Dysfunction In Donors Research Articles

Optimizing pre-donation physiologic evaluation for enhanced recovery after living liver donation - Systematic review and multidisciplinary expert panel recommendations.

While preoperative physiologic evaluation of live liver donors is routinely performed to ensure donor safety and minimize complications, the optimal approach to this evaluation is unknown. We aim to identify predonation physiologic evaluation strategies to improve postoperative short-term outcomes, enhance donor's recovery, and reduce length of stay. We also aim to provide multidisciplinary expert panel recommendations. Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. The systematic review followed PRISMA guidelines, and the recommendations were formulated using GRADE approach and experts' opinion. The search included retrospective or prospective studies, describing outcomes of physiologic evaluation predonation. The outcomes of interest were length of stay, postoperative complications (POC), recovery after donation, and mortality. PROSERO protocol ID CRD42021260662. Of 1386 articles screened, only three retrospective cohort studies met eligibility criteria. Two studies demonstrated no impact of age (<70 years) on POC. Increased body mass index's (BMI) association with POC was present in one study (23.8vs 21.7kg/m2 , OR 1.67 (1.14-2.48), P=.01) and absent in another (<30vs 30-35kg/m2 , P=.61). One study demonstrated decreased risk for postdonation subclinical hepatic dysfunction in donors with higher normal platelet count (PLT). None of the studies noted donor death. Given the scarce data on predonation physiologic testing, the expert panel recommended a battery of tests to guide clinical practice and future investigations. Advancing age (60-69 years) is not a contraindication for liver donation. There is insufficient evidence for a specific predonation BMI cut-off. Abbreviated predonation physiologic testing is recommended in all candidates. Comprehensive testing is recommended in high-risk candidates while considering the pretest probability in various populations (Quality of evidence; Low to Very Low | Grade of Recommendation; Strong).

Donor Transient Myocardial Dysfunction - Structural versus Hypoxic Brain Injury

<h3>Purpose</h3> We theorized that transient myocardial dysfunction in donors with hypoxic brain injury will have different markers, risk factors and prognosis in comparison to donors with structural brain injury. <h3>Methods</h3> All heart transplant recipients between 2010 - 2017 were categorized according to whether they received an organ from donor with structural (traumatic + stroke) versus hypoxic brain injury. Baseline donor characteristics were evaluated for association with transient myocardial dysfunction and post-transplantation outcomes (PGD, survival, freedom from rejection, and CAV) of grafts recovered from donors with transient dysfunction were compared to those without dysfunction. <h3>Results</h3> Altogether 248 donor hearts were transplanted during a study period (222 heart-alone, 12 re-do, 11 heart-kidney, 2 heart-liver and 1 heart-lung). Pre-donation transient myocardial dysfunction was detected in 14 out of 177 donors with structural brain injury (8%) and 9 out of 71 donors with hypoxic brain injury (13%). Myocardial dysfunction in donors with structural brain injury was associated with low BMI (P = .002) and elevated serum troponin (P = .032). Myocardial dysfunction in donors with hypoxic brain injury was associated with the number of blood products received before donation (P = .032). Post-transplantation outcomes of recipients who received an organ with and without transient pre-recovery dysfunction stratified by the donor cause of death are summarized in Table 1. <h3>Conclusion</h3> Transient myocardial dysfunction in donors with hypoxic brain death is quite common and is associated with different variables than in donors with structural brain death. Pre-donation transient graft dysfunction is not associated with inferior post-transplantation outcome in neither donors after structural nor hypoxic brain injury group. Organs recovered from donors after hypoxic brain death with transient dysfunction showed a trend towards less freedom from graft vasculopathy in comparison to non-dysfunctional organs.

