Outcomes of Heart Transplant Using High Donor Sequence Number Offers.

INTRODUCTION: Higher donor sequence numbers (DSNs) might spark provider concern about poor donor quality. We evaluated characteristics of high-DSN offers used for transplant and compared outcomes of high- and low-DSN transplants. MATERIALS AND METHODS: Adult isolated heart transplants between January 1, 2015, and December 31, 2022, were identified from the organ procurement and transplantation network database and stratified into high (≥42) and low (<42) DSN. Postoperative outcomes, including predischarge complications, hospital length of stay, and survival at 1 and 3 y, were evaluated using multivariable regressions. RESULTS: A total of 21,217 recipients met the inclusion criteria, with 2131 (10.0%) classified as high-DSN. Donor factors associated with greater odds of high-DSN at acceptance included older age, higher creatinine, diabetes, hypertension, and lower left ventricular ejection fraction. Recipients accepting high-DSN offers were older and more likely to be female, of blood type O, and have lower status at transplant. High- and low-DSN transplants had similar likelihood of stroke (3.2% versus 3.5%; P = 0.97), dialysis (12.3% versus 13.5%; P = 0.12), pacemaker implant (2.3% versus 2.1%; P = 0.64), had similar lengths of stay (16 [12-24] versus 16 [12-25] days, P = 0.38), and survival at 1 (91.6% versus 91.6%; aHR 0.85 [0.72-1.02], P = 0.08) and 3 y (84.2% versus 85.1%; aHR 0.91 [0.79-1.05], P = 0.21) post-transplant. CONCLUSIONS: High-DSN (≥42) was not an independent risk factor for post-transplant mortality and should not be the sole deterrent to acceptance. Accepting high-DSN organs may increase access to transplantation for lower-status candidates.

Prevalence of cognitive impairment in liver transplant recipients.

Liver transplant (LT) recipients have a high burden of cognitive impairment risk factors identified in other populations, yet little work has explored cognition in the United States LT population. We characterized prevalence of cognitive impairment (CI) in LT recipients pre-LT and ≥3 months post-LT. Adult LT recipients with cirrhosis but without active pre-LT hepatic encephalopathy (HE) were screened for CI using the Montreal Cognitive Assessment (MoCA) for CI (MoCA <24) both pre-LT and ≥3 months post-LT. The association between cognitive performance and recipient characteristics was assessed using logistic regression. Of 107 LT recipients, 36% had pre-LT CI and 27% had post-LT CI [median (Q1-Q3) MoCA 26 (23-28)]. Each 1-point increase in pre-LT MoCA was associated with 26% lower odds of post-LT cognitive impairment (aOR .74, 95% CI .63-.87, p < .001), after adjusting for recipient age, history of HE, and time since LT. In this study of cirrhosis recipients without active pre-LT HE, cognitive impairment was prevalent before LT and remained prevalent ≥3 months after LT (27%), long after effects of portal hypertension on cognition would be expected to have resolved. Our data expose an urgent need for more comprehensive neurologic examination of LT recipients to better identify, characterize, and address predictors of post-LT cognitive impairment.

A pragmatic tool to screen for pre-transplant cognitive impairment among potential candidates for liver transplant.

INTRODUCTION: Cognitive impairment (CI) among liver transplant (LT) candidates is associated with increased risk of waitlist mortality and inferior outcomes. While formal neurocognitive evaluation is the gold standard for CI diagnosis, the Montreal Cognitive Assessment (MoCA) is often used for first-line cognitive screening. However, MoCA requires specialized training and may be too lengthy for a busy evaluation appointment. An alternate approach may be the Quick Dementia Rating System (QDRS), which is patient- and informant-based and can be administered quickly. We compared potential LT candidates identified by MoCA and QDRS as potentially benefiting from further formal cognitive evaluation. METHODS: We identified 46 potential LT candidates enrolled at a single center of a prospective, observational cohort study who were administered MoCA and QDRS during transplant evaluation (12/2021-12/2022). Scores were dichotomized as (1) normal versus abnormal and (2) normal/mild impairment versus more-than-mild impairment. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of QDRS compared to MoCA. RESULTS: By MoCA, this population had a prevalence of 48% normal cognition, 48% mild, 4% moderate, and 0% severe impairment. This was categorized as 96% normal/mild and 4% more-than-mild impairment. When comparing to MoCA cognitive screening, QDRS had a sensitivity of 61%, specificity of 56%, NPV of 56%, and PPV of 61%. When identifying more-than-mild impairment, QDRS had a sensitivity of 100%, specificity of 73%, NPV of 100%, and PPV of 10%. CONCLUSION: The high sensitivity and NPV of QDRS in identifying more-than-mild impairment suggests it could identify potential LT candidates who would benefit from further formal cognitive evaluation. The ability to administer QDRS quickly and remotely makes it a pragmatic option for pre-transplant screening.

