
==== Front
8710240
1979
Clin Transplant
Clin Transplant
Clinical transplantation
0902-0063
1399-0012

38591128
10.1111/ctr.15310
nihpa2011259
Article
Performance status at the time of lung retransplant predicts long-term function
http://orcid.org/0000-0002-6494-599X
Deitz Rachel L. 1
http://orcid.org/0000-0002-9818-6098
Clifford Sarah 1
Ryan John P. 12
http://orcid.org/0000-0001-9849-6371
Chan Ernest G. 1
Coster Jenalee N. 12
http://orcid.org/0000-0001-8102-9072
Furukawa Masashi 12
Hage Chadi A. 3
http://orcid.org/0000-0003-3607-0345
Sanchez Pablo G. 12
1 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA
2 Department of Cardiothoracic Surgery, Division of Lung Transplant and Lung Failure, University of Pittsburgh Medical Center, Pittsburgh, USA
3 Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, USA
AUTHOR CONTRIBUTIONS

Rachel L. Deitz, Sarah Clifford, and Ernest G. Chan contributed to study design, analysis, interpretation, and writing. John P. Ryan contributed to statistical analysis and interpretation. Jenalee N. Coster and Masashi Furukawa contributed to interpretation and writing. Chadi A. Hage and Pablo G. Sanchez contributed to study design, analysis, interpretation, writing, and editing.

Correspondence: Rachel Deitz, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, 200 Lothrop St, Ste F441, Pittsburgh, PA 15213, USA. deitzrl@upmc.edu
24 8 2024
4 2024
08 9 2024
38 4 e15310e15310
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Background:

Lung retransplantation is offered to select patients with chronic allograft dysfunction. Given the increased risk of morbidity and mortality conferred by retransplantation, post-transplant function should be considered in the decision of who and when to list. The aim of this study is to identify predictors of post-operative disability in patients undergoing lung retransplantation.

Methods:

Data were collected from the UNOS national dataset and included all patients who underwent lung retransplant from May 2005–March 2023. Pre- and post-operative function was reported by the Karnofsky Performance Status (KPS) and patients were stratified based on their needs. Cumulative link mixed effects models identified associations between pre-transplant variables and post-transplant function.

Results:

A total of 1275 lung retransplant patients were included. After adjusting for between-group differences, pre-operative functional status was predictive of post-transplant function; patients requiring Total Assistance ( n = 740) were 74% more likely than No/Some Assistance patients (n = 535) to require more assistance in follow-up (OR 1.74, 95% CI 1.13–2.68, p = .012). Estimated one year survival of Total Assistance patients is lower than No/Some Assistance Recipients (72% vs. 82%, CI 69%–75%; 79%–86%) but similar to overall re-transplant survival (76%, CI 74%–79%).

Conclusion:

Both survival and regain of function in patients requiring Total Assistance prior to retransplant may be higher than previously reported. Pre-operative functional status is predictive of post-operative function and should weigh in the selection, timing and post-operative care of patients considered for lung retransplantation.

chronic lung allograft disease
functional status
Karnofsky Performance Status
lung retransplant
quality of life
==== Body
pmc1 | INTRODUCTION

Transplantation is recognized as the definitive therapy for patients with end-stage lung disease. Beyond its survival benefits, there is growing interest in determining the long-term impact of lung transplantation on recipient functional status and quality of life. Lung transplant recipients report meaningful improvement in health-related quality of life (HRQL) measures post-transplant which are sustained for several years until eventual decline due to the development of chronic lung allograft dysfunction (CLAD), the adverse effects of requisite immunosuppression, and other common complications.1 Lung retransplantation is offered to a subset of patients that develop chronic lung allograft disease (CLAD), primary graft dysfunction or refractory acute rejection. Graft failure is a prominent cause of death for lung transplant recipients, both those with early (< 1 year) post-transplant mortality as well as for those living beyond median survival estimates.2 While retransplantation constitutes only a small fraction (about 5%) of annual transplant volume, the number of these cases has doubled since implementation of the Lung Allocation Score (LAS) in 2005.3 Recipients who opt for retransplant experience higher morbidity and mortality compared to their initial transplant procedure.4 Given the known ethical and technical challenges of retransplantation5,6 methods to better define candidates for retransplantation must be continuously reviewed.

