Young Donors Research Articles

Total Body Irradiation and Fludarabine with Post-Transplantation Cyclophosphamide for Mismatched Related or Unrelated Donor Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation (HCT) remains the sole curative treatment for most patients with hematologic malignancies. A well-matched donor (related or unrelated) remains the preferred donor for patients undergoing allogeneic HCT; however, a large number of patients rely on alternative donor choices of mismatched related (haploidentical) or unrelated donors to access HCT. In this retrospective study, we investigated outcomes of patients who underwent mismatched donor (related or unrelated) HCT with a radiation-based myeloablative conditioning MAC regimen in combination with fludarabine, and post-transplantation cyclophosphamide (PTCy) as higher-intensity graft-versus-host disease (GVHD) prophylaxis. We retrospectively assessed HCT outcomes in 155 patients who underwent mismatched donor HCT (related/haploidentical versus unrelated [MMUD]) with fractionated-total body irradiation (fTBI) plus fludarabine and PTCy as GVHD prophylaxis at City of Hope from 2015 to 2021. Diagnoses included acute lymphoblastic leukemia (46.5%), acute myelogenous leukemia (36.1%), and myelodysplastic syndrome (6.5%). The median age at HCT was 38 years, and 126 patients (81.3%) were an ethnic minority. The Hematopoietic Stem Cell Transplantation Comorbidity Index was ≥3 in 36.1% of the patients, and 29% had a Disease Risk Index (DRI) of high/very high. The donor type was haploidentical in 67.1% of cases and MMUD in 32.9%. At 2 years post-HCT, disease-free survival (DFS) was 75.4% and overall survival (OS) was 80.6% for all subjects. Donor type did not impact OS (hazard ratio [HR], .72; 95% confidence interval [CI], .35 to 1.49; P = .37) and DFS (HR, .78; 95% CI, .41 to 1.48; P = .44), but younger donors was associated with less grade III-IV acute GVHD (HR, 6.60; 95% CI, 1.80 to 24.19; P = .004) and less moderate or severe chronic GVHD (HR, 3.53; 95% CI, 1.70 to 7.34; P < .001), with a trend toward better survival (P = .099). The use of an MMUD was associated with significantly faster neutrophil recovery (median, 15 days versus 16 days; P = .014) and platelet recovery (median, 18 days versus 24 days; P = .029); however, there was no difference in GVHD outcomes between the haploidentical donor and MMUD groups. Nonrelapse mortality (HR, .86; 95% CI, .34 to 2.20; P = .76) and relapse risk (HR, .78; 95% CI, .33 to 1.85; P = .57) were comparable in the 2 groups. Patient age <40 years and low-intermediate DRI showed a DFS benefit (P = .004 and .029, respectively). High or very high DRI was the only predictor of increased relapse (HR, 2.89; 95% CI, 1.32 to 6.34; P = .008). In conclusion, fludarabine/fTBI with PTCy was well-tolerated in mismatched donor HCT, regardless of donor relationship to the patient, provided promising results, and increased access to HCT for patients without a matched donor, especially patients from ethnic minorities and patients of mixed race.

The role of artificial intelligence measured preoperative kidney volume in predicting kidney function loss in elderly kidney donors: A multicenter cohort study.

The increasing use of kidneys from elderly donors raises concerns due to age-related nephron loss. Combined with nephrectomy, this loss of nephrons markedly increases the risk of developing chronic kidney disease (CKD). This study aimed to investigate the prognostic value of preoperative kidney cortex volume in predicting the loss of kidney function in elderly donors, by developing an artificial intelligence (AI)-based model for precise kidney volume measurement and applying it to living kidney donors. A multicenter retrospective cohort study using data from living donors who underwent donor nephrectomy between January 2010 and December 2020 was conducted. An AI segmentation model was developed and validated to measure kidney cortex volume from pre-donation computer tomographic (CT) images. The association between measured preoperative kidney volumes and post-nephrectomy renal function was analyzed through a generalized additive model. A total of 1074 living kidney donors were included in the study. Validation of the developed kidney cortex volume model showed a Dice similarity coefficient of 0.97 and a Hausdorff distance of 0.76mm. The measured cortex volumes exhibited an age-related decrease, which correlated with declining kidney function. Elderly donors showed greater decreases in estimated glomerular filtration rates (eGFR) post-donation compared to young donors (P=0.041). Larger preoperative remnant kidney cortex volume was associated with significantly less decline of eGFR post-donation than those with smaller preoperative remnant kidney cortex volume (P<0.001). This study highlights the critical role of preoperative kidney cortex volume in the donor assessment process, particularly for elderly donors. The fully automated model for measuring kidney cortex volume provides a valuable tool for predicting post-donation renal function and holds promise for enhancing donor evaluation and safety.

