Impact of deceased organ donor marijuana use on donor culture positivity and solid organ transplant recipient outcomes.

With the increasing prevalence of marijuana use in the US, many deceased organ donors have a history of marijuana use, raising concerns about infectious risks to transplant recipients. We performed a multicenter retrospective cohort study in which exposed donors were those with recent marijuana use (in the prior 12 months) and unexposed donors were those with no recent marijuana use. Primary outcomes included the following: (1) positive donor cultures for bacteria or fungi, (2) recipient infection due to bacteria or fungi within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Multivariable regression was used to evaluate the relationship between donor marijuana use and each outcome. A total of 658 recipients who received organs from 394 donors were included. Recent marijuana use was not associated with donor culture positivity (aOR: 0.84, 95% CI: 0.39-1.81, P = .65), recipient infection (aHR: 1.02, 95% CI: 0.76-1.38, P = .90), or recipient graft failure or death (aHR: 1.65, 95% CI: 0.90-3.02, P = .11). Our data suggest that organs from donors with a history of recent marijuana use do not pose significant infectious risks in the early posttransplant period.

COVID-19 in organ donors: An organ procurement organization perspective.

BACKGROUND: The COVID-19 pandemic presented a significant challenge for Organ Procurement Organizations (OPOs) with the use of SARS-CoV-2 positive donors varying widely. This study used detailed single OPO data to determine the success of using SARS-CoV-2 positive donors. METHODS: We performed a retrospective cohort study including all SARS-CoV-2 positive donors referred to the Gift of Life OPO from January 1, 2021, to June 30, 2023. Descriptive analyses were performed to characterize referral and organ utilization. RESULTS: There were 861 organ referrals with 1 positive SARS-Cov-2 test: 282 were ruled out with telephone evaluation, 431 referrals were ruled out with onsite evaluation ("evaluated nondonors") and 148 became donors. For donors who had both nasopharyngeal and lower respiratory testing completed, there was notable result discordance observed. Median cycle threshold (Ct) values were similar between donors and evaluated nondonors with no change in median donor Ct values over the study period. Transplanted organs from COVID-positive donors included 27 hearts, 88 livers, 5 pancreata, and 107 kidneys; no lung donation occurred. The proportion of COVID-positive donors significantly increased over the study period. CONCLUSION: This large volume donor referral study demonstrates increasing COVID-19 referrals progressing to donation over time, supporting the increased use of these donors for nonlung transplantation.

Messaging White and Black Next of Kin in Advance to Promote Authorization for Tissue Donation.

Introduction: Organ Procurement Organizations seek authorization for tissue donation from next-of-kin of deceased patients. Best practices for achieving contact and authorization are unknown, notably, authorization rates are lower for Black compared to White patients. Research Questions: Can next-of-kin (NOK) contact and authorization rates be improved if they are texted prior to telephone contact? Is a text message containing an infographic more effective, and does an infographic culturally tailored to Black families improve contact and authorization rates in the Black population? Design: This three-armed randomized trial compared (1) telephonic contact initiation (control condition); (2) generic text messaging prior to telephonic contact; and (3) text messaging one of two versions of an infographic prior to telephonic contact: (a) a generic infographic or (b) a culturally tailored infographic (sent to Black NOK only) at one Northeastern Organ Procurement Organization. Results: Tissue Donation Professionals (N = 47) and 2399 White and 745 Black NOK were included, of which 35.6% were registered donors. Authorization rates were much higher for White than Black (40.1% v 16.3%, P < 0.0001). The generic infographic resulted in significantly lower rates of contact for White NOK compared to the control condition 83.5% v 89.5%, P = 0.002), but study arm assignments were not otherwise associated with differences in contact or authorization rates. Conclusion: Although the analysis did not find a benefit for text messaging, it is possible that training for staff making requests and refining the content of the messaging could be more effective.

Assessing Kidney Transplantation Using ECMO-Supported Donors Within a KDPI-Based Allocation System.

