Donor Age Research Articles

Donor Type Does Not Impact Late Graft Failure Following Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis.

Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12% to 20% in haplo-HCT recipients using PTCy. The objective of this study was to determine whether donor type influenced the risk of late graft failure following reduced-intensity conditioning (RIC) HCT using PTCy-based GVHD prophylaxis. A retrospective cohort analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database among adult patients who underwent first RIC haplo or 8/8 matched unrelated donor (MUD) HCT between 2011 and 2018 for acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS) with PTCy GVHD prophylaxis. The primary outcome was incidence of late graft failure, defined as secondary graft loss in the absence of relapse or poor graft function requiring a cellular therapy intervention. A total of 1336 patients met the eligibility criteria (1151 haplo, 185 MUD). Patients in the MUD group were older (65 vs. 61 years), less ethnically diverse (95% vs. 72% White), received fewer bone marrow grafts (45% vs. 16%), and had younger donors (median age, 28 vs. 37 years old). Conditioning regimens were predominately fludarabine, cyclophosphamide, and total body irradiation (TBI; 87% haplo and 38% MUD). At 2 years, the adjusted probabilities of late graft failure for the haplo group was 6.5% (95% confidence interval [CI], 5.2-8.0) versus 5.9% (95% CI, 2.7%-10.9%) for the MUD group (P = .79). Multivariate analysis for risk factors associated with late graft failure found associations with a diagnosis of MDS (HR, 1.98; 95% CI, 1.22-3.20; P = .005), and earlier year of HCT (2015-2018 vs. 2011-2014; HR, 0.39; 95% CI, 0.24-0.64; P = .0002). A post-hoc sensitivity analysis was performed to evaluate the effect of donor age and use of peripheral blood stem cell (PBSC) grafts. Graft failure did not differ between haplo and MUD HCT (HR, 1.19; P = .67) when adjusted for donor age nor when restricted to PBSC grafts only (HR, 0.85; P = .70). In this registry-based analysis of patients undergoing RIC HCT for AML, ALL, or MDS using GVHD prophylaxis with PTCy, there was no significant difference in late graft failure rates between haplo and MUD donors. Overall rates of late graft failure were high.

Identification of a vimentin-expressing α-cell phenotype in CF and normal pancreas.

Endocrine dysfunction and diabetes can develop secondary to fibrotic diseases within the pancreas including cystic fibrosis (CF). Phenotypic shift within epithelial cells has been recognised in association with pro-fibrotic signalling. We sought evidence of endocrine cell epithelial-to-mesenchymal transition in CF and non-CF pancreas. Post mortem pancreatic sections from 24 people with CF and 10 organ donors without CF or diabetes were stained for insulin/glucagon/vimentin and Sirius Red Fast Green with collagen distribution assessed semi-quantitatively (CF) and quantitatively (non-CF). Analysis of existing single-cell RNA-sequencing data sets (three adult donors without diabetes and nine with chronic pancreatitis) for α-cell vimentin expression was performed. Cells co-expressing glucagon/vimentin were detected in a proportion (32(4,61)% (median(Q1,Q3)) of islets in all CF pancreata except donors dying perinatally. CF histopathology was characterised by peri-islet fibrosis and 60(45,80)% of islets were surrounded by collagen strands. A positive correlation between islet fibrosis and vimentin-expressing α-cells was seen in non-CF donors <31 years (r=0.972, p=0.006). A possible association with donor age was seen in all donors (r=0.343, p=0.047). Single-cell RNA-sequencing analysis of isolated islets from non-diabetic donors and donors with chronic pancreatitis confirmed presence of vimentin-positive and vimentin-negative α-cells. Differentiated α-cell function-associated gene expression was maintained. Differentially upregulated processes in co-expressing cells included pathways associated with extracellular matrix organisation, cell-cell adhesion, migratory capability and self-renewal. We have identified and characterised an intermediate epithelial/mesenchymal state in a sub-population of α-cells present throughout post-natal life which may play a role in their response to extrinsic stressors including fibrosis and ageing.

