Does anybody really know what (the kidney median waiting) time is?

The median waiting time (MWT) to deceased donor kidney transplant is of interest to patients, clinicians, and the media but remains elusive due to both methodological and philosophical challenges. We used Organ Procurement and Transplantation Network data from January 2003 to March 2022 to estimate MWTs using various methods and timescales, applied overall, by era, and by candidate demographics. After rising for a decade, the overall MWT fell to 5.19 years between 2015 and 2018 and declined again to 4.05 years (April 2021 to March 2022), based on the Kaplan-Meier method applied to period-prevalent cohorts. MWTs differed markedly by blood type, donor service area, and pediatric vs adult status, but to a lesser degree by race/ethnicity. Choice of methodology affected the magnitude of these differences. Instead of waiting years for an answer, reliable kidney MWT estimates can be obtained shortly after a policy is implemented using the period-prevalent Kaplan-Meier approach, a theoretical but useful construct for which we found no evidence of bias compared with using incident cohorts. We recommend this method be used complementary to the competing risks approach, under which MWT is often inestimable, to fill the present information void concerning the seemingly simple question of how long it takes to get a kidney transplant in the United States.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

Dispersion of sneeze droplets in a meat facility indoor environment - Without partitions.

Spreading patterns of the coronavirus disease (COVID-19) showed that infected and asymptotic carriers both played critical role in escalating transmission of virus leading to global pandemic. Indoor environments of restaurants, classrooms, hospitals, offices, large assemblies, and industrial installations are susceptible to virus outbreak. Industrial facilities such as fabrication rooms of meat processing plants, which are laden with moisture and fat in indoor air are the most sensitive spaces. Fabrication room workers standing next to each other are exposed to the risk of long-range viral droplets transmission within the facility. An asymptomatic carrier may transmit the virus unintentionally to fellow workers through sporadic sneezing leading to community spread. A novel Computational Fluid Dynamics (CFD) model of a fabrication room with typical interior (stationary objects) was prepared and investigated. Study was conducted to identify indoor airflow patterns, droplets spreading patterns, leading droplets removal mechanism, locations causing maximum spread of droplets, and infection index for workers along with stationary objects in reference to seven sneeze locations covering the entire room. The role of condensers, exhaust fans and leakage of indoor air through large and small openings to other rooms was investigated. This comprehensive study presents flow scenarios in the facility and helps identify locations that are potentially at lower or higher risk for exposure to COVID-19. The results presented in this study are suitable for future engineering analyses aimed at redesigning public spaces and common areas to minimize the spread of aerosols and droplets that may contain pathogens.

Renal transplantation: the last iteration of the rest of the world.

PURPOSE OF REVIEW: Renal transplantation systems across the world aim to achieve an optimal balance between fair access to deceased donor kidney transplants (equity) and efficient use of organs (utility). Kidney allocation systems are measured across a host of metrics, and there is no single agreed upon definition of success, which looks different for each system depending on the desired balance between equity and utility. This article evaluates the United States renal transplantation system's efforts to balance equity and utility while drawing comparisons to other national systems. RECENT FINDINGS: The United States renal transplantation system is expected to undergo major changes with the transition to a continuous distribution framework. The continuous distribution framework removes geographic boundaries and takes a flexible and transparent approach to balancing equity and utility. The framework leverages transplant professionals and community members input with mathematical optimization strategies to inform weighting of patient factors to allocate deceased donor kidneys. SUMMARY: The United States' proposed continuous allocation framework lays the groundwork for a system allowing transparent balancing of equity and utility. This system approach addresses issues common to those in many other countries.

Kidney accelerated placement project: Outcomes and lessons learned.

