Need for improvements in simultaneous heart-kidney allocation: The limitation of pretransplant glomerular filtration rate.

The incidence of simultaneous heart-kidney transplant (SHK) has increased markedly in the last 15 years. There are no universally agreed upon indications for SHK vs. heart alone (HA) transplant, and center evaluation processes vary widely. We utilized Scientific Registry of Transplant Recipients data from 2003 to 2017 to quantify changes in the practice of SHK, examine the survival of SHK vs. HA, and identify patients with marginal benefit from SHK. We used Kaplan-Meier curves and Cox proportional hazards to assess differences in survival. The incidence of SHK increased more than fourfold between 2003 and 2017 from 1.6% to 6.6% of total hearts transplanted, while the proportion of dialysis-dependent patients undergoing SHK has remained constant. SHK was associated with increased survival in dialysis-dependent patients (Median Survival SHK: 12.6 vs. HA: 7.1 years p < .0001) but not with nondialysis-dependent patients (Median Survival SHK: 12.5 vs. HA 12.3, p = .24). The marginal effect of SHK in decreasing the hazard of death diminished with increasing eGFR. Delayed graft function occurred in 26% of SHK recipients. Posttransplant chronic dialysis was similar for both operations (6.4% of HA and 6.0% of SHK). Further study is needed to define patients who benefit from SHK.

Donor-Recipient Height Mismatch Is Associated With Decreased Survival in Pediatric-to-Adult Liver Transplant Recipients.

Liver grafts from pediatric donors represent a small fraction of grafts transplanted into adult recipients, and their use in adults requires special consideration of donor size to prevent perioperative complications. In the past, graft weight or volume ratios have been adopted from the living donor liver transplant literature to guide clinicians; however, these metrics are not regularly available to surgeons accepting deceased donor organs. In this study, we evaluated all pediatric-to-adult liver transplants in the United Network for Organ Sharing Standard Transplant Analysis and Research database from 1987 to 2019, stratified by donor age and donor-recipient height mismatch ratio (HMR; defined as donor height/recipient height). On multivariable regression controlling for cold ischemia time, age, and transplantation era, the use of donors from ages 0 to 4 and 5 to 9 had increased risk of graft failure (hazard ratio [HR], 1.81 [P < 0.01] and HR, 1.16 [P < 0.01], respectively) compared with donors aged 15 to 17. On Kaplan-Meier survival analysis, a HMR < 0.8 was associated with inferior graft survival (mean, 11.8 versus 14.6 years; log-rank P < 0.001) and inferior patient survival (mean, 13.5 versus 14.9 years; log-rank P < 0.01) when compared with pairs with similar height (HMR, 0.95-1.05; ie, donors within 5% of recipient height). This study demonstrates that both young donor age and low HMR confer additional risk in adult recipients of pediatric liver grafts.

The Impact of the 2017 Kidney Allocation Policy Change on Simultaneous Liver-Kidney Utilization and Outcomes.

Historically in the United States, kidneys for simultaneous liver-kidney transplantation (SLKT) candidates were allocated with livers, prioritizing SLKT recipients over much of the kidney waiting list. A 2017 change in policy delineated renal function criteria for SLKT and implemented a safety net for kidney-after-liver transplantation. We compared the use and outcomes of SLKT and kidney-after-liver transplant with the 2017 policy. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to identify adults who received liver transplantations (LT) from August 10, 2007 to August 10, 2012; from August 11, 2012 to August 10, 2017; and from August 11, 2017 to June 12, 2019. LT recipients with end-stage renal disease (ESRD) were defined by dialysis requirement or estimated glomerular filtration rate <25. We evaluated outcomes and center-level, regional, and national practice before and after the policy change. Nonparametric cumulative incidence of kidney-after-liver listing and transplant were modeled by era. A total of 6332 patients received SLKTs during the study period; fewer patients with glomerular filtration rate (GFR) ≥50 mL/min underwent SLKT over time (5.8%, 4.8%, 3.0%; P = 0.01 ). There was also less variability in GFR at transplant after policy implementation on center and regional levels. We then evaluated LT-alone (LTA) recipients with ESRD (n = 5408 from 2012-2017; n = 2321 after the policy). Listing for a kidney within a year of LT increased from 2.9% before the policy change to 8.8% after the policy change, and the rate of kidney transplantation within 1 year increased from 0.7% to 4% (P < 0.001). After the policy change, there was no difference in patient survival rates between SLKT and LTA among patients with ESRD. Implementation of the 2017 SLKT policy change resulted in reduced variability in SLKT recipient kidney function and increased access to deceased donor kidney transplantation for LTA recipients with kidney disease without negatively affecting outcomes.