Recipient factors such as preoperative mechanical ventilation, mechanical circulatory support, LAS, and time from primary transplant are all known predictors of poor survival after retransplant.7–10 In addition, there is a known association between poor functional status and adverse outcomes after lung transplantation, including inhospital and 1-year mortality, transplant encounter length of stay, and likelihood of finding paid employment after the operation.11–14 The Karnofsky Performance Status (KPS), initially developed to quantify the functional status of cancer patients after an intervention, is a functional metric collected pre-transplant, at time of match, and post-transplant follow-up. A score from 0–100 is subdivided into three tiers, corresponding with the level of assistance needed for activities of daily living; no assistance needed, some assistance needed, or total assistance needed.15

The KPS has also previously been shown to predict survival in adult, pediatric, and redo transplant recipients14,16–17 and may be a stronger predictor of survival than LAS in lung retransplant patients.7 The objective of our study was to identify predictors of post-operative functional status in lung retransplant recipients and to evaluate the relationship between pre-and post-operative function as measured by the KPS score.

2 | MATERIALS AND METHODS

2.1 | Study population

The study was conducted using a cohort derived from the United Network for Organ Sharing (UNOS) dataset, valid as of March 31, 2023 and limited to the LAS era (May 2005–March 2023). The dataset was limited to adult (age >= 18 years old) lung transplant recipients who had one prior lung transplant (n = 1329). After excluding multiorgan transplant patients (n = 30) and those missing functional status data (n = 24) a total of 1275 patients remained for analysis. Follow-up data were linked to the transplant file by patient and procedure identifier code. Follow-up data were only included if the visit was 11 months or more following re-transplantation to exclude the period immediately following transplant that may encompass recovery and rehabilitation.

2.2 | Functional status

Functional status was categorized based on Karnofsky Score. Functional status of 80–100 was coded as “No Assistance,” 50–70 as “Some Assistance,” and 10–40 as “Total Assistance.”

2.3 | Analyses

Univariable analyses were performed to compare baseline characteristic differences between patients based on baseline functional category. Categorical variables were analyzed with Fisher’s exact test for count data, and continuous variables were analyzed with Wilcoxon rank sum test. Post hoc testing of categorical factors with more than two levels was performed by examining the adjusted standardized residuals.

We utilized multivariable cumulative linked mixed-effects models to examine the relationship between pre- and post-transplant function. Briefly, these models determine the probability of being in ordinal categories (Total Assistance > Some Assistance > No Assistance). The coefficients of the model can be transformed using the logit into odds of being in at least at particular category or higher.

Functional status at each visit (typically each year) following retransplant was categorized into one of three defined categories. The outcome variable was regressed on pretransplant functional status category while covarying for any variables that were significantly different at baseline between groups. Predictors were entered as fixed effects, and patient ID was entered as a random effect to cluster the data within individual.

Conditional probabilities were calculated using the coefficients produced by the mixed-effects models. For continuous variables, the beta was weighted by the median of the variable (e.g., LAS = 50, creatinine = 1). Conditional probabilities of each functional category at follow-up were calculated based on pre-transplant functioning, for 1-, 3- and 5-years following retransplant.

Kaplan-Meier analyses were conducted to evaluate the relationship between pre-transplant functional status and post-transplant survival. Survival differences between patients requiring No or Some assistance versus Total Assistance were compared.

All analyses were performed in R (version 4.3.0). Univariable analyses were performed using the gtsummary18 package. Values were reported as medians unless otherwise indicated. Cumulative linked mixed-effects models were performed using the CLMM (Cumulative Link Mixed Models) function of the ordinal19 package. A p < .05 was considered statistically significant for all analyses. The University of Pittsburgh Institutional Review Board provided oversight and approval of the study (STUDY20050181).

3 | RESULTS

3.1 | Study population

A sample of 1275 patients were available for analysis. Follow-up data were available for all patients with follow-up ranging from one-year to 17 years following retransplant (median 3 years, interquartile range: 2–6 years). Due to a low number of patients who required no assistance at time of retransplant (n = 61), the categories of No Assistance and Some Assistance were combined into one category. Follow-up data remained in the three ordered categories (No, Some, Total).

