Deceased Donors With HIV in the Era of the HOPE Act: Referrals and Procurement.

Background: The HIV Organ Policy Equity Act legalizes organ procurement from donors with HIV (HIV D+). A prior survey of Organ Procurement Organizations (OPOs) estimated >2000 HIV D+ referrals/year; however, only 30-35 HIV D+/year have had organs procured. Given this gap, we sought to understand HIV D+ referrals and procurements in practice. Methods: We prospectively collected data on all OPO-reported HIV D+ referrals, including reasons for nonprocurement. We evaluated trends and compared HIV D+ characteristics by procurement status using regression, chi-squared tests, and Wilcoxon rank-sum tests. Results: From December 23, 2015 to May 31, 2021, there were 710 HIV D+ referrals from 49 OPOs, of which 171 (24%) had organs procured. HIV D+ referrals increased from 7 to 15 per month (P < 0.001), and the procurement rate increased from 10% to 39% (P < 0.001). Compared with HIV D+ without procurement, HIV D+ with procurement were younger (median age 36 versus 50 y), more commonly White (46% versus 36%), and more often had trauma-related deaths (29% versus 8%) (all P < 0.001). Nonprocurement was attributed to medical reasons in 63% of cases, of which 36% were AIDS-defining infections and 64% were HIV-unrelated, commonly due to organ failure (36%), high neurologic function (31%), and cancer (14%). Nonprocurement was attributed to nonmedical reasons in 26% of cases, commonly due to no authorization (42%), no waitlist candidates (21%), or no transplant center interest (20%). Conclusions: In the early years of the HIV Organ Policy Equity Act, actual HIV D+ referrals were much lower than prior estimates; however, the numbers and procurement rates increased over time. Nonprocurement was attributed to both medical and nonmedical issues, and addressing these issues could increase organ availability.

Donor Electrocardiogram Associations With Cardiac Dysfunction, Heart Transplant Use, and Survival: The Donor Heart Study.

BACKGROUND: Potential organ donors often exhibit abnormalities on electrocardiograms (ECGs) after brain death, but the physiological and prognostic significance of such abnormalities is unknown. OBJECTIVES: This study sought to characterize the prevalence of ECG abnormalities in a nationwide cohort of potential cardiac donors and their associations with cardiac dysfunction, use for heart transplantation (HT), and recipient outcomes. METHODS: The Donor Heart Study enrolled 4,333 potential cardiac organ donors at 8 organ procurement organizations across the United States from 2015 to 2020. A blinded expert reviewer interpreted all ECGs, which were obtained once hemodynamic stability was achieved after brain death and were repeated 24 ± 6 hours later. ECG findings were summarized, and their associations with other cardiac diagnostic findings, use for HT, and graft survival were assessed using univariable and multivariable regression. RESULTS: Initial ECGs were interpretable for 4,136 potential donors. Overall, 64% of ECGs were deemed clinically abnormal, most commonly as a result of a nonspecific St-T-wave abnormality (39%), T-wave inversion (19%), and/or QTc interval >500 ms (17%). Conduction abnormalities, ectopy, pathologic Q waves, and ST-segment elevations were less common (each present in ≤5% of donors) and resolved on repeat ECGs in most cases. Only pathological Q waves were significant predictors of donor heart nonuse (adjusted OR: 0.39; 95% CI: 0.29-0.53), and none were associated with graft survival at 1 year post-HT. CONCLUSIONS: ECG abnormalities are common in potential heart donors but often resolve on serial testing. Pathologic Q waves are associated with a lower likelihood of use for HT, but they do not portend worse graft survival.

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.

Outcomes of a High-Volume Organ Procurement Organization in the Era of Increasing Donation After Circulatory Death.

Introduction: Donation after circulatory death (DCD) is rapidly increasing in the United States. Detailed data outlining the process from referral to organ transplantation is lacking. Project Aims: We sought to quantify differences at each stage along the referral to donation pathway by donor type. Additionally, we examined factors associated with successful DCD organ utilization. Design: This program evaluation analyzed data from a single organ procurement organization in 2018 to assess demographic and clinical predictors of progression through the donation process, including the role of first-person authorization in DCD. Descriptive statistics were examined by donation stage for demographic characteristics using chi-square; univariate and multivariate logistic regression was used to model predictors of utilization and authorization by organ type, respectively. Results: There were 2466 organ donation referrals during 2018, including 575 donations after brainstem death (DBD), 1890 controlled DCD referrals, and 1 uncontrolled DCD referral. Univariate and multivariate logistic regression models highlighted differences in authorization rates by donor type (DCD vs DBD) and by age, race, and ethnicity. Next-of-kin authorization was declined in 23% of first-person authorized potential DCD, highlighting issues related to the role of donor registration in DCD. Pre-mortem heparin administration was predictive of DCD organ utilization; donor age and warm ischemia time of less than 30 min was statistically significantly associated with DCD extra-renal organ utilization. Conclusion: These results provided insight into strategies for increasing authorization and transplantation of organs from DCD donors and identified areas of improvement for process standardization and policy development.