Background: Organ donors supported by extracorporeal membrane oxygenation (ECMO) have historically been considered high-risk and are judiciously utilized. This study examines transplant outcomes using renal allografts from donors supported on ECMO for nondonation purposes. Methods: Retrospective review of the Gift of Life (Pennsylvania, New Jersey, Delaware) organ procurement organization database, cross-referenced to the Organ Procurement and Transplantation Network database, assessed kidney transplants using donors supported on venoarterial (VA) and venovenous (VV) ECMO for nondonation purposes. Transplants using VA- and VV-ECMO donors were compared with Kidney Donor Profile Index (KDPI)-stratified non-ECMO donors. Regression modeling of the entire ECMO and non-ECMO populations assessed ECMO as predictive of graft survival. Additional regression of the ECMO population alone assessed for donor features associated with graft survival. Results: Seventy-eight ECMO donors yielded 128 kidney transplants (VA: 80, VV: 48). Comparing outcomes using these donors to kidney transplants using organs from KDPI-stratified non-ECMO donors, VA- and VV-ECMO donor grafts conferred similar rates of delayed graft function and posttransplant renal function to KDPI-matched non-ECMO counterparts. VA-ECMO kidneys demonstrated superior graft survival compared with the lowest-quality (KDPI 86%-100%) non-ECMO kidneys and similar graft survival to KDPI <85% non-ECMO kidneys. VV-ECMO showed inferior graft survival to all but the lowest-quality (KDPI 86%-100%) non-ECMO kidneys. VV-ECMO, but not VA-ECMO, was associated with increased risk of graft loss on multivariable regression (hazard ratios-VA: 1.02, VV: 2.18). Higher KDPI, advanced age, increased body mass index, hypertension, and diabetes were identified as high-risk features of ECMO donors. Conclusions: Kidney transplantation using appropriately selected ECMO donors can safely expand the donor pool. Ongoing studies are necessary to determine best practice patterns using kidneys from these donors.

Extracorporeal membrane oxygenation for cardiopulmonary failure in organ donation: Assessing liver transplant outcomes.

Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates the practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required extracorporeal membrane oxygenation (ECMO) support. We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ-procuring organization database for transplants performed using donors supported on ECMO for nondonation purposes. These were cross-referenced to the transplant recipients within the Organ Procurement and Transplantation Network database, and the outcomes of liver transplants using donors on ECMO support were compared with those not requiring ECMO. Organ use and nonuse patterns were then evaluated in ECMO-supported donors, identifying the factors associated with nonuse compared with the factors associated with graft failure. Thirty-nine of the 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft survival and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary nonfunction were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. Livers from donors supported on ECMO before donation appear safe to use in select transplant settings. Better understanding of the impact of predonation ECMO on liver allograft function will help guide the optimal use of these scarcely used donors.

Organ Donation From Patients on Extracorporeal Membrane Oxygenation at the Time of Death.

To describe the clinical characteristics and organ donation rate of patients supported by extracorporeal membrane oxygenation (ECMO) at the time of death. DESIGN: Retrospective observational study. Pearson chi-square and Fisher exact tests were used in statistical analyses. SETTING: One hundred twenty-seven acute care hospitals in New Jersey, Pennsylvania, and Delaware. PATIENTS: Adult and pediatric patients who were on ECMO at the time of referral to a large organ procurement organization (OPO) between 2016 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nineteen thousand nine hundred thirty patients were referred to the OPO between November 2016 and September 2020, of which 5,034 were medically suitable potential donors. Of this cohort, 143 patients were supported on ECMO at the time of OPO referral and 141 were included in analyses (median age 47 yr, 60% male). Thirty-three percent (46/141, median age 48 yr, 52% male) donated organs, compared with 50% of non-ECMO patients (p ≤ 0.0005). ECMO and non-ECMO patients had organs recovered but not transplanted at similar rates (11% vs 10%, p = 0.8). There were no significant differences in sex (p = 0.16) or ethnicity (p = 0.50) between organ donor and nondonor groups. Fifty-one percent (21/41) of organ donors donated after circulatory death and 49% (20/41) after brain death. Patients declared dead by neurologic criteria were more likely to donate (51%) than those declared dead by circulatory criteria (21%, p < 0.001). Frequency of cardiac arrest prior to ECMO was similar between donors and nondonors (p = 0.68). Thirty-nine percent (16/41) of donors had an out-of-hospital cardiac arrest (OHCA) and 51% (21/41) were cannulated via extracorporeal cardiopulmonary resuscitation (ECPR). The most common reason patients were not donors was that family declined (57%). CONCLUSIONS: One-third of patients referred to the OPO on ECMO at the time of death donated organs. While donation occurred less frequently after ECMO, ECMO and non-ECMO patients had organs used rather than discarded at a similar rate. Patients successfully donated following OHCA and/or ECPR. Clinicians should not consider ECMO a barrier to organ donation.