3.2 | Univariable analysis

Several variables differed significantly among patients that required No/Some Assistance and patients that required Total Assistance at the time of transplant (Table 1). Patients who required total assistance were less likely to have an original transplant diagnosis of obstructive disease (20% vs. 29%), and more likely to have an original diagnosis of restrictive disease (44% vs. 36%). Patients requiring total assistance were more likely to have an indication for retransplant listed as non-specific (18% vs. 12%) or primary graft failure (15% vs. 8.6%), but less likely to have an indication of obliterative bronchiolitis (65% vs. 78%) relative to some/no assistance.

Patients requiring total assistance had higher LASs (63 vs. 44, p < .001), were slightly younger (48 vs. 52 years), had lower serum creatinine (.95 vs. 1.01 mg/dL, p < .001), higher serum bilirubin (.68 vs..53 mg/dL, p < .001) and higher rates of diabetes (49% vs. 42%, p = .014) compared to those requiring some/no assistance. Patients on total assistance had higher rates of mechanical ventilation (34% vs. 2.6%, p < .001), dialysis dependence (5.8% vs.6%, p < .001), higher oxygen requirements at rest (5 vs. 3 liters/min, p < .001), were more likely to be bridged to transplant with extracorporeal membrane oxygenation (ECMO) (16% vs..6%, p < .001), and were more likely to be in the intensive care unit (ICU) (46% vs. 4.1%, p < .001). Patients requiring total assistance had shorter duration between their initial and retransplant (2.6 years vs. 3.9 years, p < .001) and shorter waitlist time (26 vs. 53 days, p < .001). There was a significant association between transplant type and functional status with patients on total assistance being less likely to undergo ipsilateral (same side as previous transplant) and contralateral (opposite side from previous) single-single transplant (p < .002).

Patients on total assistance received lungs from slightly older donors (Table 2; 32 vs. 29 years, p = .047) and were more likely to receive lungs from a donor of “other” race (5.1% vs. 1.9%, p = .014). Total assistance patients were also less likely to receive donor lungs with a positive cigarette history (33% vs. 39%, p = .035).

3.3 | Multivariable analysis

A multivariable analysis of post-transplant function demonstrated that functional status at listing was associated with post-transplant functional category during follow-up. Patients who were on total assistance at time of listing were 1.64-times more likely to be on total versus some/no assistance (OR: 1.64, 95% CI: 1.08–2.49, p = .021 (Table 3). Time from retransplant was the only other significant variable in the multivariable model with each year following retransplant conferring a 1.29-times greater risk of being in a higher assistance category (OR: 1.29, 95% CI: 1.17–1.43, p < .001).

To further examine how patient acuity at the time of retransplant may moderate preoperative Karnofsky scores and subsequent functional outcomes, we performed a subgroup analysis of total assistance patients (n = 740) admitted to the ICU at time of listing and compared them to total assistance patients who were not in the ICU. Similarly, we examined total assistance patients who were bridged to transplant with ECMO or mechanical ventilation and compared them to patients who were not bridged. There was no association between either ICU admission (p = .49) or bridge status (p = .20) and post-transplant functional status (Table 4).

3.4 | Conditional probabilities

The coefficients from the ordinal model were utilized to determine conditional probabilities for the different functional categories at different points in time following retransplant. Probabilities were calculated both for unadjusted (no covariates) and adjusted models (Table 5). In the adjusted model, at one-year post-transplant, a patient on total assistance at time of transplant had an odds of 66% of requiring no assistance, 26% of requiring some assistance, and 7% of still requiring total assistance. However, by five years post-transplant, the odds of being on total assistance was 17% for patients on total assistance at time of transplant, compared to only 11% for patients who required no/some assistance at time of transplant. Conversely, patients with higher pre-transplant function are much less likely to require assistance each year from transplant (Figure 1).

3.5 | Survival

One-, three-, and five-year survival estimates were calculated for the overall cohort and then stratified by pre-operative functional status. Compared to patients on total assistance pre-transplant, recipients with higher pre-operative Karnofsky scores had significantly longer estimated post-transplant survival (p < .0001) (Figure 2). At 1 year post-retransplant, recipients with no/some assistance have an 82% (CI 79%–86%) survival probability, notably higher than those patients requiring total assistance pre-transplant (72%, CI 69%–75%). Further out from transplant this gap widens, with 5 year survival estimates of 47% (CI 42%–51%) in those patients requiring no or some assistance and only 35% (CI 31%–39%) in those requiring total assistance pre-transplant (Table 6).