A retrospective single-center pilot study of the genetic background of the transplanted kidney.

Renal cell carcinoma (RCC) is one of the most prevalent cancers in kidney transplant recipients (KTR). The hereditary background of RCC in native kidneys has been determined, implicating its clinical importance. This retrospective single-center pilot study aimed to identify a potential genetic predisposition to RCC of the transplanted kidney and outcome in KTR who underwent single kidney transplantation between January 2000 and December 2020 and manifested RCC of the transplanted kidney. Next-generation sequencing (NGS) based germline genetic analysis from peripheral blood-derived genomic DNA (gDNA) was performed in both the recipient and donor using a gene panel targeting 226 cancer predisposition genes. The calculated incidence of RCC of the transplanted kidney among 4146 KTR was 0.43%. In fifteen KTR and donors, NGS was performed. The mean KTR age at transplantation and the diagnosis of RCC was 50.3 years (median 54; 5-67 years) and 66 years (median 66; 24-79 years), respectively. The mean donor age at transplantation and graft age at RCC diagnosis was 39.7 years (median 42; 7-68 years) and 50.2 years (median 46; 20-83 years), respectively. The mean follow-up after RCC diagnosis was 47 months (median 39.1; 0-112 months). Papillary RCC was the most prevalent (n = 8), followed by clear cell RCC (n = 6) and unspecified RCC (n = 1). Thirteen RCCs were low-stage (pT1a/b) diseases, one was pT3, and one was of unknown stage. Most RCC was higher graded. No germline pathogenic cancer-predisposition variant was found in either KTR or donors except for several variants of uncertain significance. RCC of the transplanted kidney is very rare. Germline cancer-predisposition testing has identified several variants of uncertain significance, but no germline genetic predisposition to graft RCC in KTR. Further research is needed to assess the clinical relevance of genetic testing for cancer risk in KTR.

Current Status and Future Perspective of Seoul National University Hospital-Dementia Brain Bank with Concordance of Clinical and Neuropathological Diagnosis.

This paper introduces the current status of Seoul National University Hospital Dementia Brain Bank (SNUH-DBB), focusing on the concordance rate between clinical diagnoses and postmortem neuropathological diagnoses. We detail SNUH-DBB operations, including protocols for specimen handling, induced pluripotent stem cells (iPSC) and cerebral organoids establishment from postmortem dural fibroblasts, and adult neural progenitor cell cultures. We assessed clinical-neuropathological diagnostic concordance rate. Between 2015 and September 2024, 162 brain specimens were collected via brain donation and autopsy. The median donor age was 73 years (1-94) with a male-to -female ratio of 2:1. The median postmortem interval was 9.5 hours (range: 2.5-65). Common neuropathological diagnoses included pure Lewy body disease (10.6%), Lewy body disease (LBD) with other brain diseases (10.6%), pure Alzheimer's disease-neuropathological change (ADNC) (6.0%), ADNC with other brain diseases (10.7%), vascular brain injury (15.2%), and primary age-related tauopathy (7.3%). APOE genotype distribution was following: ε3/ε3: 62.3%, ε2/ε3: 9.6%, ε2/ε4: 3.4%, ε3/ε4: 24.0%, and ε4/ε4: 0.7%. Concordance rates between pathological and clinical diagnoses were: ADNC/AD at 42.4%; LBD at 59.0%; PSP at 100%; ALS at 85.7%; Huntington's disease 100%. The varying concordance rates across different diseases emphasize the need for improved diagnostic criteria and biomarkers, particularly for AD and LBD. Tissues have been distributed to over 40 national studies. SNUH-DBB provides high-quality brain tissues and cell models for neuroscience research, operating under standardized procedures and international guidelines. It supports translational research in dementia and neurodegenerative diseases, potentially advancing diagnostic and therapeutic strategies.