Association of body mass index with post-liver transplant outcomes.

BACKGROUND: Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post-liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post-LT outcomes, including those observed in other populations to be obesity-related. METHODS: Included were 1357 LT recipients prospectively enrolled in the ambulatory pre-LT setting at 8 U.S. CENTERS: Recipient were categorized by body mass index (BMI, kg/m2 ): non-obese (BMI < 30), class 1 obesity (BMI 30-<35), and classes 2-3 obesity (BMI ≥ 35). Post-transplant complications were compared by BMI using Chi-square and rank-sum testing, logistic regression, Kaplan-Meier curves, and Cox regression. RESULTS: Classes 2-3 obesity was associated with higher adjusted odds than non-obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01-4.23, p = .047] and wound dehiscence (aOR 2.45, 95% CI 1.19-5.06, p = .02). Compared with non-obese recipients, post-LT hospital stay was significantly longer for recipients with classes 2-3 obesity [p = .01; median (Q1-Q3) 9 (6-14) vs. 8 (6-12) days) or class 1 obesity [p = .002; 9 (6-14) vs. 8 (6-11) days].  Likelihood of ICU readmission, infection, discharge to a non-home facility, rejection, 30-day readmission, and 1-year readmission were similar across BMI categories (all p > .05). CONCLUSION: Compared to non-obese recipients, obese recipients had similar post-LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity-related complications such as wound dehiscence and venous thrombosis.

Factors impacting the medication "Adherence Landscape" for transplant patients.

BACKGROUND: Medication non-adherence contributes to post-transplant graft rejection and failure; however, limited knowledge about the reasons for non-adherence hinders the development of interventions to improve adherence. We conducted focus groups with solid organ transplant recipients regarding overlooked challenges in the process of transplant medication self-management and examined their adherence strategies and perceptions towards the post-transplant medication regimen. METHODS: We conducted four focus groups with n = 31 total adult transplant recipients. Participants had received kidney, liver, or combined liver/kidney transplant at Johns Hopkins Hospital between 2014 and 2019. Focus groups were audio-recorded and transcribed. Transcripts were analyzed inductively, using the constant comparative method. RESULTS: Responses generally fell into two major categories: (1) barriers to adherence and (2) "adherence landscape". We define the former as factors directly labeled as barriers to adherence by participants and the latter as factors that heavily influence the post-transplant medication self-management process. CONCLUSIONS: We propose a shift in the way healthcare providers and researchers, address the question of medication non-adherence. Rather than asking why patients are non-adherent, we suggest that constructing and understanding patients' "adherence landscape" will provide an optimal way to align the goals of patients and providers and boost health outcomes.

Current status and future potential of ex vivo lung perfusion in clinical lung transplantation.

Lung transplantation is accepted as a well-established and effective treatment for patients with end-stage lung disease. While the number of candidates added to the waitlist continues to rise, the number of transplants performed remains limited by the number of suitable organ donors. Ex vivo lung perfusion (EVLP) emerged as a method of addressing the organ shortage by allowing the evaluation and potential reconditioning of marginal donor lungs or minimizing risks of prolonged ischemic time due to logistical challenges. The currently available FDA-approved EVLP systems have demonstrated excellent outcomes in clinical trials, and retrospective studies have demonstrated similar post-transplant survival between recipients who received marginal donor lungs perfused using EVLP and recipients who received standard criteria lungs stored using conventional methods. Despite this, widespread utilization has plateaued in the last few years, likely due to the significant costs associated with initiating EVLP programs. Centralized, dedicated EVLP perfusion centers are currently being investigated as a potential method of further expanding utilization of this technology. In the preclinical setting, potential applications of EVLP that are currently being studied include prolongation of organ preservation, reconditioning of unsuitable lungs, and further enhancement of already suitable lungs. As adoption of EVLP technology becomes more widespread, we may begin to see future implementation of these potential applications into the clinical setting.

