Multilevel Monte Carlo Methods for Stochastic Convection-Diffusion Eigenvalue Problems.

We develop new multilevel Monte Carlo (MLMC) methods to estimate the expectation of the smallest eigenvalue of a stochastic convection-diffusion operator with random coefficients. The MLMC method is based on a sequence of finite element (FE) discretizations of the eigenvalue problem on a hierarchy of increasingly finer meshes. For the discretized, algebraic eigenproblems we use both the Rayleigh quotient (RQ) iteration and implicitly restarted Arnoldi (IRA), providing an analysis of the cost in each case. By studying the variance on each level and adapting classical FE error bounds to the stochastic setting, we are able to bound the total error of our MLMC estimator and provide a complexity analysis. As expected, the complexity bound for our MLMC estimator is superior to plain Monte Carlo. To improve the efficiency of the MLMC further, we exploit the hierarchy of meshes and use coarser approximations as starting values for the eigensolvers on finer ones. To improve the stability of the MLMC method for convection-dominated problems, we employ two additional strategies. First, we consider the streamline upwind Petrov-Galerkin formulation of the discrete eigenvalue problem, which allows us to start the MLMC method on coarser meshes than is possible with standard FEs. Second, we apply a homotopy method to add stability to the eigensolver for each sample. Finally, we present a multilevel quasi-Monte Carlo method that replaces Monte Carlo with a quasi-Monte Carlo (QMC) rule on each level. Due to the faster convergence of QMC, this improves the overall complexity. We provide detailed numerical results comparing our different strategies to demonstrate the practical feasibility of the MLMC method in different use cases. The results support our complexity analysis and further demonstrate the superiority over plain Monte Carlo in all cases.

Development of a culturally targeted chatbot to inform living kidney donor candidates of African ancestry about APOL1 genetic testing: a mixed methods study.

Clinical chatbots are increasingly used to help integrate genetic testing into clinical contexts, but no chatbot exists for Apolipoprotein L1 (APOL1) genetic testing of living kidney donor (LKD) candidates of African ancestry. Our study aimed to culturally adapt and assess perceptions of the Gia® chatbot to help integrate APOL1 testing into LKD evaluation. Ten focus groups and post-focus group surveys were conducted with 54 LKDs, community members, and kidney transplant recipients of African ancestry. Data were analyzed through thematic analysis and descriptive statistics. Key themes about making Gia culturally targeted included ensuring: (1) transparency by providing Black LKDs' testimonials, explaining patient privacy and confidentiality protections, and explaining how genetic testing can help LKD evaluation; (2) content is informative by educating Black LKDs about APOL1 testing instead of aiming to convince them to undergo testing, presenting statistics, and describing how genetic discrimination is legally prevented; and (3) content avoids stigma about living donation in the Black community. Most agreed Gia was neutral and unbiased (82%), trustworthy (82%), and words, phrases, and expressions were familiar to the intended audience (85%). Our culturally adapted APOL1 Gia chatbot was well regarded. Future research should assess how this chatbot could supplement provider discussion prior to genetic testing to scale APOL1 counseling and testing for LKD candidate clinical evaluation.

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

Implementation of a culturally competent APOL1 genetic testing programme into living donor evaluation: A two-site, non-randomised, pre-post trial design.

