Older Donors Research Articles

Combined effect of unrelated donor age and HLA peptide-binding motif match status on HCT outcomes

AbstractAn HLA-mismatched unrelated donor who is class I peptide-binding motif (PBM)-matched is preferred over a PBM-mismatched donor. We hypothesized that using a younger donor (aged ≤35 years vs >35 years) could compensate for the inferior overall survival (OS) associated with PBM mismatches. We compared 6 groups: HLA-matched/younger donor (n = 10 531), HLA-matched/older donor (n = 3572), PBM-matched/younger donor (n = 357), PBM-matched/older donor (n = 257), PBM-mismatched/younger donor (n = 616), and PBM-mismatched/older donor (n = 339) in patients undergoing transplantation with conventional graft-versus-host disease prophylaxis. In multivariate analysis, HLA-matched/younger donors were associated with superior OS relative to any other group. Pairwise comparisons showed that donor age significantly impacted OS in both HLA-matched and HLA-mismatched groups. Moreover, younger donors appeared to negate the detrimental effect of PBM mismatching: the PBM-matched/younger donor group had similar OS as the HLA-matched/older donor group and the PBM-mismatched/younger donor group had similar OS as the PBM-matched/older donor group. Our study suggests that older unrelated donor age and PBM mismatching confer similarly adverse effects on OS and the impacts are additive, a finding which may widen the “acceptable” donor pool. The best OS is observed with HLA-matched/younger donors and the worst with PBM-mismatched/older donors. These findings should be validated with other data sets and with posttransplantation cyclophosphamide-based prophylaxis.

Age Matters: What Affects the Cumulative Lifespan of a Transplanted Liver?

Assess factors affecting the cumulative lifespan of a transplanted liver. Liver ageing is different from other solid organs. It is unknown how old a liver can actually get after liver transplantation (LT). Deceased donor liver transplants from 1988-2021 were queried from the United States (US) UNOS registry. Cumulative liver age was calculated as donor age + recipient graft survival. In total, 184,515 livers were included. Most were DBD-donors (n=175,343). The percentage of livers achieving >70, 80, 90 and 100years cumulative age was 7.8% (n=14,392), 1.9% (n=3,576), 0.3% (n=528), and 0.01% (n=21), respectively. The youngest donor age contributing to a cumulative liver age >90years was 59years, with post-transplant survival of 34years. In pediatric recipients, 736 (4.4%) and 282 livers (1.7%) survived >50 and 60years overall, respectively. Transplanted livers achieved cumulative age >90years in 2.86-per-1000 and >100years in 0.1-per-1000. The US population at-large has a cumulative "liver age" >90years in 5.35-per-1000 persons, and >100y in 0.2-per-1000. Livers aged>60 years at transplant experienced both improved cumulative survival ( P <0.0001) and interestingly improved survival after transplantation ( P <0.0001). Recipient warm-ischemia-time of >30minutes was most predictive of reduced cumulative liver survival overall (n=184,515, HR=1.126, P <0.001) and excluding patients with mortality in the first 6month (n=151,884, HR=0.973, P <0.001). In summary, transplanted livers frequently get as old as those in the average population despite ischemic-reperfusion-injury and immunosuppression. The presented results justify using older donor livers regardless of donation type, even in sicker recipients with limited options.

The dynamics of B-cell reconstitution post allogeneic hematopoietic stem cell transplantation: A real-world study.

The immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for preventing infections and relapse and enhancing graft-versus-tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo-HSCT has not been well studied. In this study, we analyzed the dynamics of B cells in 252 patients who underwent allo-HSCT for 2 years and assessed the impact of factors on B-cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood. We found that the B-cell reconstitution in the bone marrow was consistent with the peripheral blood (p=0.232). B-cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft-versus-host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post-1-year B-cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age-B cells-survival axis and found that B-cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival (p=0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation (p=0.037). Our findings provide valuable insights for optimizing the management of B-cell reconstitution and improving the efficacy and safety of allo-HSCT.

