Donor Age Research Articles

Factors influencing white blood cell mobilisation in healthy granulocyte donors.

Granulocyte transfusions represent a therapeutic option for severely neutropenic patients with bacterial or fungal infections that are otherwise unresponsive to conventional therapy. Prior clinical studies suggest that patients receiving higher granulocyte doses achieve superior outcomes. Consequently, suboptimal donor stimulation and collection leading to lower granulocyte doses likely correlate with worse clinical outcomes. A retrospective analysis was conducted on mobilisation data from 312 granulocyte collections from healthy donors between January 2020 and May 2023. This study was performed in a single blood donor center exclusively supporting a comprehensive cancer center. Donors underwent stimulation with 480 mcg of filgrastim (granulocyte colony stimulating factor [G-CSF]) subcutaneously and 8 mg of dexamethasone orally administered 12 to 14 h before collection. The correlation between donor characteristics (age, gender, body weight (BW), body mass index (BMI), baseline haemoglobin (Hgb), and platelet (PLT) counts) and mobilisation efficiency (Δ WBC, defined as post-mobilisation WBC count-baseline WBC count) was examined to identify factors associated with enhanced mobilisation efficiency. Additionally, the impact of multiple donations on Δ WBC in repeat donors was assessed. The median donor age was 43 years (range 18-81), with 224 male and 88 female donors. Female donors exhibited significantly higher baseline PLT counts and post-mobilisation WBC counts. However, donor gender did not significantly affect Δ WBC. A negative correlation was observed between Δ WBC and age (r = -0.235, p = 0.001), with older donors (61-81 years) exhibiting significantly lower mobilisation efficiency. BW and BMI differences had no significant effect on Δ WBC. A positive correlation was identified between baseline PLT count and Δ WBC (r = 0.140, p = 0.014), with females having significantly higher baseline PLT counts (p = 0.0004). No correlation was found between Δ WBC and baseline Hgb (r = 0.004, p = 0.477). Repeat donors showed no statistically significant change in Δ WBC with subsequent donations, with a mean interval of 136.5 days between collections. Mobilisation efficiency was not impacted by donor BW or BMI suggesting that BW-based G-CSF stimulation is not essential for optimising WBC mobilisation. Rather, a fixed single dose of 480 mcg of G-CSF and 8 mg of dexamethasone was sufficient to mobilise donors, thus reducing the procedural costs and the potential risks for medication-related side effects. The positive correlation found between baseline PLT count and Δ WBC suggests that PLT count could be used as a potential predictor of mobilisation efficiency. Mobilisation response in up to four collections in repeat granulocytes donors was not affected in subsequent donations. However, sample size is a limitation, and more data is needed for a meaningful conclusion of whether frequent granulocyte donations are safe and effective.

Removing upper age restrictions for returning donors and increasing the new donor upper age: Novel adverse event findings using a comprehensive donor vigilance system in Australia.

In July 2019, Australia removed the upper age limit for returning donors (previously 80 years) and increased the upper age for new donors from 70 to 75 years. This study assessed the safety of our new policy for our newly eligible upper age donors (NEUADs). For the period, 14 July 2019 to 30 June 2023, the relative risk (RR) of individual adverse events in NEUADs was compared with younger cohorts. There were 4529 NEUADs who made 8000 donations. The overall rates of vasovagal reactions (VVRs) were significantly lower in the NEUAD cohort. However, compared with younger donors; returning NEUADs had a significantly higher rate of loss of consciousness (RR 2.62; 95% confidence interval [CI]: 1.41-4.86) and new NEUADs had a significantly higher rate of offsite VVRs (RR 1.60; 95% CI: 1.08-2.37). Both new and returning NEUADs had significantly higher rates of VVR requiring outside medical care (RR 2.48; 95% CI: 1.28-4.79 and RR 4.45; 95% CI: 2.00-9.91 respectively). Our findings support historical findings that overall VVR rates decline with age but suggest a higher risk of more serious VVRs.

