and 90-day rejection rates, fewer 90-day readmissions, lower discharge mortality and 90-day mortality, and fewer bed days post transplant compared with those who did not participate in case management. Patients undergoing a solid organ transplant had improved clinical outcomes when they participated in a specialized case management program sponsored by their health plan.

Cardiac transplantation in transthyretin amyloid cardiomyopathy: Outcomes from three decades of tertiary center experience.

Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive and fatal cardiomyopathy. Treatment options in patients with advanced ATTR-CM are limited to cardiac transplantation (CT). Despite case series demonstrating comparable outcomes with CT between patients with ATTR-CM and non-amyloid cardiomyopathies, ATTR-CM is considered to be a contraindication to CT in some centers, partly due to a perceived risk of amyloid recurrence in the allograft. We report long-term outcomes of CT in ATTR-CM at two tertiary centers. We retrospectively evaluated ATTR-CM patients across two tertiary centers who underwent transplantation between 1990 and 2020. Pre-transplantation characteristics were determined and outcomes were compared with a cohort of non-transplanted ATTR-CM patients. Fourteen (12 male, 2 female) patients with ATTR-CM underwent CT including 11 with wild-type ATTR-CM and 3 with variant ATTR-CM (ATTRv). Median age at CT was 62 years and median follow up post-CT was 66 months. One, three, and five-year survival was 100, 92, and 90%, respectively and the longest surviving patient was Censored > 19 years post CT. No patients had recurrence of amyloid in the cardiac allograft. Four patients died, including one with ATTRv-CM from complications of leptomeningeal amyloidosis. Survival among the cohort of patients who underwent CT was significantly prolonged compared to UK patients with ATTR-CM generally (p < 0.001) including those diagnosed under age 65 years (p = 0.008) or with early stage cardiomyopathy (p < 0.001). CT is well-tolerated, restores functional capacity and improves prognosis in ATTR-CM. The risk of amyloid recurrence in the cardiac allograft appears to be low.

Letermovir Prophylaxis for High-Risk Allogenic Transplantation Recipients, Real- World Israeli Experience

Introduction: Cytomegalovirus (CMV) infection is a common complication after allogeneic hematopoietic-cell transplantation (alloHCT) causing significant morbidity and mortality. The standard approach for preventing clinically significant CMV infection (CS-CMVi) and CMV disease (CMVd), is preemptive therapy (PET) upon detection of CMV reactivation. In 2017 letermovir was approved for CMV prophylaxis in CMV-seropositive allogeneic HCT recipients from transplantation through day 100 after alloHCT. At 2020, letermovir was approved in Israel for prophylaxis in CMV-seropositive alloHCT recipients who were at higher risk for CMV reactivation (seronegative donor, HLA mismatched unrelated donor, haploidentical family donor, ex-vivo T cell depleted graft or recipient suffering from acute Graft Versus Host Disease (aGVHD) requiring >1mg/kg steroid therapy). There is paucity of real-world data regarding the efficacy and outcomes of letermovir prophylaxis in the post-transplant setting. The aim of our study was to report the real-world Israeli experience with letermovir prophylaxis in terms of incidence of CS-CMVi, CMVd and aGVHD, chronic Graft Versus Host Disease (cGVHD), survival and all-cause mortality. Methods: We retrospectively analyzed a cohort of 45 alloHCT recipients at high risk for CMV reactivation, from 4 Israeli transplant centers, who underwent alloHCT between January 2020 and -December 2021 and received letermovir prophylaxis (study group). A comparison was performed, to a matched historical cohort of 45 alloHCT recipients, who underwent alloHCT between 2014 and 2020 and were treated according to PET policy (control group). Matching was guided by the risk for CMV reactivation. Results: Demographics (recipient's age, gender, ethnicity), disease and pre-transplant characteristics (disease status at transplantation, donor match, conditioning intensity, graft source) of the two groups were comparable accept for a higher percentage of ABO minor mismatch in the control group versus the study group (37% compared to 6%, respectively; p=0.028). There was a higher rate of CS-CMVi during the first 100 days post-transplant in the control group versus the study group (53/3% compared to 35.6%, respectively; p=0.09). There was no difference in CMVd rate between the two groups as well as in relapse rate and overall survival. Acute and chronic GVHD incidence was higher in the control group compared to the study group (71.1% vs 60%; p=0.186 and 57.8% vs 33.3%; p= 0.02, respectively). Conclusions: Our real -world Israeli experience cohort of letermovir prophylaxis in high risk alloHCT recipients demonstrates a significant reduction in GVHD occurrence in patients receiving letermovir prophylaxis. GVHD is a significant cause of morbidity and mortality in alloHCT recipients. Our real-world experience is in line with the well-established contiguity and causal relation between CMV infection and GVHD, showing a reduction in CS-CMVi during the prophylaxis period with a corresponding reduction in acute and chronic GVHD. Our cohort is limited by its retrospective nature and a relatively small sample size. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ATG-F Versus ATG-T for Graft Versus Host Disease Prevention in Allogeneic Stem Cell Transplantation: A Retrospective Comparative Study