Challenges encountered in conducting donor-based research: Lessons learned from the Donor Heart Study.

Solid organ transplantation continues to be constrained by a lack of suitable donor organs. Advances in donor management and evaluation are needed to address this shortage, but the performance of research studies in deceased donors is fraught with challenges. Here we discuss several of the major obstacles we faced in the conduct of the Donor Heart Study-a prospective, multi-site, observational study of donor management, evaluation, and acceptance for heart transplantation. These included recruitment and engagement of participating organ procurement organizations, ambiguities related to study oversight, obtaining authorization for donor research, logistical challenges encountered during donor management, sustaining study momentum, and challenges related to study data management. By highlighting these obstacles encountered, as well as the solutions implemented, we hope to stimulate further discussion and actions that will facilitate the design and execution of future donor research studies.

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.

SARS-CoV-2 Antibody Serology Testing in a 3-Month-Old Organ Donor: A Case Report and Review of Available Literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a highly prevalent infectious disease. Currently, organs are not being transplanted from donors who are SARS-CoV-2 positive. It remains unclear as to how to differentiate active from recovered patients. We report our recent experience of a 3-month-old deceased organ donor who died as the result of an anoxic brain injury after a cardiopulmonary arrest (presumed sudden infant death syndrome). The child was born to a mother presumed to have coronavirus disease 2019. The donor tested negative for SARS-CoV-2 reverse transcriptase-polymerase chain reaction and positive for SARS-CoV-2 immunoglobulin A antibodies. We suspect this is the first known report of its kind and noteworthy for the organ donation and transplantation community.

Donor derived hepatitis B virus infection: Analysis of the Organ Procurement & Transplantation Network/United Network for Organ Sharing Ad Hoc Disease Transmission Advisory Committee.

Hepatitis B virus (HBV) can be transmitted from organ donor to recipient, but details of transmission events are not widely published. The Disease Transmission Advisory Committee (DTAC) evaluated 105 cases of potential donor derived transmission events of HBV between 2009-2017. Proven, probable or possible transmission of HBV occurred in 25 (23.8%) cases. Recipients of liver grafts were most commonly infected (20 of 21 exposed recipients) compared to 9 of 21 exposed non-hepatic recipients. Eleven of 25 donors were HBV core antibody (HBcAb) positive/HBV surface antigen (HBsAg) negative and infected 8/20 recipients. Of the 10 liver recipients and 1 liver-kidney recipient who received organs from these donors: six were not given antiviral prophylaxis, two developed infection after antiviral prophylaxis was discontinued, two developed HBV while on lamivudine prophylaxis, one was on antiviral prophylaxis and did not develop HBV viremia or antigenemia. One recipient of a HBcAb positive/HBsAg negative kidney developed active HBV infection. Unexpected donor-derived transmission of HBV was a rare event in reports to DTAC, but was often detected in the recipient late post-transplant. Six of 11 recipients (54.5%) of a liver from a HBcAb positive donor did not receive prophylaxis; all of these were potentially preventable with the use of anti-viral prophylaxis.

Renal cell carcinoma suspected at time of organ donation 2008-2016: A report of the OPTN ad hoc Disease Transmission Advisory Committee Registry.

All 179 reports to the OPTN of potential renal cell carcinoma (RCC) transmission from 1/1/2008 through 12/31/2016 were reviewed. Cases were divided into those with donor tumor known or suspected at time of transplant (N = 147 donors), and those in which tumor was initially found after transplant (N = 32). We sought to understand the risk of transplanting either the affected kidney, the contralateral kidney or non-renal organs from donors with a suspected/confirmed unilateral RCC. In the case of RCC found prior to transplant, transplantation of 21 kidneys following excision of tumor, 47 contralateral kidneys and 198 non-renal organs was performed. No cases of RCC transmission were documented in this population. An additional six cases of live donor kidney transplantation involving resection of RCC were reported, also without transmission. Six of 9 other recipients in whom the diagnosis of RCC became available after implantation underwent allograft nephrectomy and 3 received tumor resection. No recurrent RCC was documented. Given the low rate of transmission and available treatment options, consideration should be given to judicious use of organs from donors with small solitary RCC.

