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Objectives: To identify patient and process factors that contribute to the high cost of lung transplantation (LTx) in the perioperative period, which may allow transplant centers to evaluate situations in which transplantation is most cost-effective to inform judicious resource allocation, avoid futile care, and reduce costs., Methods: The MarketScan Research databases were used to identify 582 privately insured patients undergoing single or bilateral LTx between 2013 and 2019. The patients were subdivided into groups by disease etiology using the United Network of Organ Sharing classification system. Multivariable generalized linear models using a gamma distribution with a log link were fit to examine the associations between the etiology of lung disease and costs during the index admission, 3 months before admission, and 3 months after discharge., Results: Our results indicate that the index admission contributed the most to the total transplantation costs compared to the 3 months before admission and after discharge. The regression-adjusted mean index hospitalization cost was 35% higher for patients with pulmonary vascular disease compared to those with obstructive lung disease ($527,156 vs $389,055). The use of extracorporeal membrane oxygenation, mechanical ventilation, and surgical complications in the post-transplantation period were associated with higher costs during the index admission. Surprisingly, age ≥55 was associated with lower costs during the index admission., Conclusions: This analysis identifies pivotal factors influencing the high cost of LTx, emphasizing the significant impact of the index admission, particularly for patients with pulmonary vascular disease. These insights offer transplant centers an opportunity to enhance cost-effectiveness through judicious resource allocation and service bundling, ultimately reducing overall transplantation costs., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Introduction: Recombinant adeno-associated virus (rAAV) is a novel strategy used clinically for gene delivery, but has not been characterized in the context of organ transplantation. We sought to determine the efficacy of rAAV-mediated gene delivery during static cold storage (SCS) prior to liver transplantation., Methods: A triple-plasmid transfection protocol was used to produce rAAV subtype-9 vectors containing firefly luciferase genomes in HEK293 cells. Lewis rat liver grafts were flushed and stored in cold HTK solution. Three experimental groups received rAAV at different doses, administered via the portal vein as a bolus during SCS. A control group did not receive rAAV ( N  = 2). Recipients then underwent syngeneic liver transplantation. Bioluminescence imaging to quantify in vivo luciferase expression was performed on post-operative days 7, 14, 28, and 56., Results: Control animals demonstrated no bioluminescent activity, while animals receiving rAAV-treated livers had increasing bioluminescence, peaking at four weeks but sustained to the eight-week endpoint. This result was confirmed by experimental endpoint tissue luciferase activity assay., Discussion: rAAV mediates gene transduction in liver grafts when administered during SCS and has potential for gene therapy applications in solid organ transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Gao, Kesseli, Gonzalez, Zhang, Kahan, Krischak, Halpern, Song, Xu, Abraham, Anwar, Alderete, Asokan, Hartwig and Barbas.)

Background: Subnormothermic machine perfusion (SNMP) of liver grafts is currently less clinically developed than normothermic and hypothermic approaches, but may have logistical advantages. At intermediate temperatures, the oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, however, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability. In this study, we hypothesized that the biliary compartment would be more sensitive than perfusate in detecting graft injury during SNMP., Methods: To test this hypothesis in a rat model, we performed liver transplants with DCD and control liver grafts after 1 h of acellular room temperature machine perfusion (acRTMP) or static cold storage (SCS). Point of care liver function tests were measured in biliary and perfusate samples after 1 h of machine perfusion. Following transplantation, rats were sacrificed at 24 h for assessment of post-transplant graft function and histology., Results: All point-of-care liver function tests were significantly more concentrated in the biliary compartment than the perfusate compartment during acRTMP. DCD liver grafts could be distinguished from control liver grafts by significantly higher markers of hepatocyte injury (AST, ALT) in the biliary compartment, but not in the perfusate compartment. Classical markers of cholangiocyte injury, such as gammy-glut amyl transferase (GGT), amylase (AML), and alkaline phosphatase were detectable in the biliary compartment, but not in the perfusate compartment. In comparison to SCS, graft preservation by acRTMP produced a significant survival benefit in DCD liver transplantation (75 vs. 0%, p < 0.0030)., Conclusion: Together, these findings demonstrate that during acRTMP, the biliary compartment may be a more sensitive indicator of graft injury than the perfusate compartment. Moreover, acRTMP provides superior graft preservation to SCS in rat DCD liver transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict ofinterest., (Copyright © 2022 Abraham, Zhang, Cray, Gao, Samy, Neill, Cywinska, Migaly, Kahan, Pontula, Halpern, Rush, Penaflor, Kesseli, Krischak, Song, Hartwig, Pollara and Barbas.)