INTRODUCTION: While living donor (LD) kidney transplantation is the optimal treatment for patients with kidney failure, LDs assume a higher risk of future kidney failure themselves. LDs of African ancestry have an even greater risk of kidney failure post-donation than White LDs. Because evidence suggests that Apolipoprotein L1 (APOL1) risk variants contribute to this greater risk, transplant nephrologists are increasingly using APOL1 genetic testing to evaluate LD candidates of African ancestry. However, nephrologists do not consistently perform genetic counselling with LD candidates about APOL1 due to a lack of knowledge and skill in counselling. Without proper counselling, APOL1 testing will magnify LD candidates' decisional conflict about donating, jeopardising their informed consent. Given cultural concerns about genetic testing among people of African ancestry, protecting LD candidates' safety is essential to improve informed decisions about donating. Clinical 'chatbots', mobile apps that provide genetic information to patients, can improve informed treatment decisions. No chatbot on APOL1 is available and no nephrologist training programmes are available to provide culturally competent counselling to LDs about APOL1. Given the shortage of genetic counsellors, increasing nephrologists' genetic literacy is critical to integrating genetic testing into practice. METHODS AND ANALYSIS: Using a non-randomised, pre-post trial design in two transplant centres (Chicago, IL, and Washington, DC), we will evaluate the effectiveness of culturally competent APOL1 testing, chatbot and counselling on LD candidates' decisional conflict about donating, preparedness for decision-making, willingness to donate and satisfaction with informed consent and longitudinally evaluate the implementation of this intervention into clinical practice using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. ETHICS AND DISSEMINATION: This study will create a model for APOL1 testing of LDs of African ancestry, which can be implemented nationally via implementation science approaches. APOL1 will serve as a model for integrating culturally competent genetic testing into transplant and other practices to improve informed consent. This study involves human participants and was approved by Northwestern University IRB (STU00214038). Participants gave informed consent to participate in the study before taking part. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04910867. Registered 8 May 2021, https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000AWZ6&selectaction=Edit&uid=U0001PPF&ts=7&cx=-8jv7m2 ClinicalTrials.gov Identifier: NCT04999436. Registered 5 November 2021, https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000AYWW&selectaction=Edit&uid=U0001PPF&ts=11&cx=9tny7v.

The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir.

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRß repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRß clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.

Addressing head injury risk in youth football: are heading guidelines the answer?

BACKGROUND: Recent findings of neurodegenerative pathology in former professional football players have once again called into question the role that "heading", a fundamental aspect of the game, plays in the onset of neurological disease. By introducing guidelines aimed at limiting heading among youth players, the United Kingdom recently joined the United States as the only two nations yet to implement heading regulation in response to growing concerns surrounding football's head injury burden. PURPOSE: Evaluating the efficacy of risk mitigation strategies requires the continual reviewal of available evidence, however, youth heading guidelines have yet to undergo such an empirical evaluation. This review aims to address this absence by first discussing the literature informing heading-related health risk, followed by an assessment of the decision to limit youth heading in response to this research. MAIN FINDINGS: The risk of injury due to heading remains highly uncertain, especially as it pertains to youth players for whom epidemiological data is severely lacking. However, consideration of policy making under conditions of scientific uncertainty, as well as intrinsic risk factors of acute head injury in children and adolescents, currently warrants a precautionary approach to youth heading regulation. CONCLUSIONS: Further research must be pursued to ensure that future risk management strategies remain grounded in evidence and enhance the safety of football for vulnerable individuals. While our understanding of the neurological outcomes of heading remains limited, the adoption of heading guidelines reflects an appropriate response to uncertain risk.

Rapidly progressive crescentic diabetic nephropathy: two case reports.

Crescents are not a well recognised feature of diabetic nephropathy. We present two cases of patients presenting with a rapid decline in renal function and subacute onset of nephrotic syndrome. Glomerulonephritis screening was negative, and renal biopsy revealed non-necrotising cellular crescents and typical features of late-stage diabetic nephropathy. We review the literature for diabetic nephropathy with crescents and explore possible underlying mechanisms.

Postoperative Myocardial Injury and Outcomes in Liver and Kidney Transplant Patients.

BACKGROUND/PURPOSE: Myocardial injury after noncardiac surgery (MINS) is associated with major adverse cardiac events (MACE), but its significance post-liver and post-kidney transplantation is not well-defined. METHODS/MATERIALS: We retrospectively studied consecutive patients undergoing single-organ liver or kidney transplantation at a large tertiary transplant center. Liver and kidney transplant patients with troponins drawn within 30 days of transplantation were included. The primary exposure was MINS, defined as troponin elevation above the 99th percentile of the upper reference limit within 30 days of transplantation. The primary outcome was MACE, defined as death, myocardial infarction, revascularization, stroke, or heart failure hospitalization. RESULTS: Overall, 112 patients were included: 58 (51.7%) were liver transplant recipients, and 54 (48.3%) were kidney transplant recipients. Patients with MINS were significantly older (mean age 59 vs. 54 years, p = 0.01) and more likely to have diabetes (35% vs. 17%, p = 0.03). Other baseline characteristics were similar. Sixteen patients (14.2%) developed MACE, including 11 (9.8%) with 1-year MACE. MINS patients were significantly more likely to develop 1-year MACE (adjusted hazard ratio, 10.4; 95% confidence interval, 1.8-198). Kaplan-Meier cumulative MACE was significantly higher in the MINS group (p = 0.03). CONCLUSIONS: Liver and kidney transplant recipients with MINS are significantly more likely to develop 1-year MACE compared to those without MINS. Future prospective studies are needed to further delineate the cardiac risk and outcomes in transplanted patients.