Decellularization of Whole Human Heart Inside a Pressurized Pouch in an Inverted Orientation.

The ultimate solution for patients with end-stage heart failure is organ transplant. But donor hearts are limited, immunosuppression is required, and ultimately rejection can occur. Creating a functional, autologous bio-artificial heart could solve these challenges. Biofabrication of a heart comprised of scaffold and cells is one option. A natural scaffold with tissue-specific composition as well as micro- and macro-architecture can be obtained by decellularizing hearts from humans or large animals such as pigs. Decellularization involves washing out cellular debris while preserving 3D extracellular matrix and vasculature and allowing "cellularization" at a later timepoint. Capitalizing on our novel finding that perfusion decellularization of complex organs is possible, we developed a more "physiological" method to decellularize non-transplantable human hearts by placing them inside a pressurized pouch, in an inverted orientation, under controlled pressure. The purpose of using a pressurized pouch is to create pressure gradients across the aortic valve to keep it closed and improve myocardial perfusion. Simultaneous assessment of flow dynamics and cellular debris removal during decellularization allowed us to monitor both fluid inflow and debris outflow, thereby generating a scaffold that can be used either for simple cardiac repair (e.g. as a patch or valve scaffold) or as a whole-organ scaffold.

Proximal Roux-en-y Gastrojejunal Anastomosis with Pyloric Ring Resection Improves Gastric Emptying After Pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication of pancreaticoduodenectomy. We determined the efficiency of a new reconstruction technique, designed to preserve motilin-secreting cells and maximize the utility of their receptors, in reducing the incidence of DGE after pancreaticoduodenectomy. METHODS: From April 2005 to September 2014, 217 consecutive patients underwent pancreaticoduodenectomy at our institution. Nine patients who underwent total pancreatectomy were excluded. We compared outcomes between patients who underwent pancreaticoduodenectomy with resection of the pyloric ring followed by proximal Roux-en-y gastrojejunal anastomosis (group I, n = 90) and patients who underwent standard pancreaticoduodenectomy with the orthotopic reconstruction technique (group II, n = 118). RESULTS: Overall and clinically relevant rates of DGE were significantly lower in group I than in group II (10 and 2.2 % vs. 57 and 24 %, respectively; p < 0.05). Length of hospital stay as a result of DGE was shorter in group I than in group II. In univariate analysis, older age, comorbidities, ASA grade 4, operative time, preoperative diabetes, standard reconstruction technique, and postoperative complications were significant risk factors for DGE. In multivariate analysis, older age, standard technique, and postoperative complications were independent risk factors for DGE. CONCLUSION: Our new reconstruction technique reduces the occurrence of DGE after pancreaticoduodenectomy.

Topically applied 2-octyl cyanoacrylate (Dermabond) for prevention of postoperative pancreatic fistula after pancreaticoduodenectomy.

OBJECTIVE: We examined whether 2-octyl cyanoacrylate (Dermabond) topically applied to the pancreaticojejunostomy (PJ) anastomotic site after pancreaticoduodenectomy (PD) reduces the rate of postoperative pancreatic fistula (POPF). METHODS: Patients who underwent PD with duct-to-mucosa PJ were evaluated (n = 124). Outcome was compared between patients who received Dermabond (n = 75) after PD and historic patients who did not (n = 49). Risk factors for POPF were identified. RESULTS: Overall and clinically relevant rates of POPF were significantly lower in patients who received Dermabond than in patients who did not (2.6 % and 1.3 % vs. 22 % and 12 %, respectively; p = 0.001). In univariate analysis, pancreatic duct diameter ≤3 mm, low serum albumin level, and no Dermabond were independent risk factors for POPF; in multivariate analysis, no Dermabond was an independent risk factor for POPF. In patients with pancreatic duct diameter ≤3 mm, the rate of POPF was significantly lower in patients who received Dermabond than in patients who did not (3.5 % versus 36 %, respectively; p = 0.0001). Patients who received Dermabond had significantly shorter hospital stays and lower re-operation and re-admission rates. CONCLUSIONS: Topical application of Dermabond to the PJ anastomotic site after PD significantly reduced the rate of POPF, particularly in patients at risk.

Use of decellularized porcine liver for engineering humanized liver organ.