Definition and Analysis of Textbook Outcome: A Novel Quality Measure in Kidney Transplantation.

BACKGROUND: "Textbook outcome" (TO) is a novel composite quality measure that encompasses multiple postoperative endpoints, representing the ideal "textbook" hospitalization for complex surgical procedures. We defined TO for kidney transplantation using a cohort from a high-volume institution. METHODS: Adult patients who underwent isolated kidney transplantation at our institution between 2016 and 2019 were included. TO was defined by clinician consensus at our institution to include freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay > 75th percentile of kidney transplant patients, 90-day mortality, 30-day acute rejection, delayed graft function, and discharge with a Foley catheter. Recipient, operative, financial characteristics, and post-transplant patient, graft, and rejection-free survival were compared between patients who achieved and failed to achieve TO. RESULTS: A total of 557 kidney transplant patients were included. Of those, 245 (44%) achieved TO. The most common reasons for TO failure were delayed graft function (N = 157, 50%) and hospital readmission within 30 days (N = 155, 50%); the least common was mortality within 90 days (N = 6, 2%). Patient, graft, and rejection-free survival were significantly improved among patients who achieved TO. On average, patients who achieved TO incurred approximately $50,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in kidney transplantation was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer transplant centers a detailed performance breakdown to identify aspects of perioperative care in need of process improvement.

A developmentally regulated translational control pathway establishes the meiotic chromosome segregation pattern.

Production of haploid gametes from diploid progenitor cells is mediated by a specialized cell division, meiosis, where two divisions, meiosis I and II, follow a single S phase. Errors in progression from meiosis I to meiosis II lead to aneuploid and polyploid gametes, but the regulatory mechanisms controlling this transition are poorly understood. Here, we demonstrate that the conserved kinase Ime2 regulates the timing and order of the meiotic divisions by controlling translation. Ime2 coordinates translational activation of a cluster of genes at the meiosis I-meiosis II transition, including the critical determinant of the meiotic chromosome segregation pattern CLB3. We further show that Ime2 mediates translational control through the meiosis-specific RNA-binding protein Rim4. Rim4 inhibits translation of CLB3 during meiosis I by interacting with the 5' untranslated region (UTR) of CLB3. At the onset of meiosis II, Ime2 kinase activity rises and triggers a decrease in Rim4 protein levels, thereby alleviating translational repression. Our results elucidate a novel developmentally regulated translational control pathway that establishes the meiotic chromosome segregation pattern.

Left lateral segment liver volume is not correlated with anthropometric measures.

BACKGROUND: Liver transplantation is definitive therapy for end stage liver disease in pediatric patients. Living donor liver transplantation (LDLT) with the left lateral segment (LLS) is often a feasible option. However, the size of LLS is an important factor in donor suitability - particularly when the recipient weighs less than 10 kg. In the present study, we sought to define a formula for estimating left lateral segment volume (LLSV) in potential LLS donors. METHODS: We obtained demographic and anthropometric measurements on 50 patients with Computed Tomography (CT) scans to determine whole liver volume (WLV), right liver volume (RLV), and LLSV. We performed univariable and multivariable linear regression with backwards stepwise variable selection (p < 0.10) to determine final models. RESULTS: Our study found that previously reported anthropometric and demographics variables correlated with volume were significantly associated with WLV and RLV. On univariable analysis, no demographic or anthropometric measures were correlated with LLSV. On multivariable analysis, LLSV was poorly predicted by the final model (R2 = 0.10, Coefficient of Variation [CV] = 42.2) relative to WLV (R2 = 0.33, CV = 18.8) and RLV (R2 = 0.41, CV = 15.8). CONCLUSION: Potential LLS living donors should not be excluded based on anthropometric data: all potential donors should be evaluated regardless of their size.

Outcomes in Kidney Transplantation Between Veterans Affairs and Civilian Hospitals: Considerations in the Context of the MISSION Act.