ALDH2 regulates mesenchymal stem cell senescence via modulation of mitochondrial homeostasis

Although mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in aging and aging-related diseases, its role in the regulation of human mesenchymal stem cell (MSC) senescence has not been investigated. This study aimed to determine the role of ALDH2 in regulating MSC senescence and illustrate the potential mechanisms. MSCs were isolated from young (YMSCs) and aged donors (AMSCs). Senescence-associated β-galactosidase (SA-β-gal) staining and Western blotting were used to assess MSC senescence. Reactive oxygen species (ROS) generation and mitochondrial membrane potential were determined to evaluate mitochondrial function. We showed that the expression of ALDH2 increased alongside cellular senescence of MSCs. Overexpression of ALDH2 accelerated YMSC senescence whereas down-regulation alleviated premature senescent phenotypes of AMSCs. Transcriptome and biochemical analyses revealed that an elevated ROS level and mitochondrial dysfunction contributed to ALDH2 function in MSC senescence. Using molecular docking, we identified interferon regulatory factor 7 (IRF7) as the potential target of ALDH2. Mechanistically, ectopic expression of ALDH2 led to mitochondrial dysfunction and accelerated senescence of MSCs by increasing the stability of IRF7 through a direct physical interaction. These effects were partially reversed by knockdown of IRF7. These findings highlight a crucial role of ALDH2 in driving MSC senescence by regulating mitochondrial homeostasis, providing a novel potential strategy against human aging-related diseases.

Impact of Warm Ischemia Time on Donation After Circulatory Death Kidney Transplant Outcomes.

Efforts to address the shortage of donor organs include increasing the use of renal allografts from donors after circulatory death (DCD). While warm ischemia time (WIT) is thought to be an important factor in DCD kidney evaluation, few studies have compared the relationship between WIT and DCD kidney outcomes, and WIT acceptance practices remain variable. We conducted a single-center retrospective review of all adult patients who underwent deceased donor kidney transplantation from 2000 to 2021. We evaluated the impact of varied functional warm ischemia time (fWIT) in controlled DCD donors by comparing donor and recipient characteristics and posttransplant outcomes between high fWIT (>60min), low fWIT (≤60min), and kidneys transplanted from donors after brain death (DBD). Two thousand eight hundred eleven patients were identified, 638 received low fWIT DCD, 93 received high fWIT DCD, and 2080 received DBD kidneys. There was no significant difference in 5-year graft survival between the DCD low fWIT, high fWIT, and DBD groups, with 84%, 83%, and 83% of grafts functioning, respectively. Five-year patient survival was 91% in the low fWIT group, 92% in the high fWIT group, and 90% in the DBD group. An increase in kidney donor risk index (KDRI) (HR 3.37, 95% CI=2.1-5.7) and high CIT compared to low CIT (HR 2.12, 95% CI=1.4-3.1) have higher hazard ratios for 1-year graft failure. Increased acceptance of kidneys from selected DCD donors with prolonged fWIT may present an opportunity to increase kidney utilization while preserving outcomes. Our group specifically prioritizes the use of kidneys from younger donors, with lower KDPI, and without acute kidney injury, or risk factors for underlying chronic kidney disease.

Prevalence of the FMR1 Gene Premutation in Young Women with a Diminished Ovarian Reserve Included in an IVF Program: Implications for Clinical Practice.

The relationship between premature ovarian insufficiency (FXPOI) and premutation in the FMR1 gene is well established. In recent years, though, a potential relationship between the latter and a low ovarian reserve has been suggested. To explore it, we conducted a retrospective study in an IVF program at a university tertiary referral center in Barcelona (Spain). Data were obtained retrospectively from a total of 385 women referred for FMR1 gene testing at our institution from January 2018 to December 2021. We compared the prevalence of FMR1 gene premutation between 93 of them, younger than 35 years, with a diminished ovarian reserve (DOR), characterized by levels of anti-Mullerian hormone < 1.1 ng/mL and antral follicle count < 5; and 132 egg donors screened by protocol that served as the controls. We found a higher prevalence of FMR1 premutation in the DOR group (seven patients (7.69%)) than in the control group (one patient (1.32%)), Fisher-exact test p-value = 0.012). We concluded that compared with the general population represented by young egg donors, the prevalence of FMR1 gene premutation is higher in young patients with a diminished ovarian reserve. Although these findings warrant further prospective validation in a larger cohort of patients within DOR, they suggest that, in clinical practice, FMR1 premutation should be determined in infertile young patients with DOR in order to give them adequate genetic counselling.