Opportunities continue to be lost with a high rate of kidneys recovered for transplant but not utilized, particularly those considered less than ideal quality. The Organ Procurement and Transplantation Network (OPTN) Organ Center is tasked with allocating arguably the most difficult-to-place kidneys, and we hypothesized an accelerated placement pathway would increase utilization of kidneys placed by the Organ Center. The Kidney Accelerated Placement (KAP) project, implemented by the Organ Center from July 18, 2019 to July 15, 2020, aimed to offer kidneys with a high kidney donor profile index to programs that had a history of accepting such organs. We compared OPTN kidney match run, donor, and transplant recipient data during the project period and 1 year prior. There was no statistically significant change in the percentage of KAP-eligible donors accepted during the project period (16.4%) compared to the prior year (17.5%). Conversion from acceptance to transplant was higher under KAP (72.7% vs. 71.2%), though not significant. Waiting to accelerate placement after kidneys have been declined by multiple transplant programs locally and regionally is an intervention that may come too late to effectively increase utilization. Transplant rates of nationally shared and marginal kidneys remain a challenge, and future iterations of this project should be investigated.

The impact of machine perfusion of the heart on warm ischemia time and organ yield in donation after circulatory death.

Successful normothermic machine perfusion of heart allografts (MPH) has led to rapid growth in transplantation of donation after circulatory death (DCD) heart allografts but has introduced complexity in the procurement process. This study examines the impact of MPH use in DCD procurements on warm ischemia time (WIT) and organ yield. DCD procurements from 2019 to 2020 were identified using the OPTN database. Procurements with and without the use of MPH were compared using propensity score matching. Observed to expected (O:E) yield ratios were calculated, where the expected values were obtained using the models developed by the Scientific Registry of Transplant Recipients. In total, 1237 DCD procurements met inclusion criteria (MPH: 109 and control: 1128). After PSM, no difference was found between groups in median total WIT (24.0 min vs. 24.0 min, p = .89), but the MPH group demonstrated shorter median operative WIT (circulatory arrest to cross-clamp; 8.7 min vs. 10.9 min, p = .003). The overall organ yield of DCD heart donors was observed to be 33% higher than expected (O:E 1.33; 95% CI: 1.22-1.45). Observed yield of non-heart organs was not significantly different from expected for liver, kidney, lung, and pancreas grafts. MPH use in DCD procurements does not lead to delays in WIT and does not negatively affect organ yield of other concurrently procured organs.

SARS-CoV-2 Infections among Recent Organ Recipients, March-May 2020, United States.

We conducted public health investigations of 8 organ transplant recipients who tested positive for severe acute respiratory syndrome coronavirus 2 infection. Findings suggest the most likely source of transmission was community or healthcare exposure, not the organ donor. Transplant centers should educate transplant candidates and recipients about infection prevention recommendations.

Navigating the COVID-19 pandemic: Initial impacts and responses of the Organ Procurement and Transplantation Network in the United States.

COVID-19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (-90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (-45%), and other organs saw similar decreases: lung (-70%), heart (-43%), and liver (-37%). Deceased donors recovered dropped from 260 to 163 (-45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (-67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID-19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.

Maximizing donors' gifts: A comparison of actual and expected solid organ yield among VCA donors.

Vascularized Composite Allograft (VCA) transplantation provides life-changing transplants, but VCA adds complexity to the donation process and timing, possibly impeding solid organ donation. Expanding upon descriptive analyses, this study examines risk-adjusted predictions versus the observed number of organs donated by VCA donors. Our cohort included VCA donors in the United States during January 1, 2008-December 31, 2017 (n = 51), using OPTN Deceased Donor Registration Form data and the Scientific Registry of Transplant Recipients (SRTR) donor yield models to calculate observed-to-expected (O:E) yield ratios. Almost all VCA donors' livers (48/51; 94.1%) and kidneys (92/102; 90.2%) were transplanted, with fewer hearts (28/51; 54.9%), lungs (46/102; 45.1%), pancreata (15/51; 29.4%), and intestines (3/51; 5.9%) transplanted. O:E ratios for overall organ yield were slightly greater than expected for VCA donors (1.10; 95% CI: 1.02-1.17). Liver (1.17: 1.08-1.27) and lung yields (1.38: 1.07-1.68) were both greater than expected, while kidney, heart, and pancreas yields were similar to expected. Across VCA types, bilateral upper limb and abdominal wall donors had better-than-expected yields while uterus, face, and unilateral upper limb donors all had similar-to-expected yields. Solid organ yield among VCA donors was as good or better than predicted, suggesting that VCA donation does not compromise recovery and transplantation of lifesaving organs.