OBJECTIVE: We sought to compare kidney transplantation outcomes between Veterans Affairs (VA) and non-VA transplant centers. SUMMARY BACKGROUND DATA: Transplant care at the VA has previously been scrutinized due to geographic and systematic barriers. The recently instituted MISSION Act entered effect June 6th, 2019, which enables veteran access to surgical care at civilian hospitals if certain eligibility criteria are met. METHODS: We evaluated observed-to-expected outcome ratios (O:E) for graft loss and mortality using the Scientific Registry of Transplant Recipients database for all kidney transplants during a 15-year period (July 1, 2001-June 30, 2016). Of 229,188 kidney transplants performed during the study period, 1508 were performed at VA centers (N = 7), 7750 at the respective academic institutions affiliated with these VA centers, and 227,680 at non-VA centers nationwide (N = 286). RESULTS: Aggregate O:E ratios for mortality were lower in VA centers compared with non-VA centers at 1 month and 1 year (O:E = 0.27 vs 1.00, P = 0.03 and O:E = 0.62 vs 1.00, P = 0.03, respectively). Graft loss at 1 month and 1 year was similar between groups (O:E = 0.65 vs 1.00, P = 0.11 and O:E = 0.79 vs 1.00, P = 0.15, respectively). Ratios for mortality and graft loss were similar between VA centers and their respective academic affiliates. Additionally, a subgroup analysis for graft loss and mortality at 3 years (study period January 1, 2009-December 31, 2013) demonstrated no significant differences between VA centers, VA-affiliates, and all non-VA centers. CONCLUSIONS: Despite low clinical volume, VA centers offer excellent outcomes in kidney transplantation. Veteran referral to civilian hospitals should weigh the benefit of geographic convenience and patient preference with center outcomes.

Textbook Outcomes in Liver Transplantation.

BACKGROUND: Textbook outcome (TO) is an emerging concept within multiple surgical domains, which represents a novel effort to define a standardized, composite quality benchmark based on multiple postoperative endpoints that represent the ideal "textbook" hospitalization. We sought to define TO for liver transplantation (LT) using a cohort from a high procedural volume center. METHODS: Patients who underwent LT at our institution between 2014 and 2017 were eligible for the study. The definition of TO was determined by clinician consensus at our institution to include freedom from: mortality within 90 days, primary allograft non-function, early allograft dysfunction (EAD), rejection within 30 days, readmission with 30 days, readmission to the ICU during index hospitalization, hospital length of stay > 75th percentile of all liver transplant patients, red blood cell (RBC) transfusion requirement greater than the 75th percentile for all liver transplant patients, Clavien-Dindo Grade III complication (re-intervention), and major intraoperative complication. RESULTS: Two hundred and thirty-one liver transplants with complete data were performed within the study period. Of those, 71 (31%) achieved a TO. Overall, the most likely event to lead to failure to achieve TO was readmission within 30 days (n = 57, 37%) or reoperation (n = 49, 32%). Overall and rejection-free survival did not differ significantly between the 2 groups. Interestingly, patients who achieved TO incurred approximately $60,000 less in total charges than those who did not. When we limit this to charges specifically attributable to the transplant episode, the difference was approximately $50,000 and remained significantly less for those that achieved TO. CONCLUSIONS: Here, we present the first definition of TO in LT. Though not associated with long-term outcomes, TO in LT is associated with a significantly lower charges and costs of the initial hospitalization. A multi-institutional study to validate this definition of TO is warranted.

Machine perfusion of donor kidneys may reduce graft rejection.

Recent evidence suggests that hypothermic machine perfusion of donor kidneys reduces delayed graft function (DGF). This study addresses the effect of machine perfusion (MP) on allograft rejection in the United States. We assembled a retrospective cohort of patients undergoing kidney-alone transplants in the UNOS database from June 30, 2004 to May 31, 2017. DGF was defined as dialysis requirement in the first week post-transplant; graft rejection was defined at 6 months and 1 year. Multivariable logistic regression adjusted for recipient and donor factors evaluated the effect of MP on DGF and graft rejection. Records for 79 300 kidney transplants meeting inclusion criteria were abstracted, 42% of which underwent MP. MP kidneys came from older donors, were more likely to have been obtained following donation after cardiac death, and had longer cold ischemic times. Rates of DGF and rejection were similar between MP and static storage kidneys. Following adjustment, recipients of MP kidneys were less likely to experience rejection at 1 year (OR 0.91 [95% CI 0.86-0.97] P = .002), but not at 6 months post-transplantation (OR 0.94 [0.88-1.02] P = .07). This effect persisted following adjustment for cold ischemic time. This study adds to the accumulating evidence demonstrating improved outcomes following MP of kidneys. We encourage protocolized consideration of MP for kidney grafts.