4 | DISCUSSION

Our study sought to examine the strength of KPS as a predictor of general post-operative function by utilizing long-term follow-up data of 1275 retransplant patients from the UNOS registry. Unlike previous analyses, our methodology incorporated Karnofsky performance scores collected at all post-operative visits for lung retransplant recipients from 11 months post-operatively to up to 17 years in follow-up to create predictive models of functional status outcomes. Our results yielded several new and important findings. After covarying for factors associated with total assistance (e.g., ECMO, ventilator dependence) we found that patients requiring total assistance pre-transplant were more likely to require total assistance over time relative to recipients who required only some or no support at the time of listing. KPS scores are predictive of post-transplant outcomes independent of factors that would automatically designate a patient to a low functional status category (such as being in the ICU at the time of scoring and listing). Though low KPS scores are associated with decreased function, even severely debilitated patients have significant probability for regain of function at 1, 3 and 5 years post-retransplant. In addition to the improvement in estimates of long-term function, our investigation also found superior overall survival in retransplant patients than previously reported.

Lung retransplant remains the only definitive treatment for patients that develop CLAD, a heterogenous group that suffers from resultant obstructive or restrictive disease and has few proven treatment options.20 Previously a prohibitive option for prior lung transplant recipients, the incidence of lung retransplant continues to grow.21 Survival outcomes are notably inferior to primary transplant patients, though have improved significantly over time.22,23 In the latest International Society for Heart and Lung Transplant (ISHLT) report on retransplant, Yusen et al. (2014) reported unadjusted survival of 77% at 3-months, 64% at 1 year, 46% at 3 years, and 37% at 5 years for retransplant patients, compared to 88% at 3 months, 80% at 1 year and 65% at 3 years, and 53% at 5 years for primary lung transplant recipients.24 Our study, in which retransplant patients from 2015–2023 were evaluated, found improved survival in the retransplant cohort with 3 and 5-year survival at 54% (CI 51%–57%) and 40% (CI 37%–43%).

When stratified by Karnofsky Score, we also note a significant increase in 1 year survival estimates of Total Assistance patients. Whereas a previous UNOS registry analysis reported 1 year survival at only 56% in this group,7 this has increased dramatically in our larger and more contemporary analysis to up to 72% (CI 69%–75%). While overall retransplant Kaplan-Meier survival may not differ significantly, the increase in survival in the Total Assistance patients is notable, not dissimilar to overall survival estimated in the ISHLT report for retransplant patients at 1 year, and bolsters the argument that properly selected patients have good outcomes.

With the increase in risk of morbidity and mortality in retransplant patients, it is important to incorporate expected quality of life and functional status outcomes in patient selection. Grimm et al. (2015) evaluated KPS scores both preoperatively and at the most-recent patient follow-up and found that pre-operative scores were predictive of post-operative performance: 48% of patients requiring total assistance preoperatively remained on total assistance post-operatively.14 Kilic et al. (2013) similarly evaluated KPS in 390 retransplant patients from the UNOS database and found that preoperative KPS was predictive of both mortality and of post-operative function at a single time point (the patient’s last recorded follow-up).7

The conditional probabilities calculated in our analysis provide further estimates of functional status at fixed time intervals that illustrate the likelihood of a patient in each pre-operative functional category to require additional assistance. As would be expected, a retransplant patient that requires total assistance preoperatively has an increasing probability over time of returning to require total assistance with ADLs. These conditional probabilities, however, still suggest a much lower likelihood of requiring total assistance over time than previously reported in smaller analyses, with our estimates that 92% of patients on total assistance regain significant function by 1 year post transplant. Similarly, at 5 years post-transplant, these patients had an 82% probability of requiring no (42%) or some (41%) assistance. These estimates lend additional evidence to the argument that patients who are significantly debilitated after initial transplant may have significant regain of function after retransplant. Where prior studies have failed to use longitudinal modeling for predictability of function, these coefficients provide a framework for modeling realistic and sensible outcomes in this patient population. Further, these estimates may be utilized to risk stratify patients post-operatively and tailor longitudinal rehabilitation plans, targeting patients at greater odds of significant decline in functional status.