Ex vivo lung perfusion (EVLP) is a novel lung preservation strategy that facilitates the use of marginal allografts; however, it is more expensive than static cold storage (SCS). To understand how preservation method might affect postoperative costs, we compared outcomes and index hospitalization costs among matched EVLP and SCS preserved lung transplant (LTx) recipients at a single, high-volume institution. A total of 22 EVLP and 66 matched SCS LTx recipients were included; SCS grafts were further stratified as either standard-criteria (SCD) or extended-criteria donors (ECD). Median total preservation time was 857, 409, and 438 min for EVLP, SCD, and ECD lungs, respectively (p < .0001). EVLP patients had similar perioperative outcomes and posttransplant survival compared to SCS SCD and ECD recipients. Excluding device-specific costs, total direct variable costs were similar among EVLP, SCD, and ECD recipients (median $200,404, vs. $154,709 vs. $168,334, p =  .11). The median direct contribution margin was positive for EVLP recipients, and similar to that for SCD and ECD graft recipients (all p > .99). These findings demonstrate that the use of EVLP was profitable at an institutional level; however, further investigation is needed to better understand the financial implications of EVLP in facilitating donor pool expansion in an era of broader lung sharing., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Normothermic machine perfusion (NMP) provides clinicians an opportunity to assess marginal livers before transplantation. However, objective criteria and point-of-care (POC) biomarkers to predict risk and guide decision making are lacking. In this investigation, we characterized trends in POC biomarkers during NMP and compared primate donation after circulatory death (DCD) livers with short and prolonged warm ischemic injury. Following asystole, livers were subjected to either 5 minutes (DCD-5min, n = 4) or 45 minutes (DCD-45min, n = 4) of warm ischemia time. Livers were flushed with heparinized UW solution, and preserved in cold storage before NMP. During flow-controlled NMP, circulating perfusate and tissue biopsies were collected at 0, 2, 4, 6, and 8 hours for analysis. DCD-45min livers had greater terminal portal vein pressure (8.5 vs. 13.3 mm Hg, P = 0.027) and terminal portal vein resistance (16.3 vs. 32.4 Wood units, P = 0.005). During perfusion, DCD-45min livers had equivalent terminal lactate clearance (93% vs. 96%, P = 0.344), greater terminal alanine aminotransferase (163 vs. 883 U/L, P = 0.002), and greater terminal perfusate gamma glutamyltransferase (GGT) (5.0 vs. 31.7 U/L, P = 0.002). DCD-45min livers had higher circulating levels of flavin mononucleotide (FMN) at hours 2 and 4 of perfusion (136 vs. 250 ng/mL, P = 0.029; and 158 vs. 293 ng/mL, P = 0.003; respectively). DCD-5min livers produced more bile and demonstrated progressive decline in bile lactate dehydrogenase, whereas DCD-45min livers did not. On blinded histologic evaluation, DCD-45min livers demonstrated greater injury and necrosis at late stages of perfusion, indicative of nonviability. Conclusion: Objective criteria are needed to define graft viability during NMP. Perfusate lactate clearance does not discriminate between viable and nonviable livers during NMP. Perfusate GGT and FMN may represent POC biomarkers predictive of liver injury during NMP., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

Background: Livers from "nonideal" but acceptable donors are underutilized; however, organ procurement organization (OPO) metrics do not assess how OPO-specific practices contribute to these trends. In this analysis, we evaluated nonideal liver donor avoidance or risk aversion among OPOs and within US donation service areas (DSAs)., Methods: Adult donors in the United Network for Organ Sharing registry who donated ≥1 organ for transplantation between 2007 and 2019 were included. Nonideal donors were defined by any of the following: age > 70, hepatitis C seropositive, body mass index > 40, donation after circulatory death, or history of malignancy. OPO-specific performance was evaluated based on rates of nonideal donor pursuit and consent attainment. DSA performance (OPO + transplant centers) was evaluated based on rates of nonideal donor pursuit, consent attainment, liver recovery, and transplantation. Lower rates were considered to represent increased donor avoidance or increased risk aversion., Results: Of 97 911 donors, 31 799 (32.5%) were nonideal. Unadjusted OPO-level rates of nonideal donor pursuit ranged from 88% to 100%. In a 5-tier system of overall risk aversion, tier 5 DSAs (least risk-averse) and tier 1 DSAs (most risk-averse) had the highest and lowest respective rates of non-ideal donor pursuit, consent attainment, liver recovery, and transplantation. On average, recovery rates were over 25% higher among tier 5 versus tier 1 DSAs. If tier 1 DSAs had achieved the same average liver recovery rate as tier 5 DSAs, approximately 2100 additional livers could have been recovered during the study period., Conclusion: Most OPOs aggressively pursue nonideal liver donors; however, recovery practices vary widely among DSAs. Fair OPO evaluations should consider early donation process stages to best disentangle OPO and center-level practices., Competing Interests: S.E.H. is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number TL1TR002555. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objectives: Complement activation in organs from deceased donors is associated with allograft injury and acute rejection. Because use of organs from donors after circulatory death is increasing, we characterized relative levels of complement activation in organs from donors after brain death and after circulatory death and examined associations between donor complement factor levels and outcomes after kidney and liver transplant., Materials and Methods: Serum samples from 65 donors (55 donations after brain death, 10 donations after circulatory death) were analyzed for classical, lectin, alternative, and terminal pathway components by Luminex multiplex assays. Complement factor levels were compared between groups, and associations with posttransplant outcomes were explored., Results: Serum levels of the downstream complement activation product C5a were similar in organs from donors after circulatory death versus donors after brain death. In organs from donors after circulatory death, complement activation occurred primarily via the alternative pathway; the classical, lectin, and alternative pathways all contributed in organs from donors after brain death. Donor complement levels were not associated with outcomes after kidney transplant. Lower donor complement levels were associated with need for transfusion, reintervention, hospital readmission, and acute rejection after liver transplant., Conclusions: Complement activation occurs at similar levels in organs donated from donors after circulatory death versus those after brain death. Lower donor complement levels may contribute to adverse outcomes after liver transplant. Further study is warranted to better understand how donor complement activation contributes to posttransplant outcomes.