Predictors of Ultrasound Failure to Detect Hepatocellular Carcinoma.

Current guidelines recommend ultrasound (US) for hepatocellular carcinoma (HCC) surveillance in cirrhosis. We assess predictors of decreased US sensitivity for detecting HCC. At a single center in the United States, all HCC patients evaluated for liver transplantation (LT) received an abdominal US. From 2007-2015, consecutive patients presenting for untreated lesions found on computed tomography (CT) or magnetic resonance imaging (MRI) within 3 months of US were compared with US findings. Multivariate logistic regression models compared US sensitivities by patient characteristics. Of 1007 patients completing LT evaluation, 47.5% had indeterminate or previously treated nodules and were excluded; 10.4% had imaging that was too far apart or nondiagnostic. Median Model for End-Stage Liver Disease (MELD) of the cohort (n= 352) was 11 (interquartile range [IQR], 9-14), median body mass index (BMI) was 28 kg/m2 (IQR, 25-32 kg/m2 ), 39% had received locoregional therapy, and 10% had moderate/large ascites. Per-patient sensitivity of US compared with CT/MRI was 0.82 (95% confidence interval, 0.76-0.86). Patients with BMI ≥ 30 kg/m2 had a US sensitivity of 0.76 versus 0.87 for BMI < 30 kg/m2 (P = 0.01). MELD and ascites did not affect sensitivity. US sensitivity was decreased in patients with nonalcoholic steatohepatitis (NASH) versus other etiologies (0.59 versus 0.84; P = 0.02). Relative to CT/MRI, US is significantly less sensitive in patients with NASH or BMI ≥ 30 kg/m2 . Further study is necessary to examine the added value of cross-sectional imaging for patients with NASH or obesity.

Biases in the reporting of hepatocellular carcinoma tumor sizes on the liver transplant waiting list.

We investigated the possibility that patients with hepatocellular carcinoma (HCC) listed for liver transplant with tumors just outside stage T2 size criteria may be inaccurately reported as just meeting the tumor size criteria for transplant. The United Network for Organ Sharing/Standard Transplant Analysis and Research database identified 12,958 patients listed for liver transplants with HCC exception points from 2006 to 2013, 9,168 of whom were listed with one tumor. A logistic power peak function was fitted to the single-tumor size histogram, with the fitted values representing unbiased expected values. The difference between the observed and expected tumor counts for 2.0 cm and 5.0 cm was 238 (22%) and 66 (57%), respectively. This suggests that up to 304 (3.0%) patients with tumors outside of transplant criteria had their measurements recorded at the margins of eligibility. A risk-adjusted Poisson model evaluated the ratio of observed to expected HCC recurrence by tumor size. There were 435 HCC recurrences among 6,049 transplants. Only 2.0-cm tumors had observed to expected recurrence differing from 1 (ratio 0.73, 95% confidence interval 0.57-0.94), indicating a 27% lower than expected rate of recurrence. CONCLUSION: Higher than expected observed tumor counts at the lower transplant criteria margin were corroborated by lower than expected HCC recurrence, suggesting that tumor sizes at the margins of HCC transplant criteria may be subject to inaccurate reporting. (Hepatology 2017;66:1144-1150).

Disability in patients with end-stage liver disease: Results from the functional assessment in liver transplantation study.