Haploidentical stem cell donor choice for patients with acute myeloid leukemia: a study from the ALWP of the EBMT

AbstractThere is a paucity of information to guide the selection of the most suitable donor in haploidentical (Haplo) hematopoietic stem cell transplantation (HSCT). For this reason, from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we conducted a retrospective analysis to evaluate the impact of Haplo donor characteristics on outcomes in patients with acute myeloid leukemia (AML) who received graft-versus-host disease prophylaxis with posttransplant cyclophosphamide (PTCy). The primary end point was graft-versus-host disease (GVHD)-free and relapse-free survival (GRFS). Overall, 2200 patients were included. The median age of donors was 37 years (range, 8-71); 820 (37%) were females, including 458 (21%) who were used for male recipients. In addition, 1631 donors (74%) donated peripheral blood (PB). Multivariable analysis identified certain donor-related risk factors with a detrimental impact on transplant outcomes. The use of PB, older donors’ ages (>37 years), and female donors to male recipients negatively affected GRFS. Donor’s age and female donor-to-male recipient combination also affected nonrelapse mortality, leukemia-free survival, and overall survival. In conclusion, donor-related variables significantly influence outcomes in patients with AML after Haplo-HSCT with PTCy. When possible, younger donors and male donors for male recipients should be prioritized. The use of bone marrow can additionally prevent GVHD.

Active Donor Management Goals in Serial Donors After Brain Death.

Management of potential organ donors is crucial in the donation process, considering that hemodynamic instability is quite common. In the this single-center retrospective observational study, we analyzed 87 utilized brain death donors consecutively admitted to our intensive care unit from January 1, 2019, to December 31, 2022. We assessed the achievement of donor management goals during the observation period, and we also evaluated whether the achieve-ment of donor goals differed between younger and older donors (arbitrary age cutoff of 65 years). In our series, mean age of donors was 67 ± 18 y, and organ-per-donor ratio was 2.3. The number of donor goals significantly increased during the 6-hour observation period (P < .001) and all donor goals were achieved in most donors (84/87) at the end of the observation period with no changes in the use and dose of vasoactive drugs. With respect to age, the number of donor goals was significantly higher in older donors at first evaluation, but goals significantly increased in both age subgroups of donors at the end of the 6-hour observation period. Our data strongly suggested that a strict hemodynamic monitoring schedule allows the achievement of donor goals both in older and in younger brain death donors. We confirmed our previous findings that hemodynamic management in brain death donors is influenced by age. A strict hemodynamic monitoring schedule of brain death donors is useful to consistently achieve donor goals.

Exploratory neutron tomography of articular cartilage

To investigate the feasibility of using neutron tomography to gain new knowledge of human articular cartilage degeneration in osteoarthritis (OA). Different sample preparation techniques were evaluated to identify maximum intra-tissue contrast. Human articular cartilage samples from 14 deceased donors (18-75 years, 9 males, 5 females) and 4 patients undergoing total knee replacement due to known OA (all female, 61-75 years) were prepared using different techniques: control in saline, treated with heavy water saline, fixed and treated in heavy water saline, and fixed and dehydrated with ethanol. Neutron tomographic imaging (isotropic voxel sizes from 7.5 to 13.5µm) was performed at two large scale facilities. The 3D images were evaluated for gradients in hydrogen attenuation as well as compared to images from absorption X-ray tomography, magnetic resonance imaging, and histology. Cartilage was distinguishable from background and other tissues in neutron tomographs. Intra-tissue contrast was highest in heavy water-treated samples, which showed a clear gradient from the cartilage surface to the bone interface. Increased neutron flux or exposure time improved image quality but did not affect the ability to detect gradients. Samples from older donors showed high variation in gradient profile, especially from donors with known OA. Neutron tomography is a viable technique for specialized studies of cartilage, particularly for quantifying properties relating to the hydrogen density of the tissue matrix or water movement in the tissue.