Transcriptomic comparison of corneal endothelial cells in young versus old corneas

Corneal endothelial cells, situated on the innermost layer of the cornea, are vital for maintaining its clarity and thickness by regulating fluid. In this study, we investigated the differences in the transcriptome between young and old corneal endothelial cells using next-generation sequencing (NGS). Cultured endothelial cells from both young and elderly donors were subjected to NGS to unravel the transcriptomic landscape. Subsequent analyses, facilitated by Metascape, allowed for the dissection of gene expression variances, unearthing pivotal biological pathways. A total of 568 genes showed differences, and were related to Endomembrane system organization, nuclear receptors meta pathway, efferocytosis, etc. Notably, a reduction in the expression of 260 genes was observed in the aged cells form old donors, and in the related analysis, eukaryotic translation initiation, integrator complex, and Hippo YAP signaling were significant. Conversely, 308 genes exhibited elevated expression levels in the elderly, correlating with processes including transition metal ion transport and glycoprotein biosynthesis. In conclusion, our investigation has revealed critical genes involved in the aging process of corneal endothelial cells and elucidated their underlying biological pathways. These insights are instrumental in selecting targets for therapeutic intervention, thereby facilitating the advancement of novel therapeutic approaches for the restoration and preservation of corneal endothelial cell function.

Association of the Mayo-Adhesive Probability Score With the Total Operative Time of Hand-Assisted Laparoscopic Donor Nephrectomy.

Living-donor kidney transplantation (LDKT) is often performed using hand-assisted laparoscopic donor nephrectomy (HALDN). Adherent perinephric fat (APF) can complicate HALDN, increasing operative time. The Mayo Adhesive Probability (MAP) score predicts APF preoperatively. This study investigates the association between MAP score and operative time in patients undergoing HALDN. This cross-sectional study included 133 patients undergoing HALDN at Shifa International Hospital, Islamabad, Pakistan, from December 2021 to July 2023. The primary outcome was total operative time, defined as incision-to-closure duration. The predictor of interest was the MAP score, calculated from preoperative CT scans assessing posterior renal fat thickness and perinephric fat stranding. Data collection included demographic and clinical characteristics of the patients. Data analysis was done using IBM SPSS Statistics software, version 25 (IBM Corp., Armonk, NY), to determine a significant association between the mean operative time across different MAP scores and other parameters, taking a p-value <0.05 as significant. The mean donor age was 35.1 ± 10.1 years, and females were predominant (85, 63.9%). Most patients had a MAP score of 0 (76.7%) and an American Society of Anesthesiologists (ASA) score of one (81.2%). The mean operative time was 196.86 + 53.81 minutes. The MAP score was not significantly associated with operative time (p = 0.244). Mean operative time did not significantly differ across MAP score groups (p = 0.148). There was a significant association between gender and MAP score, with females having lower scores (p = 0.001). No significant correlations were found between operative time and MAP score, gender, or ASA score (p > 0.05). The MAP score does not significantly correlate with operative time in HALDN among the studied population. Interestingly, a significant association was noted between lower MAP scores and female gender, adding to the understanding of gender-specific characteristics in laparoscopic donor nephrectomy and highlighting the need for further research to validate the utility of this score in diverse clinical settings and populations. These results underline the need for larger, multicentered studies to validate the utility of the MAP score in predicting operative complexity across diverse clinical settings and populations.Our study contributes to the ongoing efforts to optimize preoperative planning and enhance outcomes in LDKT cases.

Comparative Analysis of the Therapeutic Potential of Extracellular Vesicles Secreted by Aged and Young Bone Marrow-Derived Mesenchymal Stem Cells in Osteoarthritis Pathogenesis.