Cirrhosis leads to sarcopenia and functional decline that can severely impact one's ability to function at home and in society. Self-reported disability scales to quantify disability-Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL)-are validated to predict mortality in older adults. To evaluate disability in liver transplantation (LT) candidates and quantify its impact on outcomes, consecutive outpatients ≥18 years listed for LT with laboratory Model for End-Stage Liver Disease scores of ≥12 at a single high-volume US LT center were assessed for ADLs and IADLs during clinic visits. Multivariate competing risk models explored the effect of disabilities on wait-list mortality (death or delisting for illness). Of 458 patients, 36% were women, median (interquartile range [IQR]) age was 60 years (IQR, 54-64 years), and initial Model for End-Stage Liver Disease-Sodium (MELD-Na) was 17 (IQR 14-20). At first visit, 31% had lost ≥ 1 ADL, and 40% had lost ≥ 1 IADL. The most prevalent ADL deficits lost were continence (22%), dressing (12%), and transferring (11%); the most prevalent IADLs lost were shopping (28%), food preparation (23%), and medication management (22%). After adjustment for age, MELD-Na, and encephalopathy, dressing (subdistribution hazard ratio [SHR], 1.7; 95% confidence interval [CI], 1.0-2.8; P = 0.04), toileting (SHR, 1.9; 95% CI, 1.1-3.5; P = 0.03), transferring (SHR, 1.9; 95% CI, 1.1-3.0; P = 0.009), housekeeping (SHR, 1.8; 95% CI, 1.2-3.0; P = 0.009), and laundry (SHR, 2.2; 95% CI, 1.3-3.5; P = 0.002) remained independent predictors of wait-list mortality. In conclusion, ADL/IADL deficits are common in LT candidates. LT candidates would benefit from chronic disease management programs developed to address the impact of cirrhosis on their daily lives. Liver Transplantation 23 292-298 2017 AASLD.

Evaluating the validity of model for end-stage liver disease exception points for hepatocellular carcinoma patients with multiple nodules <2 cm.

Liver transplant allocation policy does not give model for end-stage liver disease (MELD) exception points for patients with a single hepatocellular carcinoma (HCC) <2 cm in size, but does give points to patients with multiple small nodules. Because standard-of-care imaging for HCC struggles to differentiate HCC from other nodules, it is possible that a subset of patients receiving liver transplant for multiple nodules <2 cm in size does not have HCC. We evaluate risk of post-transplant HCC recurrence and wait-list dropout for patients with multiple small nodules using competing risks regression based on the Fine and Gray model. We identified 5002 adult HCC patients in the OPTN/UNOS dataset diagnosed and transplanted between January 2006 and September 2010. Compared to patients with >1 tumor <2 cm, risk of developing recurrence was significantly higher in patients with one or more tumors with only one tumor ≥2 cm (SHR 1.63, p = 0.009), as well as in patients with 2-3 tumors ≥2 cm (SHR 1.84, p = 0.02). Dropout risk was not significantly different among size categories. HCC recurrence risk was significantly lower in patients with multiple nodules <2 cm in size than in those with larger tumors, supporting the possibility that some patients received unnecessary transplants. The priority given to these patients must be re-examined.

Time to transplantation as a predictor of hepatocellular carcinoma recurrence after liver transplantation.

In the United States, there are significant geographic disparities in the time to transplantation for patients with hepatocellular carcinoma (HCC); it is possible that rapid transplantation contributes to higher rates of posttransplant HCC recurrence because there is insufficient time for the tumor biology to manifest. In this study, we compared HCC recurrence in rapid transplant patients and their slower transplant counterparts. We identified adult liver transplantation (LT) candidates in the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) data set who were granted an initial exception for an HCC diagnosis between January 1, 2006 and September 30, 2010 and underwent transplantation in the same time window. Patients were followed until HCC recurrence, non-HCC-related death, or last follow-up. The cumulative incidence of HCC recurrence was compared for patients waiting ≤ 120 days and patients waiting >120 days from an HCC exception to LT. The association between the risk of posttransplant recurrence and the wait time was further evaluated via competing risks regression with the Fine and Gray model. For 5002 LT recipients with HCC, the median wait time from an exception to LT was 77 days, and it varied from 30 to 169 days by UNOS region. The cumulative incidence of posttransplant HCC recurrence was 3.3% [95% confidence interval (CI) = 2.8%-3.8%] and 5.6% (95% CI = 5.0%-6.3%) within 1 and 2 years, respectively. The rate of observed recurrence within 1 year of transplantation was significantly lower for patients waiting >120 days versus patients waiting ≤ 120 days (2.2% versus 3.9%, P = 0.002); however, the difference did not persist at 2 years (5.0% versus 5.9%, P = 0.09). After we accounted for clinical factors, the HCC recurrence risk was reduced by 40% for patients waiting >120 days (subhazard ratio = 0.6, P = 0.005). In conclusion, the risk of HCC recurrence within the first year after transplantation may be lessened by the institution of a mandatory waiting time after an exception is granted.