Background: Magnetic sphincter augmentation (MSA) is a promising minimally invasive surgical technique for management of gastroesophageal reflux disease (GERD); however, device implantation after transplantation has not been studied and may be concerning in these immunosuppressed patients. We explored the safety of the LINX Reflux Management System (MSA device) for management of GERD following lung transplantation (LTx)., Methods: Lung transplant recipients who underwent LINX implantation at our institution between 2017 and 2019 were followed prospectively in the Reflux Following Lung Transplantation and Associated Treatment Registry. Ambulatory pH testing and acid-suppressing medication use were compared before and after LINX implantation. One-year outcomes and change in pulmonary function were compared between matched LINX and fundoplication groups., Results: Of 17 patients who underwent post-lung transplant LINX implantation, 8 (47.1%) agreed to undergo post-LINX pH testing. Three/eight (37.5%) patients achieved normal esophageal acid exposure time; 14 (82.4%) remained on acid-suppressing medication at one-year under the direction of their transplant teams. One-year patient survival and change in pulmonary function were similar between groups. LINX patients experienced more early side effects., Conclusions: Use of the LINX MSA device in a cohort of lung transplant recipients at our institution was associated with similar short-term safety compared to traditional fundoplication, however assessment of efficacy was limited. Further investigation is needed to characterize the long-term efficacy of LINX implantation after LTx., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-3276). MGH reports grants from Torax, during the conduct of the study. The other authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Lungs from "nonideal," but acceptable donors are underutilized; however, organ procurement organization (OPO) metrics do not reflect the extent to which OPO-specific practices contribute to these trends. We developed a comprehensive system to evaluate nonideal lung donor avoidance, or risk aversion among OPOs. Adult donors in the UNOS registry who donated ≥1 organ for transplantation between 2007 and 2018 were included. Nonideal donors had any of age>50, smoking history ≥20 pack-years, PaO 2 /FiO 2 ratio ≤350, donation after circulatory death, or increased risk status. OPO-level risk aversion in donor pursuit, consent attainment, lung recovery, and transplantation was assessed. Among 83916 donors, 70372 (83.9%) were nonideal. Unadjusted OPO-level rates of nonideal donor pursuit ranged from 81 to 100%. In a three-tier system of overall risk aversion, tier 3 OPOs (least risk-averse) had the highest rates of nonideal donor pursuit, consent attainment, lung recovery, and transplantation. Tier 1 OPOs (most risk-averse) had the lowest rates of donor pursuit, consent attainment, and lung recovery, but higher rates of transplantation compared to tier 2 OPOs (moderately risk-averse). Risk aversion varies among OPOs and across the donation process. OPO evaluations should reflect early donation process stages to best differentiate over- and underperforming OPOs and encourage optimal OPO-specific performance., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Despite growing evidence of comparable outcomes in recipients of donation after circulatory death and donation after brain death donor lungs, donation after circulatory death allografts continue to be underused nationally. We examined predictors of nonuse., Methods: All donors who donated at least 1 organ for transplantation between 2005 and 2019 were identified in the United Network for Organ Sharing registry and stratified by donation type. The primary outcome of interest was use of pulmonary allografts. Organ disposition and refusal reasons were evaluated. Multivariable regression modeling was used to assess the relationship between donor factors and use., Results: A total of 15,458 donation after circulatory death donors met inclusion criteria. Of 30,916 lungs, 3.7% (1158) were used for transplantation and 72.8% were discarded primarily due to poor organ function. Consent was not requested in 8.4% of donation after circulatory death offers with donation after circulatory death being the leading reason (73.4%). Nonuse was associated with smoking history (P < .001), clinical infection with a blood source (12% vs 7.4%, P = .001), and lower PaO 2 /FiO 2 ratio (median 230 vs 423, P < .001). In multivariable regression, those with PaO 2 /FiO 2 ratio less than 250 were least likely to be transplanted (adjusted odds ratio, 0.03; P < .001), followed by cigarette use (0.28, P < .001), and donor age >50 (0.75, P = .031). Recent transplant era was associated with significantly increased use (adjusted odds ratio, 2.28; P < .001)., Conclusions: Nontransplantation of donation after circulatory death lungs was associated with potentially modifiable predonation factors, including organ procurement organizations' consenting behavior, and donor factors, including hypoxemia. Interventions to increase consent and standardize donation after circulatory death donor management, including selective use of ex vivo lung perfusion in the setting of hypoxemia, may increase use and the donor pool., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Patterns of use of older donor lungs within this previously underused donor population are poorly characterized. This study examined factors associated with the use of older donor lung allografts and factors associated with survival in recipients of these lungs., Methods: Adult donors in the United Network for Organ Sharing registry who donated 1 or more organs for transplantation between 2006 and 2018 were analyzed and stratified into older (age >55 years) and younger (age ≤55 years) cohorts. Multivariable logistic and Cox regression were used to identify factors associated with transplantation of older donor lungs and factors associated with survival, respectively., Results: Overall, 