Evaluation of cytomegalovirus "Blips" in high-risk kidney/kidney-pancreas transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality after solid organ transplantation. While guidelines suggest using highly sensitive QNAT assays for CMV detection, there is no defined viral load to guide initiation of preemptive therapy. This study evaluates the progression to quantifiable CMV (DNAemia) following a CMV "blip" in high-risk (D+/R) kidney/kidney-pancreas (KP) transplant recipients. METHODS: This is a single center, retrospective study. A CMV "blip" was defined as the first positive QNAT assay below the level of quantification (<1.37 × 102 IU/ml or <200 viral copies). Subsequent CMV QNAT assays were followed to assess the progression from blip to CMV DNAemia for 1 year following transplant. RESULTS: A total of 134 patients were included in the study. Fifty-three (39.6%) patients had their first positive CMV QNAT value below the level of quantification, a "CMV blip." Of these 53 patients, 69.8% (n = 37) progressed to DNAemia while 30.2% (n = 16) did not. The median time from transplant to the first CMV blip was 68 (46-97) days and most patients with viral blips (71.1%) were on prophylaxis. No differences in patient characteristics were found among those who progressed from blip to DNAemia and those who only had a blip. CONCLUSIONS: In CMV high-risk kidney/KP transplant recipients, CMV blips progressed to CMV DNAemia in the majority of cases. This progression typically occurred 2-3 weeks following the initial blip. CMV blips are common early posttransplant despite prophylaxis and likely represent an early marker of CMV infection.

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.

Leucine and Sildenafil Combination Therapy Reduces Body Weight and Metformin Enhances the Effect at Low Dose: A Randomized Controlled Trial.

BACKGROUND: This study evaluated the potential of activating the fuel-sensing enzymes Adenine monophosphate (AMP)-activated protein kinase and the deacetylase sirtuin1, to promote weight loss. We tested the efficacy of a fixed dose combination of the amino acid leucine and 2 well-characterized agents with established safety profiles to modulate energy metabolism and facilitate weight loss. STUDY QUESTION: Will a combination of l-leucine with low-dose metformin and sildenafil produce a novel synergistic interaction that reduces body weight? STUDY DESIGN: We conducted a 24-week randomized controlled trial evaluating the effect on weight loss of leucine 1.1 g and sildenafil 1.0 mg or 4.0 mg, with and without metformin 500 mg (Leu/Sil 1.0, Leu/Sil 4.0, Leu/Met/Sil 1.0, and Leu/Met/Sil 4.0 twice/day). We enrolled 267 participants who were 18-65 years of age without diabetes and with the body mass index (BMI) of 30-45 kg/m2. MEASURES AND OUTCOMES: The primary endpoint was percentage weight change after 24 weeks. Adverse events were evaluated. The primary analysis was performed using the perprotocol population analysis of covariance estimation. Subgroup analyses of patients residing above certain threshold limits at baseline and in populations at increased risk of obesity were assessed post-hoc as exploratory end points. RESULTS: Placebo-adjusted mean bodyweight reductions in the Leu/Met/Sil 1.0, Leu/Met/Sil 4.0, and Leu/Sil 4.0 groups were -1.99%, -1.69%, and -1.67% (P = 0.015, 0.035, and 0.036, respectively). The most common adverse events were gastrointestinal-related and occurred in the metformin-treated groups consistent with metformin treatment. In African Americans, Leu/Met/Sil 1.0 produced 5.4% mean weight loss. In participants with BMI <40 kg/m2 treated with Leu/Met/Sil 1.0, the weight loss increased to 2.84%, particularly in participants with baseline insulin ≥12mU/L (3.5%). CONCLUSIONS: Leu/Met/Sil 1.0 and 4.0 and Leu/Sil 4.0 reduced body weight, but Leu/Met/Sil 1.0 was associated with robust weight loss in African Americans, and individuals with BMI 30-39.9 kg/m2, especially participants with hyperinsulinemia.

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

Risk factors for development of acute kidney injury in hospitalised adults in Zimbabwe.