Assessment of Tie2-Rejuvenated Nucleus Pulposus Cell Transplants from Young and Old Patient Sources Demonstrates That Age Still Matters.

Cell transplantation is being actively explored as a regenerative therapy for discogenic back pain. This study explored the regenerative potential of Tie2+ nucleus pulposus progenitor cells (NPPCs) from intervertebral disc (IVD) tissues derived from young (<25 years of age) and old (>60 years of age) patient donors. We employed an optimized culture method to maintain Tie2 expression in NP cells from both donor categories. Our study revealed similar Tie2 positivity rates regardless of donor types following cell culture. Nevertheless, clear differences were also found, such as the emergence of significantly higher (3.6-fold) GD2 positivity and reduced (2.7-fold) proliferation potential for older donors compared to young sources. Our results suggest that, despite obtaining a high fraction of Tie2+ NP cells, cells from older donors were already committed to a more mature phenotype. These disparities translated into functional differences, influencing colony formation, extracellular matrix production, and in vivo regenerative potential. This study underscores the importance of considering age-related factors in NPPC-based therapies for disc degeneration. Further investigation into the genetic and epigenetic alterations of Tie2+ NP cells from older donors is crucial for refining regenerative strategies. These findings shed light on Tie2+ NPPCs as a promising cell source for IVD regeneration while emphasizing the need for comprehensive understanding and scalability considerations in culture methods for broader clinical applicability.

From Young to Old: Mimicking Neuronal Aging in Directly Converted Neurons from Young Donors.

A substantial challenge in human brain aging is to find a suitable model to mimic neuronal aging in vitro as accurately as possible. Using directly converted neurons (iNs) from human fibroblasts is considered a promising tool in human aging since it retains the aging-associated mitochondrial donor signature. Still, using iNs from aged donors can pose certain restrictions due to their lower reprogramming and conversion efficacy than those from younger individuals. To overcome these limitations, our study aimed to establish an in vitro neuronal aging model mirroring features of in vivo aging by acute exposure on young iNs to either human stress hormone cortisol or the mitochondrial stressor rotenone, considering stress as a trigger of in vivo aging. The impact of rotenone was evident in mitochondrial bioenergetic properties by showing aging-associated deficits in mitochondrial respiration, cellular ATP, and MMP and a rise in glycolysis, mitochondrial superoxide, and mitochondrial ROS; meanwhile, cortisol only partially induced an aging-associated mitochondrial dysfunction. To replicate the in vivo aging-associated mitochondrial dysfunctions, using rotenone, a mitochondrial complex I inhibitor, proved to be superior to the cortisol model. This work is the first to use stress on young iNs to recreate aging-related mitochondrial impairments.

The brain-protective mechanism of fecal microbiota transplantation from young donor mice in the natural aging process via exosome, gut microbiota, and metabolomics analyses

The natural aging process is accompanied by changes in exosomes, gut microbiota, and metabolites. This study aimed to reveal the anti-aging effect and mechanisms of fecal microbiota transplantation (FMT) from young donors on the natural aging process in mice by analyzing exosomes, gut microbiota, and metabolomics. Aging-relevant telomeric length, oxidative stress indexes in brain tissue, and serum cytokine levels were measured. Flow analysis of T-regulatory (Treg), CD4+, and CD8+ cells was performed, and the expression levels of aging-related proteins were quantified. High-throughput sequencing technology was used to identify differentially expressed serum exosomal miRNAs. Fecal microbiota was tested by 16 S rDNA sequencing. Changes in fecal metabolites were analyzed by UPLC-Q-TOF/MS. The results indicated that the expression of mmu-miR-7010–5p, mmu-miR-376b-5p, mmu-miR-135a-5p, and mmu-miR-3100–5p by serum exosomes was down-regulated and the abundance of opportunistic bacteria (Turicibacter, Allobaculum, Morganella.) was decreased, whereas the levels of protective bacteria (Akkermansia, Muribaculaceae, Helicobacter.) were increased after FMT. Metabolic analysis identified 25 potential biomarkers. Correlation analysis between the gut microbiota and metabolites suggested that the relative abundance of protective bacteria was positively correlated with the levels of spermidine and S-adenosylmethionine. The study indicated that FMT corrected brain injury due to aging via lipid metabolism, the metabolism of cofactors and vitamins, and amino acid metabolism.