Preoperative Evaluation of Liver Parenchyma of Potential Donors in Living Donor Liver Transplantation

BackgroundHepatic steatosis carries a risk of postoperative liver dysfunction in donors and graft nonfunction in recipients. This article discusses the evaluation of fatty infiltration in donor liver parenchyma on multidetector computed tomography. Materials and methodsThe methods of hepatic fat estimation include measurement of hepatic attenuation in HU and calculation of the liver attenuation index (LAI). Liver attenuation values reflect the degree of steatosis. Average attenuation of liver parenchyma is calculated by placing the circular region of interest of at least 1 cm2 area at multiple places in the liver on noncontrast CT images. Splenic attenuation is measured by placing the circular region of interest at its upper, middle, and lower poles. The LAI is the difference between mean hepatic attenuation and mean splenic attenuation. ResultsA total of 52 donors were evaluated as potential recipients (34 men, 18 women; mean age, 33.2 years; range, 23-55 years). In 34 donors liver attenuation index (LAI) values were from 2 HU to 22 HU. An LAI > 5 HU correctly predicted the absence of significant macrovesicular steatosis. These donors were acceptable for a liver transplant. The LAI values of −10 to 5 HU were suggestive of mild to moderate steatosis (6%-30%); 18 (34.6%) volunteers did not proceed to donation because of negative LAI < −5 HU. In 2 cases with LAI of −7 and LAI of −8 liver biopsy was performed, and 30% steatosis was confirmed in the pathohistologic examination. Unacceptable liver biopsy result was considered as contraindication for donation. The LAI values of < −10 HU were suggestive of moderate to severe hepatic steatosis of 30% or greater. In these cases liver biopsy is not needed, as such donors are not acceptable for liver transplant. ConclusionComputed tomography imaging provides a detailed evaluation of fatty infiltration in donor liver parenchyma.

Impairment of the Akt pathway in transplanted Type 1 diabetic hearts is associated with post-transplant graft injury.

The use of 'marginal' hearts, such as from donors with diabetes mellitus (DM), could offer an opportunity to expand the donor pool in cardiac transplantation. Previous studies have shown that the phosphatidylinositol-3-kinase (PI3K)/Akt pathway is altered after ischaemia/reperfusion injury in the diabetic myocardium. We hypothesized that DM-induced cardiac dysfunction in donors is further impaired after heart transplantation and that PI3K/Akt-pathway alterations may be one of the underlying pathomechanisms. In the donor rats, DM was induced with a single dose of streptozotocin. Non-diabetic rats only received citrate buffer. After 8 weeks, the donor left ventricular (LV) cardiac function was measured. Then, the hearts were heterotopically transplanted into non-diabetic recipients. We evaluated LV graft function 1.5 h after transplantation via a Millar catheter system at different LV volumes. Histological analyses were performed, and the expression of 84 genes involved in PI3K/Akt signalling was profiled. DM was associated with significantly decreased LV contractility and impaired relaxation. After transplantation, in the DM group, the grafts' systolic function (LV systolic pressure 112 ± 31 vs 155 ± 60 mmHg; dP/dtmax 2676 ± 896 vs 3584 ± 1779 mmHg/s, P < 0.05) and diastolic function (dP/dtmin 924 ± 205 vs 1748 ± 512 mmHg/s, P < 0.05) were significantly reduced at an intraventricular volume of 170 µl. The expression of 10 genes involved in PI3K/Akt signalling, as well as the phosphorylated Akt/total Akt protein expression ratio, were significantly down-regulated in the diabetic heart after transplantation. DM-induced cardiac dysfunction is further impaired after transplantation. Targeting the PI3K/Akt pathway may result in a functional amelioration of the a priori-diseased myocardia, which could increase the number of potential cardiac donors.

Organ Dysfunction and Failure Following Brain Death Do Not Preclude Successful Donation.