The Development of a Predictive Model for Postoperative Renal Function in Living Kidney-Transplant Donors

Background/Objectives: The accurate prediction of postoperative renal function (post-RF) in living kidney donors is essential for optimizing donor safety and long-term health. After nephrectomy, renal function can be significantly altered, owing to the functional adaptation of the remaining kidney; however, the extent of this has not been investigated. This study aimed to examine how various donor factors affect functional adaptation after nephrectomy, and to develop a new predictive model. Methods: In total, 310 patients who underwent donor nephrectomy were included. Preoperative split renal function (pre-SRF) of the remaining kidney was measured. Post-RF was measured 1 month after surgery. The functional adaptation rate was calculated from the difference between pre-SRF and post-RF. Multiple regression analysis was performed to develop a predictive formula for post-RF, incorporating donor age and pre-SRF. Results: The median age of the donors was 60 years, and 38.7% were men. The median pre-SRF was 36.4 mL/min/1.73 m2. The median functional adaptation rate was 26.8%, with donor age, pre-SRF, and a history of hyperuricemia (HUA) being significant predictors of the functional adaptation rate. The equation for post-RF was established as 0.94 × pre-SRF − 0.12 × age + 18.87 mL/min/1.73 m2. The estimated post-RF showed a high coefficient of determination (R2 = 0.76), with a mean bias of –0.01 mL/min/1.73 m2. Conclusions: Donor age, pre-SRF, and HUA are key predictors of renal functional adaptation after nephrectomy. The developed formula accurately estimates post-RF, supporting clinical decision-making and donor counseling for living kidney donations.

Effects of blood donor characteristics and storage on red blood cell haemoglobin β S-nitrosylation.

In the setting of tissue hypoxia, S-nitrosylated haemoglobin (SNO-Hb) plays crucial roles in the control of blood flow. This is associated with decreased oxygen affinity to haemoglobin and increase in tissue oxygenation. Red blood cell (RBC) transfusion is primarily performed to improve tissue oxygenation in anaemic patients. RBCs after storage undergo a variety of biochemical and functional alterations, including deficiency of nitric oxide (NO) bioactivity. However, how donor characteristics affect NO levels during RBC storage is unclear. We sought to investigate the association of blood donor age, gender and storage duration with NO and SNO-Hb levels in blood units. Blood samples from 42 healthy younger (≤30 years) and older (≥45 years) donors were collected and stored for up to 42 days. Total NO kits were used to detect total nitrite and nitrate levels in blood storage solution. SNO-Hb levels in RBCs were detected and analysed by quantitative mass spectrometry. Total NO levels in the blood storage solution significantly increased with donor age and storage duration. Proteomic analysis revealed that RBCs from older donors, particularly older females, significantly lost SNO-Hb during storage. Our findings indicate that RBCs from older donors are associated with reduced SNO-Hb levels and increased NO metabolites in storage solution after ≥35 days storage. The findings suggest stored RBCs from older donors may have reduced capacity to deliver oxygen to tissues under hypoxia. A shorter shelf life may be required for storing RBCs from older donors, particularly older females.

Differential morphophysiological and epigenetic responses during in vitro multiplication of Quercus robur depending on donor age and plant growth regulators

In the in vitro cloning of specific individuals of woody species, a challenge can be the low viability of explants collected from old mature donor trees due to the recalcitrance of their plant material. Other factors, such as the auxin–cytokinin balance, must also be considered. We investigated how in vitro conditions and donor age can modulate the regeneration capacity, morphophysiology, and DNA methylation of Quercus robur. Explants from two different donors (70- and 600-year-old trees) were subjected to 8 different treatments, which consisted of 0, 1.25, 3.5, or 7.0 µM 6-benzylaminopurine (BAP) combined with two concentrations of 0 or 0.5 µM 1-naphthaleneacetic acid (NAA). In the absence of BAP, there was no shoot induction, and root formation was achieved only in the shoots of the 70-year-old clone. Shoot number was lower in the shoots of the 600-year-old clone. Both clones showed increased regeneration capacity under BAP exposure, which was positively correlated with 8-hydroxydeoxyguanosine (8-oxo-dG) levels and the antioxidant capacity of total phenolics. In contrast, shoot induction was negatively correlated with 5-methylcytosine (m5C) levels. Treatments with increased BAP concentrations induced the development of anatomical and biochemical characteristics such as underdeveloped tissues and/or delayed tissue development, and this effect was less intense in the 600-year-old clone. Global hypomethylation strongly correlates with guanine hyperoxidation and the de novo regeneration response. Our results suggest that explants collected from fully mature trees may have different growth regulator supplementation needs due to the ‘donor age’ factor. Older clones may require a higher concentration of cytokinins to ensure a regenerative response.