A Cross-Sectional Study of Measles-Specific Antibody Levels in Australian Blood Donors-Implications for Measles Post-Elimination Countries.

Passive immunisation with normal human immunoglobulin (NHIG) is recommended as post-exposure prophylaxis (PEP) for higher-risk measles contacts where vaccination is contraindicated. However, the concentration of measles-specific antibodies in NHIG depends on antibody levels within pooled donor plasma. There are concerns that measles immunity in the Australian population may be declining over time and that blood donors' levels will progressively decrease, impacting levels required to produce effective NHIG for measles PEP. A cross-sectional study of Australian plasmapheresis donors was performed using an age-stratified, random sample of recovered serum specimens, collected between October and November 2019 (n = 1199). Measles-specific IgG antibodies were quantified by ELISA (Enzygnost anti-measles virus IgG, Siemens), and negative and equivocal specimens (n = 149) also underwent plaque reduction neutralisation testing (PRNT). Mean antibody levels (optical density values) progressively decreased from older to younger birth cohorts, from 2.09 [±0.09, 95% CI] to 0.58 [±0.04, 95% CI] in donors born in 1940-1959 and 1990-2001, respectively (p < 0.0001). This study shows that mean measles-specific IgG levels are significantly lower in younger Australian donors. While current NHIG selection policies target older donors, as younger birth cohorts become an increasingly larger proportion of contributing donors, measles-specific antibody concentrations of NHIG will progressively reduce. We therefore recommend monitoring measles-specific antibody levels in future donors and NHIG products in Australia and other countries that eliminated measles before the birth of their youngest blood donors.

Seroprevalence of infectious markers HCV, HBV, HIV and the agent of syphilis among blood donors from the blood transfusion center (BTC of Constantine) in a hospital in eastern Algeria

Microbial agents transmitted by blood transfusion, HBV, HCV, HIV and syphilis remain a major problem for transfusion safety. The objective of this study is to determine the seroprevalence of infectious markers in order to contribute to the improvement of the safe and sufficient supply of blood. This is a retrospective cross-sectional study carried out at the BTC SMK laboratory in Constantine covering the period from January 2019 to December 2021. Our sample is mainly composed of voluntary, adult, young and male donors. 9155 donors who underwent a screening examination during the period (2019-2021). The seroprevalence of HBV, HCV, HIV and syphilis was respectively 0.40%, 0.12%, 0%, 0.14%, with a male predominance whose age group [36-45 [ presents the highest frequency of HCV, HBV and syphilis. Our results justify donor selection and screening tests.

Unrelated hematopoietic stem cell donor registries: present reality and future prospects.

Stem cell donor registries play an important role in providing stem cell products from unrelated donors to patients with severe blood diseases. In this review, important aspects of donor registry work, current challenges and possible future developments are discussed. The current growth in global unrelated stem cell donations is in line with the long-term trend, indicating that donor registries have overcome the COVID-19 pandemic. A key challenge for donor registries is the recruitment of donors from disadvantaged populations to create greater equity in access to unrelated stem cell transplantation. In addition, recruiting young donors and increasing the availability of donors who are already registered are important goals. In recent years, numerous studies have looked at the context of these themes and the development of possible solutions. The international community of donor registries, together with the World Marrow Donor Association, has helped many patients in need of a stem cell transplant over the past decades and is, therefore, a bright example of international collaboration for a good cause. It is currently addressing a number of challenges to effectively help as many patients as possible from various populations also in the future.

Interplay between donor age and HLA-DP matching in 10/10 HLA-matched unrelated donor HCT

AbstractIn 10/10 HLA-matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) with calcineurin-inhibitor (CNI)-based prophylaxis, T-cell epitope DP-matched and permissive mismatched donors are associated with similar overall survival (OS) whereas donors with nonpermissive mismatches should be avoided. Younger unrelated donors are also favored over older donors. We explored outcomes associated with different combinations of DP-matching and donor age (dichotomized at 35 years) to further guide donor selection. Using a Center for International Blood and Marrow Transplant Research data set, we categorized 10 783 patients into 6 groups: DP-matched/younger donor (n = 1591), DP-matched/older donor (n = 526), permissive-mismatched/younger donor (n = 3845), permissive-mismatched/older donor (n = 1184), nonpermissive mismatched/younger donor (n = 2659), and nonpermissive mismatched/older donor (n = 978). We noted that younger donor age, rather than DP matching, was associated with better OS. Younger donors with permissive mismatches were associated with improved OS compared with older matched donors. Furthermore, younger donors with nonpermissive mismatches were associated with improved OS compared with older donors with permissive mismatches. Our study adds further information about the association of DP matching and donor age with HCT outcomes. Donor age should be prioritized over DP matching in patients undergoing 10/10 HLA-MUD with CNI prophylaxis. Among those with younger donors, permissive-mismatched or DP-matched donors are preferred over nonpermissive mismatched donors.