Osteoarthritis (OA), a joint disease, burdens global healthcare due to aging and obesity. Recent studies show that extracellular vesicles (EVs) from bone marrow-derived mesenchymal stem cells (BMSCs) contribute to joint homeostasis and OA management. However, the impact of donor age on BMSC-derived EV efficacy remains underexplored. In this study, we investigated EV efficacy from young BMSCs (2-month-old) in mitigating OA, contrasting them with EVs from aged BMSCs (27-month-old). The study used destabilisation of the medial meniscus (DMM) surgery on mouse knee joints to induce accelerated OA. Cartilage degeneration markers and senescence markers' expression levels were investigated in response to EV treatment. The therapeutic impact of EVs on chondrocytes under inflammatory responses was also evaluated. Despite having similar morphologies, EVs from young BMSCs markedly decreased senescence and improved chondroprotection by activating the PTEN pathway while simultaneously suppressing the upregulation of the PI3K/AKT pathways, proving to be more effective than those from older BMSCs invitro. Furthermore, intraperitoneal injections of EVs from young donors significantly mitigated OA progression by preserving cartilage and reducing synovitis in a surgical OA model using DMM in mice. These findings highlight that donor age as a critical determinant in the therapeutic potential of BMSC-derived EVs for clinical use in OA treatment.

Initial pig developmental stage influences intestinal organoid growth but not cellular composition.

Intestinal organoids are promising tools in the context of animal experiment reduction but a thorough characterization of the impact of the origin of intestinal stem cells (ISC) on organoid phenotype is needed to routinely use this cellular model. Our objective was to evaluate the effect of ISC donor age on the growth, morphology and cellular composition of intestinal organoids derived from pig. Organoids were derived from jejunal and colonic ISC obtained from 1-, 7-, 28-, 36- and 180-day-old pigs and passaged three times. We first confirmed by qPCR that the expression of 18% of the >80 studied genes related to various intestinal functions differed between jejunal and colonic organoids after two passages (p < 0.05). Growth and morphology of organoids depended on intestinal location (greater number and larger organoids derived from colonic than jejunal ISC, p < 0.05) but also pig age. Indeed, when ISC were derived from young piglets, the ratio of organoids to spheroids was greater (p < 0.05), spheroids were larger during the primary culture but smaller after two passages (p < 0.05) and organoids were smaller after one passage (p > 0.05) compared to ISC from older pigs. Finally, no difference in cellular composition, evaluated by immunostaining of markers of the major intestinal cell types (absorptive, enteroendocrine and goblet cells) was observed between organoids originating from 7- or 180-day-old pigs, but differences between intestinal site origins were noticed. In conclusion, while the age of the tissue donor affected organoid growth and morphology, it did not influence the phenotype.

HLA and Non-HLA Factors for Donor Selection in Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide GvHD Prophylaxis.

Human leukocyte antigen (HLA) mismatches in stem cell transplantation can be well-tolerated with the use of post-transplant cyclophosphamide (PTCy) for graft-versus-host-disease (GvHD) prophylaxis. Haploidentical (Haplo) and HLA-mismatched unrelated donors become acceptable donors. This review focuses on Haplo and unrelated donor selection in the context of PTCy-transplant for hematological malignancy, in comparison with conventional GvHD prophylaxis. Evaluating patient's donor-specific antibody (DSA) is critical in donor selection regardless of donor type or the use of PTCy. High DSA levels and positive C1q increase the risk of engraftment failure and unsuccessful desensitization. On the other hand, the degree of donor HLA matching is less critical under PTCy compared to conventional GvHD prophylaxis. Donor age was found to be important, as younger donors improve survival outcomes. HLA-B leader match appears to be preferable. The impacts of donor gender, donor cytomegalovirus serostatus, and ABO mismatch are unclear or non-significant. Additionally, available studies suggest that, in PTCy-transplant, preferred Haplo-donors are HLA class II mismatched (DRB1 mismatch and DPB1 non-permissive), siblings or offspring over parents, and if parent, father over mother, while preferred unrelated donors are HLA class I matched. Further study is warranted.

Retrospective Clinical Outcomes of Keratoplasty Using Human Donor Corneas Preserved in Eusol-C Hypothermic Storage Medium.