BACKGROUND: Acute kidney injury (AKI) is predominantly a disease of low and middle-income countries. Despite this, there is a particular paucity of data regarding AKI in Africa. Most published studies were conducted prior to the most recent Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI. This prospective, observational, cohort study examines AKI amongst newly admitted acute medical inpatients in a large, urban, tertiary hospital in Harare, Zimbabwe. METHODS: All newly admitted, adult, medical patients in separate, randomly selected, 24-hour periods were included. Baseline demographic information, comorbidities, nephrotoxic medication use, and reason for admission were recorded on a standardised data capture record. A serum creatinine measurement was performed on all patients at the time of admission and again after 48 hours. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and AKI was defined using the most recent KDIGO definition as an increase in the serum creatinine of greater than 26.5µmol/L within 48 hours, with admission creatinine used as a baseline measurement. RESULTS: 253 patients were included in the analysis; 137 patients (54.2%) were female; 100 patients (39.5%) had HIV infection. 36 patients (14.2%) met the KDIGO criteria for AKI during the 48-hour follow-up period. AKI was more common among males (19.8% vs 9.5%; p = 0.019). The AKI group had a higher serum creatinine at presentation than those without AKI (296.5µmol/L vs 91.0µmol/L; p<0.001) and at 48 hours (447.7µmol/L vs 77.1µmol/L; p<0.001). In logistic regression, AKI was related negatively to female sex (OR 0.461, 95% CI 0.211, 1.003; p = 0.051) and positively predicted by the presence of comorbid hypertension (OR 3.292, 95% CI 1.52, 7.128; p = 0.003) and chronic kidney disease (OR 6.034, 95% 1.792, 20.313; p = 0.004). CONCLUSIONS: KDIGO-defined AKI was common in hospitalised patients in Sub-Saharan Africa and was predicted by male sex, a history of comorbid hypertension and a history of comorbid chronic kidney disease.

Can Distributed Nuclear Power Address Energy Resilience and Energy Poverty?

Alex Gilbert is a Project Manager at the Nuclear Innovation Alliance, where he oversees technical and regulatory work on commercializing advanced reactors. He is also a non-resident Fellow at the Payne Institute, where he conducts research on energy markets, climate policy, and outer space resources governance, and Adjunct Faculty at Johns Hopkins University. Alex has a Master of Energy Regulation and Law and Certificate in Climate Law from Vermont Law School and a BA in Environmental Studies and International Relations from Lake Forest College. Dr. Morgan Bazilian is the Director of the Payne Institute and a Professor of public policy at the Colorado School of Mines. Previously, he was lead energy specialist at the World Bank. He has over two decades of experience in the energy sector and is regarded as a leading expert in international affairs, policy, and investment. He is a Member of the Council on Foreign Relations. Dr. Bazilian has testified before the U.S. Senate and the Irish Oireachtas on issues of energy security.

Kidney transplantation across minor ABO incompatibility: the use of A2 to B transplants.

PURPOSE OF REVIEW: On 4 December 2014, the new kidney allocation system (KAS) went into effect. As part of this system, UNOS approved for the first time a national system with a specific mechanism affording priority to allocate kidneys across so-called 'minor ABO incompatibility' from blood group A2 donors into blood group B recipients. This significantly increased the number of such transplants done and the opportunities to learn about the specifics of such transplants. RECENT FINDINGS: A2 to B transplants have been demonstrated to be well tolerated, effective, and cost-effective ways of addressing disparities in the allocation system. Further data about the use of anti-A titers and the limits to successful transplant have better defined the bounds of who can benefit from such transplants. SUMMARY: The success thus far with A2 to B transplants should increase comfort and acceptance of the allocation policy changes and we should see further increases in centers willing to use such transplants to better address inequalities in the system.

Pre-Operative Cardiovascular Testing and Post-Renal Transplant Clinical Outcomes.