202,477 donors were included and stratified by age (older, 40,406 [20%]; younger, 162,071 [80%]). Compared with younger donors, older donors had an increased rate of consent for donation not requested by organ procurement organizations (7.5% vs 1.7%). Donor factors significantly associated with decreased lung use included male sex, increasing donor age, black race, Hispanic ethnicity, cigarette use, cocaine use, donation after circulatory death status, and PaO 2 /FiO 2 (P/F ratio) lower than 350. In recipients of older donor lungs, increasing donor age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01, 1.05), recipient age 47 years or older (HR 1.03; 95% CI, 1.02, 1.04), and male sex (HR, 1.19; 95% CI, 1.02, 1.39) portended worse survival., Conclusions: Barriers in consenting practices, concerns about organ function, and recipient survival prevent the widespread use of aged allografts for lung transplantation. Better understanding of factors associated with worse outcomes of older donors and modification of organ procurement organization consenting practices may increase the use of these higher-risk donor organs., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Outcomes after kidney transplantation (KTx) remain limited by delayed graft function (DGF) and acute rejection. Non-invasive biomarkers may help identify patients at increased risk for these events. We examined the association between the systemic immune-inflammation index (SII), a novel inflammatory biomarker, and outcomes after KTx and evaluated its ability to predict post-transplant prognosis., Patients and Methods: Adult patients who underwent primary KTx at our institution between 2016-2019 were included. SII was calculated from pre-transplant complete blood counts as the ratio of the neutrophil count to the lymphocyte count multiplied by the platelet count. The cutoff between high and low SII was determined by maximizing the area under the curve. Multivariable logistic and Cox regression were used to identify factors associated with DGF and patient, rejection-free, and graft survival respectively., Results: Overall, 378 KTx recipients were included; 224 (59.3%) had high SII. On unadjusted analysis, high SII was associated with reduced odds of DGF, and improved patient and rejection-free survival. After adjustment, high SII was independently associated with improved patient survival alone. Multivariable models incorporating SII performed well for the prediction of DGF (c-statistic=0.755) and patient survival (c-statistic=0.786), though rejection-free survival was more difficult to predict (c-statistic=0.635)., Conclusion: SII demonstrated limited utility as an independent predictor of outcomes after KTx. However, in combination with other clinically relevant parameters, SII is a useful predictor of post-KTx prognosis. Validation of this novel inflammatory biomarker in a multi-institutional study is needed to further elucidate its practical applications in transplantation., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In the United States, an overall national decline in organ transplants has accompanied the substantial burden of COVID-19. Amidst significant regional variations in COVID-19, lung transplantation (LTx) remains a critical life-saving operation. Our LTx practice during the early pandemic may provide a blueprint for managing LTx in an era of continued community prevalence. Patients who underwent LTx at our institution between March 1 and May 20, 2020 were included. Recipient, operative, and donor characteristics were compared to those from our program in 2019, and COVID-19 testing practices were evaluated for March, April, and May to understand how our practice adapted to the pandemic. Our program performed 36 LTx, 33% more than the same period in 2019. Recipient, operative, and donor characteristics during COVID-19 were similar to those in 2019. By April 1, all donors and recipients underwent pretransplant COVID-19 testing, all returning negative results. To date, no recipients have developed posttransplant COVID-19. At our institution, pretransplant COVID-19 testing, use of local donor lungs, and avoidance of donors from areas of increased community penetration supported a safe and effective LTx practice during the early COVID-19 pandemic. Continued follow-up is required to ensure the long-term safety of these newly transplanted patients., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: HIV-infected (HIV+) donor to HIV+ recipient (HIV D+/R+) transplantation might improve access to transplantation for people living with HIV. However, it remains unknown whether transplant candidates living with HIV will accept the currently unknown risks of HIV D+/R+ transplantation., Methods: We surveyed transplant candidates living with HIV from 9 US transplant centers regarding willingness to accept HIV+ donor organs., Results: Among 116 participants, the median age was 55 years, 68% were men, and 78% were African American. Most were willing to accept HIV+ living donor organs (87%), HIV+ deceased donor organs (84%), and increased infectious risk donor organs (70%). Some (30%) were concerned about HIV superinfection; even among these respondents, 71% were willing to accept an HIV D+ organ. Respondents from centers that had already performed a transplant under an HIV D+/R+ transplantation research protocol were more willing to accept HIV+ deceased donor organs (89% vs. 71%, P = 0.04). Respondents who chose not to enroll in an HIV D+/R+ transplantation research protocol were less likely to believe that HIV D+/R+ transplantation was safe (45% vs. 77%, P = 0.02), and that HIV D+ organs would work similar to HIV D- organs (55% vs. 77%, P = 0.04), but more likely to believe they would receive an infection other than HIV from an HIV D+ organ (64% vs. 13%, P < 0.01)., Conclusions: Willingness to accept HIV D+ organs among transplant candidates living with HIV does not seem to be a major barrier to HIV D+/R+ transplantation and may increase with growing HIV D+/R+ transplantation experience.