Muscle fibroblasts and stem cells stimulate motor neurons in an age and exercise‐dependent manner

AbstractExercise preserves neuromuscular function in aging through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct cocultures of embryonic rat motor neurons with either human MuSC or FIB, RNA sequencing revealed profound differential regulation of the motor neuron transcriptome, with FIB generally favoring neuron growth and cell migration and MuSC favoring production of ribosomes and translational machinery. Conditioned medium from FIB was superior to MuSC in preserving motor neurons and increasing their maturity. Lastly, we established the importance of donor age and exercise status and found an age‐related distortion of motor neuron and muscle cell interaction that was fully mitigated by lifelong physical activity. In conclusion, we show that human muscle FIB and MuSC synergistically stimulate the growth and viability of motor neurons, which is further amplified by regular exercise.

Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium

BackgroundHuman induced pluripotent stem cells represent a scalable source of youthful tissue progenitors and secretomes for regenerative therapies. The aim of our study was to investigate the potential of conditioned medium (CM) from hiPSC-mesenchymal progenitors (hiPSC-MPs) to stimulate osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (MSCs). We also investigated whether prolonged cultivation or osteogenic pre-differentiation of hiPSC-MPs could enhance the stimulatory activity of CM.MethodsMSCs were isolated from 13 donors (age 20–90 years). CM derived from hiPSC-MPs was added to the MSC cultures and the effects on proliferation and osteogenic differentiation were examined after 14 days and 6 weeks. The stimulatory activity of hiPSC-MP-CM was compared with the activity of MSC-derived CM and with the activity of CM prepared from hiPSC-MPs pre-cultured in growth or osteogenic medium for 14 days. Comparative proteomic analysis of CM was performed to gain insight into the molecular components responsible for the stimulatory activity.ResultsPrimary bone marrow-derived MSC exhibited variability, with a tendency towards lower proliferation and tri-lineage differentiation in older donors. hiPSC-MP-CM increased the proliferation and alkaline phosphatase activity of MSC from several adult/aged donors after 14 days of continuous supplementation under osteogenic conditions. However, CM supplementation failed to improve the mineralization of MSC pellets after 6 weeks under osteogenic conditions. hiPSC-MP-CM showed greater enhancement of proliferation and ALP activity than CM derived from bone marrow-derived MSCs. Moreover, 14-day cultivation but not osteogenic pre-differentiation of hiPSC-MPs strongly enhanced CM stimulatory activity. Quantitative proteomic analysis of d14-CM revealed a distinct profile of components that formed a highly interconnected associations network with two clusters, one functionally associated with binding and organization of actin/cytoskeletal components and the other with structural constituents of the extracellular matrix, collagen, and growth factor binding. Several hub proteins were identified that were reported to have functions in cell-extracellular matrix interaction, osteogenic differentiation and development.ConclusionsOur data show that hiPSC-MP-CM enhances early osteogenic differentiation of human bone marrow-derived MSCs and that prolonged cultivation of hiPSC-MPs enhances CM-stimulatory activity. Proteomic analysis of the upregulated protein components provides the basis for further optimization of hiPSC-MP-CM for bone regenerative therapies.Graphical

Factors Influencing Corneal Endothelial Cell Density after Descemet Stripping Automated Endothelial Keratoplasty