Validating posttransplant hepatocellular carcinoma recurrence data in the United Network for Organ Sharing database.

The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database is the most comprehensive collection of liver transplantation data, but the quality of these data with respect to hepatocellular carcinoma (HCC) recurrence has not been well assessed. In this study, we compared observed HCC recurrence rates in the UNOS database to expected rates calculated with a hierarchical model for recurrence adjusted for recipient and tumor characteristics. We used the UNOS Standard Transplant Analysis and Research data set for adult transplant patients with an initial exception for an HCC diagnosis granted between January 1, 2006 and September 30, 2010 who underwent transplantation within the same time window. We developed a risk-adjusted Poisson model with patients as the unit of analysis, random effects for transplant centers, and years of follow-up as an offset to predict expected recurrences for each center. To further investigate the possibility of underreporting, we imputed expected recurrences for non-HCC deaths. In all, 5034 HCC liver transplant recipients were identified, and 6.8% experienced recurrence at a median of 1 year after transplantation. The covariate-adjusted shrinkage estimates of the observed/expected HCC recurrence ratios by transplant center ranged from 0.6 to 1.76 (median = 0.97). The 95% confidence intervals for the shrinkage ratios included unity for every center, and this indicated that none could be unambiguously identified as having lower or higher than expected HCC recurrence rates. Imputing outcomes for patients potentially experiencing unreported recurrence changed the center-specific shrinkage ratios to 0.72 to 1.39 (median = 0.98), with no centers having a shrinkage ratio significantly different from 1. The observed HCC recurrence rate was not significantly lower than the expected rate at any center, and this suggests that no systematic underreporting has occurred. This study validates the OPTN HCC recurrence data and supports their potential for further analysis.

Association of the Affordable Care Act on Access to and Outcomes After Kidney or Liver Transplant: A Transplant Registry Study.

BACKGROUND: To evaluate the effect of the Affordable Care Act (ACA) Medicaid expansion on payor mix among patients on the kidney and liver transplant waiting list as well as waiting list and post-transplant outcomes. DESIGN: Using the Scientific Registry of Transplant Recipients, we performed a secondary data analysis of all patients on the kidney and liver transplant waiting list from 2007 to 2018. We described changes in payor mix by timing of state Medicaid expansion. We used competing risks models to estimate cause-specific hazard ratios for the effects of insurance and era on death/delisting and transplant. We used a Poisson regression model to estimate the effect of insurance and era on incidence rate ratio of inactivations on the waiting list. We used Cox proportional hazards models to estimate the effect of insurance and era on graft and patient survival. RESULTS: A decade after implementation of the ACA, the prevalence of Medicaid beneficiaries listed for transplant increased by 2.5% (from 7.4% to 9.9%) for kidney and by 2.6% (15.3% to 17.9%) for liver. Expansion states had greater increases than nonexpansion states (kidney 3.8% vs 0.6%, liver 5.3% vs -1.8%). Among wait-listed patients, the magnitude of association of Medicaid insurance vs private insurance with transplant decreased over time for kidney candidates (era 1 subdistribution hazard ratio (SHR), 0.62 [95% CI, 0.60-0.64] vs era 3 SHR, 0.77 [95% CI, 0.74-0.70]) but increased for liver candidates (era 1 SHR, 0.85 [95% CI, 0.83-0.90] vs era 3 SHR 0.79 [95% CI, 0.77-0.82]). Medicaid-insured kidney and liver recipients had greater hazards of graft failure; this did not change over time (kidney: HR, 1.23 [95% CI, 1.06-1.44] liver: HR, 1.05 [95% CI, 0.94-1.17]). CONCLUSIONS: For the millions of patients with chronic kidney and liver diseases, implementation of the ACA has resulted in only modest increases in access to transplant for the publicly insured vs the privately insured.

Subnormothermic ex vivo lung perfusion attenuates graft inflammation in a rat transplant model.

