Dataset Information

Genotypes and Variants of BKPyV in Organ Donors after Brain Death.

ABSTRACT: Kidney transplantation from a donor with latent BKPyV might be the cause of serious complications, such as BK virus-associated nephropathy. The aim of the study was to determine the prevalence of BKPyV infection in donors after brain death (DBDs), to analyse the molecular variation of BKPyV and to compare clinical and inflammation parameters of DBDs infected with various genotypes of BKPyV. BKPyV was investigated in blood and urine samples of 103 DBDs using PCR followed by sequencing and bioinformatic analysis, and the viral load was assessed by qPCR. Clinical parameters, including cellular markers of inflammation were assessed. The results confirm high prevalence of BKPyV (48%),and genotype IV (49%) over genotype I (43%) and the co-infection with genotypes I and IV in 8.2%. Viral load ranged from 10² to 10⁷ copies/mL, with an average of 1.92 × 10⁶ copies/mL. No specific markers for BKPyV infection were detected among the parameters tested. Infection with genotype I may be associated with the adverse impact on thekidney function, while infection with genotype IV was associated with the anemia Not only the viral load but also the genotype of BKPyV may have an impact on the course of infection.

SUBMITTER: Furmaga J

PROVIDER: S-EPMC9409029 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Genotypes and Variants of BKPyV in Organ Donors after Brain Death.

Furmaga Jacek J Kowalczyk Marek M Furmaga-Rokou Olga O Rokos Christos A CA Zapolski Tomasz T Krakowski Leszek L Jakubczak Andrzej A Rudzki Sławomir S

International journal of molecular sciences 20220815 16

Kidney transplantation from a donor with latent BKPyV might be the cause of serious complications, such as BK virus-associated nephropathy. The aim of the study was to determine the prevalence of BKPyV infection in donors after brain death (DBDs), to analyse the molecular variation of BKPyV and to compare clinical and inflammation parameters of DBDs infected with various genotypes of BKPyV. BKPyV was investigated in blood and urine samples of 103 DBDs using PCR followed by sequencing and bioinfo ...[more]

PMID: 36012435

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Project description:BackgroundDemand for organs exceeds the number of transplants available, underscoring the need to optimize organ donation procedures. However, protocols for determining brain death (BD)/death by neurological criteria (DNC) vary considerably worldwide. In Denmark, digital subtraction angiography (DSA) is the only legally approved confirmatory test for diagnosing BD/DNC. We investigated the effect of the time delay caused by (repeat) confirmatory DSA on the number of organs donated by patients meeting clinical criteria for BD/DNC. We hypothesized that, first, patients investigated with ≥2 DSAs donate fewer organs than those investigated with a single DSA; second, radiological interpretation of DSA is subject to interrater variability; and third, residual intracranial circulation is inversely correlated with inotropic blood pressure support.MethodsAll DSAs performed over a 7-year period as part of BD/DNC protocols at Rigshospitalet, Copenhagen University Hospital, Denmark, were included. Clinical data were extracted from electronic health records. DSAs were reinterpreted by an independent neurinterventionist blinded to the original radiological reports.ResultsWe identified 130 DSAs in 100 eligible patients. Patients with ≥2 DSAs (n = 20) donated fewer organs (1.7 +/- 1.6 SD) than patients undergoing a single DSA (n = 80, 2.6 +/- 1.7 organs, p = 0.03), and they became less often donors (n = 12, 60%) than patients with just 1 DSA (n = 65, 81.3%; p = 0.04). Interrater agreement of radiological DSA interpretation was 88.5% (Cohen's kappa = 0.76). Patients with self-maintained blood pressure had more often residual intracranial circulation (n = 13/26, 50%) than patients requiring inotropic support (n = 14/74, 18.9%; OR = 0.23, 95% CI [0.09-0.61]; p = 0.002).DiscussionIn potential donors who fulfill clinical BD/DNC criteria, delays caused by repetition of confirmatory DSA result in lost donors and organ transplants. Self-maintained blood pressure at the time of clinical BD/DNC increases the odds for residual intracranial circulation, creating diagnostic uncertainty because radiological DSA interpretation is not uniform. We suggest that avoiding unnecessary repetition of confirmatory investigations like DSA may result in more organs donated.

Project description:ImportanceThe effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear.ObjectiveTo evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU).Design, setting, and participantsThe Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020.InterventionsHospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care.Main outcomes and measuresThe primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group.ResultsAmong the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006).Conclusions and relevanceThis cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist.Trial registrationClinicalTrials.gov Identifier: NCT03179020.

Project description:BackgroundControlled donation after circulatory death (cDCD) has become a standard in liver, kidney, and lung transplantation (LTx). Based on recent innovations in ex vivo heart preservation, heart transplant centers have started to accept cDCD heart allografts. Because the heart has very limited tolerance to warm ischemia, changes to the cDCD organ procurement procedures are needed. These changes entail delayed ventilation and prolonged warm ischemia for the lungs. Whether this negatively impacts lung allograft function is unclear.MethodsA retrospective analysis of cDCD lungs transplanted between 2012 and February 2022 at the Medical University of Vienna was performed. The heart + lung group consisted of cases in which the heart was procured by a cardiac team for subsequent normothermic ex vivo perfusion. A control group (lung group) was formed by cases where only the lungs were explanted. In heart + lung group cases, the heart procurement team placed cannulas after circulatory death and a hands-off time, collected donor blood for ex vivo perfusion, and performed rapid organ perfusion with Custodiol solution, after which the heart was explanted. Up to this point, the lung procurement team did not interfere. No concurrent lung ventilation or pulmonary artery perfusion was performed. After the cardiac procurement team left the table, ventilation was initiated, and lung perfusion was performed directly through both stumps of the pulmonary arteries using 2 large-bore Foley catheters. This study analyzed procedural explant times, postoperative outcomes, primary graft dysfunction (PGD), duration of mechanical ventilation, length of intensive care unit (ICU) stay, and early survival after LTx.ResultsA total of 56 cDCD lungs were transplanted during the study period. In 7 cases (12.5%), the heart was also procured (heart + lung group); in 49 cases (87.5%), only the lungs were explanted (lung group). Basic donor parameters were comparable in the 2 groups. The median times from circulatory arrest to lung perfusion (24 minutes vs 13.5 minutes; P = .002) and from skin incision to lung perfusion (14 minutes vs 5 minutes; P = .005) were significantly longer for the heart + lung procedures. However, this did not affect post-transplantation PGD grade at 0 hours (P = .851), 24 hours (P = .856), 48 hours (P = .929), and 72 hours (P = .874). At 72 hours after transplantation, none of the lungs in the heart + lung group but 1 lung (2.2%) in lung group was in PGD 3. The median duration of mechanical ventilation (50 hours vs 41 hours; P = .801), length of ICU stay (8 days vs 6 days; P = .951), and total length of hospital stay (27 days vs 25 days; P = .814) were also comparable in the 2 groups. In-hospital mortality occurred in only 1 patient of the lung group (2.2%).ConclusionsAlthough prioritized cDCD heart explantation is associated with delayed ventilation and significantly longer warm ischemic time to the lungs, post-LTx outcomes within the first year are unchanged. Prioritizing heart perfusion and explantation in the setting of cDCD procurement can be considered acceptable.

Dataset Information

Genotypes and Variants of BKPyV in Organ Donors after Brain Death.

Publications

Genotypes and Variants of BKPyV in Organ Donors after Brain Death.

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