Purpose: To identify determinants of corneal endothelial cell density at 12 months after Descemet stripping automated endothelial keratoplasty (DSAEK).Methods: This study included patients with bullous keratopathy who underwent DSAEK with internationally sourced donor corneas from March 2021 to March 2022. We assessed various preoperative factors in recipients (age, cause of bullous keratopathy, intraocular pressure, visual acuity, anterior chamber volume, depth and angle, pupil size, white-to-white corneal diameter, and preoperative corneal endothelial cell density) and donors (age, death to preservation time, preservation to transplantation time, death to transplantation time, corneal endothelial cell density, trephine size, and precut tissue thickness). We analyzed factors influencing corneal endothelial cell density up to 12 months after keratoplasty.Results: This study involved 53 patients, with an average recipient age of 65.9 ± 14.6 years prior to surgery. Donor corneas had an average endothelial cell density of 2,871.6 ± 271.6 cells/mm<sup>2</sup>. At 6 and 12 months postoperatively, endothelial cell densities had decreased by 36.9% and 47.2%, respectively, compared with preoperative levels. Multivariate linear regression analysis indicated that endothelial cell densities at 3 and 12 months postoperatively were linked to recipient age and anterior chamber depth.Conclusions: Corneal endothelial cell density after DSAEK typically stabilized after initial decline; higher densities were found in older recipients and individuals with shallower anterior chambers.

Acute Kidney Injury in Deceased Organ Donors: Risk Factors And Impacts on Transplantation Outcomes.

Acute kidney injury in deceased donors (D-AKI) is one of the common causes of donor kidney discard. The risk factors for D-AKI and its impact on kidney transplantation outcomes are not yet fully understood. This single-center, retrospective cohort study included 388 donors referred between June 2021 and December 2022. D-AKI was defined and staged according to kidney disease: Improving global outcomes criteria, and donor clinical variables were analyzed to identify risk factors for D-AKI. Delayed graft function and estimated glomerular filtration rate (eGFR) at 6 mo were evaluated in 369 kidney grafts transplanted from donors with and without D-AKI. AKI was present in 171 deceased donors (44.1%), with 117 (30.2%) classified as AKI stage 1 and 54 (14%) as AKI stages 2 or 3. Donor history of hypertension (odds ratio [OR] 1.93; 95% confidence interval [CI], 1.21-3.10; P = 0.005), history of diabetes (OR 2.2; 95% CI, 1.21-3.98; P = 0.008), and anoxia as the cause of death (OR 2.61; 95% CI, 1.5-4.61; P < 0.001) were independently associated with an increased risk of D-AKI. Multivariable mixed models identified donor age (β -0.49; 95% CI, -0.71 to -0.28; P < 0.001) as the only independent risk factor for lower eGFR at 6 mo. D-AKI was not associated with delayed graft function or lower eGFR at 6 mo. Hypertension, diabetes, and anoxia as the cause of death were identified as risk factors for AKI in deceased donors. D-AKI should not be used as the sole criterion to assess the risk of poor graft outcomes. A broader range of donor variables should be considered when evaluating graft viability.

Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy

Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time. To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes. This population-based cohort study used data from the prospectively maintained UK Transplant Registry from all 23 UK kidney transplant centers from January 1, 2013, to December 31, 2021; follow-up was until the date of data extraction (October 2023). Participants comprised 7183 adult recipients of DCD kidney-alone transplants. Duration of TTD, defined as time from WLST to donor mechanical asystole. Primary outcome was 12-month estimated glomerular filtration rate (eGFR; for the main eGFR model, variables with significant right skew [histogram visual assessment] were analyzed on the log2 scale), with secondary outcomes of delayed graft function and graft survival (censored at death or 5 years). This study included 7183 kidney transplant recipients (median age, 56 years [IQR, 47-64 years]; 4666 men [65.0%]). Median donor age was 55 years (IQR, 44-63 years). Median TTD was 15 minutes (range, 0-407 minutes), with 885 kidneys transplanted from donors with TTD over 1 hour and 303 kidneys transplanted from donors with TTD over 2 hours. Donor TTD was not associated with recipient 12-month eGFR on adjusted linear regression (change per doubling of TTD, -0.25; 95% CI, -0.68 to 0.19; P = .27), nor with delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P = .65) or graft survival (adjusted hazard ratio, 1.00; 95% CI, 0.95-1.07; P = .92). These findings were confirmed with restricted cubic spline models (assessing nonlinear associations) and tests of interaction (including normothermic regional perfusion). In contrast, donor asystolic time, cold ischemic time, and reperfusion time were independently associated with outcomes. Compared with a theoretical 1-hour maximum wait time, the UK policy (minimum 3-hour wait time) has been associated with 885 extra DCD transplants compared with 6298 transplants (14.1% increase). In this cohort study of DCD kidney recipients, donor TTD was not associated with posttransplant outcomes, in contrast to subsequent ischemic times. Altering international transplant practice to mandate minimum 3-hour donor wait times could substantially increase numbers of kidney transplants performed without prejudicing outcomes.