P-318 Reproductive ageing: the seed, the soil, or both?

Abstract Study question Is it all about the embryo? Can a single euploid blastocyst transfer sustain reproductive outcomes in women with advanced reproductive age? Summary answer Despite euploid embryo transfer, endometrial senescence appears to play a crucial role in determining reproductive success, particularly in older patients undergoing in vitro fertilization (IVF). What is known already Advanced reproductive age significantly impairs oocyte and embryo quality. Effective crosstalk and synchronization between embryo and endometrium are pivotal for successful pregnancies, both in vivo and in vitro. Implantation failure remains a persistent challenge in IVF, exacerbated by delayed family planning trends. The transfer of euploid blastocysts through preimplantation genetic testing for aneuploidy (PGT-A) is a potential strategy to address implantation issues, decrease miscarriages, and shorten time-to-pregnancy. However, a significant proportion of IVF treatments remain unsuccessful, suggesting critical factors beyond the embryo. Study design, size, duration This retrospective study analyzed 457 single euploid blastocyst transfers performed by two doctors at a private IVF center from January to November 2023. Inclusion criteria encompassed cases with PGT-A indications (advanced maternal age, repeated implantation failure, recurrent pregnancy loss, etc.) or cases where embryo biopsy was patient-requested. The primary outcome was ongoing pregnancy rate (OPR), with secondary outcomes including pregnancy rate (PR) and clinical pregnancy rate (CPR). Participants/materials, setting, methods Participants were categorized into four groups: Group 1 (&amp;lt; 35 years old; N = 100), Group 2 (35-37 years old; N = 102), Group 3 (38-40 years old; N = 118), and Group 4 (&amp;gt; 41 years old; N = 87). A control group (oocyte donation; N = 50) with single euploid embryo transfers showed a mean recipient age of 43 years. Donors were always less than 32 years old. Endometrial preparation protocols were consistent across all groups. Chi-square test was used to compare groups. Main results and the role of chance Among the 457 transfers analyzed, with a mean female age of 37 years, the overall PR was 71.3%, CPR was 64.8%, and OPR was 60.2%. Groups showed no differences in demographic variables and cycle parameters. Group 1 demonstrated higher PR (83.3%), CPR (78.4%), and OPR (73.5%) compared to Group 2 (PR 70.9%, p = 0.034; CPR 66%, p = 0.047; OPR 62.1%, p = 0.081), Group 3 (PR 68.2%, p = 0.009; CPR 61.2%, p = 0.005; OPR 56.6%, p = 0.008), and Group 4 (PR 65%, p = 0.002; CPR 56.1%, p &amp;lt; 0.001; OPR 51.2%, p = 0.001). Furthermore, the control group (oocyte recipients) showed significantly lower PR (68%, p = 0.031), CPR (54%, p = 0.002), and OPR (46%, p &amp;lt; 0.001) compared to Group 1, but not with the other groups. These findings demonstrate that even with euploid embryos originating from young donors, older women exhibited lower pregnancy rates than young women transferring single euploid blastocysts from their own oocytes and similar rates compared to those with advanced reproductive age transferring their own euploid blastocysts, implying that endometrial ageing may disproportionately influence IVF treatment outcomes. Limitations, reasons for caution The retrospective design introduces inherent bias, notably selection bias and unmeasured confounders. This preliminary data did not account for male infertility factors and their impact on embryo quality. Wider implications of the findings Reproductive aging appears to be influenced by factors beyond the embryo itself, especially in women above 35 years. Further research is warranted to elucidate the causes and impact of reproductive aging on implantation potential, aiming to refine clinical practices and enhance the success of IVF treatments. Trial registration number not applicable

The impact of donor-recipient age difference on graft survival after heart transplant in adults with congenital heart disease