Background: Graft versus host disease (GVHD) is one of the major complications in allogeneic stem cell transplantation, leading to excessive post-transplant morbidity and mortality. Anti-Thymocyte Globulin (ATG) is a widely used anti GVHD prophylaxis adjunct, in addition to a calcineurin inhibitor and either methotrexate or mycophenolate mofetil. Among available ATG sera are antithymocyte globulin (ATG-T) (Sanofi Genzyme, Cambridge MA), derived from rabbit vaccination with human thymocytes, and the anti-T-lymphocyte globulin (ATG-F) (Neovii, Rapperswil, Switzerland, ATG Fresenius®), derived from the human Jurkat T-cell line. Data comparing the two agents, regarding transplant outcomes is still lacking. Methods: Since 2015, ATG-F (15 mg/kg) has become the preferred prophylactic agent at the Hadassah medical center. We retrospectively compared the transplant outcomes between 52 patients treated prophylactically with ATG-F (15 mg/kg) during 2015-2018 and 46 patients treated with ATG-T (10 mg/kg), during 2011-2018. Our research aims were directed towards investigating rates of engraftment, infections, GVHD, relapse, and overall survival. Results Demographic, disease and pre-transplant characteristics (median age, gender, disease status at transplantation entry, age adjusted comorbidity index) of the two groups were mostly similar. There was no significant difference in median recipient and donor age, and conditioning regimen intensity. There was a higher rate of patients transplanted for MDS and secondary AML in the ATG-F group while a higher rate of lymphoproliferative diseases in the ATG-T group (p=0.038). Comparing patients' characteristics for the available risk factors for GVHD, there was a borderline significant higher incidence of HLA mismatch in the ATG-T group compared to the ATG-F group (39.1% Vs. 21.2%; p=0.052), and a significantly higher number of patients received single agent cyclosporine in the ATG-T group (30.4% vs 3.8%, p<0.01). In terms of risk factors for infections, there was a significantly higher incidence of positive CMV-IgG in both donor and recipient in the ATG-F vs ATG-T group, 82.4% vs 60.9%, p=0.022). Analyzing transplant outcomes, the incidence of acute GVHD of any grade was significantly higher in the ATG-T group (p=0.007, Fig. 1), while the incidence of grade 3-4 acute GVHD was comparable (p=0.186). Incidence of any grade and moderate-severe chronic GVHD was comparable in both groups (p>0.05). There was no statistically significant difference in disease-free survival and overall survival rates between the groups (p>0.05). A combined analysis of moderate-severe chronic GVHD-free, relapse-free survival (GRFS) showed no difference between the groups (p=0.686, Fig. 2). Median time to absolute neutrophil count (ANC) and Platelet engraftment was 15 vs. 14 and 16 vs. 17 days in the ATG-T and ATG-F group, respectively. There was no difference in the incidence of bacteremia or CMV reactivation between the two groups (p=0.79; p=0.704, respectively). Conclusion Our retrospective study shows that ATG-F was non-inferior to ATG-T regarding engraftment rate, incidence of grade 3-4 acute GVHD and moderate-severe chronic GVHD, disease free survival and overall survival. The higher incidence of acute GVHD of any grade detected in the ATG-T group might reflect the higher rate of HLA mismatch and combination with single agent cyclosporine prophylaxis. Study limitations include its retrospective nature and changes in transplant care over the study years. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 12848: Infections Requiring Hospitalization in Patients One Year Post Heart Transplant