The present study is not without limitations. While the KPS provides detail about the ability to care for oneself, clinically a KPS score of 10 and 40 may be vastly different, and adjunct support needs of individual patients post-operatively that provide insight into quality of life (such as ongoing need for dialysis, ECMO, positive pressure ventilation) are not delineated here. Second, KPS scores are subjective, and collected by a variety of clinical staff (i.e., nurses, transplant coordinators) by which inter-rater reliability may be low. Lastly, this registry analysis cannot account for all intrinsic and extrinsic post-transplant factors that may impact the decline or preservation of performance status.

5 | CONCLUSION

In summary, using UNOS follow-up data on functional status of 1275 lung-retransplant patients, we found that pre-operative Karnofsky score is predictive of both survival and post-transplant longitudinal function. Patients requiring total assistance at time of transplant are much more likely to continue to require significant assistance post-transplant, with one in six of these patients reverting to their pre-operative needs at 5 years post-transplant. A significant portion of patients, however, have notable regain of function as well as acceptable survival outcomes when compared to the retransplant group at large. The present analysis highlights the utility in evaluating long-term data in this cohort to better inform our predictions of post-operative function and survival. In turn, we may provide better guidance for physicians, patients, and caregivers in making the determination to undergo retransplantation, as well as to aid in patient selection, timing, and post-operative recovery in retransplant patients.

ACKNOWLEDGMENTS

This work was supported in part by Health Resources and Services Administration contract 234-2005-370011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Funding information

Health Resources and Services Administration, Grant/Award Number: 234-2005-370011C

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available in United Network for Organ Sharing at https://optn.transplant.hrsa.gov/data/view-data-reports/request-data/. These data were derived from the following resources available in the public domain:—United Network for Organ Sharing, https://optn.transplant.hrsa.gov/data/view-data-reports/request-data/

FIGURE 1 Adjusted probability of total assistance post-retransplant.

FIGURE 2 Kaplan-Meier survival by functional status.

TABLE 1 Comparison of baseline recipient characteristics between functional status groups.