BackgroundThe impact of donor-recipient age difference in adult congenital heart disease (ACHD) patients undergoing heart transplant (HT) is unknown. MethodsACHD patients (≥18 years old) who underwent HT (2000-2020) were identified using the United Network for Organ Sharing database. Graft survival through 10 years based on donor-recipient age difference was evaluated by comparing outcomes of donors >5 years older than recipient (Older), donors within 5 years of recipient age (Equal Age), and donors >5 years younger than recipient (Younger, reference group). Cox multivariable analysis was performed to evaluate the effect of donor-recipient age difference on early and late graft survival. ResultsA total of 1,275 ACHD patients underwent HT (60% male, median 35 years-old (interquartile range 24-46) with median graft survival of 13.7 years (95% confidence interval [CI] 11.7-16.0). Compared to Younger donors (n=306 [24%]), graft survival was similar with Equal Age donors (n=698 [55%]; Log rank p=0.61), though significantly reduced with Older donors (n=271 [21%]; Log rank p=0.03). In multivariable analysis, late graft survival was similar with Equal Age donors but lower with Older donors (adjusted hazard ratio [aHR] 1.63, 95% CI 1.16-2.28, p=0.005), with a trend of reduced survival with Older donors in recipients <30 or ≥40 years-old. ConclusionsGraft survival in ACHD patients undergoing HT was similar for those with Younger and Equal Age donors. Recipients with Older donors had reduced 10-year survival, possibly related to increased risk in those <30 and ≥40 years-old. These data help inform optimal donor age for ACHD patients requiring HT.

Poster 240: Radiographic and Patient-Reported Outcomes of Patellar Denovo Procedure in Shouldered Versus Unshouldered Patella Cartilage Lesions

Objectives: Unique challenges exist in treating patellar cartilage defects such as the contour of the articular surface and the high dynamic shear and compressive forces at the trochlear articulation. When considering restoration techniques osteochondral autograft or allograft can be used when the underlying bone is also involved but for isolated chondral defects, cell-based restoration is the standard of care. Previous literature has demonstrated that success of these cell-based therapies depends on a fully shouldered, stable rim of healthy cartilage to achieve repair stability. More recently, particulated juvenile articular cartilage (PJAC), minced hyaline cartilage from young donors, has demonstrated promising and practical results in the treatment of symptomatic articular defects of the patella and other surfaces. The newer cell-based techniques are more stable than previous options such as autologous chondrocyte implantation (ACI). The purpose of this study is to compare clinical outcomes of PJAC in patients with shouldered versus unshouldered full-thickness cartilage defects of the patella. We hypothesized that there will be no significant difference in short-term clinical outcomes and radiographic cartilage fill between shouldered and unshouldered lesions. Methods: A retrospective review of prospectively collected data was conducted on patients treated with PJAC for a full-thickness symptomatic patellar cartilage lesion between March 2014 and August 2019. Magnetic resonance imaging (MRI) was performed for all patients at 6, 12, and 24 months postoperatively and analyzed for percent fill, categorized by 0% to 33%, 34% to 66%, and 67% to 100% fill. Patient-reported outcome measures (PROMs) were obtained preoperatively and at 1, 2 and &gt;2 years postoperatively. Arthroscopic images were independently assessed, and cartilage defect characteristics were documented as shouldered or unshouldered by an orthopaedic surgery resident and an orthopaedic surgery sports fellow. Percent fill on MRI and clinical outcome scores (International Knee Documentation Committee, Kujala, Knee injury and Osteoarthritis Outcome Score – Physical Function Short-Form [KOOS-PS], Knee injury and Osteoarthritis Outcome Score – Quality of Life, The Hospital for Special Surgery Pediatric Functional Activity Brief Scale) were analyzed and correlated with the shouldered or unshouldered classification of the lesions. Results: Between March 2014 and August 2019, a total of 70 lesions in 65 patients were treated with PJAC for patellar cartilage lesions. The mean patient age was 26.6 years old (range, 14 – 51) and 76% (n = 53) were female. Twenty-five (36%) knees had undergone prior surgery and average symptom duration was 7.5 years. The average patellar lesion size was 277 mm2 (range, 77 – 800 mm2), the average number of allografts packets used was 2.4 (range, 1 – 5), and the average donor age was 46.1 months (range, 1 – 120). Arthroscopic pictures were available for 64 out of 70 lesions. There was perfect inter-rater reliability of whether the lesions were considered to have a continuous, stable rim (shouldered) or not (unshouldered). Thirty-two lesions were shouldered and the remaining 32 lesions were unshouldered according to their intraoperative pictures. Patients with shouldered lesions reported a significantly lower duration of symptoms than those with unshouldered lesions (5.29 ± 7.12 years vs.10.11 ± 9.85 years, p &lt; 0.05). Patients with shouldered lesions were also significantly more likely to have a prior knee surgery (p &lt; 0.05). Patients did not differ significantly by MRI percent fill in the shouldered versus unshouldered groups (Figure 1). There were no significant differences in baseline, 1-, or 2-year patient-reported outcomes based between patients with shouldered and unshouldered lesions (Table 1). The only statistically significant difference in outcomes was a lower score for KOOS-PS in the unshouldered group at &gt;2 years compared to the shouldered group (p &lt; 0.05), and in the change in KOOS-PS from baseline to 2-years between the 2 groups (p &lt;0.05). Conclusions: Patellofemoral joint cartilage defects are difficult to treat due to their unique thickness and topography. Historically, emphasis has been placed on having a stable, fully shouldered defect in order to achieve success of repair with microfracture or ACI. However, with the increased stability of newer cell-based treatments, these unshouldered cartilage lesions do well both clinically and radiographically. Our study found no significant differences between the shouldered and unshouldered groups with regard to both clinical outcomes as well as radiographic cartilage fill. This suggests that, with newer cartilage restoration techniques, whether a lesion is shouldered does not affect the outcomes achieved by these procedures. [Figure: see text]