BACKGROUND: Cardiovascular disease, a major contributor to morbidity and mortality in chronic kidney disease and kidney transplant patients, is closely evaluated before kidney transplant. We aimed to characterize pre-transplant cardiac testing practices and post-transplant cardiac outcomes at a single academic center. METHODS: This was a retrospective, single-center analysis of consecutive adults receiving first renal transplant from 1/1/2016 to 6/31/2017. Data included demographics, medical history, and medications. Pre-transplant workup included echocardiograms, cardiac stress testing, coronary computed tomography, left heart catheterization (LHC), and any revascularization. Outcomes included all-cause mortality, cardiac mortality, myocardial infarction (MI), and myocardial injury. RESULTS: Our analysis included 235 patients with mean follow-up of 1.6 ±â€¯0.53 years. Of these, 219 (93%) patients had non-invasive functional testing before transplant, with 198 normal and 21 abnormal. The most common modalities were dobutamine stress echocardiogram (88) and pharmacological myocardial perfusion imaging (60). Twenty-four (10%) patients had an LHC, including 14 abnormal studies, and 10 who subsequently underwent successful revascularization. There were 3 deaths, 2 that were cardiac-specific. There were no ST-elevation MIs and 1 Type I non-ST-elevation MI (NSTEMI), occurring 2 days after transplant. Of those patients with a 30-day post-operative troponin, 30 (13%) patients had an elevation due to a type II NSTEMI or myocardial injury. CONCLUSIONS: Non-invasive functional testing is common prior to renal transplantation, with most being normal. Few patients are revascularized before transplantation. Perioperative death and acute coronary syndrome are rare, but troponin elevations due to type II NSTEMI and myocardial injury are common.

Fully automated analysis of OCT imaging of human kidneys for prediction of post-transplant function.

Current measures for assessing the viability of donor kidneys are lacking. Optical coherence tomography (OCT) can image subsurface tissue morphology to supplement current measures and potentially improve prediction of post-transplant function. OCT imaging was performed on donor kidneys before and immediately after implantation during 169 human kidney transplant surgeries. A system for automated image analysis was developed to measure structural parameters of the kidney's proximal convoluted tubules (PCTs) visualized in the OCT images. The association of these structural parameters with post-transplant function was investigated. This study included kidneys from live and deceased donors. 88 deceased donor kidneys in this study were stored by static cold storage (SCS) and an additional 15 were preserved by hypothermic machine perfusion (HMP). A subset of both SCS and HMP deceased donor kidneys were classified as expanded criteria donor (ECD) kidneys, with elevated risk of poor post-transplant function. Post-transplant function was characterized as either immediate graft function (IGF) or delayed graft function (DGF). In ECD kidneys stored by SCS, increased PCT lumen diameter was found to predict DGF both prior to implantation and following reperfusion. In SCD kidneys preserved by HMP, reduced distance between adjacent lumen following reperfusion was found to predict DGF. Results suggest that OCT measurements may be useful for predicting post-transplant function in ECD kidneys and kidneys stored by HMP. OCT analysis of donor kidneys may aid in allocation of kidneys to expand the donor pool as well as help predict post-transplant function in transplanted kidneys to inform post-operative care.

Lesson From the New York City Out-of-Hospital Uncontrolled Donation After Circulatory Determination of Death Program.

STUDY OBJECTIVE: In 2006, the Institute of Medicine emphasized substantial potential to expand organ donation opportunities through uncontrolled donation after circulatory determination of death (uDCDD). We pilot an out-of-hospital uDCDD kidney program for New York City in partnership with communities that it was intended to benefit. We evaluate protocol process and outcomes while identifying barriers to success and means for improvement. METHODS: We conducted a prospective, participatory action research study in Manhattan from December 2010 to May 2011. Daily from 4 to 12 pm, our organ preservation unit monitored emergency medical services (EMS) frequencies for cardiac arrests occurring in private locations. After EMS providers independently ordered termination of resuscitation, organ preservation unit staff determined clinical eligibility and donor status. Authorized parties, persons authorized to make organ donation decisions, were approached about in vivo preservation. The study population included organ preservation unit staff, authorized parties, passersby, and other New York City agency personnel. Organ preservation unit staff independently documented shift activities with daily operations notes and teleconference summaries that we analyzed with mixed qualitative and quantitative methods. RESULTS: The organ preservation unit entered 9 private locations; all the deceased lacked previous registration, although 4 met clinical screening eligibility. No kidneys were recovered. We collected 837 notes from 35 organ preservation unit staff. Despite frequently recounting protocol breaches, most responses from passersby including New York City agencies were favorable. No authorized parties were offended by preservation requests, yielding a Bayesian posterior median 98% (95% credible interval 76% to 100%). CONCLUSION: In summary, the New York City out-of-hospital uDCDD program was not feasible. There were frequent protocol breaches and confusion in determining clinical eligibility. In the small sample of authorized persons we encountered during the immediate grieving period, negative reactions were infrequent.