Objective: To evaluate the clinical outcomes of cornea transplantation (penetrating keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty, and deep anterior lamellar keratoplasty) using donor corneas stored in Eusol-C hypothermic storage medium compared to corneas stored in organ-culture. Methods: The clinical outcomes of 92 patients who underwent corneal transplantation with human donor corneas stored in Eusol-C medium at 2-8 °C were retrospectively evaluated. The control group consisted of 169 patients who received corneas organ-cultured at 31 °C. Donor age, sex, death-to-preservation time, and storage time were recorded. Endothelial cell (EC) density (ECD), EC mortality, and EC morphology scores were evaluated during storage in both groups. Complication rates, visual outcomes, and corneal transparency were monitored for up to six months. Results: The mean storage in Eusol-C time was 7.7 ± 2.5 days, while organ-culture time was 14.2 ± 4.0 days. In the Eusol-C group, ECD was 2398 ± 354 cells/mm2, with an average EC morphology score of 3.4 ± 0.7/4. Approximately 28% of the corneas in the Eusol-C group had no EC mortality. In the organ-culture group, ECD was 2256 ± 328 cells/mm2, with an average EC morphology score of 3.5 ± 0.5/4, and 42% were devoid of EC mortality. No complications, such as re-bubbling, were observed in both groups during surgery. Transparent corneas were achieved in 81.3% of the Eusol-C group the day after surgery. Mean corrected distance visual acuity (CDVA) at 3 and 6 months was 4.5 ± 4.0/10 and 5.4 ± 3.7/10 for the Eusol-C group and 5.0 ± 2.9/10 and 5.7 ± 2.8/10 for the organ-culture group, with no statistical differences observed between the groups. No graft failure was observed up to three months. Graft rejection occurred in the Eusol-C group and in the organ-culture group in, respectively, one and two cases at the six-month follow-up. Conclusions: Comparable surgical outcomes were achieved with donor corneas stored in both hypothermic Eusol-C and organ-culture media.

13 Donor age effects on embryo morphokinetics in Holstein cattle: insights into prepubertal embryo development

13 Donor age effects on embryo morphokinetics in Holstein cattle: insights into prepubertal embryo development

Aging and cell expansion enhance microRNA diversity in small extracellular vesicles produced from human adipose-derived stem cells

Adipose-derived stem cells (ASCs) and their small extracellular vesicles (sEVs) hold significant potential for regenerative medicine due to their tissue repair capabilities. The microRNA (miRNA) content in sEVs varies depending on ASC status; however, the effects of aging and cell passage on miRNA profiles remain unclear. In this study, we examined the effects of donor age and cell expansion on ASC characteristics and transcriptome using ASCs obtained from three young and three old donors. Cell expansion significantly impaired stem cell properties, notably reducing proliferation and differentiation capacities. In contrast, donor age had minimal effects on ASCs. RNA sequencing (RNA-seq) revealed differences in gene expression related to stemness, phagocytosis, and metabolic processes influenced by cell expansion. To investigate miRNA variability, we performed small RNA-seq on sEVs collected from ASCs of all six donors. The miRNA profiles were influenced by donor age and cell passage. Interestingly, functional enrichment analysis indicated that advanced donor age and increased cell passage may enhance the production of miRNAs associated with organ development through various pathways. These findings suggest that donor age and cell expansion differentially influence ASC characteristics and sEV miRNA content, highlighting the need for disease-specific conditioning of ASCs to optimize the therapeutic effects of sEVs in clinical applications.

The Chondrogenic Potential of the Bovine Tendon Sheath - a Novel Source of Stem Cells for Cartilage Repair.