Haploidentical Versus Mismatched Unrelated Donor Hematopoietic Cell Transplantation: HLA Factors and Donor Age Considerations

HLA-mismatched unrelated donors and haploidentical related donors are suitable stem cell sources for hematopoietic cell transplantation (HCT) when patients lack HLA-matched donors. Clinical outcome after mismatched HCT is influenced by HLA factors including the similarity of peptide-binding motifs (PBMs) between the patient and unrelated donor, and of the HLA-B leader in unrelated and haploidentical donors. Whether these factors can aid in the selection between mismatched unrelated and haploidentical donors is not known. To address this question, we investigated outcomes between the two donor types defined by matching for the PBM and leader peptide. We compared PBM-matched (n = 614) and mismatched (n = 958) MMUDs with calcineurin-inhibitor-based prophylaxis to four haploidentical groups that received post-transplant cyclophosphamide (PTCy)-based prophylaxis. The haploidentical groups were B-leader matched/DRB1-mismatched (n = 722), B-leader matched/DRB1-matched (n = 154), B-leader mismatched/DRB1-mismatched (n = 493), and B-leader mismatched/DRB1-matched (n = 63). Multivariate analysis showed that the B-leader matched/DRB1-mismatched haploidentical group had the best overall survival (OS) compared to the PBM-matched MMUD, while other haploidentical groups had comparable OS. The PBM-mismatched MMUD showed the poorest outcomes, similar to the B-leader mismatched/DRB1-matched haploidentical group. Among non-HLA factors, donor age was the most significant predictor of OS. These results suggest that a B-leader matched/DRB1 mismatched haploidentical donor might be the preferred choice among donors of similar age. If such a donor is not available, the youngest donor from either PBM-matched unrelated or other haploidentical groups could be a beneficial choice. These findings need validation with both donor groups receiving PTCy-based graft-versus-host disease prophylaxis.

Comparing the release of growth factors when partially demineralized tooth matrix is mixed with platelet rich fibrin and injectable platelet rich fibrin: An in-vitro observational study

Abstract Context: Platelet concentrates are rich in growth factors that assist in regenerative medicine to promote healing and tissue regeneration. Similarly, partially demineralized tooth is a storehouse of many growth factors, assisting in bone regeneration. Hence, the present study aimed to quantify the release of growth factors from different platelet concentrates individually and when mixed with a partially demineralized tooth matrix. Method: Human growth factors such as bFGF, EGF, PDGF-AB, TGF-beta-1, and VEGF-A present in platelet-rich fibrin and injectable platelet-rich fibrin from young and old male and female donors were quantified separately. Then these platelet concentrates were then mixed with a partially demineralized tooth matrix, which was powdered using a Smart Dentin Grinder. An enzyme-linked immunosorbent assay was used for the quantification of growth factors. Results: The release of growth factors, such as platelet-rich fibrin and injectable platelet-rich fibrin, was not statistically significant; however, it was significantly greater when i-PRF was mixed with a partially demineralized tooth matrix. Conclusion: The study revealed that the expression of growth factors was significantly greater when a partially demineralized tooth matrix was mixed with injectable platelet-rich fibrin than when combined with platelet-rich fibrin.

Influence of donor age and donor-recipient age difference on intimal hyperplasia in pediatric patients with young and adult donors vs. adult patients after heart transplantation.