Late effects in a high-risk population of breast cancer survivors.

PURPOSE: To better understand the impact of cancer and treatment on outcomes and guide program development, we evaluated breast cancer survivors at risk for long-term medical and psychosocial issues who participated in survivorship care visits (SVs) at Johns Hopkins Hospital. METHODS: We conducted a prospective survey study of women with stage I-III breast cancer who participated in SVs from 2010-2016. The same 56-item questionnaire administered at SV and follow-up included an assessment of symptoms, social factors, demographics, anxiety, depression, and comorbidities. We added the Godin Exercise questionnaire to the follow-up. RESULTS: In 2018, 74 participants were identified as disease-free and mailed a follow-up survey; 52 (70.3%) completed the survey. At a median follow-up time of 3.1 years after diagnosis, participants were less likely to be employed (54% vs. 67%) than at the SV. About two-thirds were sedentary, and this was associated with high body mass index (p = 0.02). Sufficiently active participants (≥ 150 min per week of moderate-intensity activity) were less likely to report pain (p = 0.02) or fatigue (p = 0.001). Although 19% had moderate/severe anxiety or depression at follow-up, participants who reported employment satisfaction were less likely to be depressed (p = 0.02). CONCLUSIONS: Awareness of issues faced by survivors is critical for enhancing care and developing models to identify patients who might benefit most from targeted long-term interventions. IMPLICATIONS FOR CANCER SURVIVORS: Interventions to address physical activity, persistent symptoms, and mental health are critical for breast cancer survivors.

Kidney transplant outcomes in recipients with visual, hearing, physical and walking impairments: a prospective cohort study.

BACKGROUND: Disability in general has been associated with poor outcomes in kidney transplant (KT) recipients. However, disability can be derived from various components, specifically visual, hearing, physical and walking impairments. Different impairments may compromise the patient through different mechanisms and might impact different aspects of KT outcomes. METHODS: In our prospective cohort study (June 2013-June 2017), 465 recipients reported hearing, visual, physical and walking impairments before KT. We used hybrid registry-augmented Cox regression, adjusting for confounders using the US KT population (Scientific Registry of Transplant Recipients, N = 66 891), to assess the independent association between impairments and post-KT outcomes [death-censored graft failure (DCGF) and mortality]. RESULTS: In our cohort of 465 recipients, 31.6% reported one or more impairments (hearing 9.3%, visual 16.6%, physical 9.1%, walking 12.1%). Visual impairment was associated with a 3.36-fold [95% confidence interval (CI) 1.17-9.65] higher DCGF risk, however, hearing [2.77 (95% CI 0.78-9.82)], physical [0.67 (95% CI 0.08-3.35)] and walking [0.50 (95% CI 0.06-3.89)] impairments were not. Walking impairment was associated with a 3.13-fold (95% CI 1.32-7.48) higher mortality risk, however, visual [1.20 (95% CI 0.48-2.98)], hearing [1.01 (95% CI 0.29-3.47)] and physical [1.16 (95% CI 0.34-3.94)] impairments were not. CONCLUSIONS: Impairments are common among KT recipients, yet only visual impairment and walking impairment are associated with adverse post-KT outcomes. Referring nephrologists and KT centers should identify recipients with visual and walking impairments who might benefit from targeted interventions pre-KT, additional supportive care and close post-KT monitoring.

Evolving Impact of COVID-19 on Transplant Center Practices and Policies in the United States.

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19-positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.

Mitochondrial membrane potential and delayed graft function following kidney transplantation.

Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P = .002) and donation after cardiac death donors (75% vs 12%, P = .004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.08 1.381.78 , P = .01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.

Liver transplantation and waitlist mortality for HCC and non-HCC candidates following the 2015 HCC exception policy change.