Characterization of a human H3N8 influenza virus

In 2022 and 2023, novel reassortant H3N8 influenza viruses infected three people, marking the first human infections with viruses of this subtype. Here, we generated one of these viruses (A/Henan/4-10CNIC/2022; hereafter called A/Henan/2022 virus) by using reverse genetics and characterized it. In intranasally infected mice, reverse genetics-generated A/Henan/2022 virus caused weight loss in all five animals (one of which had to be euthanized) and replicated efficiently in the respiratory tract. Intranasal infection of ferrets resulted in minor weight loss and moderate fever but no mortality. Reverse genetics-generated A/Henan/2022 virus replicated efficiently in the upper respiratory tract of ferrets but was not detected in the lungs. Virus transmission via respiratory droplets occurred in one of four pairs of ferrets. Deep-sequencing of nasal swab samples from inoculated and exposed ferrets revealed sequence polymorphisms in the haemagglutinin protein that may affect receptor-binding specificity. We also tested 90 human sera for neutralizing antibodies against reverse genetics-generated A/Henan/2022 virus and found that some of them possessed neutralizing antibody titres, especially sera from older donors with likely exposure to earlier human H3N2 viruses. Our data demonstrate that reverse genetics-generated A/Henan/2022 virus is a low pathogenic influenza virus (of avian influenza virus descent) with some antigenic resemblance to older human H3N2 viruses and limited respiratory droplet transmissibility in ferrets. This work was supported by the Japan Program for Infectious Diseases Research and Infrastructure (JP23wm0125002), and the Japan Initiative for World-leading Vaccine Research and Development Centers (JP233fa627001) from the Japan Agency for Medical Research and Development (AMED).

Donor complication rates in whole blood, plasma and platelet donors: Age versus experience.

Many blood banks use upper age limits for donors out of concern for a higher donor complication rate in older donors. Experienced donors are known to have lower donor complication rates, and older donors are often more experienced, confounding the effect of age on donor complication rate. We studied donor complication rates in whole blood, plasma, and plateletpheresis donors from 2012 to 2022. Donor complication rates were compared between age groups in inexperienced (<20th donation) and experienced (≥20th donation) donors. In addition to this direct comparison, we made use of logistic regression with finer-grained experience groups, to further quantify the effects of age, experience and other factors on donor complication rate. While overall rate of vasovagal reaction was lower, rate of moderate/severe vasovagal syncope was highest in 70-79 year donors, however, only reached significance for plasma donors. Furthermore, rates of failed stab were highest in this age group. Hematoma rate showed a U-shaped pattern with regard to age, where the rate was not higher in the 70-79 year age group than in the 18-23 year age group. Pain decreased with age, however, rates were higher in the 70-79 year age group than in the 65-69 year age group. When properly accounting for donor experience, donor complication rate profiles clearly change with age. The increased risk for moderate/severe vasovagal syncope in older donors should be clearly communicated. Extra caution is needed if these donors are accepted for first-time donations.

Investigation of sex-based differences in the immunotoxicity of silver nanoparticles

The growing application of silver nanoparticles (AgNPs) in consumer, healthcare, and industrial products has raised concern over potential health implications due to increasing exposure. The evaluation of the immune response to nanomaterials is one of the key criteria to assess their biocompatibility. There are well-recognized sex-based differences in innate and adaptive immune responses. However, there is limited information available using human models. The aim was to investigate the potential sex-based differences in immune functions after exposure to AgNPs using human peripheral blood mononuclear cells (PBMCs) and plasma from healthy donors. These functions include inflammasome activation, cytokine expression, leukocyte proliferation, chemotaxis, plasma coagulation, and complement activation. AgNPs were characterized by dynamic light scattering and transmission electron microscopy. Inflammasome activation by AgNPs was measured after 6- and 24-hours incubations. AgNPs-induced inflammasome activation was significantly higher in the females, especially for the 6-hour exposure. No sex-based differences were observed for Ag ions controls. Younger donors exhibited significantly more inflammasome activation than older donors after 24-hours exposure. IL-10 was significantly suppressed in males and females after exposure. AgNPs suppressed leukocyte proliferation similarly in males and females. No chemoattractant effects, no alterations in plasma coagulation, or activation of the complement were observed after AgNPs exposure. In conclusion, the results highlight that there are distinct sex-based differences in inflammasome activation after exposure to AgNPs in human PBMCs. The results highlight the importance of considering sex-based differences in inflammasome activation induced by exposure to AgNPs in any future biocompatibility assessment for products containing AgNPs.

Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe. Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Use of 50 years or older donors in septuagenarian recipients for liver transplantation: Potential to expand the donor pool: Old livers for old transplant recipients

BackgroundWhile younger donors have better liver transplant (LT) outcomes, the median age of both the donor and recipient pools is rising. The impact of using donors ≥50 years on the LT outcomes of septuagenarians is unknown. MethodsFrom 2011–2021, outcomes in septuagenarian LT recipients from donor livers <50 year-old (DON<50) and donor livers ≥50 year-old (DON≥50) were analyzed using the United Network for Organ Sharing database. Post-LT survival analysis was performed with the Kaplan-Meier method and multivariable Cox proportional-hazards model. A propensity score was utilized to conduct one-to-one matching using 14 recipient variables (1230-pairs). ResultsThere were 2797 septuagenarian deceased-donor LT recipients during the study period. Of these, 1487 (53.2 %) were DON <50 with median age of 34 years and 1310 (46.8 %) were DON ≥50 with median age of 60 years. The number of LT for septuagenarians has increased over the last decade. The causes of donor and recipient deaths were different between two groups. Post-LT one-year survival (DON<50: 89.3 % vs. DON≥50: 88.3 %) and five-year survival (DON<50: 41.4 % vs DON≥50: 42.8 %) were comparable. Multivariable Cox proportional-hazards model showed that donor age ≥50 years is not associated with increased mortality after LT in the matched cohort (HR: 1.04, 95 % CI: 0.88–1.24, P = 0.63). ConclusionsThe utilization of carefully selected donor livers older than 50 years may be a viable option for septuagenarian LT candidates by lowering their waitlist time and can maximize the organ utilization without compromising the outcomes.

The Impact of Age Group in Hierarchical Forecasting of Monthly Blood Donations in Zimbabwe.

To meet the blood requirements for transfusion therapy, blood banks need to ensure that blood inventories are maintained at desirable levels. There is a rising global need for optimal ways to manage blood supply and demand using statistical models in blood inventory planning and management. Thus, blood donation forecasting using donor-specific characteristics such as donor type and age is critical in managing the blood bank inventory. The monthly blood donation data covering the period 2007 to 2018, collected from the National Blood Service Zimbabwe (NBSZ) was used in this study. The data is first disaggregated based on donor age, and further disaggregation is performed for each age group based on donor type. The hierarchical forecasting approaches, namely the bottom-up, top-down and the optimal combination methods were used in the data analysis. The Error-Trend-Seasonality (ETS) and Autoregressive Integrated Moving Average (ARIMA) methods are used in the hierarchical forecasting approaches to generate the forecasts. New blood donors account for more than 55% of blood donations in Zimbabwe. The younger donors (16-29 years) dominate the blood donations, accounting for 89.2% of the donations. Young and new donors account for nearly 50% of the donations. The middle-aged and older donors have lower blood donations. The bottom-up approach under the ARIMA model outperformed all the other approaches. The future projections show that new and young donors will increase in blood donations, regular donations will decline slightly while the occasional donations are projected to remain constant. Hierarchical forecasting is a unique approach in that the different aggregation levels reveal important features of the blood donation data. The lower percentage of regular donations is worrisome to blood authorities as it points to new blood donors not returning for further donations. Blood authorities need to develop policies that will encourage new and young donor categories to become regular donors.

In Vitro Osteogenesis Study of Shell Nacre Cement with Older and Young Donor Bone Marrow Mesenchymal Stem/Stromal Cells.

Bone void-filling cements are one of the preferred materials for managing irregular bone voids, particularly in the geriatric population who undergo many orthopedic surgeries. However, bone marrow mesenchymal stem/stromal cells (BM-MSCs) of older-age donors often exhibit reduced osteogenic capacity. Hence, it is crucial to evaluate candidate bone substitute materials with BM-MSCs from the geriatric population to determine the true osteogenic potential, thus simulating the clinical situation. With this concept, we investigated the osteogenic potential of shell nacre cement (SNC), a bone void-filling cement based on shell nacre powder and ladder-structured siloxane methacrylate, using older donor BM-MSCs (age > 55 years) and young donor BM-MSCs (age < 30 years). Direct and indirect cytotoxicity studies conducted with human BM-MSCs confirmed the non-cytotoxic nature of SNC. The standard colony-forming unit-fibroblast (CFU-F) assay and population doubling (PD) time assays revealed a significant reduction in the proliferation potential (p < 0.0001, p < 0.05) in older donor BM-MSCs compared to young donor BM-MSCs. Correspondingly, older donor BM-MSCs contained higher proportions of senescent, β-galactosidase (SA-β gal)-positive cells (nearly 2-fold, p < 0.001). In contrast, the proliferation capacity of older donor BM-MSCs, measured as the area density of CellTrackerTM green positive cells, was similar to that of young donor BM-MSCs following a 7-day culture on SNC. Furthermore, after 14 days of osteoinduction on SNC, scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS) showed that the amount of calcium and phosphorus deposited by young and older donor BM-MSCs on SNC was comparable. A similar trend was observed in the expression of the osteogenesis-related genes BMP2, RUNX2, ALP, COL1A1, OMD and SPARC. Overall, the results of this study indicated that SNC would be a promising candidate for managing bone voids in all age groups.