Understanding Dermatologic Concerns Among Persons Experiencing Homelessness: A Scoping Review and Discussion for Improved Delivery of Care.

There is a paucity of information surrounding dermatologic care for persons experiencing homelessness (PEH). This scoping review aims to map existing literature and provide a summary of the most common cutaneous manifestations among PEH, risk factors for dermatologic disease, describe any reported interventions, as well as identify research gaps for future studies. Search strategies developed for MEDLINE and hand searching yielded 486 articles. Out of the 486 articles screened, 93 articles met the inclusion criteria. The majority were cohort studies, cross-sectional studies, and case-control studies concentrated in North America and Europe. Excluding the pediatric population, the prevalence of dermatologic conditions ranged from 16.6% to 53.5%. Common skin conditions described in PEH were: acne, psoriasis, seborrheic dermatitis, atopic dermatitis, and lichen simplex chronicus. There were no studies comparing the extent or severity of these cutaneous diseases in PEH and the general population. PEH have a higher prevalence of skin infections and non-melanoma skin cancers. This scoping review has direct implications on public health interventions for PEH and highlights the need for evidence-based interventions to provide optimum and safe dermatologic healthcare for PEH. We propose several recommendations for improved care delivery, including addressing upstream factors and comorbidities impacting skin health, providing trauma informed care, reducing barriers to care, preventing and managing skin conditions, as well as including PEH in the planning and implementation of any proposed intervention.

Can donor narratives yield insights? A natural language processing proof of concept to facilitate kidney allocation.

Although expedited placement could ameliorate stagnant kidney utilization, precisely identifying difficult-to-place organs is crucial to mitigate potential harms associated with this policy. Existing algorithms have only leveraged structured data from the Organ Procurement and Transplantation Network (OPTN); however, detailed, free text case information about a donor exists. No known research exists about the utility of these data. We developed a model to predict the probability of delay or discard for adult deceased kidney donors between 2010 and 2018, leveraging donor free text data. The resultant model had a c-statistic of 0.75 compared to 0.80 ( Reduced Probability of Delay or Discard [model], r-PODD) and 0.77 ( Kidney Donor Profile Index, KDPI) on the test dataset. Analysis of the top predictive words suggest both known and potentially novel clinical factors (ie, a known factor such as hypertension vs a novel factor such as stents), and nuanced social factors (intravenous drug use) could negatively affect kidney utilization. These findings suggest that donor narratives have utility; the natural language processing (NLP) model is only moderately correlated with existing indices and provides directional evidence about additional cardiovascular risk factors that may affect kidney utilization. More research is needed to understand the potential to enhance existing indices of kidney utilization to better enable and mitigate the effects of policy interventions such as expedited placement.

An international comparison of deceased donor kidney utilization: What can the United States and the United Kingdom learn from each other?

In transplant, meaningful international comparisons in organ utilization are needed. This collaborative study between the United Kingdom (UK) and the United States (US) aimed to develop a kidney utilization metric allowing for legitimate intercountry comparisons. Data from the UK and US transplant registries, including all deceased donor kidneys recovered from 2006 to 2017, were analyzed. To identify a potentially comparable kidney utilization rate (UR), several denominators were assessed. We discovered that the proportion of transplanted kidneys from elderly donors in the UK (10.7%) was 18 times greater than that in the US (0.6%). Conversely, en bloc pediatric kidney transplant was more common in the US. Donation after circulatory death utilization has risen in both countries but is twice as prevalent in the UK (39% of transplants) vs the US (20%). In addition, US and UK URs are not directly comparable due to fundamental system differences. However, using a suite of URs revealed practice areas likely to yield the most benefit if improved, such as efforts to increase kidney offer acceptance in the US and to reduce postacceptance discard in the UK. Methods used in this study, including novel intracountry risk-adjusted UR trend logistic regression analyses, can be translated to other international transplant registries in pursuit of further global learning opportunities.

