Number Of Donors Research Articles

An investigation to improve a nonlinear mixed-effects approach for EC50 estimation based on multi-donor dose–response data

ABSTRACT Dose–response relationships are important in assessing the efficacy and potency of compounds, which can usually be characterized by a 4-parameter logistic (4-PL) model estimating EC50, slope factor, lower asymptote, and upper asymptote. EC50, the concentration of a compound that induces a response halfway between the baseline and maximum, is a key quantity to evaluate compound potency. For multi-donor dose–response data, it is often of interest to estimate the overall EC50 (i.e. the average EC50 of the population of donors) and its 95% confidence interval (CI). A few multi-donor EC50 estimation methods have been proposed in the literature. Jiang and Kopp-Schneider (2014) systematically compared the meta-analysis approach and the nonlinear mixed-effects approach and concluded that the meta-analysis approach is simple and robust to summarize EC50 estimates from multiple experiments, especially suited in the case of a small number of experiments, while the nonlinear mixed-effects approach has the issue of convergence failures probably due to overparameterization. In this article, we propose a modification of the nonlinear mixed-effects approach by using the stochastic approximation expectation-maximization (SAEM) algorithm to estimate model parameters and using multiple starting points to search for globally optimal values, which can substantially alleviate the issue of convergence failures even for small number of donors (e.g. n = 3), and achieve a smaller absolute median bias and better coverage probability of 95% confidence interval than the meta-analysis approach when the number of donors is not too small (e.g. n ≥ 7).

Questions on travel and sexual behaviours negatively impact ethnic minority donor recruitment: Effect of negative word-of-mouth and avoidance.

Donor selection questions differentially impacting ethnic minorities can discourage donation directly or via negative word-of-mouth. We explore the differential impact of two blood safety questions relating to (i) sexual contacts linked to areas where human immunodeficiency virus (HIV) rates are high and (ii) travelling to areas where malaria is endemic. Epidemiological data are used to assess infection risk and the need for these questions. We report two studies. Study 1 is a behavioural study on negative word-of-mouth and avoiding donation among ethnic minorities (n = 981 people from National Health Service Blood and Transplant (NHSBT) and the general population: 761 were current donors). Study 2 is an epidemiology study (utilizing NHSBT/UK Health Security Agency (UKHSA) surveillance data on HIV-positive donations across the UK blood services between1996 and 2019) to assess whether the sexual risk question contributes to reducing HIV risk and whether travel deferral was more prevalent among ethnic minorities (2015-2019). Studies 1 and 2 provide complementary evidence on the behavioural impact to support policy implications. A high proportion of people from ethnic minorities were discouraged from donating and expressed negative word-of-mouth. This was mediated by perceived racial discrimination within the UK National Health Service. The number of donors with HIV who the sexual contact question could have deferred was low, with between 8% and 9.3% of people from ethnic minorities deferred on travel compared with 1.7% of White people. Blood services need to consider ways to minimize negative word-of-mouth, remove questions that are no longer justified on evidence and provide justification for those that remain.

Recipients' age, fresh embryo and blastocyst-stage embryo transfer as favorable factors in a transnational oocyte donation program.

In Italy, egg donation is being allowed again following the ruling by the Constitutional Court N. 162/2014. Nevertheless, the number of voluntary donors is insignificant, probably because no reimbursement is provided. Therefore, the great majority of egg donation cycles are performed by using imported cryopreserved oocytes from foreign countries. However, recent evidence has questioned the overall efficacy of this strategy in comparison with the shipment of frozen sperm and vitrified embryos. Retrospective cohort study, conducted at ANDROS Day Surgery Clinic Palermo, Italy in the period 2016-2022, with the objective of evaluating the efficiency of each batch of vitrified oocytes, in terms of completed cycles. The cryopreserved donated oocytes came from a single Spanish clinic (Next Fertility, Valencia, Spain). The primary outcome was the cumulative live birth rate (CLBR). The secondary outcomes were the cumulative ongoing pregnancy rate (COPR), the cumulative clinical pregnancy rate (CCPR) and the miscarriage rate. The CLBR totaled 35.1%, the COPR 36.8%, the CCPR 49.2% and the miscarriage rate 24.7%. In the multivariate analysis, the probability of success was significantly higher in younger recipients, in fresh embryo transfer and in blastocyst-stage embryo transfer. Our "transnational" donation program with vitrified oocytes has good success rates. The main focus of our analysis is the negative effect of advancing recipient age on success rates, outlining a possible, important role of age-related uterine factor on implantation mechanisms. This aspect should be emphasized during the counselling with couples much more than is routinely done.

