Experience With a New Process - Condition T - for Uncontrolled Donation After Circulatory Determination of Death in a University Emergency Department.

BACKGROUND: In the United States, organ donation after circulatory death (DCD) determination is increasing among those who are removed from life-sustaining therapy but is rare when death is unexpected. We created a program for uncontrolled DCD (uDCD). METHODS: A comprehensive program was created to train personnel to identify and respond quickly to potential donors after unexpected death. The process termed Condition T was implemented in the emergency department (ED) of 2 academic medical centers. All ED deaths were screened for uDCD potential. Eligible donors included patients with preexisting donor designation who received cardiopulmonary resuscitation, failed to respond, and were pronounced dead. RESULTS: Over 350 nurses, physicians, perfusionists, organ procurement personnel, and administrators were trained. From February 2009 to June 2010, a total of 18 patients were potential Condition T candidates. Six Condition T responses were triggered. Three donors underwent cannulation, and 4 organs were recovered (3 kidney and 1 liver) from 2 donors. Time from Condition T trigger to perfusion with organ preservation solution ranged from 14 to 22.3 minutes. Perfusion duration was 197 and 221 minutes. No recovered organs were transplanted because biopsies showed prolonged warm ischemia. CONCLUSIONS: It is feasible to create a process to rapidly intervene in the ED for uDCD. However, no organ transplants resulted. The utility and sustainability of an uDCD program in this particular setting are questionable.

A Cross-sectional Survey of Comprehension and Satisfaction of Spanish-Reading Adults Regarding RÁPIDO as a Stroke Awareness Acronym.

ABSTRACT: BACKGROUND: Delay time to hospital arrival may be influenced by lack of recognition of stroke signs and the necessity to seek emergency medical, which in turn is influenced by language barriers to, a modifiable risk factor, stroke awareness education. The objective was to determine the comprehension and satisfaction of a Spanish stroke awareness acronym, RÁPIDO, among community-living, Hispanic and Latino, Spanish-reading adults. METHODS: A 33-item survey was completed by 166 adults. Data on sociodemographics, language preferences, stroke education, and comprehension and satisfaction with RÁPIDO were collected. Descriptive characteristics were calculated. Fisher exact tests were performed to determine whether reading language (group 1, only or predominantly reads in Spanish; group 2, reads in Spanish and English equally or reads predominately in English) influenced survey responses. Responses to open-ended questions were categorized. RESULTS: Sixty-nine percent of the participants were born outside of the United States, 82% currently resided in the United States, 34% read only or predominately in Spanish, and 7% had a stroke. Most participants thought RÁPIDO was informative, eye-catching, and easily remembered. Significant differences were found between reading language preference groups for correctly identifying RÁPIDO images for facial drooping (group 1, 80%; group 2, 95%; P ≤ .001) and dizziness/loss of balance (group 1, 54%; group 2, 73%; P = .027). Eighty percent or more of all participants were able to correctly interpret RÁPIDO images for facial drooping, blurry vision, impaired speech, and call emergency services. Adding "911" to the RÁPIDO image of the clock was a common suggestion. CONCLUSIONS: RÁPIDO was well received among the participants. Modifications to RÁPIDO images representing dizziness/loss of balance and arm weakness, and the addition of "911" may improve its usefulness. Obtaining more extensive feedback across the United States and testing the effect of RÁPIDO on increasing knowledge of stroke signs and retention of that knowledge are necessary next steps.

Between-hospital variability in organ donation after resuscitation from out-of-hospital cardiac arrest.

INTRODUCTION: Survival and recovery after out-of-hospital cardiac arrest (OHCA) varies between hospitals, with better outcomes associated with high-volume and specialty care. We evaluated if there is a similar relationship with organ donation after OHCA. METHODS: We studied a cohort of adults resuscitated from OHCA from 2010 to 2018, treated at one of 112 hospitals served by a regional organ procurement organization (OPO). We obtained hospital-level characteristics from Centers for Medicare and Medicaid Services and Health Resources and Services Administration and obtained patients' clinical information from the OPO health record. We excluded patients with no potential to donate on initial referral. Our primary exposure was treatment at a high-volume hospital (defined > 500 eligible cases during the study period) and our primary outcomes were suitability to donate after full medical evaluation, successful organ procurement and organ transplantation. We used mixed effects models to quantify between-hospital variability in the primary outcomes. RESULTS: Overall, 9792 patients were included and 796 (8%) were organ donors. We identified significant between-hospital variation in odds of donation (median odds ratio 1.64 [95% CI 1.42-2.02]). Hospital volume explained the greatest proportion of variability. High volume centers had a higher proportion of referrals with potential to donate (16.9 vs 12.2%), actual donation (10.3 vs 6.2%), and successful transplantation (9.4 vs 5.7%). Overall, 2032/7763 (26%) of recovered transplantable organs in this region were procured from OHCA patients. CONCLUSION: High volume centers are more likely to refer and procure transplantable organs from patients with non-survivable OHCA.