Introduction: Immunosuppression of heart transplant (txp) recipients increases risk of infection. This study will identify the most common pathogens and characterize the most at-risk patients. Methods: We performed a single center retrospective cohort study at the University of Rochester. Demographics, pretransplant characteristics, and infections requiring rehospitalization were obtained (table 1) from electronic records of patients who received a txp from January 1, 2011 through July 1, 2020. Chi-square, t-test, and Wilcoxon rank-sum test assessed association between mortality, infection risk and other variables. Results: We identified 132 patients who received txp but excluded 4 due to incomplete data, 10 (7.6%) patients died during index admission while 12 (9.4%) more patients died in the year following their txp. Infections occurring 1 month post txp were associated with mortality (p-adj 0.026). Prior sternotomies (n=65, 50.8%) were associated with both mortality and bacterial infection (p-adj &lt;0.01). EBV mismatch (n= 7, 5.5%) was associated with infections during months 7-12 post-txp (p-adj 0.027). Unknown pathogens (20) were the most common cause of rehospitalization followed by Pseudomonas (13) (Fig 1). Conclusions: Our study identifies patient risk of rehospitalization due to infection in the year following txp. Prior sternotomies were associated with worse outcomes. We hypothesize this is due to scarring and is worth studying prospectively. Patients with EBV mismatch had higher rates of infections in months 7-12, a finding not previously described. There was higher mortality associated with infections that required hospitalization in the first month.

Uniconazole and Adaptability of Transplantations by Enhancing the Competition Tolerance in a High Sowing Density of Rapeseed Blanket Seedlings

Having nursery rapeseed (Brassica napus L.) seedlings at a high density in a tray is an indispensable step to realizing mechanized transplanting for rapeseed. The reduction in seedling quality caused by high sowing density is one of the key factors affecting transplanting quality and yield. Uniconazole has been considered as a potential plant growth regulator to improve plant growth under diverse unfavorable circumstances. In two sowing densities (400 and 800 seeds per tray), an experiment was carried out between 2021 and 2022 to investigate the effects of uniconazole seed-coating treatments on pre-transplant and post-transplant seedling characteristics. The results demonstrate that uniconazole treatment can effectively reduce the high-density-induced reduction in seedling dry matter and leaf area, stem thinness, and stem and petiole overgrowth. Further evidence that uniconazole can improve seedling quality, enhance yield, and lessen yield loss due to high-density sowing was provided by yield at maturity. However, because of the uncontrolled growth during the late stage in the tray, the relative growth rate of seedlings after transplant in the transplant shock stage revealed that lower doses of uniconazole treatment have a negative effect on the seedling recovery. The results of principal coordinate analysis and partial correlation analysis proved that the yield and net assimilation rate were related to the improvement of seedling high-density tolerance by uniconazole treatment. Consequently, 500–750 mg L−1 uniconazole coating per 100 g of seeds in 5 mL is recommended by this study, considering the potential risk of seedling emergence and growth caused by an overdose of uniconazole treatment.

Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients

Posttransplant hyperparathyroidism is common, and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of posttransplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients. Retrospective observational cohort study. We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B, and D-insured patients who received their first kidney transplant in 2007-2013. We excluded patients with pretransplant parathyroidectomy. Calendar year of transplantation and pretransplant patient characteristics. (1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years after transplant; (2) 90-day outcomes after posttransplant parathyroidectomy and cinacalcet initiation. Temporal trends and pretransplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively. The inclusion criteria were met by 30,127 patients, of whom 10,707 used cinacalcet before transplant, 551 underwent posttransplant parathyroidectomy, and 5,413 filled≥1 prescription for cinacalcet. The rate of posttransplant parathyroidectomy was stable over time. By contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pretransplant cinacalcet use were strongly associated with posttransplant parathyroidectomy and cinacalcet use. Roughly 1 in 4 patients were hospitalized within 90 days of posttransplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (vs cinacalcet initiation) was not associated with an increase in acute kidney injury. We lacked access to laboratory data to help assess the severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries. Almost one-fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for posttransplant hyperparathyroidism.