Advance Care Directive Preferences in Women Veterans: A Snapshot.

Prior research characterizes mainly male veteran preferences at end of life using the Veterans Administration Advance Directive (VA AD), there has been no specific studies focusing on women veteran's preferences concerning whether the AD is to be strictly (S) followed or to serve as a general guide (G). The purpose of this study was to describe women veteran preferences for life-sustaining treatments (LSTs) in various illness situations to assist providers in discussing end-of-life decisions. Additionally, we compared previously published LST preferences of male veterans with the study's sample. Using a descriptive retrospective approach, data was collected from 484 women veterans ADs between January 2010 and December 2019. Findings revealed that women tended to trend in the same direction as men, preferring to have advance directives serve as general guidance over being strictly followed. Unconscious/Coma/Vegetative was the only factor that was statistically significant for affecting the choice of following the AD.

Impact of deceased organ donor injection drug use on donor culture positivity and recipient outcomes.

BACKGROUND: Due to the ongoing opioid epidemic in the United States, deceased organ donors increasingly have a history of injection drug use (IDU), raising concerns about infectious risks to solid organ transplant (SOT) recipients. We sought to determine how recent IDU among deceased organ donors impacted donor culture results and recipient outcomes. METHODS: A retrospective cohort study was performed at three transplant centers. Exposed donors were those with "recent IDU" (in the prior 12 months). Primary outcomes included (1) positive donor cultures for bacteria or Candida species, (2) recipient bacterial or Candida infection within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Mixed effects multivariable regression models were used to evaluate the relationship between recent donor IDU and each outcome. RESULTS: A total of 658 SOT recipients who received organs from 394 donors were included. Sixty-six (17%) donors had a history of recent IDU. Recent IDU in donors was associated with a significantly increased odds of donor culture positivity (aOR 3.65, 95% CI 1.06-12.60, p = .04) but was not associated with SOT recipient infection (aHR 0.98, 95% CI 0.71-1.36, p = .92) or graft failure or death (aHR 0.67, 95% CI 0.29-1.51, p = .33). CONCLUSION: Donors with recent IDU are more likely to have positive cultures, but their recipients' outcomes are unaffected, suggesting organs from donors with recent IDU may be safely utilized.

Impact of donor multidrug-resistant organisms on solid organ transplant recipient outcomes.

BACKGROUND: The impact of donor colonization or infection with multidrug-resistant organisms (MDROs) on solid organ transplant (SOT) recipient outcomes remains uncertain. We thus evaluated the association between donor MDROs and risk of posttransplant infection, graft failure, and mortality. METHODS: A multicenter retrospective cohort study was performed. All SOT recipients with a local deceased donor were included. The cohort was divided into three exposure groups: recipients whose donors had (1) an MDRO, (2) a non-MDRO bacterial or candidal organism, or (3) no growth on cultures. The primary outcomes were (1) bacterial or invasive candidal infection within 3 months and (2) graft failure or death within 12 months posttransplant. Mixed effect multivariable frailty models were developed to evaluate each association. RESULTS: Of 658 total SOT recipients, 93 (14%) had a donor with an MDRO, 477 (73%) had a donor with a non-MDRO organism, and 88 (13%) had a donor with no organisms on culture. On multivariable analyses, donor MDROs were associated with a significantly increased hazard of infection compared to those with negative donor cultures (adjust hazard ratio [aHR] 1.63, 95% CI 1.01-2.62, p = .04) but were not associated with graft failure or death (aHR 0.45, 95% CI 0.15-1.36, p = .16). CONCLUSIONS: MDROs on donor culture increase the risk of early posttransplant infection but do not appear to affect long-term graft or recipient survival, suggesting organ donors with MDROs on culture may be safely utilized. Future studies aimed at reducing early posttransplant infections associated with donor MDROs are needed.