A systematic review and meta-analysis of factors contributing to post-kidney transplant anemia and the effect of erythropoietin-stimulating agents

BackgroundThe effects of various risk and associated factors on post-kidney transplant anemia (PTA) have not been fully compared and estimated. This meta-analysis aims to elucidate factors contributing to PTA and determine the influence of erythropoietin-stimulating agents (ESAs) on renal outcomes, thus offering potential pathways for enhanced management strategies post-transplant.MethodsA systematic review was conducted in electronical database. Studies reporting on risk factors (with cause-effect relationships) and associated factors (without definite cause-effect relationships) of PTA, and the effects of ESAs on post-kidney transplant outcomes, were included. Pooled odds ratios (ORs) and weighted mean differences (WMDs) were analyzed using random-effects models.ResultsThis systematic review encompassed 38,233 patients from 85 studies. Factors increased PTA risk included African American, older donor age, human antigen leukocyte mismatches, and low pre-transplant hemoglobin levels. Poor allograft function, high interleukine-6, Cytomegalovirus, delayed graft function, allograft rejections, immunosuppressive medications, and renin-angiotensin system blockades were associated with PTA. Native autosomal dominant polycystic kidney disease was a protective factor against PTA. Administration of ESAs with the aim of normalizing hemoglobin levels in patients with chronic allograft dysfunction slowed the decline in eGFR and reduce the risk of death, with a pooled OR of 0.36 (95% CI: 0.14 to 0.89; p = 0.040).ConclusionsThe risks and associated factors for PTA have been elucidated, underscoring the need for individualized treatment approaches. Late ESA therapy, aimed at hemoglobin normalization, suggests a renal-protective effect and reduced mortality, which should be considered in the management of PTA.Systematic review registrationPROSPERO CRD42024545330.

Deciphering influence of donor age on adipose-derived stem cells: in vitro paracrine function and angiogenic potential

Background: As fat grafting is commonly used as a filler, Adipose-derived stem/stromal cells (ASC) have been reported to be key player in retention rate. Paracrine and differentiation potential of those cells confer them strong pro-angiogenic capacities. However, a full characterization of the influence of aging on ASC has not been reported yet. Here we’ve investigated the effect of age on paracrine function, stemness and angiogenic potential of ASC. Methods: ASC were extracted from young and old adult donors. We assessed stromal vascular fraction cell populations repartition, ASC stemness potential, capability to differentiate into mesenchymal lineages as well as their secretome. Angiogenic potential was assessed using a sprouting assay, an indirect co-culture of ASC and dermal microvascular endothelial cells (EC). Total vascular sprout length was measured, and co-culture soluble factors were quantified. Pro-angiogenic factors alone or in combination as well as ASC-conditioned medium (CM) were added to EC to assess sprouting induction. Results: Decrease of endothelial cells yield and percentage is observed in cells extracted from adipose tissue of older patients, whereas ASC percentage increased with age. Clonogenic potential of ASC is stable with age. ASC can differentiate into adipocytes, chondrocytes and osteoblasts, and aging does not alter this potential. Among the 25 analytes quantified, high levels of pro-angiogenic factors were found, but none is significantly modulated with age. ASC induce a significantly longer vascular sprouts compared to fibroblasts, and no difference was found between young and old ASC donors on that parameter. Higher concentrations of FGF-2, G-CSF, HGF and IL-8, and lower concentrations of VEGF-C were quantified in EC/ASC co-cultures compared to EC/fibroblasts co-cultures. EC/ASC from young donors secrete higher levels of VEGF-A compared to old ones. Neither soluble factor nor CM without cells are able to induce organized sprouts, highlighting the requirement of cell communication for sprouting. CM produced by ASC supporting development of long vascular sprouts promote sprouting in co-cultures that establish shorter sprouts. Conclusion: Our results show cells from young and old donors exhibit no difference in all assessed parameters, suggesting all patients could be included in clinical applications. We emphasized the leading role of ASC in angiogenesis, without impairment with age, where secretome is a key but not sufficient actor.