The Collaborative Innovation and Improvement Network (COIIN): Effect on donor yield, waitlist mortality, transplant rates, and offer acceptance.

The Organ Procurement and Transplantation Network implemented the Collaborative Improvement and Innovation Network (COIIN) to improve the use of donors with kidney donor profile index >50%. COIIN recruited 2 separate cohorts of kidney transplant programs. Cohort A included 19 programs of 44 applicants (January 1, 2017, to September 30, 2017), and cohort B included 39 programs of 47 applicants (October 1, 2017, to June 30, 2018). We investigated the effect of COIIN on kidney yield (number of kidneys transplanted from donors from whom any organ was recovered), offer acceptance, deceased donor transplant rates, and waitlist mortality rates for January 1, 2016, to March 31, 2019. COIIN did not notably affect kidney yield or waitlist mortality rates. Cohort A, but not cohort B, had significantly higher deceased donor transplant and offer acceptance rates during its intervention period than programs not in COIIN (adjusted transplant rate ratio: cohort A, 1.08 1.171.27 , cohort B, 0.94 1.011.08 ; adjusted offer acceptance ratio: cohort A, 1.08 1.181.29 , cohort B, 0.93 1.001.08 ). Thus, COIIN improved the use of kidneys at programs in cohort A but not at those in cohort B. Further research is necessary to understand the different effects for cohorts A and B, and further monitoring of posttransplant outcomes is required.

National landscape of HIV+ to HIV+ kidney and liver transplantation in the United States.

The HIV Organ Policy Equity (HOPE) Act, enacted on November 21, 2013, enables research on the transplantation of organs from donors infected with human immunodeficiency virus (HIV) (HIV+) into HIV+ individuals who, prior to transplantation, are infected with HIV. In 2015, the Organ Procurement and Transplantation Network revised organ allocation policies on November 21, and on November 23, the Secretary of Health and Human Services published research criteria and revised the Final Rule accordingly. The HOPE Act appears to be underutilized to date. As of December 31, 2018, there were 56 donors recovered (50 donors transplanted) resulting in 102 organs transplanted (31 liver, 71 kidney). As of December 31, 2018, 212 registrations were indicated on the waiting list as willing to accept an HIV+ kidney or liver, most of which were waiting in active status. Due to the limited number of transplants performed to date, definitive safety conclusions cannot be reached at this time, though current data suggest that 1-year patient and graft survival does not deviate in a major way from that observed in HIV+ recipients of non-HIV+ organs or non-HIV+ recipients. As safety data are reviewed and disseminated, it is anticipated that HOPE participation will increase should safety signals remain low.

Vascularized composite allotransplantation in the United States: A descriptive analysis of the Organ Procurement and Transplantation Network Data.

On July 3, 2014, the Organ Procurement and Transplantation Network/United Network for Organ Sharing was charged with the oversight of vascularized composite allograft (VCA) procurement and transplantation in the United States. As of December 31, 2017, 61 VCA programs at 27 centers were approved in the United States. Fifty candidates have been added to the waiting list at 15 centers. Twenty-eight VCA transplants have been performed at 14 programs (10 upper limb, 10 uterus, 5 craniofacial, 1 scalp, 1 abdominal wall, and 1 penile). Twenty-two VCAs were procured from 21 deceased donors, resulting in 109 non-VCA organs transplanted (15 hearts, 3 intestine, 40 kidney, 20 livers, 24 lungs, and 7 pancreata). Six uterus transplants were performed from living donors. Fourteen candidates were still waiting at 9 centers on December 31, 2017. Two of the 10 uterus recipients had live births and 3 still had viable grafts. Seventeen of 18 nonuterus recipients had functioning grafts. At present, VCA is an emerging field with a small number of patients transplanted. Data on posttransplant survival and functional outcomes continue to be collected to further the understanding of this complex and evolving field. Further systematic data are important for policy refinement and assurance of patient safety.

Risk of ESRD in prior living kidney donors.