Organ donation after resuscitation from cardiac arrest.

BACKGROUND: We compared the characteristics and outcomes of post-arrest donors to those of other donors, described the proportion of post-arrest decedents who donated, and compared their characteristics to post-arrest decedents who did not donate. METHODS: We performed a retrospective cohort study including patients who died at a single academic medical center from January 1, 2010 to February 28, 2019. We linked our registry of consecutive post-arrest patients to donation-related data from the Center for Organ Procurement and Recovery (CORE). We used data from CORE to identify donor eligibility, first person designation, family approaches to seek consent for donation, and approach outcomes. We determined number of organs procured and number transplanted, stratified by donor type (brain death donors (BDD) vs donors after circulatory determination of death (DCD)). RESULTS: There were 12,130 decedents; 1525 (13%) were resuscitated from cardiac arrest. CORE staff approached families of 836 (260 (31%) post-arrest, 576 (69%) not post-arrest) to request donation. Post-arrest patients and families were more likely to authorize donation (172/260 (66%) vs 331/576 (57%), P = 0.02), and more likely to be DCDs (50/146 (34%) vs 55/289 (19%), P < 0.001). Overall, 4.1 ±â€¯1.5 organs were procured and 2.9 ±â€¯1.9 transplanted per BDD, which did not differ by post-arrest status, 3.2 ±â€¯1.2 organs were procured and 1.8 ±â€¯1.1 transplanted per DCD. Number of organs transplanted per DCD did not differ by post-arrest status. Unfavorable arrest characteristics were more common among post-arrest organ donors compared to non-donors. CONCLUSION: Patients resuscitated from cardiac arrest with irrecoverable brain injury have excellent potential to become organ donors.

Outcomes of Deceased Donor Kidney Transplantation Using Expanded Criteria Donor Kidneys Following Pulsatile Preservation.

Aim We compared the outcomes of transplanting expanded criteria donor (ECD) kidneys undergoing machine perfusion (MP) versus cold storage (CS). Material and methods Data on all expanded criteria deceased donor kidney transplants performed at the University of Pittsburgh Medical Center from January 2003 through December 2012 were collected from an in-house electronic repository. There were 78 patients in the MP group and 101 patients in the CS group. The majority of the ECD kidneys were imported from other organ procurement organizations: 69 of 73 in the MP group (94.5%, 5 from unknown sources); and 90 of 99 in the CS group (91%), 2 from an unknown source). Most of the patients in the MP group (77 of 78) received a combination of MP and static CS. MP was performed just prior to transplantation in all MP patients. We used descriptive statistics to characterize our sample. We used logistic regression analysis to model the binary outcome of delayed graft function (DGF; i.e., "yes/no") and Cox (proportional hazard) regression to model time until graft failure. The Kaplan-Meier product-limit method was used to estimate survival curves for graft and patient survival. Results A total of 179 transplants were done from ECD donors (MP, 78; CS, 101). The mean static cold storage time was 14 ± 4.1 hours and the mean machine perfusion time was 11.2 ± 6.3 hours in the MP group. The donor creatinine was higher (1.3 ± 0.6 mg/dl vs. 1.2 ± 0.4 mg/dl, p = 0.01) and the cold ischemia time was longer (28.9 ± 10 hours vs. 24 ± 7.9 hours, p = 0.0003) in the MP patients. There were no differences between the two groups in DGF rate (20.8% [MP] vs. 25.8% [CS], p = 0.46), six-year patient survival (74% [MP] vs. 63.2% [CS], p = 0.11), graft survival (64.3% [MP] vs. 51.5% [CS], p = 0.22), and serum creatinine levels (1.5 mg/dl vs. 1.5 mg/dl) on univariate analysis. On unadjusted analysis, MP subjects without DGF had longer graft survival compared to CS subjects with DGF (p < 0.0032) and MP subjects with DGF (p < 0.0005). MP subjects without DGF had longer death-censored graft survival compared to CS subjects with DGF (p < 0.0077) and MP subjects with DGF (p < 0.0016). However, on regression analysis, MP subjects had longer graft survival than CS subjects when DGF was not present. MP subjects without DGF had longer patient survival compared to CS subjects with DGF (p < 0.0289), on unadjusted analysis. MP subjects had a reduced risk of graft failure (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.17, 0.68) and death-censored graft failure (HR, 0.44; 95% CI, 0.19, 1.00), compared to CS subjects when DGF was not present. Conclusions Reduction of DGF rates for imported ECD kidneys is vital to optimize outcomes and increase their utilization. One strategy to decrease DGF rates may be to reduce static CS time during transportation, by utilizing a portable kidney perfusion machine.

Donor biomarkers as predictors of organ use and recipient survival after neurologically deceased donor organ transplantation.