The cellular mechanisms underlying impaired function of aged liver grafts have not been fully elucidated, but mitochondrial dysfunction appears to be contributory. Sirtuin1 has been identified as a key mediator of mitochondrial recovery following ischemia-reperfusion injury. The purpose of this study was to determine whether differences exist in sirtuin-1 expression/activity in old vs. young liver grafts and to determine correlations with mitochondrial function, graft metabolic function, and graft injury. Old and young rat liver grafts (N = 7 per group) were exposed to 12 h of static cold storage (SCS), followed by a 2 h period of graft reperfusion ex vivo. Sirtuin1 expression and activity, mitochondrial function, graft metabolic function, and graft injury were compared. Sirtuin1 expression is upregulated in young, but not old, liver grafts in response to cold storage and reperfusion. This is associated with diminished tissue ATP, antioxidant defense, and graft metabolic function in old liver grafts. There was no evidence of increased inflammation or histologic injury in old grafts. Sirtuin1 expression is diminished in old liver grafts and correlates with mitochondrial and metabolic function. The sirtuin pathway may represent a target for intervention to enhance the function of aged liver grafts.

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., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: In 2013, the Organ Procurement and Transplantation Network began requiring transplant centers in the United States to collect and report postdonation living kidney donor follow-up data at 6 months, 1 year, and 2 years. Despite this requirement, <50% of transplant centers have been able to collect and report the required data. Previous work identified a number of barriers to living kidney donor follow-up, including logistical and administrative barriers for transplant centers and cost and functional barriers for donors. Novel smartphone-based mobile health (mHealth) technologies might reduce the burden of living kidney donor follow-up for centers and donors. However, the attitudes and perceptions toward the incorporation of mHealth into postdonation care among living kidney donors are unknown. Understanding donor attitudes and perceptions will be vital to the creation of a patient-oriented mHealth system to improve living donor follow-up in the United States., Objective: The goal of this study was to assess living kidney donor attitudes and perceptions associated with the use of mHealth for follow-up., Methods: We developed and administered a cross-sectional 14-question survey to 100 living kidney donors at our transplant center. All participants were part of an ongoing longitudinal study of long-term outcomes in living kidney donors. The survey included questions on smartphone use, current health maintenance behaviors, accessibility to health information, and attitudes toward using mHealth for living kidney donor follow-up., Results: Of the 100 participants surveyed, 94 owned a smartphone (35 Android, 58 iPhone, 1 Blackberry), 37 had accessed their electronic medical record on their smartphone, and 38 had tracked their exercise and physical activity on their smartphone. While 77% (72/93) of participants who owned a smartphone and had asked a medical question in the last year placed the most trust with their doctors, nurses, or other health care professionals regarding answering a health-related question, 52% (48/93) most often accessed health information elsewhere. Overall, 79% (74/94) of smartphone-owning participants perceived accessing living kidney donor information and resources on their smartphone as useful. Additionally, 80% (75/94) perceived completing some living kidney donor follow-up via mHealth as useful. There were no significant differences in median age (60 vs 59 years; P=.65), median years since donation (10 vs 12 years; P=.45), gender (36/75, 36%, vs 37/75, 37%, male; P=.57), or race (70/75, 93%, vs 18/19, 95%, white; P=.34) between those who perceived mHealth as useful for living kidney donor follow-up and those who did not, respectively., Conclusions: Overall, smartphone ownership was high (94/100, 94.0%), and 79% (74/94) of surveyed smartphone-owning donors felt that it would be useful to complete their required follow-up with an mHealth tool, with no significant differences by age, sex, or race. These results suggest that patients would benefit from an mHealth tool to perform living donor follow-up., (©Ann K Eno, Alvin G Thomas, Jessica M Ruck, Sarah E Van Pilsum Rasmussen, Samantha E Halpern, Madeleine M Waldram, Abimereki D Muzaale, Tanjala S Purnell, Allan B Massie, Jacqueline M Garonzik Wang, Krista L Lentine, Dorry L Segev, Macey L Henderson. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 09.10.2018.)