We studied End-Stage Renal Disease (ESRD) in living kidney donors (LKDs) who donated in the United States between 1994 and 2016 (n = 123 526), using Organ Procurement and Transplantation Network and Centers for Medicare and Medicaid Services data. Two hundred eighteen LKDs developed ESRD, with a median of 11.1 years between donation and ESRD. Absolute 20-year risk was low but not uniform, with risk associated with race, age, and sex and increasing exponentially over time. LKDs had increased risk of ESRD if they were male (adjusted hazard ratio [aHR]: 1.75, 95% confidence interval [95%CI]: 1.33-2.31), had higher BMI (aHR: 1.34 per 5 kg/m2 , 95%CI: 1.10-1.64) or lower estimated GFR (aHR: 0.89 per 10 mL/min, 95% CI: 0.80-0.99), were first-degree relatives of the recipient (parent: [aHR: 2.01, 95% CI: 1.26-3.21]; full sibling [aHR: 1.87, 95%CI: 1.23-2.84]; identical twin [aHR: 19.79, 95%CI: 7.65-51.24]), or lived in lower socioeconomic status neighborhoods at donation (aHR: 0.87 per $10k increase; 95%CI: 0.77-0.99). We found a significant interaction between donation age and race, with higher risk at older ages for white LKDs (aHR: 1.26 per decade, 95%CI: 1.04-1.54), but higher risk at younger ages for black LKDs (aHR: 0.75 per decade, 95%CI: 0.57-0.99). These findings further inform risk assessment of potential LKDs.

A randomized, placebo-controlled phase I trial of live, attenuated herpes zoster vaccine in subjects with end-stage renal disease immunized prior to renal transplantation.

BACKGROUND: Solid organ transplant recipients are at increased risk for reactivation of herpes zoster, or shingles, and have a higher frequency of serious complications including post-herpetic neuralgia. A live, attenuated shingles vaccine is effective and approved for individuals 50 years and older. The vaccine is contraindicated following transplantation, but may be used in patients with renal failure. Utilization of the vaccine has been poor in patients with end-stage renal disease, including those awaiting transplant, owing to concerns for safety, efficacy, and potential sensitization prior to transplant. METHODS: We conducted a phase I, randomized, placebo-controlled study of the safety and immunogenicity of live, attenuated Oka strain shingles vaccine in subjects prior to or awaiting renal transplant at 3 US centers. Subjects received vaccine a minimum of 4 weeks prior to transplant. RESULTS: The vaccine was safe and well-tolerated. There were no cases of herpes zoster or rash illness. There was no change in donor-specific antibody or calculated panel reactive antibody after vaccination during the follow-up period. There were no rejection episodes. There was a significant 2.1-fold rise in geometric mean titer of anti-VZV antibody at 5 weeks post-vaccine. CONCLUSIONS: The data suggest that the shingles vaccine is safe in subjects with ESRD awaiting transplant. Antibody responses were similar to those seen previously in adults >50 years of age and are consistent with a protective response.

Social, economic, and policy implications of organ preservation advances.

PURPOSE OF REVIEW: Despite over 60 years of progress in the field of since the first organ transplant, insufficient organ preservation capabilities still place profound constraints on transplantation. These constraints play multiple and compounding roles in the predominant limitations of the field: the severe shortages of transplant organs, short-term and long-term posttransplant outcomes and complications, the unmet global need for development of transplant infrastructures, and economic burdens that limit patient access to transplantation and contribute to increasing global healthcare costs. This review surveys ways that advancing preservation technologies can play a role in each of these areas, ultimately benefiting thousands if not millions of patients worldwide. RECENT FINDINGS: Preservation advances can create a wide range of benefits across many facets of organ transplantation, as well as related areas of transplant research. As these technologies mature, so will the policies around their use to maximize the benefits offered by organ preservation. SUMMARY: Organ preservation advances stand to increase local and global access to transplantation, improve transplant outcomes, and accelerate progress in related areas such as immune tolerance induction and xenotransplantation. This area holds the potential to save the healthcare system many billions of dollars and reduce costs across many aspects of transplantation. Novel preservation technologies, along with other technologies facilitated by preservation advances, could potentially save millions of lives in the coming years.