The human hand is traumatized more frequently than any other bodily part. Trauma and pathological processes (e.g., rheumatoid arthritis, osteoarthritis) commonly implicate the finger joints and specifically damage also the layer of articular cartilage. Endeavors are now being made to surgically repair such cartilage lesions biologically using tissue-engineering approaches that draw on donor cells and/or donor tissues. The tendon sheaths, particularly their inner layers, i.e., the peritendineum, surround the numerous tendons in the hand. The peritendineum is composed of mesenchymal tissue. We hypothesize that this tissue harbors pluripotent mesenchymal stem cells and thus could be used for cartilage repair, irrespective of the donor's age. Using a bovine model (young calves vs. adult cows), the pluripotentiality of the peritendineal stem cells, namely, their osteogenicity, chondrogenicity, and adipogenicity, was investigated by implementing conventional techniques. Subsequently, the chondrogenic potential of the peritendineal tissue itself was analyzed. Its differentiation into cartilage was induced by the application of specific growth factors (members of the TGF-β-superfamily). The characteristics of the tissue formed were evaluated structurally (immuno) histochemically, histomorphometrically, and biochemically (gene expression and protein level). Our data confirm that the bovine peritendineum contains stem cells whose pluripotentiality is independent of donor age. This tissue could also be induced to differentiate into cartilage, likewise, irrespective of the donor's age. Preliminary investigations with adult human peritendineal biopsy material derived from the hand's peritendineal flexor tendon sheaths revealed that this tissue can also be induced to differentiate into cartilage.

Alexithymia and estimated 10-year cardiovascular disease risk in healthy adults: a community-based cross-sectional study.

This cohort study aimed to explore whether and to what extent alexithymia would be associated with cardiovascular disease (CVD) risk over an estimated 10-year period, over and above established clinical cofactors (i.e., depressive symptoms, quality of life, sociodemographic, anthropometric, lifestyle, and biological data), in a low-risk population of blood donors. A sample of 1,021 adult Italian blood donors (age 46.9 ± 8.39; 61.2% men) was consecutively recruited. The 10-year-CVD risk score was estimated using the CUORE risk score (CRS). Sociodemographic, lifestyle, anthropometric, biological, and psychological (i.e., quality of life, depressive symptoms, and alexithymia) CVD risk data were assessed using validated self-report measures or clinical records. As expected, most participants (78.5%) had a low CVD risk (CRS < 3%) and an overall low-risk profile for all the parameters. Compared with subjects at low risk of CVD (n = 911, 78.5%), those with high risk (i.e., rated ≥3 on CUORE risk assessment; n = 250, 21.5%) reported higher levels of alexithymia (p < 0.001). Subjects with higher alexithymia (n = 236, 23.1%) reported higher levels of psychosocial impairment, depressive symptoms, and biological risk variables for CVD. Alexithymia was significantly associated with 10-year CVD risk (OR = 1.02, 95% CI = 1.01-1.04, p = 0.009), even after adjusting for key sociodemographic and clinical risk variables. Although limited by the cross-sectional design, this study is the first to show that alexithymia leads to a higher risk for 10-year CVD estimate in healthy subjects with low-risk profile, regardless of known biomarkers and traditional CVD risk factors.

Role of the Lymphocyte Count-to-C-Reactive Protein Ratio in the Risk Stratification for High EASE Scores After Living Donor Liver Transplantation: A Retrospective Observational Cohort Study.

Background: Early allograft failure (EAF) significantly contributes to mortality, necessitating re-transplantation following liver transplantation. The EAF simplified estimation (EASE) score has been recently developed to predict EAF. We aimed to assess the predictive capacity of high EASE scores for EAF and postoperative outcomes and to evaluate the association between the lymphocyte count-to-C-reactive protein ratio (LCR) and high EASE scores after living donor liver transplantation (LDLT). Methods: We retrospectively analyzed the data of 808 patients who underwent LDLT. After excluding 16 patients with incomplete laboratory data, the final cohort included 792 patients. Patients with EASE scores ≥-0.74 were categorized into the high EASE group. Multivariate logistic regression was used to examine the association between the LCR and high EASE scores. Results: High EASE scores demonstrated superior predictive accuracy for EAF development relative to that of the early allograft dysfunction (EAD) model (p = 0.018) and were more closely associated with overall mortality (p = 0.033). A preoperative LCR < 12.7 significantly increased the odds (odds ratio, 3.3; confidence interval, 1.997-5.493) of exhibiting high EASE scores post-LDLT, alongside preoperative hematocrit levels, operative duration, intraoperative continuous renal replacement therapy, administered calcium dose, mean heart rate, and donor age. Conclusions: The EASE score could offer enhanced utility for predicting EAF and overall mortality following LDLT relative to that of EAD. Identifying and managing risk factors, including low LCR values, for elevated EASE scores is essential for improving patient prognoses.