Variable	N	Overall, N = 1275	No/some assistance, N = 535	Total assistance, N = 740	p-Valuea	
Primary insurance type, n (%)	1275				.36	
Other		12 (.9)	6 (1.1)	6 (.8)		
Private		617 (48)	247 (46)	370 (50)		
Public		646 (51)	282 (53)	364 (49)		
Primary insurance type, n (%)	1275				.069	
Other		12 (.9)	6 (1.1)	6 (.8)		
Private		617 (48)	247 (46)	370 (50)		
Public—Medicaid		132 (10)	48 (9.0)	84 (11)		
Public—Medicare		491 (39)	228 (43)	263 (36)		
Public—other		20 (1.6)	6 (1.1)	14 (1.9)		
Public—VA		3 (.2)	0 (0)	3 (.4)		
Highest education obtained, n (%)	1177				.23	
College/technical school		615 (52)	249 (50)	366 (54)		
Graduate degree		116 (9.9)	57 (12)	59 (8.6)		
None/grade school/high school		446 (38)	188 (38)	258 (38)		
Disease diagnosis, n (%)	1201				.007	
Obstructive		287 (24)	145 (29)*	142 (20)*		
Restrictive		490 (41)	183 (36)*	307 (44)*		
Suppurative		352 (29)	147 (29)	205 (29)		
Vascular		72 (6.0)	31 (6.1)	41 (5.9)		
Indication for redo transplant, n (%)	1052				<.001	
Acute rejection		21 (2.0)	8 (1.9)	13 (2.1)		
Nonspecific		162 (15)	50 (12)*	112 (18)*		
Obliterative bronchiolitis		736 (70)	334 (78)*	402 (65)*		
Primary graft failure		133 (13)	37 (8.6)*	96 (15)*		
Lung allocation score, Median (IQR)	1275	50 (41–77)	44 (38–52)	63 (45–87)	<.001	
Age at listing, Median (IQR)	1275	50 (33–60)	52 (34–60)	48 (32–60)	.041	
Sex, n (%)	1275				.53	
Female		552 (43)	226 (42)	326 (44)		
Male		723 (57)	309 (58)	414 (56)		
Race, n (%)	1275				.088	
Black		87 (6.8)	33 (6.2)	54 (7.3)		
Hispanic		127 (10.0)	42 (7.9)	85 (11)		
Other		24 (1.9)	13 (2.4)	11 (1.5)		
White		1037 (81)	447 (84)	590 (80)		
Body mass index (kg/m2), Median (IQR)	1260	22.7 (19.2–26.4)	22.4 (19.5–26.0)	23.0 (19.1–26.6)	.42	
Serum creatinine (mg/dL), Median (IQR)	1273	1.00 (.77–1.29)	1.01 (.80–1.30)	.95 (.70–1.26)	<.001	
Serum bilirubin (mg/dL), Mean (SD)	1259	.62 (1.03)	.53 (.86)	.68 (1.13)	<.001	
Diabetes, n (%)	1269	588 (46)	225 (42)	363 (49)	.014	
Dialysis after listing, n (%)	1271	46 (3.6)	3 (.6)	43 (5.8)	<.001	
Mechanical ventilation, n (%)	1275	267 (21)	14 (2.6)	253 (34)	<.001	
O2 Requirement at rest, median (IQR)	1137	4 (2–6)	3 (2–5)	5 (3–10)	<.001	
Bridged with ECMO, n (%)	1275	119 (9.3)	3 (.6)	116 (16)	<.001	
ICU at transplant, n (%)	1275	366 (29)	22 (4.1)	344 (46)	<.001	
Initial and redo ltx type, n (%)	1203				.002	
Ipsilateral single-single		49 (4.1)	14 (2.8)*	35 (5.0)*		
Contralateral single-single		234 (19)	126 (25)*	108 (16)*		
Single-double		117 (9.7)	50 (9.9)	67 (9.6)		
Double-single		174 (14)	65 (13)	109 (16)		
Double-double		629 (52)	252 (50)	377 (54)		
Time Between First and Second Transplant (years), Median (IQR)	1203	3.2 (1.6–6.0)	3.9 (2.2–6.9)	2.6 (1.0–5.3)	<.001	
Waitlist Time (days), Median (IQR)	1275	37 (12–111)	53 (21–158)	26 (8–83)	<.001	
Annual center volume, median (IQR)	1274	46 (29–83)	43 (29–70)	50 (29–93)	.003	
a Fisher’s Exact Test for Count Data with simulated p-value (based on 2000 replicates); Wilcoxon rank sum test; Fisher’s Exact Test for Count Data.

* p < .05 post hoc.

TABLE 2 Comparison of baseline donor and transplant characteristics among preoperative functional status cohorts.

Variable	N	Overall, N = 1275	No/Some Assistance, N = 535	Total Assistance, N = 740	p-Valuea	
Donor Age (years), Median (IQR)	1275	31 (22–45)	29 (21–45)	32 (22–45)	.047	
Donor Sex, n (%)	1275				.25	
Female		517 (41)	207 (39)	310 (42)		
Male		758 (59)	328 (61)	430 (58)		
Donor Race, n (%)	1275				.014	
Black		258 (20)	111 (21)	147 (20)		
Hispanic		230 (18)	106 (20)	124 (17)		
Other		48 (3.8)	10 (1.9)*	38 (5.1)*		
White		739 (58)	308 (58)	431 (58)		
Donor BMI (kg/m2), Median (IQR)	1274	25.1 (22.2–28.5)	25.2 (22.3–28.6)	25.1 (22.2–28.5)	.63	
Cigarette History, n (%)	1265	445 (35)	203 (39)	242 (33)	.035	
Donor Cause of Death, n (%)	1254				.60	
Anoxia		270 (22)	116 (22)	154 (21)		
CNS Tumor		11 (.9)	5 (1.0)	6 (.8)		
CVA/Stroke		395 (31)	154 (29)	241 (33)		
Head Trauma		578 (46)	249 (48)	329 (45)		
Donor Type, n (%)	1275				.44	
DBD		1242 (97)	519 (97)	723 (98)		
DCD		33 (2.6)	16 (3.0)	17 (2.3)		
a Wilcoxon rank sum test; Pearson’s Chi-squared test.