BACKGROUND: New bioartificial liver devices are needed to supplement the limited supply of organ donors available for patients with end-stage liver disease. Here, we report the results of a pilot study aimed at developing a humanized porcine liver by transplanting second trimester human fetal hepatocytes (Hfh) co-cultured with fetal stellate cells (Hfsc) into the decellularized matrix of a porcine liver. MATERIAL AND METHODS: Ischemic livers were removed from 19 Yorkshire swine. Liver decellularization was achieved by an anionic detergent (SDS). The decellularized matrix of three separate porcine liver matrices was seeded with 3.5 × 10(8) and 1 × 10(9) of Hfsc and Hfh, respectively, and perfused for 3, 7, and 13 d. The metabolic and synthetic activities of the engrafted cells were assessed during and after perfusion. RESULTS: Immunohistologic examination of the decellularized matrix showed removal of nuclear materials with intact architecture and preserved extracellular matrix (ECM) proteins. During perfusion of the recellularized matrices, measurement of metabolic parameters (i.e., oxygen concentration, glucose consumption, and lactate and urea production) indicated active metabolism. The average human albumin concentration was 29.48 ± 7.4 µg/mL. Immunohistochemical analysis revealed cell differentiation into mature hepatocytes. Moreover, 40% of the engrafted cells were actively proliferating, and less than 30% of cells were apoptotic. CONCLUSION: We showed that our decellularization protocol successfully removed the cellular components of porcine livers while preserving the native architecture and most ECM protein. We also demonstrated the ability of the decellularized matrix to support and induce phenotypic maturation of engrafted Hfh in a continuously perfused system.

Preservation of evidence during pediatric organ donation: a modified thoracotomy procedure designed to increase consent in medical examiner cases.

Deceased potential organ donors are often under the jurisdiction of medical examiners/ coroners. In these deaths, the medical examiner/coroner has the statutory responsibility of determining cause and manner of death but is also responsible for presenting findings from the complete autopsy in court. The ability to analyze findings such as location, nature, and age of rib fractures and patterned skin injuries may be crucially important to legal disposition, even though those findings may not be critical to determination of cause and/or manner of death. Potential alteration or destruction of those findings is one reason why a medical examiner/coroner may deny organ donation. We present here a modified surgical approach to accessing thoracic organs in children so that posterior rib fractures, which have particular significance in child abuse cases, can be preserved unaltered for subsequent autopsy. This simple modification of surgical technique has greatly facilitated the mutual goals of the medical examiner and the designated organ procurement organization in our jurisdiction, and it has thus decreased the frequency of denials of organ donation.

Morphological features of advanced hepatocellular carcinoma as a predictor of downstaging and liver transplantation: an intention-to-treat analysis.

In selected patients, locoregional therapy (LRT) has been successful in downstaging advanced hepatocellular carcinoma (HCC) so that the conventional criteria for liver transplantation (LT) can be met. However, the factors that predict successful treatment are largely unidentified. To determine these factors, we analyzed our experience with multimodal LRT in downstaging advanced HCC before LT in a retrospective cohort study. Thirty-two patients with advanced HCC exceeding conventional and expanded criteria for LT underwent therapy, but only those patients whose tumors were successfully downstaged were considered for LT. Eighteen patients (56%) had their tumors successfully downstaged; 14 patients (44%) did not. No intergroup differences existed with respect to patient characteristics or the types and number of treatments. However, mean alpha-fetoprotein levels were significantly higher in the non-downstaged group than in the downstaged group (P < 0.048), and significantly more patients in the non-downstaged group had infiltrative tumors (P = 0.0001). The median survival time was 42 and 7 months for the downstaged and non-downstaged groups, respectively (P = 0.0006). Fourteen patients (43.3%) underwent LT. After a median follow-up period of 35 months (range, 1.5-50 months) after LT, 2 patients (14.2%) developed tumor recurrence. The Kaplan-Meier survival rates after LT were 92% at 1 year and 75% at 2 years. The noninfiltrative expanding tumor type was the sole predictor of successful downstaging and improved outcome on univariate and multivariate analyses. Our study suggests that, in patients with advanced HCC, morphological characteristics of the tumor may predict a good response to downstaging and an improved outcome after LT.

Major liver resection for hepatocellular carcinoma in the morbidly obese: a proposed strategy to improve outcome.

BACKGROUND: Morbid obesity strongly predicts morbidity and mortality in surgical patients. However, obesity's impact on outcome after major liver resection is unknown. CASE PRESENTATION: We describe the management of a large hepatocellular carcinoma in a morbidly obese patient (body mass index >50 kg/m2). Additionally, we propose a strategy for reducing postoperative complications and improving outcome after major liver resection. CONCLUSION: To our knowledge, this is the first report of major liver resection in a morbidly obese patient with hepatocellular carcinoma. The approach we used could make this operation nearly as safe in obese patients as it is in their normal-weight counterparts.