Faculty Bibliography

A widely accepted severe acute respiratory syndrome 2 (SARS-CoV-2) vaccine could protect vulnerable populations, but the willingness of solid organ transplant recipients (SOTRs) to accept a potential vaccine remains unknown.

OBJECTIVES/OBJECTIVE:The creation and maintenance of durable hemodialysis access is critically important for reducing patient morbidity and controlling overall costs within health systems. Our objective was to quantify the costs associated with hemodialysis access creation and its maintenance over time within a rate-controlled health system where charges equate to payments. METHODS:The Maryland Health Services Cost Review Commission administrative claims database was used to identify patients who underwent first-time access creation from 2012-2020. Patients were identified using CPT codes for access creation, and costs were accrued for the initial encounter and all subsequent outpatient access-related encounters. T-tests and Wilcoxon tests were used to compare reinterventions and access-related costs ($USD) between arteriovenous fistulae (AVF) and arteriovenous grafts (AVG). Multivariable modeling was used to quantify the association of access type with charge variation. RESULTS:Overall, 12,716 patients underwent first-time access creation (69.3% AVF vs. 30.7% AVG). There was no difference in freedom from reintervention between the two access types at any point following creation (HR: 1.03, 95%CI: 0.97-1.10); however, AVF were associated with a lower number of cumulative reinterventions (1.50 vs. 2.24) compared to AVG (P<0.0001). AVF was associated with lower overall costs in the year of creation ($9,388 vs. $13,539, P<0.0001), a difference that remained significant over the subsequent 3 years. The lower costs associated with AVF were present both in the costs associated with creation and subsequent maintenance. On multivariable analysis, AVF was associated with a $3,557 reduction in total access-related costs versus AVG (95%CI -$3828, -3287). CONCLUSION/CONCLUSIONS:AVF require fewer interventions and are associated with lower costs at placement and over the first three years of maintenance compared to AVG. The use of AVF for first-time hemodialysis access represents an opportunity for healthcare savings in appropriately selected patients with a high preoperative likelihood of AVF maturation.

Transplant recipients were excluded from the initial clinical trials determining safety and efficacy of the landmark COVID-19 vaccines. Further, there is increasing evidence that immunosuppressed transplant recipients have a blunted antibody response to COVID-19 vaccination. In a concerning report by Sattler et al. in this issue of the JCI, kidney transplant recipients not only lacked a humoral response following two doses of Pfizer BNT162b2, but also displayed substantial impairment of the cellular response to SARS-CoV-2 antigens. This Commentary addresses potential strategies for transplant providers to evaluate and augment vaccine immunogenicity given the likelihood that COVID-19 will remain a world-wide threat to the health of transplant recipients.

In the seven years since the HIV Organ Policy Equity (HOPE) Act made HIV-positive organ donation to HIV-positive recipients legally permissible in the United States, there have been fewer HIV-positive organ donations than expected. Organ procurement organizations (OPOs) play a key role in the transplant system and barriers at OPOs may be partly responsible for the relatively low number of HIV-positive donors. To understand potential OPO barriers, we conducted semi-structured interviews with 20 OPO staff members. Interviews were recorded, transcribed, and analyzed using a conventional content analytic approach with two coders. OPO staff had high levels of knowledge about HOPE. Many had evaluated referrals of HIV-positive donors and approached families for authorization. Barriers to HIV-positive organ recovery identified included obtaining authorization for donation, potentially disclosing HIV status to next-of-kin, and fear of HIV infection among those engaged in organ recovery. Strategies to overcome these barriers include providing continuing education about the specific tasks required to procure organs from HIV-positive donors, implementing targeted interventions to reduce fear of infection, and developing partnerships with HIV advocacy and care organizations. Given the central role OPOs play, HIV-positive donations are unlikely to occur in significant numbers unless these barriers can be overcome.

Organ transplant patients have poor immune responses to COVID-19 vaccines; thus designing vaccine strategies to protect this vulnerable population from SARS-CoV-2 infection is crucial.

BACKGROUND:While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) recipients remains sparse. METHODS:US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development. RESULTS:Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p < .001). Priming dose antibody response was associated with younger recipient age (p = .04), transplant-to-vaccination time ≥6 years (p < .01), and lack of anti-metabolite maintenance immunosuppression (p < .001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported. CONCLUSIONS:HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed.

BACKGROUND AND AIMS:Frailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality. APPROACH AND RESULTS:Adults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0-4.8) for 3-month mortality, 4.2 (95% CI, 4.1-4.4) for 6-month mortality, and 4.2 (95% CI, 4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79. CONCLUSIONS:LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.

BACKGROUND:Patients with multiple myeloma (MM) were excluded from the original SARS-CoV-2 mRNA vaccine trials, which may influence vaccine hesitancy in this population. We prospectively characterized the safety and immunogenicity of two-dose SARS-CoV-2 mRNA vaccination in 44 patients with MM, who underwent vaccination from 12/17/2020 to 3/18/2021. RESULTS:Rates adverse reactions were low and consistent with those documented in vaccine trials. Among those on MM therapy, 93% developed detectable anti-receptor binding domain (RBD) antibodies after dose 2, while 94% of patients not on MM therapy seroconverted. CONCLUSIONS:Two-dose SARS-CoV-2 mRNA vaccination is mildly reactogenic and leads to high rates of seroconversion in patients with MM. These findings can provide reassurance to MM patients who are hesitant to receive SARS-CoV-2 mRNA vaccines.

Organ procurement organizations (OPOs) evaluate referrals for deceased organ donation in the United States. Efforts to expand the donor pool, such as the HIV organ policy equity (HOPE) Act that permits transplants from HIV-positive donors to HIV-positive recipients, can only succeed if OPOs pursue referrals. However, relatively little is known about how OPO staff evaluate referrals. To better understand this process, OPO staff completed a discrete choice experiment to quantify the relative importance of seven donor characteristics on the decision to pursue a theoretical donor. Relative importance was defined by Partworth utility using a hierarchical Bayesian conditional logit model. There were 51 respondents from 36 of 58 OPOs in the United States. Of the seven attributes, organ and tissue potential were the most influential, followed by age, type of death, HIV status, donor registration, and Hepatitis C status. To be preferred to an HIV-negative donor, an HIV-positive donor needed to have the potential to donate two additional organs. These data provide insight into the preferences of OPO referral staff and may help explain the lower than expected number of HIV-positive transplants performed since the passage of the HOPE Act.