TABLE 3 Cumulative linkedmixed models predicting post-transplant total assistance.

Characteristic	OR (95% CI)a	p-Value	
Functional status at listing			
No/some assistance	—		
Total assistance	1.64 (1.08 to 2.49)	.021	
LAS at listing	1.01 (.99 to 1.03)	.35	
Creatinine (mg/dl)	1.08 (.70 to 1.65)	.73	
Bilirubin	1.03 (.71 to 1.49)	.87	
O2 Requirement at Rest	1.02 (.98 to 1.06)	.44	
ECMO at Listing	.66 (.15 to 3.04)	.60	
Ventilator at Listing	.66 (.26 to 1.69)	.39	
Dialysis after listing			
No	—		
Yes	4.09 (.75 to 22.3)	.10	
Years since retransplant	1.29 (1.17 to 1.43)	<.001	
Diagnosis group			
Obstructive	—		
Restrictive	1.02 (.61 to 1.71)	.93	
Suppurative	.76 (.40 to 1.44)	.39	
Vascular	1.57 (.65 to 3.82)	.32	
Indication for Retransplant			
Acute rejection	—		
Nonspecific	.74 (.14 to 3.84)	.72	
Obliterative bronchiolitis	.49 (.10 to 2.45)	.39	
Primary graft failure	.79 (.15 to 4.29)	.78	
BMI	`.99 (.94 to 1.05)	.76	
Initial Tx/retransplant type			
Ipsilateral single-single	—		
Contralateral single-single	.48 (.15 to 1.48)	.20	
Single-double	.31 (.09 to 1.03)	.056	
Double-single	.65 (.21 to 2.00)	.45	
Double-double	.32 (.11 to.93)	.037	
Center volume	1.01 (1.00 to 1.01)	.032	
a OR,Odds Ratio; CI, Confidence Interval.

TABLE 4 Univariable prediction of post-transplant function in patients requiring total assistance at time of transplant.

Characteristic	N = 740	OR (95% CI)a	p-Value	
Location at transplant				
Non-ICU		—		
ICU		1.14 (.79 to 1.64)	.49	
Bridge at transplant				
No ICU, No Bridge		—		
ICU + Bridge		1.30 (.87 to 1.95)	.20	
a OR, Odds Ratio; CI, Confidence Interval.

TABLE 5 Conditional probability of functional status category post-transplant.

Function at 1 year post retransplant—unadjusted	
Baseline function	No assistance	Some assistance	Total assistance	
No/some assistance	.85	.12	.03	
Total assistance	.48	.07	.45	
Function at 1 year post retransplant—adjusted	
Baseline function No assistance	Some assistance	Total assistance		
No/some assistance	.76	.19	.04	
Total assistance	66	.26	.07	
Function at 3 years post retransplant—unadjusted	
Baseline function	No assistance	Some assistance	Total assistance	
No/some assistance	.80	.16	.04	
Total assistance	.46	.09	.45	
Function at 3 years post retransplant—adjusted	
Baseline function	No assistance	Some assistance	Total assistance	
No/some assistance	.66	.27	.07	
Total assistance	.54	.34	.11	
Function at 5 years post retransplant—unadjusted	
Baseline function	No assistance	Some assistance	Total assistance	
No/some assistance	.74	.21	.05	
Total assistance	.42	.12	.46	
Function at 5 years post retransplant—adjusted	
Baseline function	No assistance	Some assistance	Total assistance	
No/some assistance	.54	.35	.11	
Total assistance	.42	.41	.17	

TABLE 6 Kaplan-Meier estimates of survival post-transplant.

Characteristic	1 Year	3 Year	5 Year	
Overall	76% (74% to 79%)	54% (51% to 57%)	40% (37% to 43%)	
Functional status				
No/some assistance	82% (79% to 86%)	61% (57% to 66%)	47% (42% to 51%)	
Total assistance	72% (69% to 75%)	48% (44% to 52%)	35% (31% to 39%)	

CONFLICT OF INTEREST STATEMENT

The authors report no relevant disclosures.
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