High Rate of Kidney Graft Failure after Simultaneous Heart-Kidney Transplantation.

The indications and outcomes of Simultaneous heart-kidney transplantation (SHKT) remain sub-optimally defined. Risk factors for renal graft failure after SHKT also remain poorly defined. We analyzed the renal graft outcomes among SHKT recipients using United Network for Organ Sharing database from 2015-2020. To evaluate for factors associated with poor renal outcomes, we compared SHKT and kidney transplantation alone (KTA) recipients using propensity score matching. Among SHKT recipients, rate of primary non-function (PNF) of kidney graft was 3%, 30-day kidney graft failure rate was 7.0%, and the 30-day post-transplant mortality rate was 4.1%. The incidence of delayed kidney graft function (KDGF) was 27.5%. Kidney graft failure was seen early post-SHKT with most common causes of patient death (43.9%) and PNF of kidney graft (41.5%). One-year and two-year patient survival was 89.2% and 86.5%, and one-year and two-year freedom from kidney graft failure was 85.4% and 82.7%, respectively. In subgroup analysis of SHKT recipients, use of pre-transplant mechanical cardiac support (adjusted Odds Ratio (aOR) 2.57, P=0.017), higher cPRA (aOR 1.76, P=0.016), and older donor age per 10 years (aOR 1.94, P=0.001) were associated with PNF. Pre-transplant extracorporeal membrane oxygenation support was associated with the increased risk of 30-day recipient mortality (aOR 5.55, P=0.002). Increased 30-day graft failure was seen in SHKT recipients with pre-transplant mechanical cardiac support (aOR 1.77, P=0.038) and dialysis at time of transplant (aOR 1.72, P=0.044). Multivariable Cox-Hazard analysis demonstrated that SHKT, when compared to KTA, is associated with increased kidney graft failure (Hazard Ratio, 2.56, P<0.001) and recipient mortality (Hazard Ratio: 2.65, P<0.001). SHKT is associated with high rates of kidney graft failure. Identification of risk factors for renal graft failure can help optimize recipient selection for SHKT vs Kidney after HT, especially after introduction of the new safety-net policy.

Usage of older donors is associated with higher mortality after heart transplantation: A UNOS observational study

IntroductionUtilization of heart from older donors is variable across centers with uncertain outcomes of recipients. We sought to utilize a national registry to examine usage and outcomes of heart transplant recipients from older donors. We also explored the impact of current donor heart allocation scheme on outcomes of hearts from older donors. MethodsThis observational study utilized the United Network for Organ Sharing database between 2015 and 2023 with donors categorized into age < 45 years or ≥ 45 years and evaluated organ disposition and geographical variation. 30-day, 1- and 3- year mortality, and graft failure rates were compared amongst recipients as per donor age group. We also evaluated annual trends in HT for each group over the follow-up period. Results24,966 adult donors were recovered: 3,742 (15.0%) were ≥ 45 years; 3,349 (15.6%) adults received heart from such donors with significant geographical variation, and a declining utilization in the transplantation rate in current donor allocation system. Donors with age ≥ 45 years had higher comorbidities and were allotted with a significantly shorter ischemic time to recipients who were significantly less likely to receive temporary mechanical circulatory support and more likely female. Unadjusted and adjusted, 30-day mortality were similar but 1- and 3-year mortality and graft failure rates were significantly higher in recipients of such donors. spline analysis suggested a higher 1-year mortality risk at older donor age with risk increasing after age 40 years. ConclusionsOlder donor age was associated with worsened 1- and 3-year mortality and graft failure for heart transplant recipients.