Optimal selection and allocation of donor hearts is a relevant aspect in transplantation medicine. Donor age and cardiac allograft vasculopathy (CAV) affect post-transplant mortality. To what extent donor age impacts intimal hyperplasia (CAVIH) in pediatric and adult patients after heart transplantation (HTx) is understudied. In a cohort of 98 HTx patients, 58 pediatric (24.1% with adult donors) and 40 adult patients, we assessed the effect of donor age and donor-recipient age difference (D-R) on the continuous parameter of maximal intima thickness (mIT) in optical coherence tomography. We evaluated their predictive value regarding higher mIT and the prevalence of CAVIH, defined as mIT > 0.3 mm, and compared it to established CAV risk factors. In the overall population, donor age correlated with mIT (p < 0.001), while in the pediatric subpopulation, both donor age and D-R correlated with mIT (p < 0.001 and p = 0.002, respectively). In the overall population, donor age was a main predictor of higher mIT and CAVIH (p = 0.001 and p = 0.01, respectively) in addition to post-transplant interval, arterial hypertension, and dyslipidemia. In the pediatric patients, dyslipidemia remained a main predictor of both higher mIT and CAVIH (p = 0.004 and p = 0.040, respectively), while donor age and D-R were not. While there was an effect of the non-modifiable parameter of donor age regarding maximal intimal thickness, a stronger association was seen between the modifiable risk factor dyslipidemia and higher maximal intimal thickness and CAVIH in both the overall population and the pediatric subpopulation.

Long-term Outcomes After Kidney Transplantation From DBD Donors Aged 70 y and Older.

Transplantation of kidneys from elderly donations after brain death (DBD) donors has increased owing to organ shortages. We aimed to assess the impact on long-term kidney transplant outcomes from DBD donors aged 70 y and older compared with kidneys from younger donors. From 2007 to 2022, 2274 first single kidney transplantations from DBD donors were performed at our center. Data from 1417 kidney transplant recipients receiving a DBD organ were included and categorized into 3 groups according to donor age: 70 y and older (n = 444, median age 74 y), 60-69 y (n = 527, median age 64 y), and a reference group consisting of donors aged 45-54 y (n = 446, median age 50 y). Kaplan-Meier plots and multivariate Cox regression with correction for recipient, donor, and transplant characteristics were used to investigate patient and kidney graft survival outcomes. The median patient follow-up time was 9.3 y (interquartile range, 5.3-13.1). The adjusted hazard ratios for patient death in recipients of kidneys from DBD donors aged 70 y and older compared with 60-69 y and 45-54 y were 1.12 (95% confidence interval [CI], 0.92-1.36; P = 0.26) and 1.62 (95% CI, 1.26-2.07; P < 0.001), respectively. Compared with recipients of donors aged 60-69 y and 45-54 y, the adjusted hazard ratios for kidney graft loss in recipients of donors aged 70 y and older were 1.23 (95% CI, 1.02-1.48; P = 0.029) and 1.94 (95% CI, 1.54-2.45; P < 0.001), respectively. Transplantation of kidneys from DBD donors aged 70 y and older resulted in acceptable long-term outcomes and is encouraging.

Extra-islet cells expressing insulin or glucagon in the pancreas of young organ donors

AimsThe existence of insulin- or glucagon-expressing extra-islet endocrine cells scattered in the pancreas is well-known, but they have been sparsely characterized. The aim of this study was to examine their density, distribution, transcription-factor expression, and mitotic activity in young non-diabetic subjects.MethodsMultispectral imaging was used to examine PDX1, ARX, Ki67, insulin and glucagon in extra-islet endocrine cells in pancreatic tissue from organ donors aged 1–25 years.ResultsExtra-islet insulin- or glucagon-positive cells were frequent in all donors (median 17.3 and 22.9 cells/mm2 respectively), with an insulin:glucagon cell ratio of 0.9. The density was similar regardless of age. PDX1 localized mainly to insulin-, and ARX mainly to glucagon-positive cells but, interestingly, many of the cells were negative for both transcription factors. Double-hormone-positive cells were rare but found in all age groups, as were insulin-positive cells expressing ARX and glucagon-positive cells expressing PDX1. Extra-islet endocrine cells with Ki67 expression were present but rare (0–2%) in all age groups.ConclusionsExtra-islet endocrine cells are more frequent than islets. The preserved extra-islet cell density during pancreas volume-expansion from childhood- to adulthood indicates that new cells are formed, possibly from replication as cells with mitotic activity were discovered. The lack of transcription-factor expression in many cells indicates that they are immature, newly formed or plastic. This, together with the mitotic activity, suggests that these cells could play an important role in the expansion of beta-cell mass in situations of increasing demand, or in the turnover of the endocrine cell population.