Donor age contributes more to the rheological properties of stored red blood cells than donor sex and biological age distribution

Variation in the quality of stored red cell concentrates (RCCs) has been linked to the biological age distribution of red blood cell (RBCs) subpopulations within blood products. Teen male RCCs contain higher proportions of biologically old RBC subpopulations, with poorer quality. This study sought to assess the contribution of donor sex and age on the deformability characteristics of different ages of RBC subpopulations in stored RCCs. On days 5, 14, 21, and 42 of hypothermic storage, RCCs from healthy teen male, senior male, teen female and senior female donors were biologically age profiled. The deformability of the resulting young (Y-RBCs) and old (O-RBCs) RBC subpopulations in addition to unseparated RBCs was assessed using ektacytometry. Over storage, donor age influenced the rheological profile of RBC subpopulations, with teen male RCCs having the largest reduction in Ohyper (the osmolality in the hypertonic region corresponding to 50% of the EImax). The strongest correlations between Ohyper and MCHC (R2 > 0.5) were witnessed with O-RBCs from senior donors, and to a lesser extent with teen males. O-RBCs from teens, particularly males, had higher elongation indices both under isotonic conditions and in the presence of an increasing osmotic gradient. Consistent across RBCs regardless of their biological age, teen samples were discovered to be more rigid (higher KEI). The donor-to-donor variation in age distribution of RBC subpopulations and its downstream effect on deformability serves as further evidence that factors beyond chronological aging could potentially impact the quality of red cell concentrates and variations in transfusion outcomes.

Factors Affecting the Density of Corneal Endothelial Cells Cultured from Donor Corneas.

We investigated which specific correlation exists between the endothelial cell density (ECD) of corneal endothelial cell (CEC) cultures and the features of the donor corneas from which they originate. CEC cultures were prepared from one donor cornea or by pooling together cells of more corneas from elderly donors with ECDs lower or higher than 2000 cells/mm2. The ECDs of such primary cultures were evaluated and showed that that ECDs > 2000 cells/mm2 can be obtained only when CECs are isolated from (1) corneas of young donors; (2) at least two elderly donor corneas (if ECD > 2000 cells/mm2), or three elderly donor corneas (if ECD < 2000 cells/mm2). Secondary cultures are all characterized by ECDs < 2000 cells/mm2. Our study highlights the difficulties in obtaining cultures with ECDs > 2000 cells/mm2. Even if achievable with corneas from young donors, this becomes a challenging task when corneas from elderly donors are used (i.e., the overall majority of those collected by eye banks) and particularly when corneas from elderly donors with ECD < 2000 cells/mm2 are used. Pooling more of two corneas to obtain suitable CECs could technically overcome the problem. The above issues should be tackled appropriately before moving into clinical studies.

Risk of transfusion-associated malaria in sub-Saharan Africa: The case of Mali.

Malaria is a health threat in sub-Saharan Africa, where Plasmodium is not tested in blood bags. Our objective was to determine the prevalence of plasmodial carriage in blood bags and the associated factors, and the involvement of these bags in the occurrence of malaria in recipients. From 1st April to 30th November, 2020, we conducted a prospective cross-sectional study of 348 blood bags stored at 4°C in Bamako. Using SPSS 21.0 software, statistical analyses were performed using a binary logistic regression model with a significance threshold of p < 0.05 and the odds ratio (OR) framed by its 95% confidence interval (CI). During this period, 348 blood bags were transfused into 108/152 hospitalised patients, generating a transfusion frequency of 71.1%, with a prevalence of plasmodial carriage of 22%. Among the 54 initially malaria-negative recipients, all 20 (37%) who received malaria-positive blood bags and slept under long-acting insecticide-treated nets (LLINs) developed malaria. We recorded 33.3% deaths. Donor age ≤ 34 years (p = 0.011; OR = 2.55[CI.95% = 1.25-5.23]), replacement donation (p = 0.000; OR = 0.04[CI.95% = 0.0-0.19]) and not regular use of LLINs by donors (p = 0.048; OR = 0.53[CI.95% = 0.29-1]) were factors associated with plasmodial carriage of blood bags. CD4 count<200 cells/mm3 (p = 0.002; OR = 0.2[CI.95% = 0.10-0.52]), severe anaemia (p = 0.034; OR = 0.26[CI.95% = 0.10-0.90]) and decompensated anaemia (p = 0.034; OR = 3.88[CI.95% = 1.11-13.56]) were factors independently associated with recipient death. The prevalence of plasmodial carriage among blood donors is increasing in Mali. Transfusion malaria is a reality to be feared, with the risk increasing with the level of malaria endemicity of the blood donor.