Myeloablative Haploidentical Donor Hematopoietic Transplantation Using Post-Transplantation Cyclophosphamide and Antithymocyte Globulin

Haploidentical donor (haplo-) hematopoietic stem cell transplantation (HSCT) with post-transplantation cyclophosphamide (PTCy) is now performed on a large scale worldwide. Our patient outcomes did not completely reflect the results published by other groups. We herein present the results of 60 patients with hematologic malignancies treated homogeneously on a modified version of the standard protocol by adding ATG as an additional graft-versus-host disease (GVHD) prophylaxis measure. This was a retrospective analysis of 60 haplo-HSCT recipients using a myeloablative conditioning regimen with antithymocyte globulin and PTCy for GVHD prophylaxis. At 5 years, overall survival was 59.2%, relapse-free survival (RFS) was 48.6%, and chronic GVHD (cGVHD) and relapse-free survival was 40%. The median time to neutrophil and platelet engraftment was 16 days and 28.5 days, respectively. The rates of grade II-IV acute GVHD and extensive cGVHD were 46.7% and 23.3%, respectively. The cumulative incidence of relapse was 30%, nonrelapse mortality was 21.6%, and transplantation-related mortality was 11%. Higher Disease Risk Index and 50% HLA match were associated with lower RFS. Female donor to male recipient and older donor age were associated with an elevated risk of cGVHD. The use of PTCy might not yield the same results in different populations. Many remaining questions need to be addressed in randomized trials, including optimal graft source and donor, date of calcineurin inhibitor initiation, personalized or targeted dose of PTCy, immune reconstitution, and others.

Prevalence, incidence, risk factors and residual risk associated with viral infections among eligible Brazilian blood donors.

Knowledge regarding the profile of eligible blood donors presenting positive results in laboratory screening is essential for reducing transfusion-transmitted human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Our study aimed to evaluate the prevalence, incidence, predictor variables and residual risk (RR) of HIV/HBV/HCV in blood bags donated in Minas Gerais, Brazil. This study analysed data retrieved from the records of a large blood bank relating to donations collected at multiple centres within the period 2012-2018, during which 1 991 120 blood bags were screened using immunoassays and nucleic acid tests (NATs). Multilevel modelling was used to investigate the association between sex, civil status and age group with HIV/HBV/HCV. RR was estimated from the incidence values (restricted to negative and positive tests within the study period) and window periods for infections. The prevalence in first time donors, incidence and RR of HCV (223.73 cases per 100 000; 54.84 per 100 000 persons-year and 1.6527 per 100 000, respectively) were higher than those of HIV (172.65 cases per 100 000; 28.25 per 100 000 persons-year and 0.8514 per 100 000) and HBV (168.17 cases per 100 000; 18.54 per 100 000 persons-year and 0.5588 per 100 000). The odds of acquiring infection were greater in male, single and older donors. Sixteen donors were identified as seronegative and NATs+ during the 7-year span of the study. Our study has clarified some spatiotemporal trends regarding HIV/HBV/HCV infections in donated blood in Brazil. The results will contribute to the formulation of directives addressed to high-risk donors.

THE RELATIONSHIP BETWEEN MICROSTRUCTURE AND MECHANICAL RESPONSE IN THE HUMAN MENISCUS

To characterize the microstructural organization of collagen fibers in human medial menisci and the response to mechanical loading in relation to age. We combine high resolution imaging with mechanical compression to visualize the altered response of the tissue at the microscale. Menisci distribute the load in the knee and are predominantly composed of water and specifically hierarchically arranged collagen fibers. Structural and compositional changes are known to occur in the meniscus during aging and development of osteoarthritis. However, how microstructural changes due to degeneration affect mechanical performance is still largely unknown [1].Fresh frozen 4 mm Ø plugs of human medial menisci (n=15, men, 20-85 years) with no macroscopic damage nor known diseases from the MENIX biobank at Skåne University Hospital were imaged by phase contrast synchrotron tomography at the TOMCAT beamline (Paul Scherrer Institute, CH). A rheometer was implemented into the beamline to perform in-situ stress relaxation (2 steps 15% and 30% strain) during imaging (21 keV, 2.75μm pixel size). 40s scans were acquired before and after loading, while 14 fast tomographs (5s acquisitions) were taken during relaxation. The fiber 3D orientations and structural changes during loading were determined using a structure tensor approach (adapting a script from [1]). The 3D collagen fiber orientation in menisci revealed alternating layers of fibers. Two main areas are shown: surfaces and bulk. The surface layers are a mesh of randomly oriented fibers. Within the bulk 2-3 layers of fibers are visible that alternate about 30° to each other. Structural degeneration with age is visible and is currently being quantified. During stress-relaxation all menisci show a similar behavior, with samples from older donors being characterized by larger standard deviation Furthermore, the behavior of the different layers of fibers is tracked during relaxation showing how fibers with different orientation respond to the applied loading.Acknowledgments: We thank PSI for the beamtime at the TOMCAT beamline X02DA, and funding from Swedish Research Council (2019-00953), under the frame of ERA PerMed, and the Novo Nordisk Foundation through MathKOA (NNF21OC0065373).