OBJECTIVE: Ex vivo lung perfusion has emerged as a novel technique to safely preserve lungs before transplantation. Recent studies have demonstrated an accumulation of inflammatory molecules in the perfusate during ex vivo lung perfusion. These proinflammatory molecules, including damage-associated molecular patterns and inflammatory cytokines, may contribute to acute and chronic allograft dysfunction. At present, ex vivo lung perfusion is performed clinically at normothermic temperature (37°C). The effect of lowering temperature to the subnormothermic range during ex vivo lung perfusion has not been reported. In this study, we hypothesized that lower ex vivo lung perfusion temperature will lead to a reduction in allograft inflammation and result in improved post-transplant graft function. METHODS: Lewis rat heart-lung blocs underwent 4 hours of ex vivo lung perfusion in 3 temperature groups: 37°C (MP37), 30°C (MP30), and 25°C (MP25). In the control group, lung grafts were preserved by static cold storage before transplantation. After ex vivo lung perfusion or static cold storage, the left lung was transplanted for 2 hours before the animal was killed. Sera and tissue were collected and analyzed. RESULTS: There were no differences in partial pressure of arterial oxygenation to fraction of inspired oxygen ratios during 4 hours of ex vivo lung perfusion between temperature groups. Tumor necrosis factor α significantly increased in the MP37 group during ex vivo lung perfusion, whereas this was not seen at lower temperatures. Extracellular DNA and high-mobility group box 1 perfusate concentrations increased significantly during ex vivo lung perfusion in all groups, but the rate of increase was diminished at lower temperature. Two hours post-transplant, there were no significant differences in partial pressure of arterial oxygenation to fraction of inspired oxygen ratios of the lung graft or serum damage-associated molecular pattern levels among groups. On histologic grading after transplantation, greater injury was observed in the MP30 and MP37 groups, but not MP25, when compared with static cold storage. CONCLUSIONS: Subnormothermic ex vivo lung perfusion at 25°C reduces the production of inflammatory mediators during ex vivo lung perfusion and is associated with reduced histologic graft injury after transplantation.

A simple scoring system to estimate perioperative mortality following liver resection for primary liver malignancy-the Hepatectomy Risk Score (HeRS).

BACKGROUND: Selection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections. METHODS: The 2005-2015 NSQIP database was queried for patients undergoing liver resection for primary liver malignancy. We first developed a model that incorporated the extent of resection (1 point for major hepatectomy) and a MELD-Na score category of low (MELD-Na =6, 1 point), medium (MELD-Na =7-10, 2 points) or high (MELD-Na >10, 3 points) with a score range of 1-4, called the Hepatic Resection Risk Score (HeRS). We tested the predictive value of this model on the dataset using logistic regression. We next developed an optimal multivariable model using backwards sequential selection of variables under logistic regression. We performed K-fold cross validation on both models. Receiver operating characteristics were plotted and the optimal sensitivity and specificity for each model were calculated to obtain positive and negative predictive values. RESULTS: A total of 4,510 patients were included. HeRS was associated with increased odds of 30-day mortality [HeRS =2: OR =3.23 (1.16-8.99), P=0.025; HeRS =3: OR =6.54 (2.39-17.90), P<0.001; HeRS =4: OR =13.69 (4.90-38.22), P<0.001]. The AUC for this model was 0.66. The AUC for the optimal multivariable model was higher at 0.76. Under K-fold cross validation, the positive predictive value (PPV) and negative predictive value (NPV) of these two models were similar at PPV =6.4% and NPV =97.7% for the HeRS only model and PPV =8.4% and NPV =98.1% for the optimal multivariable model. CONCLUSIONS: The HeRS offers a simple heuristic for estimating 30-day mortality after resection of primary liver malignancy. More complicated models offer better performance but at the expense of being more difficult to integrate into clinical practice.

A Historical Cohort in Kidney Transplantation: 55-Year Follow-Up of 72 HLA-Identical, Donor-Recipient Pairs.

The impact of HLA matching on graft survival has been well characterized in renal transplantation, with a higher degree of matching associated with superior graft survival. Additionally, living donor grafts are known to confer superior survival compared to those from deceased donors. The purpose of this study is to report our multi-decade institutional experience and outcomes for patients who received HLA-identical living donor grafts, which represent the most favorable scenario in kidney transplantation. We conducted a retrospective analysis of these graft recipients performed at a Duke University Medical Center between the years of 1965 and 2002. The recipients demonstrated excellent graft and patient survival outcomes, superior to a contemporary cohort, with median patient and graft survival of 24.2 and 30.9 years, respectively, among Duke recipients vs. 16.1 and 16.0 years in a cohort derived from national data. This study offers a broad perspective on the importance of HLA matching and graft type, and demonstrates a historical best-case-scenario in renal transplantation.