Organs from deceased donors with suspected false-positive HIV screening tests were generally discarded due to the chance that the test was truly positive. However, the HIV Organ Policy Equity (HOPE) Act now facilitates use of such organs for transplantation to HIV-infected (HIV+) individuals. In the HOPE in Action trial, donors without a known HIV infection who unexpectedly tested positive for anti-HIV antibody (Ab) or HIV nucleic acid test (NAT) were classified as suspected false-positive donors. Between March 2016 and March 2018, 10 suspected false-positive donors had organs recovered for transplant for 21 HIV + recipients (14 single-kidney, 1 double-kidney, 5 liver, 1 simultaneous liver-kidney). Median donor age was 24 years; cause of death was trauma (n = 5), stroke (n = 4), and anoxia (n = 1); three donors were labeled Public Health Service increased infectious risk. Median kidney donor profile index was 30.5 (IQR 22-58). Eight donors were HIV Ab+/NAT-; two were HIV Ab-/NAT+. All 10 suspected false-positive donors were confirmed to be HIV-noninfected. Given the false-positive rates of approved assays used to screen > 20 000 deceased donors annually, we estimate 50-100 HIV false-positive donors per year. Organ transplantation from suspected HIV false-positive donors is an unexpected benefit of the HOPE Act that provides another novel organ source., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: With passage of the HIV Organ Policy Equity (HOPE) Act, people living with HIV (PLWH) can donate organs to PLWH awaiting transplant. Understanding knowledge and attitudes regarding organ donation among PLWH in the United States is critical to implementing the HOPE Act., Methods: PLWH were surveyed regarding their knowledge, attitudes, and beliefs about organ donation and transplantation at an urban academic HIV clinic in Baltimore, MD, between August 2016 and October 2016. Responses were compared using Fisher exact and χ tests., Results: Among 114 survey respondents, median age was 55 years, 47.8% were female, and 91.2% were African American. Most were willing to be deceased donors (79.8%) or living donors (62.3%). Most (80.7%) were aware of the US organ shortage; however, only 24.6% knew about the HOPE Act, and only 21.1% were registered donors. Respondents who trusted the medical system or thought their organs would function adequately in recipients were more likely to be willing to be deceased donors (P < 0.001). Respondents who were concerned about surgery, worse health postdonation, or need for changes in HIV treatment because of donation were less likely to be willing to be living donors (P < 0.05 for all). Most believed that PLWH should be permitted to donate (90.4%) and that using HIV+ donor organs for transplant would reduce discrimination against PLWH (72.8%)., Conclusions: Many of the PLWH surveyed expressed willingness to be organ donors. However, knowledge about the HOPE Act and donor registration was low, highlighting a need to increase outreach.

Isoelectric focusing (IEF) of the Fab' derivative of murine monoclonal antibody ZCE-025 is known to detect at least six bands having isoelectric points (pI) ranging from 5.4 to 7.8. Chromatofocusing was employed to separate these bands. Electrophoresis of the starting materials under nonreducing conditions indicated all of the materials to migrate as Fab'. The electrophoresis of urine samples obtained from Balb/c and nude mice 8 hr after the i.v. injection of the various 125I bands revealed the low pI bands to migrate approximately as a 125I-Fab'. The higher pI band activity was located in lower molecular weight regions. Serum samples taken at 8 hr postinjection from the above mice revealed a series of what appeared to be high molecular weight complexes and some low molecular weight species. Biodistribution studies in comparison Balb/c mice and nude mice revealed that the low pI 125I-Fab' bands gave an organ and tumor uptake at 8 hr very similar to Fab', while the high pI 125I-Fab' bands were rapidly excreted into the urine and feces and did not concentrate in the tumor. The data suggest that the population of molecules making up the Fab' of this antibody is heterogeneous and variably stable. Theoretically, some of the entities observed could be counter productive to successful radioimmunoimaging. It is also possible that some of the labeled molecules are associating in vivo with endogenous proteins that might, in some Mabs, affect the biodistribution of the radiopharmaceutical.

A program was developed to extract from brain SPECT data global as well as regional concentrations of a radiopharmaceutical while allowing for improved subjective evaluation of its distribution. This program was used to process the data obtained from 17 normal subjects, 20 min, 2 hr, and 4 hr after the injection of iodine-labeled iodoamphetamines. The mean absolute cortical uptake at these three time periods was 0.921 (+/- 0.185), 0.803 (+/- 0.107), and 0.748 (+/- 0.103) in arbitrary units (+/- s.d.), respectively. The regional distribution of the tracer became more uniform with time due to an uneven washout rate. The cerebellum was noted to have a very high variability in its uptake and a high washout rate, making it unsuitable as an internal standard for relative quantification. Finally, a repeat study was performed on 10 subjects. No significant difference could be demonstrated in the mean uptake of the group at 2 and 4 hr, however the difference observed in the 20 min uptake values was significant at the p = 0.05 level.

We report the first case of 90Y-conjugated monoclonal antibody (MoAb) administration for human radioimmunotherapy. Ten mCi 90Y-labeled antiidiotype (anti-Id) MoAb were administered to a patient with B-cell lymphoma whose tumor successfully imaged with 111In-labeled anti-Id MoAb. No significant toxicities were observed. More than 2 g of unlabeled anti-Id MoAb were administered while clearing the circulating IgM idiotype prior to administration of the 90Y-MoAb. Transient partial regression of disease was observed. Serial fine needle aspirations of a malignant lymph node documented in vivo anti-Id penetration into a site that did not image by radioimmunoscintigraphy. The radiosensitivity of B-cell lymphoma, the tumor specificity of anti-Id, the antitumor activity of anti-Id alone, and the safe administration of 10 mCi 90Y-labeled anti-Id MoAb in this report suggest further investigation of this radioimmunoconjugate for therapy of B-cell lymphoma is warranted.

Comparisons were made of thyroid uptake of three commercially available preparations of 131I, using a double-blind design, in 125 patients with normal thyroid function. Uptakes with Squibb Iodotope Diagnostic capsules were significantly lower than those with Squibb Iodotope Oral liquid at 4 hr (p less than 0.01) and 24 hr (p less than 0.05) after ingestion in both the general population and in all patients less than 45 years of age. Uptakes of Radiocaps I-131 (Abbott Laboratories) and Iodotope Oral liquid were indistinguishable under identical conditions. Our findings indicate that interference with either absorption or metabolism of a pharmaceutical can result from the vehicle used to administer it.