Historically, exception points for hepatocellular carcinoma (HCC) led to higher transplant rates and lower waitlist mortality for HCC candidates compared to non-HCC candidates. As of October 2015, HCC candidates must wait 6 months after initial application to obtain exception points; the impact of this policy remains unstudied. Using 2013-2017 SRTR data, we identified 39  350 adult, first-time, active waitlist candidates and compared deceased donor liver transplant (DDLT) rates and waitlist mortality/dropout for HCC versus non-HCC candidates before (October 8, 2013-October 7, 2015, prepolicy) and after (October 8, 2015-October 7, 2017, postpolicy) the policy change using Cox and competing risks regression, respectively. Compared to non-HCC candidates with the same calculated MELD, HCC candidates had a 3.6-fold higher rate of DDLT prepolicy (aHR = 3.49 3.69 3.89 ) and a 2.2-fold higher rate of DDLT postpolicy (aHR = 2.09 2.21 2.34 ). Compared to non-HCC candidates with the same allocation priority, HCC candidates had a 37% lower risk of waitlist mortality/dropout prepolicy (asHR = 0.54 0.63 0.73 ) and a comparable risk of mortality/dropout postpolicy (asHR = 0.81 0.95 1.11 ). Following the policy change, the DDLT advantage for HCC candidates remained, albeit dramatically attenuated, without any substantial increase in waitlist mortality/dropout. In the context of sickest-first liver allocation, the revised policy seems to have established allocation equity for HCC and non-HCC candidates.

Survivorship care visits in a high-risk population of breast cancer survivors.

PURPOSE: Breast cancer survivors face numerous challenges after diagnosis and treatment. Several models have been developed to attempt to improve quality of care. Here, we describe characteristics and outcomes of patients who participated in survivorship visits (SV) at Johns Hopkins (JH). METHODS: We retrospectively reviewed charts of breast cancer patients who participated in an optional SV 1-3 months after completing locoregional therapy and initial systemic therapy. We report patient demographics, comorbidities, tumor characteristics, treatments, and responses to symptom questionnaires. We compared the characteristics of SV participants to stage I-III analytical cases in the 2010-2015 JH Cancer Registry (JHCR). RESULTS: We identified 87 women with stage I-III breast cancer who participated in SVs from 2010 to 2016. Compared to patients in the JHCR (n = 2942), SV participants were younger, more likely to be African American and more likely to have a higher TNM stage, hormone receptor-negative disease, and HER2-positive disease. They were more likely to have received chemotherapy and radiation therapy. They also have similar recurrence rates despite the SV cohort's shorter median follow-up time. Among SV participants, the prevalence of comorbidities including peripheral neuropathy, anemia, lymphedema, anxiety, deep vein thrombosis, and depression increased significantly from time of diagnosis to most recent follow-up. CONCLUSIONS: Compared to the JHCR cohort, SV participants had higher risk cancers and a high frequency of comorbidities potentially associated with breast cancer and therapy. These high-risk patients may benefit most from specific interventions targeting survivorship care, and their experiences may help improve care delivery models.

Perspectives on implementing mobile health technology for living kidney donor follow-up: In-depth interviews with transplant providers.

BACKGROUND: United States transplant centers are required to report follow-up data for living kidney donors for 2 years post-donation. However, living kidney donor (LKD) follow-up is often incomplete. Mobile health (mHealth) technologies could ease data collection burden but have not yet been explored in this context. METHODS: We conducted semi-structured in-depth interviews with a convenience sample of 21 transplant providers and thought leaders about challenges in LKD follow-up, and the potential role of mHealth in overcoming these challenges. RESULTS: Participants reported challenges conveying the importance of follow-up to LKDs, limited data from international/out-of-town LKDs, and inadequate staffing. They believed the 2-year requirement was insufficient, but expressed difficulty engaging LKDs for even this short time and inadequate resources for longer-term follow-up. Participants believed an mHealth system for post-donation follow-up could benefit LKDs (by simplifying communication/tasks and improving donor engagement) and transplant centers (by streamlining communication and decreasing workforce burden). Concerns included cost, learning curves, security/privacy, patient language/socioeconomic barriers, and older donor comfort with mHealth technology. CONCLUSIONS: Transplant providers felt that mHealth technology could improve LKD follow-up and help centers meet reporting thresholds. However, designing a secure, easy to use, and cost-effective system remains challenging.

Use of Twitter in communicating living solid organ donation information to the public: An exploratory study of living donors and transplant professionals.