HLA Compatibility and Graft Survival Rates Among Related and Unrelated Donors in Renal Transplantation

Human leukocyte antigen (HLA) compatibility between donors and recipients plays a critical role in graft survival in renal transplantation. This study evaluates the impact of HLA mismatching on graft survival and rejection among renal transplant patients with related and unrelated donors, considering factors such as age, sex, ABO blood type, and anti-HLA antibodies. We investigated graft survival rates between related and unrelated donors in a prospective cohort study conducted from 2018 to 2020 at Cho Ray Hospital and People's Hospital 115 in Vietnam, involving 126 related and 82 unrelated donor-recipient pairs. Over a 32-month follow-up, there was no significant difference in the rates of suspected graft rejection (p=0.75) or graft loss (p=0.095) between the two groups. However, related donors exhibited significantly higher overall survival (p=0.0086) and better event-free survival (p=0.0025) compared to unrelated donors. HLA matching and ABO type did not show any association with suspected graft rejection in either group. Notably, unrelated donors older than five years increased the risk of suspected graft rejection (HR=4.22), and positive anti-HLA antibodies also increased this risk (HR=4.5). Conversely, male-male donor-recipient pairs significantly reduced the risk of graft rejection by 88% compared to female-female pairs. The study concludes that while HLA matching is not difference for related and unrelated donor groups, factors such as donor age, same-sex pairs, and the presence of anti-HLA antibodies are significant risk factors for graft rejection in unrelated donors. Enhancing monitoring and developing strategies for unrelated donors are essential to improve graft survival outcomes in renal transplantation.

Impact of Cold Ischemia Time and Donor Age on Donation After Circulatory Death Kidney Transplant Outcomes: A UNOS Mate-Kidney Analysis.

The association between prolonged cold ischemia times (CIT), donor age, and outcomes in kidney transplant recipients (KTRs) from donors after circulatory death (DCD) remains uncertain. We aimed to compare allograft outcomes in DCD-donor KTRs according to CIT and age. UNOS database study (2010-2024) of DCD-donor KTRs on tacrolimus maintenance. We developed a mate-kidney analysis, comparing outcomes where one mate kidney had CIT >24 and the other ≤24h. We evaluated patient death, all-cause allograft failure, and death-censored graft failure (DCGF) using multivariable stratified Cox proportional hazards models. We compared outcomes across age groups (≥50 or <50 years) and 6-h-period CIT deltas between mate kidneys. We assessed delayed graft function (DGF) occurrence with multivariable conditional logistic regression. We included 4092 DCD-donor mate-kidney pairs. There were no differences between CIT >24 versus ≤24h in patient death (aHR 1.12, 95% CI 0.97-1.30), all-cause allograft failure (aHR 1.10, 95% CI 0.98-1.24), or DCGF (aHR 1.07, 95% CI 0.90-1.27). Similar results were observed when comparing outcomes by age group and 6-h-period CIT deltas between mate kidneys. Compared to shorter CITs, CITs >24h were associated with increased DGF likelihood (aOR 1.42, 95% CI 1.25-1.60), as were increasing CIT deltas. CITs >24h in DCD-donor KTRs were not associated with adverse allograft outcomes, irrespective of age group. However, prolonged CITs were associated with increased DGF likelihood. Increasing the acceptance of both mate kidney from DCD donors should be considered despite projected CITs >24h.

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.