312.3: Outcomes of Duct-To-Duct Biliary Anastomosis in Pediatric Liver Transplantation Using Left Sided Graft

Background: Roux-en-Y hepaticojejunostomy(HJ) is the standard-of-care for biliary reconstruction in pediatric liver transplantation(LT), especially in left sided grafts. This study aimed to investigate the learning curve and the risk of biliary complication of duct-to-duct biliary anastomosis(DDA) in pediatric LT using left sided grafts. Method: This was a retrospective study from a surgical unit of a university-affiliated center. From 2017-2020, DDA was performed in pediatric LT with a high hilar dissection and patch anastomosis technique under a prospective protocol.(Figure 1) The exclusion criteria were: 1) disease mandated HJ, 2) widely separated graft bile ducts that ductoplasty was infeasible, 3) native biliary anatomical factors that rendered a patch infeasible. Size discrepancy was not a contraindication. The primary endpoint was the risk of biliary complication at 1-year after LT. Results: During study period, 137 pediatric recipients fulfilled inclusion and were considered eligible for DDA, 110 (80.3%) patients had DDA. The pre-transplant characteristics were listed in table 1. The first 40 patients belonged to learning curve period and after that, more patients were eligible for DDA (7.2% vs. 15.1%, P<0.001). The overall risk of biliary complication at 1-year was 2.9% (4/137) and it was higher in the learning phase (9.1% vs 1.3%, P=0.045). Of the 4 biliary complications: 1 had bile leakage and stricture and required endoscopic stenting; 3 had biliary stricture with 2 required conversion to HJ and 1 had endoscopic stenting. All 4 patients have normal graft function at time of analysis. There was only one hospital mortality (1/137, 0.7%) and was due to post-operative bleeding and was unrelated to biliary complication. Graft survival rates at 1-and 3-year after DDA were 98.2% and 96.8% respectively. Conclusion: DDA was safe and feasible with excellent perioperative and long-term outcomes and should be considered the primary choice for biliary reconstruction in eligible pediatric transplant patients.

Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant.

BACKGROUNDCholangiocarcinoma (CC) is a rare tumor that arises from the epithelium of the bile ducts. It is classified according to anatomic location as intrahepatic, perihilar, and distal. Intrahepatic CC (ICC) is rare in patients with cirrhosis due to causes other than primary sclerosing cholangitis. Mixed hepatocellular carcinoma-CC (HCC-CC) is a rare neoplasm that shows histologic findings of both HCC and ICC within the same tumor mass. Due to the difficulties in arriving at the correct diagnosis, patients eventually undergo liver transplantation (LT) with a presumptive diagnosis of HCC on imaging when, in fact, they have ICC or HCC-CC.AIMTo evaluate the outcomes of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma on pathological examination after liver transplant.METHODSPropensity score matching was used to analyze tumor recurrence (TR), overall mortality (OM), and recurrence-free survival (RFS) in LT recipients with pathologically confirmed ICC or HCC-CC matched 1:8 to those with HCC. Progression-free survival and overall mortality rates were computed with the Kaplan-Meier method using Cox regression for comparison.RESULTSOf 475 HCC LT recipients, 1.7% had the diagnosis of ICC and 1.5% of HCC-CC on pathological examination of the explant. LT recipients with ICC had higher TR (46% vs 11%; P = 0.006), higher OM (63% vs 23%; P = 0.002), and lower RFS (38% vs 89%; P = 0.002) than those with HCC when matched for pretransplant tumor characteristics, as well as higher TR (46% vs 23%; P = 0.083), higher OM (63% vs 35%; P = 0.026), and lower RFS (38% vs 59%; P = 0.037) when matched for posttransplant tumor characteristics. Two pairings were performed to compare the outcomes of LT recipients with HCC-CC vs HCC. There was no significant difference between the outcomes in either pairing.CONCLUSIONPatients with ICC had worse outcomes than patients undergoing LT for HCC. The outcomes of patients with HCC-CC did not differ significantly from those of patients with HCC.