Impact of donor age ≥65 years on graft survival in large lung transplant cohorts

BackgroundAlthough the demand for allografts continuously surpasses the supply, the majority of lungs offered for transplant are declined based on various factors, including donor age. This in turn sustains the wait-list mortality of patients with end-stage pulmonary disease. MethodsIn this single center, observational cohort study we investigated the impact of donor age on graft survival. We additionally, compared our center’s data to data reported to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry. Kaplan-Meier method was used to describe overall graft survival. Multivariate Cox proportional hazards regression was used to assess clinical features associated with graft loss. ResultsBetween January 2010 and December 2023, the Alfred performed 1101 single and double lung transplant and the combined ISHLT cohort totaled 32,200 transplants. At the Alfred, grafts originating from donors ≥65 years were used in 13.3% of lung transplant cases and univariate analysis showed no impact of donor age ≥65 on graft survival (HR 0.86, p=0.34). In the combined cohort, North America had a lower proportion of donors aged ≥65 years compared to Europe and the Alfred (2.4% vs 9.8% vs 13.3%, p<0.001). The univariate analysis showed a negative impact of donor age ≥65 on graft survival (HR 1.16, p<0.001). However, this did not hold in a multivariate model (HR 1.06, p=0.298) when adjusted for center experience and recipient characteristics. ConclusionDonor age might impact outcomes to a lesser degree than previously suggested. Therefore, appropriately assessed age-extended lungs should be routinely considered for lung transplantation.

The State of Combined Thoracoabdominal Triple Organ Transplantation in the United States

BackgroundAs triple organ transplants (TOT) have become more common, we evaluate patient characteristics, risk factors, and clinical outcomes of patients undergoing thoracoabdominal TOT. MethodsThis retrospective study utilized data from heart-lung-liver (HLL), heart-lung-kidney (HLK), heart-kidney-liver (HKL), and heart-kidney-pancreas (HKP) recipients from the UNOS registry between 1989 and 2023. Recipient and donor characteristics and risk factors for mortality were analyzed using Cox regression hazard models. Recipient survival up to 10-years were analyzed using the Kaplan-Meier method. ResultsDuring the study period, 81 TOTs were performed (13 HLLs, 13 HLKs, 46 HKLs, 9 HKPs). There were no statistically significant differences in long-term survival between TOTs (p=0.13). However, HLL and HLK recipients had significantly worse (p<0.0001) and improved (p<0.0001) survival, respectively, when compared to heart-lung, isolated heart, and lung transplant recipients. HLK was associated with improved survival (HR:0.22, p=0.033). We found no differences in survival among HKL (p=0.24) and HKP (p=0.19) recipients compared to their dual- and single-organ counterparts. TOTs after 2007 (HR: 0.29, p=0.003) were associated with improved survival, whereas increased recipient age (HR:1.06, p=0.037), eGFR (HR:1.02, p=0.005), and donor age (HR:1.05, p=0.031) were associated with higher mortality. ConclusionsThe prevalence of TOTs has dramatically increased over the past decade. While overall survival between TOTs appears similar, adding a liver to a heart-lung transplant may be associated with a poorer prognosis compared to adding a kidney. A careful, multidisciplinary approach to patient selection and management remains paramount in optimizing outcomes for high-risk patients undergoing TOTs.

Early Complications in Kidney Donors and Course of Health-related Quality of Life 12 mo After Donation: An Analysis of the Swiss Organ Living-Donor Health Registry.