Cortical and subcortical p‐tau density in CTE: Comparison to Alzheimer’s disease

AbstractBackgroundThe unique lesion of chronic traumatic encephalopathy (CTE) is the perivascular deposition of hyperphosphorylated tau at the depth of the cortical sulci. The distribution and molecular composition of p‐tau is distinct from Alzheimer’s disease (AD), but differential diagnostic challenges remain. Understanding disease differences in regional density of p‐tau will inform differential diagnosis and interpretation of in vivo biomarkers. Here, we compared autopsy‐confirmed CTE and AD across cortical and subcortical measurements of p‐tau density.MethodThe sample included 109 brain donors with stage III/IV CTE, and 109 age (+/‐ 3 years) and sex similar brain donors with autopsy‐confirmed AD. While the original sample was similar, there is missing data across regions due to older cases not having AT8 stains. CTE was neuropathologically diagnosed using published criteria. NIA‐Reagan was used for AD. Neuropathologists used semi‐quantitative rating scales (0=none, 3=severe) to evaluate p‐tau severity in the dorsolateral frontal cortex (DLFC), inferior orbital frontal cortex (IFC), superior temporal cortex (STC), inferior parietal cortex (IPC), CA1, CA2, and CA4, entorhinal cortex (EC), and amygdala. Digital slide scanning of AT8 tissue was done for quantitative assessment of p‐tau density in the DLFC, STC, IPC, CA1, CA2/3, CA4, and calcarine cortex. Regression and analysis of variance models compared disease groups on each outcome, controlling for age.ResultOn the semi‐quantitative rating scales, those with autopsy‐confirmed CTE had greater p‐tau severity in the CA4‐hippocampus compared with AD (OR=4.43, p=0.003); in contrast, AD had greater p‐tau severity in the CA1‐hippocampus (OR=0.07), EC (OR=0.10), and amygdala (OR=0.24) (ps&lt;0.05). There were no differences for the CA2‐hippocampus. Regarding cortical regions, those with AD had greater p‐tau severity on the DLFC, IFC, STC, and IPC (ORs=0.03‐0.16, ps&lt;0.05). A similar pattern was found for the quantitative p‐tau density data: CTE had greater p‐tau density in CA4‐ (marginal mean difference=7.45) and CA2/3 (marginal mean difference=9.86) (ps&lt;0.01) and AD had higher density of p‐tau across the other regions (i.e., DLFC, IPC, STC, calcarine).ConclusionCompared with AD, CA4‐hippocampus was most affected in CTE. AD had greater p‐tau density across cortical regions. Findings inform neuropathological differential diagnosis and interpretation of in vivo biomarkers in CTE and AD.

Effect of Transplanted Liver Fat Percentage on Organ Survival: A Retrospective Review.

Liver transplant is the most effective therapeutic option for patients with end-stage liver disease, nonalcoholic steatohepatitis, and acute liver failure. We evaluated whether the percentage of hepatic fat percentage affected transplant outcomes to determine whether livers with varying severity of macrosteatosis should be considered suitable for donation. We analyzed data from 381 patients with liver failure who received liver transplant at Montaseriyeh Hospital in Mashhad, Iran, between 2013 and 2022. Clinical and demographical data were collected, and we examined frozen-section slides of pretransplant biopsy specimens from donor livers. Liver allograft macrosteatosis was categorized into 4 groups according to severity of steatosis: <10%, 10% to 20%, 20% to 30%, and >30%. The mean age of recipients was 49 years; mean age of donors was 37 years. The mean liver survival rate was approximately 56 months. A total of 115 recipients (30%) died after liver transplant, with graft rejection as the leading cause of death (38%). Grafts with hepatic macrosteatosis <10% contributed to the largest share (87%). No significant differences were observed in the indication for liver transplant, life outcome, cause of death after liver transplant, or mean rate of liver survival among the 4 groups. Also, there was no significant correlation between the severity of liver macrosteatosis and graft or patient survival. Our findings suggest that livers with varying degrees of macrosteatosis are safe for transplant and should not be excluded from the donor pool.