PURPOSE: We sought to build prediction models for organ transplantation and recipient survival using both biomarkers and clinical information. MATERIALS AND METHODS: We abstracted clinical variables from a previous randomized trial (n = 556) of donor management. In a subset of donors (n = 97), we measured two candidate biomarkers in plasma at enrollment and just prior to explantation. RESULTS: Secretory leukocyte protease inhibitor (SLPI) was significant for predicting liver transplantation (C-statistic 0.65 (0.53, 0.78)). SLPI also significantly improved the predictive performance of a clinical model for liver transplantation (integrated discrimination improvement (IDI): 0.090 (0.009, 0.210)). For other organs, clinical variables alone had strong predictive ability (C-statistic >0.80). Recipient 3-years survival was 80.0% (71.9%, 87.0%). Donor IL-6 was significantly associated with recipient 3-years survival (adjusted Hazard Ratio (95%CI): 1.26(1.08, 1.48), P = .004). Neither clinical variables nor biomarkers showed strong predictive ability for 3-year recipient survival. CONCLUSIONS: Plasma biomarkers in neurologically deceased donors were associated with organ use. SLPI enhanced prediction within a liver transplantation model, whereas IL-6 before transplantation was significantly associated with recipient 3-year survival. Clinicaltrials.gov: NCT00987714.

Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma.

The MYCN oncogene is amplified in approximately 25% of neuroblastoma tumors and is the most significant negative prognostic factor. The direct transcriptional targets of MYCN in MYCN-amplified tumors have not been defined. Microarray analysis of RNA from neuroblastoma primary cell cultures revealed 10-fold higher MCM7 expression in MYCN-amplified versus nonamplified tumors. MCM7 is an essential component of DNA replication licensing factor, a hexameric protein complex that regulates DNA synthesis during the cell cycle, preventing rereplication and ensuring maintenance of DNA euploidy. Additional experiments demonstrated markedly increased expression of MCM7 RNA and protein in MYCN-amplified neuroblastoma tumors and cell lines. Induction of MYCN in conditional cell lines results in increased expression of endogenous MCM7 mRNA and a 3-fold increase in protein levels. In addition, luciferase activity from MCM7 promoter/luciferase gene reporter constructs was significantly increased under MYCN-induced conditions. Specific electrophoretic mobility shifts of MCM7 promoter sequences are detected in extracts of MYCN-amplified cells. These findings demonstrate that in neuroblastoma, the MYCN oncogene directly activates genes required for DNA replication, and this may contribute to neoplastic transformation of these MYCN-amplified tumors.

Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial.

BACKGROUND: Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multicenter randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases the number of organs transplanted. METHODS: We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A "protocol-guided fluid therapy" algorithm targeting the cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor, and our primary analysis was intention to treat. Secondary analyses included: (1) modified intention to treat where only subjects able to receive the intervention were included and (2) 12-month survival in transplant recipients. The study was stopped early. RESULTS: We enrolled 556 donors: 279 protocolized care and 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76 % of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor (95 % CI 3.14-3.63) with protocolized care compared to 3.29 usual care (95 % CI 3.04-3.54; mean difference, 0.1, 95 % CI -0.25 to 0.45; p = 0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95 % CI 3.23-3.8), but not statistically significantly (mean difference, 0.23, 95 % CI -0.15 to 0.61; p = 0.23). Among the 1,430 recipients of organs from study subjects with data available, 56 deaths (7.8 %) occurred in the protocolized care arm and 56 (7.9 %) in the usual care arm in the first year (hazard ratio: 0.97, p = 0.86). CONCLUSIONS: In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor.

Improving the utilization of medical crisis teams (Condition C) at an urban tertiary care hospital.

PURPOSE: Serious clinical deterioration precedes most cardiopulmonary arrests, and there is evidence that organized responses to this deterioration may prevent a substantial proportion of in-hospital deaths. We aimed to increase the utilization of our medical crisis response team (Condition C) to impact this source of mortality. METHODS: We have examined the change in numbers of Condition Cs and the main alternative response strategy (sequential stat pages) after the implementation of 4 strategies to increase Condition C utilization: (1) immediate reviews of all sequential STAT pages, (2) feedback to caregivers responsible for delays in Condition C activation, (3) creation of objective criteria for invoking a crisis response, and (4) dissemination of objective criteria through posting in units, e-mail, and in-service oral presentations. RESULTS: Over a 3-year period, interventions were followed by increased use of organized responses to medical crises (Condition Cs) and decreased numbers of disorganized responses (sequential STAT pages). The interventions that involved objective definition and dissemination of criteria for initiating the Condition C response were followed by 19.2 more Condition Cs monthly (95% confidence interval [CI], 12.1-26.3; P<0001) and 5.7 fewer sequential STAT pages monthly (95% CI, 3.2-8.2). The interventions that involved giving feedback to medical personnel based on review of their care were not associated with changes in the measures. CONCLUSION: Utilization of an important patient safety measure may be increased by focused interventions at an urban tertiary care hospital.