Since 1998, the Swiss Organ Living-Donor Health Registry (SOL-DHR) has recorded peri- and postoperative complications of living kidney (LK) donors, as reported by all Swiss transplant centers and has collected follow-up data prospectively. We analyzed the early complications of 2379 consecutive individuals who donated a kidney between January 1998 and June 2022 and assessed their health-related quality of life (HRQoL) 1 y after donation. In total, 447 early complications in 404/2379 LK donors (17.0%) were reported to the SOL-DHR. The frequency of donors with major complications (ie, Dindo-Clavien classification 3/4) was 2.4%. In total, 31 donors needed reoperation, and in 13/31 (42%), donors reoperation was necessary because of bleeding complications. Independent risk factors for major early complications were older donor age (P = 0.005) and type of surgical approach (ie, the laparoscopic retroperitoneal compared with laparoscopic transabdominal surgery; P = 0.01), but not sex. We observed a U-shaped association of body mass index, where very low/high body mass indexes had higher odds of major early complications, without reaching statistical significance. Although HRQoL was affected by kidney donation, 96.5% of donors indicated that they would donate their kidney again. The only independent risk factor for low HRQoL based on mental health scores was worsening EB after living kidney donation (P < 0.0001). Overall, living kidney donation is a safe procedure, however, donor age and type of surgical approach affect the risk of complications. A decline in emotional bonding with the recipient after donation may worsen the quality of life of the donor.

Shear viscoelastic properties of human orbital fat.

The shear viscoelastic behavior of eye's supporting orbital fat is unstudied in humans, yet is important during and after rapid movement. This investigation quantified viscoelastic characteristics of human orbital fat in constitutive form suitable for numerical simulation. Fresh human orbital fat was harvested postmortem from 6 male and 7 female donors of average age 78±13years. Fat samples were trimmed to disks of 20±3.0 (standard deviation) mm average diameter and 2.1±0.2mm thickness. In 8 samples each, the following four testing protocols were performed: strain sweep from 0.0015 to 50% at 1Hz; viscometry at 0.1s-1 shear rate; stress relaxation at physiological temperature; and frequency sweep from 0.159 to 15.9Hz at 0.5% strain to validate the Prony series parameters fitting stress relaxation behavior. Orbital fat exhibited viscoelastic behavior under dynamic shear with a 0.5% linear viscoelastic strain limit. Storage modulus G' averaged 737±310Pa, and loss modulus G″ averaged 197±76Pa. Values were similar for strain and frequency sweep testing. At rupture, shear stress averaged 617±366Pa and rupture strain averaged 200±70%. The long-term relaxation modulus averaged 646±264Pa at 100s. Frequency sweep testing validated the parameters of the Prony series fitted to the experimental stress relaxation data. Human orbital fat is linearly viscoelastic within a range typical of biological materials, and exhibits similar viscoelastic behavior for strain and frequency sweep testing. Stress relaxation data for human orbital fat has been parameterized for constitutive models that can be implemented in finite element analysis.

Donor and Recipient Factors Associated with Primary Graft Dysfunction Following Lung Transplantation: A DMG Registry Analysis

Current risk-adjusted models to predict primary graft dysfunction (PGD) following lung transplantation (LTx) do not include bedside donor critical care data. Donor management goals (DMG) represent predefined critical care endpoints aimed at optimizing multi-organ donor management. Here, we sought to identify novel predictors to better understand the relationship between donor management and PGD following LTx. We used the national DMG registry to identify a cohort of LTx recipients linked to their respective donors between January 1st, 2015 and March 1st, 2023. Grade 3 PGD (PGD3) was defined according to modified ISHLT criteria. Multivariable modeling was performed to identify risk factors for the development of PGD3. A total of 2704 eligible patients were identified of which 643 (23.8%) developed PGD3. After multivariable modeling, the likelihood of PGD3 was greater with increased donor age (OR 1.06 [1.02, 1.10] per 5 year change, p=0.003), increased donor serum pH at the time of authorization (OR 1.14 [1.02, 1.25] per 0.1 increase, p=0.016), donor history of cocaine use (OR 1.34 [1.05, 1.71], p=0.020), and increased recipient central venous pressure (1.03 [1.01, 1.06], p=0.005). Recipients who received donor lungs in which the DMG for PF ratio was met had a lower likelihood of developing PGD3 (OR 0.63 [0.46, 0.86], p=0.006). This study leverages a novel detailed donor management database to identify factors associated with the development of PGD3. These factors may be used to recognize donors and recipients that may benefit from early interventions to improve short-term outcomes.