Antibiotic Utilization in Deceased Organ Donors.

Antibiotic use in deceased organ donors has not been previously described. In a retrospective cohort of 440 donors, we found 427 (97%) received at least one antibiotic course, 312 (71%) received broad-spectrum antibiotics, and 61 (14%) received potentially redundant antibiotics during their terminal hospitalization, suggesting a need for stewardship.

Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma.

The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1-4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413.

Impact of deceased donor multidrug-resistant bacterial organisms on organ utilization.

The extent to which donor multidrug-resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at 4 transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed donors had no MDRO-positive cultures. Only cultures obtained during the donor's terminal hospitalization were evaluated. Multivariable regression was used to determine the association between donor MDRO and (1) number of organs transplanted per donor and (2) the match run at which each organ was accepted. Subsequently, we restricted the analysis to donors with MDR-Gram-negative (GN) organisms. Of 440 total donors, 29 (7%) donors grew MDROs and 7 (2%) grew MDR-GNs. There was no significant association between donor MDRO and either measure of organ utilization. However, donor MDR-GNs were associated with a significant reduction in the number of organs transplanted per donor (incidence rate ratio 0.43, 95% confidence interval [CI] 0.39-0.48, P < .01), and organs were accepted significantly further down the match list (relative count 5.08, 95% CI 1.64-15.68, P = .01). Though donor MDR-GNs were infrequent in our study, their growing prevalence could meaningfully reduce the donor pool over time.

Risk factors for multidrug-resistant organisms among deceased organ donors.

Donor infection or colonization with a multidrug-resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71-9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09-19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03-55.75, P = .047), and exposure to antibiotics with a narrow gram-negative spectrum (HR 1.13, 95% CI 1.00-1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.

Identifying Educational Needs and Practice Gaps of European Hematologists and Hematology Nurses in the Treatment and Management of Multiple Myeloma.

This needs-assessment aimed to identify clinical challenges faced by hematologists and hematology nurses in the diagnosis, treatment, and management of multiple myeloma, as well as contextual barriers hindering optimal care of patients with multiple myeloma. This manuscript focuses on key findings in relation to decision-making regarding new treatment options. A mixed methods study consisting of qualitative (from semistructured interviews) and quantitative data (from an online survey) was conducted in 8 European countries among hematologists and hematology nurses. The triangulated data led to the identification of 3 key findings related to decision-making: (1) Educational needs regarding mechanisms of action and side effect profiles of new therapies, (2) educational needs regarding the sequencing and combination of new agents with current therapies, and (3) contextual barriers to the integration of new agents. Specific knowledge and skill gaps were identified as causalities of the educational needs, providing information to guide future educational programs. Of note, 34% of hematologists and 69% of nurses reported suboptimal knowledge of the mechanisms of action of new agents and 30% of hematologists reported suboptimal skills integrating new agents in combination with current treatments. This needs-assessment highlighted the importance to address the educational needs and their underlying causes through medical education activities to ensure hematologists and hematology nurses are up-to-date with the latest treatments in the field as they become available. The contextual barriers identified should be considered when designing the educational programs to ensure content is applicable to the clinical reality of learners.

Outcome of organs procured from donors on extracorporeal membrane oxygenation support: an analysis of kidney and liver allograft data.

INTRODUCTION: Extracorporeal membrane oxygenation has become rescue therapy for adults with overwhelming cardiac and/or respiratory failure. Not all patients are saved, creating a new cohort of potential organ donors. This study examines the outcomes of liver and kidney allografts procured from donors on extracorporeal membrane oxygenation (ECMO). METHODS: A retrospective review was conducted through the local organ procurement organization. Donors on ECMO prior to notification were classified into donation after brain death (DBD) and donation after cardiac death (DCD). We compared short-term outcome data against published standards. RESULTS: Between 1995 and 2012, 97 organs were procured from 41 donors supported on ECMO. There were 68 kidneys donated, 51 were transplanted and 17 discarded. Excluding extended criteria donors, 29 DBD and 13 DCD kidneys were transplanted from donors supported on ECMO. Delayed graft function occurred in 34% of DBD kidneys and 38% of DCD kidneys. Kidney allograft survival at one yr was 93%. Twenty-four livers were procured, nine discarded, and 15 transplanted. Ninety-three percent of liver transplant recipients were alive with graft function at one yr. CONCLUSIONS: Donation after brain death kidneys procured from donors on ECMO perform similarly to non-ECMO organs with regard to delayed graft function (DGF), one-yr graft survival and function. Livers from ECMO donors have a higher discard rate than non-ECMO donors, but function similarly at six months and one yr.

