Faculty Bibliography

Neutralizing antibody (nAb) responses are attenuated in solid organ transplant recipients (SOTRs) despite severe acute respiratory syndrome-coronavirus-2 vaccination. Preexposure prophylaxis (PrEP) with the antibody combination tixagevimab and cilgavimab (T+C) might augment immunoprotection, yet in vitro activity and durability against Omicron sublineages BA.4/5 in fully vaccinated SOTRs have not been delineated. Vaccinated SOTRs, who received 300 + 300 mg T+C (ie, full dose), within a prospective observational cohort submitted pre and postinjection samples between January 31, 2022, and July 6, 2022. The peak live virus nAb was measured against Omicron sublineages (BA.1, BA.2, BA.2.12.1, and BA.4), and surrogate neutralization (percent inhibition of angiotensin-converting enzyme 2 receptor binding to full length spike, validated vs live virus) was measured out to 3 months against sublineages, including BA.4/5. With live virus testing, the proportion of SOTRs with any nAb increased against BA.2 (47%-100%; P < .01), BA.2.12.1 (27%-80%; P < .01), and BA.4 (27%-93%; P < .01), but not against BA.1 (40%-33%; P = .6). The proportion of SOTRs with surrogate neutralizing inhibition against BA.5, however, fell to 15% by 3 months. Two participants developed mild severe acute respiratory syndrome-coronavirus-2 infection during follow-up. The majority of fully vaccinated SOTRs receiving T+C PrEP achieved BA.4/5 neutralization, yet nAb activity commonly waned by 3 months postinjection. It is critical to assess the optimal dose and interval of T+C PrEP to maximize protection in a changing variant climate.

Background Pre-liver transplant (LT) sarcopenia is associated with poor survival. Methods exist for measuring body composition with use of CT scans; however, it is unclear which components best predict post-LT outcomes. Purpose To quantify the association between abdominal CT-based body composition measurements and post-LT mortality in a large North American cohort. Materials and Methods This was a retrospective cohort of adult first-time deceased-donor LT recipients from 2009 to 2018 who underwent pre-LT abdominal CT scans, including at the L3 vertebral level, at Johns Hopkins Hospital. Measurements included sarcopenia (skeletal muscle index [SMI] <50 in men and <39 in women), sarcopenic obesity, myosteatosis (skeletal muscle CT attenuation <41 mean HU for body mass index [BMI] <25 and <33 mean HU for BMI ≥25), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio. Covariates in the adjusted models were selected with use of least absolute shrinkage and selection operator regression with lambda chosen by means of 10-fold cross-validation. Cox proportional hazards models were used to quantify associations with post-LT mortality. Model discrimination was quantified using the Harrell C-statistic. Results A total of 454 recipients (median age, 57 years [IQR, 50-62 years]; 294 men) were evaluated. In the adjusted model, pre-LT sarcopenia was associated with a higher hazard ratio (HR) of post-LT mortality (HR, 1.6 [95% CI: 1.1, 2.4]; C-statistic, 0.64; P = .02). SMI was significantly negatively associated with survival after adjustment for covariates. There was no evidence that myosteatosis was associated with mortality (HR, 1.3 [95% CI: 0.86, 2.1]; C-statistic, 0.64; P = .21). There was no evidence that BMI (HR, 1.2 [95% CI: 0.95, 1.4]), VAT (HR, 1.0 [95% CI: 0.98, 1.1]), SAT (HR, 1.0 [95% CI: 0.97, 1.0]), and VAT/SAT ratio (HR, 1.1 [95% CI: 0.90, 1.4]) were associated with mortality (P = .15-.77). Conclusions Sarcopenia, as assessed on routine pre-liver transplant (LT) abdominal CT scans, was the only factor significantly associated with post-LT mortality. © RSNA, 2022 See also the editorial by Ruehm in this issue.

BACKGROUND:Early post-kidney transplantation (KT) changes in physiology, medications, and health stressors likely impact body mass index (BMI) and likely impact all-cause graft loss and mortality. METHODS:/month) using adjusted Cox proportional hazards models. RESULTS:), BMI increase was associated with higher all-cause mortality (aHR = 1.09, 95% CI: 1.05-1.14), all-cause graft loss (aHR = 1.05, 95% CI: 1.01-1.09), and mortality with functioning graft (aHR = 1.10, 95% CI: 1.05-1.15) risks, but not death-censored graft loss risks, relative to stable weight. Among individuals without obesity, BMI increase was associated with lower all-cause graft loss (aHR = .97, 95% CI: .95-.99) and death-censored graft loss (aHR = .93, 95% CI: .90-.96) risks, but not all-cause mortality or mortality with functioning graft risks. CONCLUSIONS:BMI increases in the 3 years post-KT, then decreases in years 3-5. BMI loss in all adult KT recipients and BMI gain in those with obesity should be carefully monitored post-KT.