Alterations in the kallikrein-kinin system predict death after heart transplant

Heart transplantation remains the definitive treatment for end stage heart failure. Because availability is limited, risk stratification of candidates is crucial for optimizing both organ allocations and transplant outcomes. Here we utilize proteomics prior to transplant to identify new biomarkers that predict post-transplant survival in a multi-institutional cohort. Microvesicles were isolated from serum samples and underwent proteomic analysis using mass spectrometry. Monte Carlo cross-validation (MCCV) was used to predict survival after transplant incorporating select recipient pre-transplant clinical characteristics and serum microvesicle proteomic data. We identified six protein markers with prediction performance above AUROC of 0.6, including Prothrombin (F2), anti-plasmin (SERPINF2), Factor IX, carboxypeptidase 2 (CPB2), HGF activator (HGFAC) and low molecular weight kininogen (LK). No clinical characteristics demonstrated an AUROC > 0.6. Putative biological functions and pathways were assessed using gene set enrichment analysis (GSEA). Differential expression analysis identified enriched pathways prior to transplant that were associated with post-transplant survival including activation of platelets and the coagulation pathway prior to transplant. Specifically, upregulation of coagulation cascade components of the kallikrein-kinin system (KKS) and downregulation of kininogen prior to transplant were associated with survival after transplant. Further prospective studies are warranted to determine if alterations in the KKS contributes to overall post-transplant survival.

Post-Lung Transplantation Outcomes and Ex Vivo Histopathological Findings in Severe Post-Covid-19 Pulmonary Disease-A Single-Center Experience.

BackgroundA significant proportion of patients with severe and persistent coronavirus disease 2019 (COVID-19) require continuous ventilatory support and occasional extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS). Lung transplantation is a treatment option for patients who develop severe ARDS.MethodsOur lung transplant database was retrospectively reviewed for patients who underwent lung transplantation for COVID-19 pulmonary disease at Memorial Hermann Hospital, Texas Medical Center, Houston, Texas, from January 2020 to March 2022. We evaluated outcomes of patients who were followed in our clinic at least 6 months post-transplant. Pretransplant patient characteristics, COVID-19-related treatment, histopathology results, and postdischarge course were evaluated.ResultsAmong a total of 13 lung transplant recipients, 6 consecutive patients were identified who had a minimum of 6 months of follow-up post–lung transplantation. The average age of patients was 55 years, with a male predominance. The median time to transplantation was 111 days. All 6 patients had significant postinfectious complications due to COVID-19 before transplant. Histopathological findings from explanted lungs showed a predominance of fibrotic change. There were no reported cases of rejection or graft dysfunction. 5 patients had minimal to no post-transplant infectious complications. One patient died 218 days post-transplant from infectious complications.ConclusionsFive out of six lung transplant recipients at our institution have demonstrated excellent long-term outcomes after index hospitalization, for a mean follow-up of 13 months post–lung transplantation. Lung transplantation for lung fibrosis due to COVID-19 is an acceptable salvage treatment option. Larger studies are warranted to confirm these findings.

Pretransplant characteristics of kidney transplant recipients that predict posttransplant outcome.

Better characterization of the potential kidney transplant recipient using novel biomarkers, for example, pretransplant plasma endotrophin, will lead to improved outcome after transplantation. This mini-review will focus on current knowledge about pretransplant recipients’ characteristics, biomarkers, and immunology. Clinical characteristics of recipients including age, obesity, blood pressure, comorbidities, and estimated survival scores have been introduced for prediction of recipient and allograft survival. The pretransplant immunologic risk assessment include histocompatibility leukocyte antigens (HLAs), anti-HLA donor-specific antibodies, HLA-DQ mismatch, and non-HLA antibodies. Recently, there has been the hope that pretransplant determination of markers can further improve the prediction of posttransplant complications, both short-term and long-term outcomes including rejections, allograft loss, and mortality. Higher pretransplant plasma endotrophin levels were independently associated with posttransplant acute allograft injury in three prospective European cohorts. Elevated numbers of non-synonymous single-nucleotide polymorphism mismatch have been associated with increased allograft loss in a multivariable analysis. It is concluded that there is a need for integration of clinical characteristics and novel molecular and immunological markers to improve future transplant medicine to reach better diagnostic decisions tailored to the individual patient.