Two patients who had decreased pulmonary artery blood flow to the right lung showed increased clarity of rib detail on a bone scan over the affected hemithorax as contrasted with the uninvolved side. Decreased blood background is postulated to result in enhancement of rib detail on the affected side.

Monoclonal antibodies (MoAbs) against carcinoembryonic antigen were successfully radiolabeled with 111In, and the radiopharmaceutical was characterized in vitro and in normal and tumor-bearing mice. The 111In-MoAb proved to be stable in vitro and in vivo under normal conditions, although instability could be induced in vitro with large quantities of iron-free transferrin. Animal distribution studies with 111In-MoAb demonstrated tumor localization superior to 67Ga and pharmacokinetics that were highly similar to those of endogenously labeled 75Se-MoAb. The 111In-MoAb followed first-order kinetics and fit a two-compartmental model when studied in nude mice bearing human colon tumors known to express carcinoembryonic antigen. Significant quantities of radiolabel appeared in tissues other than tumor, with liver and skin having the highest concentrations. Sufficient tumor/background ratios were formed for scanning purposes. The data indicate that 111In-MoAb may prove to be effective as a radiopharmaceutical for tumor imaging.

Manganese, a trace metal, is known to localize in mitochondria. Because mitochondria are abundant in heart muscle, the possible utility of radioactive manganese as a myocardial imaging agent was examined in 25 rats and six dogs. Myocardial uptake of Mn-54 in rats was found to exceed that of thallium-201; myocardium-to-blood ratios averaged 306:1 versus 48:1 for Tl-201. In the dog, uptake of Mn-54 by ischemic myocardium was reduced by 17-75% compared with normal myocardium. Thus, radioactive manganese appears promising as an intravenous myocardial imaging agent, and might be useful in studying the function of myocardial mitochondria by external imaging.

Carcinoembryonic antigen (CEA) is currently being used as a target antigen in the radioimmunodetection of cancer. Circulating CEA may adversely affect the outcome of such studies by formation of intravascular immune complexes. The following studies were undertaken to expand our knowledge of the production, secretion, and pharmacokinetics of CEA, since these factors should have a direct bearing on the serum levels of CEA encountered in radioimmunodetection. The production of CEA was assessed in nude mice given implants of the T-380 CEA secreting human colon tumor. Serum CEA rose linearly as the tumors enlarged; however, the concentration of CEA per g of extracted tumor remained constant throughout the weight range studied. The secretory rate of the T-380 tumor was determined by surgically removing all blood flow to the liver and gastrointestinal tract of the nude mouse model. This procedure removes the known sites of CEA degradation. Serum CEA levels rose progressively following surgery, the values being directly related to the tumor size. The secretory rate was also proportional to tumor size but was a constant 13.8 +/- 3.6 (S.D.) ng/g tumor/hr when expressed on a per g tumor basis. To determine if the serum levels of CEA observed in patients could be due to unique differences in the clearance rates of each patient's CEA, serum from three patients with CEA levels of 2150, 709, and 58 ng/ml was administered i.v. to groups of mice at the original and diluted concentrations. The kinetics of all samples followed a single exponential clearance pattern with a half-time of about 2.5 hr. This was dramatically different from the kinetics of tumor-extracted CEA which exhibited a multiexponential pattern, the first component having a half-time of 3 min. These data suggest that CEA secreted by a tumor is in some way different from that adhering to the tumor. If the secreted CEA truly has a monoexponential clearance with a fixed rate as the experiments suggest, the absolute values of serum CEA are either entirely a function of the tumor secretory rate, or else the product having the short half-time is not measured in serum samples obtained from patients.

Iodine-131-tetracycline (131I-TET) was prepared by allowing tetracycline hydrochloride to react with radioiodide in acidic methanol (labeling efficiency greater than 85%). This preparation was found to be stable at--4 degrees C for at least 72 hr. Some minimal in vivo breakdown did occur. The 131I-TET, 67Ga, and several 99mTc compounds were studied in a rat hepatoma model. The incorporation of the radiopharmaceuticals into the tumor occurred rapidly, with peak levels at 0.5 and 24 hr after injection for 131I-TET and 67Ga, respectively. The clearnace of the radiopharmaceutical from nonviable tumor was slower than for viable tumor, and by 72 hr after injection the greatest concentration of radioactivity appeared in the nonviable fraction. All normal tissues showed faster clearance than did tumor tissue, regardless of viability. Decreasing the quantity of 131I-TET injected increased the percent of uptake in the nonviable tumor tissue but had no effect on the viable tumor uptake. Of the 99mTc compounds studied, the phosphates developed the highest tumor-to-background ratios. Unfortunately these ratios were not as high as those achieved for 67Ga or 131I-TET.