Neighborhood socioeconomic deprivation may have important implications on disparities in liver transplant (LT) evaluation. In this retrospective cohort study, we constructed a novel dataset by linking individual patient-level data with the highly granular Area Deprivation Index (ADI), which is advantageous over other neighborhood measures due to: specificity of Census Block-Group (versus Census Tract, Zip code), scoring, and robust variables. Our cohort included 1377 adults referred to our center for LT evaluation 8/1/2016-12/31/2019. Using modified Poisson regression, we tested for effect measure modification of the association between neighborhood socioeconomic status (nSES) and LT evaluation outcomes (listing, initiating evaluation, and death) by race and ethnicity. Compared to patients with high nSES, those with low nSES were at higher risk of not being listed (aRR = 1.14; 95%CI 1.05-1.22; p < .001), of not initiating evaluation post-referral (aRR = 1.20; 95%CI 1.01-1.42; p = .03) and of dying without initiating evaluation (aRR = 1.55; 95%CI 1.09-2.2; p = .01). While White patients with low nSES had similar rates of listing compared to White patients with high nSES (aRR = 1.06; 95%CI .96-1.17; p = .25), Underrepresented patients from neighborhoods with low nSES incurred 31% higher risk of not being listed compared to Underrepresented patients from neighborhoods with high nSES (aRR = 1.31; 95%CI 1.12-1.5; p < .001). Interventions addressing neighborhood deprivation may not only benefit patients with low nSES but may address racial and ethnic inequities.

Antibody responses to SARS-CoV-2 vaccination are reduced in solid organ transplant recipients (SOTRs). We report that increased levels of pre-existing antibodies to seasonal coronaviruses are associated with decreased antibody response to SARS-CoV-2 vaccination in SOTRs, supporting that antigenic imprinting modulates vaccine responses in this immunosuppressed population.

IMPORTANCE/UNASSIGNED:Frailty has been recognized as a risk factor for mortality after liver transplant (LT) but little is known of its association with functional status and health-related quality of life (HRQL), termed global functional health, in LT recipients. OBJECTIVE/UNASSIGNED:To evaluate the association between pre-LT and post-LT frailty with post-LT global functional health. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This prospective cohort study was conducted at 8 US LT centers and included adults who underwent LT from October 2016 to February 2020. EXPOSURES/UNASSIGNED:Frail was defined by a pre-LT Liver Frailty Index (LFI) score of 4.5 or greater. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Global functional health at 1 year after LT, assessed using surveys (Short Form-36 [SF-36; summarized by physical component scores (PFC) and mental component summary scores (MCS)], Instrumental Activities of Daily Living scale) and performance-based tests (LFI, Fried Frailty Phenotype, and Short Physical Performance Battery). RESULTS/UNASSIGNED:Of 358 LT recipients (median [IQR] age, 60 [53-65] years; 115 women [32%]; 25 [7%] Asian/Pacific Islander, 21 [6%] Black, 54 [15%] Hispanic White, and 243 [68%] non-Hispanic White individuals), 68 (19%) had frailty pre-LT. At 1 year post-LT, the median (IQR) PCS was lower in recipients who had frailty vs those without frailty pre-LT (42 [31-53] vs 50 [38-56]; P = .002), but the median MCS was similar. In multivariable regression, pre-LT frailty was associated with a -5.3-unit lower post-LT PCS (P < .001), but not MCS. The proportion who had difficulty with 1 or more Instrumental Activities of Daily Living (21% vs 10%) or who were unemployed/receiving disability (38% vs 29%) was higher in recipients with vs without frailty. In a subgroup of 210 recipients with LFI assessments 1 year post-LT, 13% had frailty at 1 year post-LT. Recipients who had frailty post-LT reported lower adjusted SF-36-PCS scores (coefficient, -11.4; P < .001) but not SF-36-MCS scores. Recipients of LT who had frailty vs those without frailty 1 year post-LT also had worse median (IQR) Fried Frailty Phenotype scores (1 [1-2] vs 1 [0-1]) and higher rates of functional impairment by a Short Physical Performance Battery of 9 or less (42% vs 20%; P = .01). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, pre-LT frailty was associated with worse global functional health 1 year after LT. The presence of frailty after LT was also associated with worse HRQL in physical, but not mental, subdomains. These data suggest that interventions and therapeutics that target frailty that are administered before and/or early post-LT may help to improve the health and well-being of LT recipients.

BACKGROUND:Tixagevimab and Cilgavimab (T + C) is authorized for pre-exposure prophylaxis (PrEP) against Coronavirus Disease 2019 (COVID-19) in solid organ transplant recipients (SOTRs), yet patient-reported outcomes after injection are not well described. Furthermore, changes in risk tolerance after T + C PrEP have not been reported, of interest given uncertain activity against emerging Omicron sublineages. METHODS:Within a national prospective observational study, SOTRs who reported receiving T + C were surveyed for 3 months to ascertain: (1) local and systemic reactogenicity, (2) severe adverse events with focus on cardiovascular and alloimmune complications, and (3) breakthrough COVID-19, contextualized through (4) changes in attitudes regarding COVID-19 risk and behaviors. RESULTS:At 7 days postinjection, the most common reactions were mild fatigue (29%), headache (20%), and pain at injection sites (18%). Severe adverse events were uncommon; over 3 months of follow-up, 4/392 (1%) reported acute rejection and one (.3%) reported a myocardial infarction. Breakthrough COVID-19 occurred in 9%, 16-129 days after receiving full dose (300/300 mg) T + C, including two non-ICU hospitalizations. Most surveyed SOTRs (65%) felt T + C PrEP was likely to reduce their COVID-19 risk, and 70% reported increased willingness to engage in social activities such as visiting friends. However, few felt safe to return to in-person work (20%) or cease public mask-wearing (15%). CONCLUSIONS:In this prospective study of patient-reported outcomes, T + C was well tolerated with few serious events. Several COVID-19 breakthroughs were reported, notable as most SOTRs reported changes in risk tolerance after T + C. These results aid counseling of SOTRs regarding real-world safety and effectiveness of T + C.