Medical and economic impacts of managing corneas from older donors at the tissue bank-a single-center retrospective study spanning over 12 years.

To evaluate the impact of corneas from donors over 80 years of age on the activity of the North of France Tissue Bank and to determine the potential cost implications for banks using corneas from older donors. We analyzed data from a single-center retrospective cohort study of 6,023 corneas preserved at the Lille Tissue Bank between 2012 and 2023. Donors, unrestricted by age, were divided into two groups: younger (≤ 80 years) and older (> 80 years). Corneas were categorized based on endothelial cell density (ECD). Data were collected from patients who underwent corneal transplantation. A financial impact model was created to assess the effects of using corneas from different age groups on the overall benefits of corneal transplant procedures. The average donor age was 67.5 ± 14.5 years. The median age of donors gradually increased from 66 to 73 years over the 12-year study period, with donors over 80 years old representing more than 24% since 2021. Corneas from older donors had a higher discard rate (62.53% vs. 39.66%) due to poor endothelial quality and serological concerns (both p < 0.0001). Additionally, these corneas had lower ECD, with a larger proportion deemed unsuitable for grafting due to low ECD (30% vs. 8.2%). Corneas from younger donors were more often used for endothelial transplants, which require higher ECD. The mean economic benefit per cornea showed a moderate negative correlation with donor age. The net benefit of corneal transplants decreased as the proportion of donors aged over 80 years increased. It is predicted that a net benefit of zero would be attained when the proportion of donors over 80 years is 44.4%. Using corneas from donors over 80 years of age can help alleviate the shortage of donor tissue and be effective if certain quality standards are met. However, additional costs incurred by eye banks must be factored into this equation.

Analysing lapsing rates among first-time blood donors at a blood centre in Zimbabwe using survival analysis.

blood centres are often faced with the problem of donor lapsing resulting in loss of donors from the already strained donor pool. In Zimbabwe, 70% of the donated blood comes from younger donors aged 40 years and below, who at the same time, have high attrition rates. This study seeks to apply the concept of survival analysis in analysing blood donor lapsing rates. in analysing the donor lapsing and retention rates, data on 450 first-time blood donors at the National Blood Service Zimbabwe, in Harare´s blood bank for the period 2014 to 2017 was extracted from the donors´ database. The Cox proportional hazards (Cox PH) and Kaplan-Meier methods were applied in the analysis. Donor demographic characteristics suspected of having effect on donor lapsing and retention were identified and analysed. the study findings show that 56.9% of the donors had lapsed by the end of the four-year study period. Results from the multiple Cox PH model indicate that donor age had a significant effect on blood donor retention time (p = 0.000918 < 0.05). The hazard ratio (HR) = 0.615 with 95% CI: (0.461; 0.820) shows that the relatively older donors had a lower hazard (38.5% lower) of lapsing compared to the hazard for younger donors. The effect of gender, blood donor group and donation time interval on donor retention and attrition were not statistically significant. Male donors had HR = 1.03; 95% CI (0.537; 1.99) with (p = 0.922 > 0.05) and donors with a 4-month interval between donations had HR = 1.31; 95% CI (0.667; 2.59) with (p = 0.430 > 0.05). the study confirmed the problem of donor attrition faced by blood centres. The age of the donor had a significant effect on the retention time of blood donors before lapsing. The older the blood donor, the lower the risk of lapsing. The Zimbabwe National Blood Service (NBSZ) Blood Centre authorities should have a critical mass of individuals above 40 years as potential blood donors because of their reliability in blood donation according to the study findings.