Organ dysfunction is common after neurologic determination of death (NDD) but before organ collection. Reliable markers for graft success following transplant of these organs would be useful. We sought to determine the relationship between the donor after neurologic determination of death (DNDD) pathophysiology and successful organ donation. Donor information was obtained through the local organ procurement organization. Donor demographics and clinical data points for cardiovascular, renal, respiratory, hepatic, hematological and neuroendocrine systems were reviewed 12h before and 12h after neurologic determination of death was declared. The worst values were utilized for analysis and generation of the organ-specific Sequential Organ Failure Assessment (SOFA) scores. SOFA scores were calculated and used to quantify the degree of organ dysfunction. The NDD non-donors for a specific organ were used as a comparison control group. The control group refers to DNDD patients whose specific organs were not transplanted. Lack of use was mostly due to discard by the transplant team as a result of unsuitability of the organ caused by deterioration or possible donor-specific pathology. One hundred and five organ donors were analyzed. Mean age was 35.0 (±13.6), 78.1% male, median GCS 3, interquartile range (IQR) 3-4 and median injury severity score 32 (IQR 25-43). Of the successful donors, organ-specific severe dysfunction (SOFA 3 or 4) occurred in 96, 27.5 and 3.3% of cardiac, lung and liver donors, respectively. There was no significant difference between the levels of organ dysfunction in donors versus non-donors except lung donors, in which the median lowest partial pressure of arterial oxygen-to-fraction of inspired oxygen (P/F) ratio in the non-donor was 194 (IQR 121.8-308.3) compared to the median lowest P/F ratio in the donor which was 287 (IQR 180-383.5), p=0.02. In the recipients, graft failure 6months after transplantation was reported in one kidney recipient (0.74%) (peak donor creatinine=1mg/dL) and in five pancreas recipients (11.4%). The median peak glucose of the pancreas donors in failed recipients was 178mg/dL (IQR 157-213), whereas in the functioning recipients, the median glucose of their donors was not different (185mg/dL, IQR 157-216), p=0.394. Current measures of organ failure and dysfunction do not predict the success of organ donation. Successful donor management in the face of severe organ dysfunction and failure can result in lives saved.

Assessment of cardiac allograft systolic function by global longitudinal strain: From donor to recipient.

Cardiac allografts are routinely evaluated by left ventricular ejection fraction (LVEF) before and after transplantation. However, myocardial deformation analyses with LV global longitudinal strain (GLS) are more sensitive for detecting impaired LV myocardial systolic performance compared with LVEF. We analyzed echocardiograms in 34 heart donor-recipient pairs transplanted at Duke University from 2000 to 2013. Assessments of allograft LV systolic function by LVEF and/or LV GLS were performed on echocardiograms obtained pre-explanation in donors and serially in corresponding recipients. Donors had a median LVEF of 55% (25th, 75th percentile, 54% to 60%). Median donor LV GLS was -14.6% (-13.7 to -17.3%); LV GLS was abnormal (ie, >-16%) in 68% of donors. Post-transplantation, LV GLS was further impaired at 6 weeks (median -11.8%; -11.0 to -13.4%) and 3 months (median -11.4%; -10.3 to -13.9%) before recovering to pretransplant levels in follow-up. Median LVEF remained ≥50% throughout follow-up. We found no association between donor LV GLS and post-transplant outcomes, including all-cause hospitalization and mortality. GLS demonstrates allograft LV systolic dysfunction in donors and recipients not detected by LVEF. The clinical implications of subclinical allograft dysfunction detected by LV GLS require further study.

Current methods of assessing platelet function: relevance to transfusion medicine

Current methods of assessing platelet function: relevance to transfusion medicine

C34T AMP deaminase 1 gene mutation protects cardiac function in donors.

Dysfunction of the donor heart is an important clinical problem that could be affected by genetic factors. We tested the hypothesis that possession of the C34T nonsense mutation in AMPD1 gene, which is known to improve survival in chronic heart failure, protects against cardiac dysfunction in donors. Genetic analysis for C34T mutation was performed by single-stranded conformational polymorphism (SSCP) in 22 donor hearts used for transplantation, 10 unused donor hearts with acute heart failure (HF), 37 patients with chronic HF, and 207 healthy controls. We found a significantly higher frequency of the mutation among donors with healthy hearts used for transplantation (31.8%) as compared to control population (13.5%, P < 0.001) and a lower frequency in dysfunctional donor hearts (5.0% P = 0.025); the frequency of the C34T mutation in patients with chronic heart failure (14.8%) was not different from that of a control population. The presence of the C34T mutation in AMPD1 gene appears to be protective against acute heart failure in cardiac donors.