BACKGROUND: As transplant centers start leveraging Twitter for information dissemination and public engagement, it is important to understand current living solid organ donation-related Twitter use. METHODS: We identified public Twitter profiles available in 01/2017 that referenced living organ donation and analyzed the use of donation-related Twitter handles, names, or profile information. Tweets were manually abstracted and qualitatively analyzed for common themes. Social media influence of those tweeting about living donation was evaluated using Klout score. RESULTS: We identified 93 donors, 61 professionals, 12 hospitals, and 19 organizations that met eligibility criteria. Social media influence was similar across these groups (P = 0.4). Donors (16%) and organizations (23%) were more likely than professionals (7%) or hospitals (0%) to include transplant-related educational information in their profiles (P = 0.007). Living donation-related tweets were most commonly donation stories (33%), news reports (20%), reports about new transplant research (15%), and sharing transplant candidates' searches for donors (14%). CONCLUSIONS: This exploratory study of living donors and transplant professionals, hospitals, and organizations on Twitter provides insight into how the social media platform may be used to communicate about and disseminate information about living donation.

Call for improved design and reporting in soft tissue sarcoma studies: A systematic review and meta-analysis of chemotherapy and survival outcomes in resectable STS.

New evidence and systemic therapies demand an updated analysis of chemotherapy for soft tissue sarcoma. We completed a meta-analysis of chemotherapy in localized STS, assessing OS, PFS, and local and distant recurrence (local recurrence-free survival [LRFS] and distant recurrence-free survival [DRFS]). Ten studies, totaling 3157 patients, were included. A pooled analysis for 5-year OS, progression-free survival, LRFS, and DRFS showed no benefit of chemotherapy over locoregional therapy alone for all-comers or site-specific STS. We make recommendations to improve outcome reporting and quality indices.

Factors associated with perceived donation-related financial burden among living kidney donors.

The perception of living kidney donation-related financial burden affects willingness to donate and the experience of donation, yet no existing tools identify donors who are at higher risk of perceived financial burden. We sought to identify characteristics that predicted higher risk of perceived financial burden. We surveyed 51 living kidney donors (LKDs) who donated from 01/2015 to 3/2016 about socioeconomic characteristics, predonation cost concerns, and perceived financial burden. We tested associations between both self-reported and ZIP code-level characteristics and perceived burden using Fisher's exact test and bivariate modified Poisson regression. Donors who perceived donation-related financial burden were less likely to have an income above their ZIP code median (14% vs. 72%, P = .006); however, they were more likely than donors who did not perceive burden to rent their home (57% vs. 16%, P = .03), have an income <$60 000 (86% vs. 20%, P = .002), or have had predonation cost concerns (43% vs. 7%, P = .03). Perceived financial burden was 3.6-fold as likely among those with predonation cost concerns and 10.6-fold as likely for those with incomes <$60 000. Collecting socioeconomic characteristics and asking about donation-related cost concerns prior to donation might allow transplant centers to target financial support interventions toward potential donors at higher risk of perceiving donation-related financial burden.

Geographic disparity in kidney transplantation under KAS.

The Kidney Allocation System fundamentally altered kidney allocation, causing a substantial increase in regional and national sharing that we hypothesized might impact geographic disparities. We measured geographic disparity in deceased donor kidney transplant (DDKT) rate under KAS (6/1/2015-12/1/2016), and compared that with pre-KAS (6/1/2013-12/3/2014). We modeled DSA-level DDKT rates with multilevel Poisson regression, adjusting for allocation factors under KAS. Using the model we calculated a novel, improved metric of geographic disparity: the median incidence rate ratio (MIRR) of transplant rate, a measure of DSA-level variation that accounts for patient casemix and is robust to outlier values. Under KAS, MIRR was 1.75 1.811.86 for adults, meaning that similar candidates across different DSAs have a median 1.81-fold difference in DDKT rate. The impact of geography was greater than the impact of factors emphasized by KAS: having an EPTS score ≤20% was associated with a 1.40-fold increase (IRR = 1.35 1.401.45 , P < .01) and a three-year dialysis vintage was associated with a 1.57-fold increase (IRR = 1.56 1.571.59 , P < .001) in transplant rate. For pediatric candidates, MIRR was even more pronounced, at 1.66 1.922.27 . There was no change in geographic disparities with KAS (P = .3). Despite extensive changes to kidney allocation under KAS, geography remains a primary determinant of access to DDKT.