Whole-body diffusion-weighted MR imaging for assessment of treatment response in myeloma.

PURPOSE: To determine the feasibility of whole-body diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of treatment response in myeloma. MATERIALS AND METHODS: This prospective single-institution study was HIPAA-compliant with local research ethics committee approval. Written informed consent was obtained from each subject. Eight healthy volunteers (cohort 1a) and seven myeloma patients (cohort 1b) were imaged twice to assess repeatability of quantitative apparent diffusion coefficient (ADC) estimates. Thirty-four additional myeloma patients (cohort 2) underwent whole-body DW imaging before treatment; 26 completed a posttreatment imaging. Whole-body DW data were compared before and after treatment by using qualitative (ie, observer scores) and quantitative (ie, whole-body segmentation of marrow ADC) methods. Serum paraproteins and/or light chains or bone marrow biopsy defined response. RESULTS: Whole-body DW imaging scores were significantly different between observers (P < .001), but change in scores between observers after treatment was not (P = .49). Sensitivity and specificity for detecting response according to observer scores were 86% (18 of 21 patients) and 80% (4 of 5 patients) for both observers. ADC measurement was repeatable: mean coefficient of variation was 3.8% in healthy volunteers and 2.8% in myeloma patients. Pretreatment ADC in cohort 2 was significantly different from that in cohort 1a (P = .03), but not from that in cohort 1b (P = .2). Mean ADC increased in 95% (19 of 20) of responding patients and decreased in all (five of five) nonresponders (P = .002). A 3.3% increase in ADC helped identify response with 90% sensitivity and 100% specificity; an 8% increase (greater than repeatability of cohort 1b) resulted in 70% sensitivity and 100% specificity. There was a significant negative correlation between change in ADC and change in laboratory markers of response (r = -0.614; P = .001). CONCLUSION: Preliminary work demonstrates whole-body DW imaging is a repeatable, quantifiable technique for assessment of treatment response in myeloma.

Donor hemodynamic profile presages graft survival in donation after cardiac death liver transplantation.

Obligatory exposure to a period of warm ischemia is the defining feature of liver allografts from donation after cardiac death (DCD) donors. We explored novel methods for characterizing the dynamic aspects of donor warm ischemia that might be useful in assessing organ quality. The hemodynamic profile during donor warm ischemia was retrospectively studied for 110 Maastricht category III DCD donors. Three methods were used to summarize the hemodynamic changes after extubation: (1) the area under the systolic blood pressure curve (AUCSBP), (2) the slope of the systolic blood pressure regressed onto the time from extubation until cross-clamping, and (3) the slope of the systolic blood pressure regressed onto the time from extubation but calculated with only the values during the first 10 minutes after extubation (SBP10). Stepwise multivariate Cox models were created to study the association of these measures with graft survival. The duration of the donor warm ischemia time (23.6 ± 8.5 minutes) was not associated with graft survival (P = 0.35), although AUCSBP and SBP10 demonstrated significant associations (P = 0.02 and P = 0.05, respectively) in a univariate analysis. Multivariate regression models incorporating donor and recipient covariates indicated that among all covariates, SBP10 had the closest association with graft survival (hazard ratio = 1.08, P = 0.01). This association was even stronger when SBP10 was dichotomized into values above or below the median (-7.2 mm Hg/minute). Patients with SBP10s steeper than the median had an estimated 5-year graft survival rate of 76%, whereas patients with slopes less than the median had a 5-year survival rate of 45% (P < 0.007). In conclusion, the incorporation of novel methods for characterizing the donor warm ischemia time may help in selecting DCD liver allografts with favorable outcomes.