Studies were performed to determine the effect of tumor size on the incorporation of radiolabeled monoclonal antitumor antibodies (MoAbs) into human tumors growing in nude mice. The colon tumors ranged in size from 0.03-1.6 g, the melanoma from 0.1 to 6.7 g, and the lymphoma from 0.06 to 10.2 g. Indium-111 was primarily used as the radiolabel, however, both 125I and 111In were used as tracers for the MoAb in one experiment. The per g radiopharmaceutical uptake by tumors was inversely proportional to tumor size when tumor specific MoAb was administered. This finding was independent of the radiolabel and was demonstrable when the mice bore two tumors of differing size. When the MoAb was not specific for the tumor, the data were less well defined and a statistically significant correlation with size did not occur. These data are strong evidence for a decrease in per g uptake of labeled tumor specific antibodies as tumors increase in size.

Studies were performed to determine the effect of the radiolabel and circulating carcinoembryonic antigen (CEA) on the pharmacodynamics of monoclonal anti-CEA antibodies (MoAbs). The studies were performed in normal BALB/c mice and in nude mice bearing human colon tumors. Three different tumors were used, each of which produced CEA levels characteristic of that particular tumor's secretory rate. The CEJ-326 MoAb labeled with either 111In or 125I was used in all studies. Circulating CEA induced the removal of 125I and 111In MoAbs from the vascular compartment. Liver concentrations of 111In increased and 125I levels decreased as the CEA secretory rate of the tumor rose. This indicates that circulating CEA complexes form in the vascular compartment which, in an animal model, are removed by the liver and spleen. This results in decreased tumor uptake of the labeled MoAb. The iodinated MoAb complexes are dehalogenated while the 111In is retained by the liver. This dehalogenation may account for the relatively low liver activity observed in radioimmunoimaging with intact radioiodinated anti-CEA MoAbs, provided the CEA complexes are similarly removed from the vascular compartment by the human liver.

The distribution and kinetics of six human and one murine monoclonal IgM antibodies (MoAb) were studied in BALB/c mice. Labeling was with 111In, 75Se, and 125I. The monomers and pentamers of certain MoAbs were studied. Human distribution studies were also performed. The serum containing [111In]MoAb was obtained from one of the patients 24 hr after administration and injected into mice which were then killed and assayed for 111In distribution. In general, the [75Se] and [111In]MoAbs had distribution and kinetic patterns that were similar while the 125I-labeled MoAbs dehalogenated after 4 hr. Monomers and pentamers had highly similar distributions suggesting that the distribution of IgMs may be based on factors other than molecular size. The murine IgM showed a somewhat different distribution in mice than did human IgMs. Serum from the patient containing [111In]MoAb had a distribution in mice similar to that of the patient with high liver and gastrointestinal uptake. The human imaging indicates that it is possible to target tumor with human IgM MoAbs, but significant problems remain in regard to their clinical use.

Because of the large number of different immunoconjugates which can be produced from monoclonal antibody-directed anti-cancer therapy, it would be useful to have in vivo tumor models to compare such preparations. Although historically human leukemias-lymphomas have been difficult to establish in athymic mice we have succeeded in establishing human T-cell tumors from primary MOLT-4 cultures in 290 of 353 animals and have successfully transferred tumors in 42 of 45 animals during ten serial passages. The potential utility of this model for testing immunoconjugates of murine monoclonal antibody T101 have been confirmed by: (a) in all 148 tumors sampled including all passaged tumors the human T-cell antigen, T65, was expressed in a manner identical to that of cultured cells; (b) 111In-T101 was concentrated preferentially in the tumor; and (c) T101 injected by both the i.p. and i.v. routes bound to tumor and induced antigenic modulation to the same extent as that observed previously in vitro and in human studies.

Loculation of instilled 99mTc-sulfur colloid solution in the peritoneal cavity was observed in a patient being considered for intracavitary therapy with 32P-chromic phosphate. Since intracavitary instillation of a therapeutic dose of a radiopharmaceutical agent into a loculated space would risk therapeutic failure and tissue necrosis, prior instillation of a tracer nuclide is recommended to insure adequate dispersion before beginning such therapy.

Characterization of several high-affinity murine monoclonal anticarcinoembryonic antigen (CEA) antibodies suggested good specificity except for cross-reactivity with an antigen on granulocytes and erythrocytes which was different from the previously described normal cross-reacting antigen of granulocytes. In vivo studies in athymic mice using an indium conjugate of an anti-CEA monoclonal antibody (MoAb) revealed excellent specific uptake in colorectal carcinoma xenografts. Studies were conducted in humans to determine the limitations produced by the cross-reactivity with granulocytes and erythrocytes. Patients with metastatic colorectal cancer received 3 to 6 mg of anti-CEA MoAb over 10 min or 2 hr. In five of six trials, the MoAb infusion was associated with a 40 to 90% decrease in circulating granulocytes and systemic toxicity including fever, rigors, and emesis. One patient had no change in cell count and had no toxicity. Radionuclide scans with 111In-anti-CEA MoAb showed marked uptake in the spleen when cells were eliminated, and in the liver, especially when pretreatment CEA levels were high. Metastatic tumor sites failed to concentrate the isotope. This study emphasizes the potential limitations for radioimmunodetection and/or radioimmunotherapy imposed by reactivity with circulating cells, and suggests that certain toxic reactions associated with MoAb infusions are related to destruction of circulating cells rather than allergic reactions to mouse protein. It also emphasizes how variables such as dose and binding affinity of antibody, radioisotope used, and assessment at different observation points can obscure lack of antibody specificity.