Culture on organ and tissue donation in the community of Medical School, Veracruz Region

Abstract Introduction Organ donation is a life-saving activity, yet there is a disparity between the high number of recipients and the minimal number of donors. Objetives To determine the level of organ and tissue donation culture for transplant purposes among faculty members and undergraduate medical interns at a Medical School Methods A cross-sectional and prospective study was conducted from January 2023 to 2024, including faculty members and undergraduate medical interns from the Medical School at the University of Veracruz - Veracruz Region. The main study variable was the culture of organ and tissue donation for transplant purposes, quantified through three dimensions: knowledge, attitude, and training, assessed using a validated instrument (Cronbach’s alpha: 0.6). The entire described population was included, and they were approached in different areas to invite them to participate in this research. Results 225 subjects (55 faculty members) agreed to participate. 97% of participants expressed support for organ donation. Among those not in favor of donation, 33% feared receiving poor medical care as donors, and 17% viewed donation as a business. Organ donation culture was deemed sufficient in 10.98% and outstanding in 71.76% of participants. The most common level of knowledge was outstanding (52%), 70% of the studied population showed a ‘very positive’ attitude towards organ and tissue donation. Training history was evaluated as an associated factor with knowledge about organ donation (OR/CI95%), identifying an association between lack of training and levels of sufficient knowledge (2.5/1.2-4.9) and outstanding knowledge (0.3/0.1-0.7), as well as with sufficient culture (9.6/1.2-73.0) and outstanding culture (0.1/0.04-0.4) (p < 0.05) Conclusions It is imperative to strengthen training programs for faculty and undergraduate personnel, as quality training enhances knowledge and culture within this essential area of healthcare personnel formation. Key messages • University professors should have accurate information on organ donation and sensitize future physicians on the subject, as this could be a crucial step for future interactions in favor of donation. • It is necessary to eradicate misinformation about organ donation in teachers and students of medical schools, since they are the basis for education and awareness on this issue in the population.

In vitro growth of secondary follicles from cryopreserved-thawed ovarian cortex.

Can secondary follicles be obtained from cultured cryopreserved-thawed human ovarian cortical tissue? We obtained high-quality secondary follicles from cultured cryopreserved-thawed human ovarian cortical tissue from cis female donors (cOVA), but not from trans masculine donors (tOVA) in the same culture conditions. The in vitro growth of oocytes present in unilaminar follicles into metaphase II stage (MII) oocytes has been previously achieved starting from freshly obtained ovarian cortical tissue from adult cis female donors. This involved a multi-step culture protocol and the first step included the transition from unilaminar follicles to multilayered secondary follicles. Given that the ovarian cortex (from both cis female and trans masculine donors) used for fertility preservation is cryopreserved, it is crucial to investigate the potential of unilaminar follicles from cryopreserved-thawed ovarian cortex to grow in culture. Cryopreserved-thawed ovarian cortical tissue from adult trans masculine donors (n = 3) and adult cis female donors (n = 3) was used for in vitro culture following the first culture step described in two published culture protocols (7-8 days and 21 days) and compared to freshly isolated ovarian cortex from trans masculine donors (n = 3) and to ovarian cortex prior to culture. Ovarian cortical tissue was obtained from adult trans masculine donors undergoing gender-affirming surgery while using testosterone, and from adult cis female donors undergoing oophorectomy for fertility preservation purposes before chemotherapy. The ovarian cortex was fixed either prior (day 0) or after the culture period. Follicular survival, growth, and morphology were assessed through histology and immunofluorescence. We quantified the different stages of follicular development (primordial, primary, secondary, and atretic) after culture and observed an increase in the percentage of secondary follicles as well as an increase in COLIV deposition in the stromal compartment regardless of the culture media used. The quality of the secondary follicles obtained from cOVA was comparable to those prior to culture. However, in the same culture conditions, the secondary follicles from tOVA (fresh and cryo) showed low-quality secondary follicles, containing oocytes with small diameter, granulosa cells that expressed abnormal levels of KRT19 and steroidogenic-marker STAR and lacked ACTA2+ theca cells, when compared to tOVA secondary follicles prior to culture. The number of different donors used was limited. Our study revealed that cryopreserved-thawed cOVA can be used to generate high-quality secondary follicles after culture and those can now be further tested to evaluate their potential to generate functional MII oocytes that could be used in the clinic. However, using the same culture protocol on tOVA (fresh and cryo) did not yield high-quality secondary follicles, suggesting that either the testosterone treatment affects follicular quality or adapted culture protocols are necessary to obtain high-quality secondary follicles from tOVA. Importantly, caution must be taken when using tOVA to optimize folliculogenesis in vitro. This research was funded by the European Research Council Consolidator Grant OVOGROWTH (ERC-CoG-2016-725722 to J.S.D.V. and S.M.C.D.S.L.), the Novo Nordisk Foundation (reNEW NNF21CC0073729 to H.C., F.W., J.S.D.V., S.M.C.D.S.L.), and China Scholarship Council (CSC 202008320362 and CSC 202008450034 to H.C. and F.W.), respectively. The authors have no conflicts of interest to declare. N/A.

Serological profile of voluntary blood donors in a blood bank of tertiary health care centre- An institution-based study

Background: The safe transfusion of blood facilities is an essential component of an efficient, excellent healthcare sector. Unsafe blood transfusions can be a cause of transfusion-transmitted infections and can be lethal. The present study was conducted to find out the seroprevalence of HBsAg, HCV, HIV, malarial parasites, and syphilis in voluntary blood donors in a tertiary care center. Materials and methods: This prospective study was conducted at the blood bank of the Shri Mahant Indiresh Hospital, Dehradun. 16413 samples from all blood donations were screened for HBsAg, HCV, HIV 1 and 2, malaria, and syphilis. Samples were collected in vacutainers at the time of blood donation and screened for HIV 1and2, HBsAg, and HCV using the fourth-generation enzyme-linked immunosorbent assay technique. Syphilis was tested by Treponema antibodies using the VITROS Syphilis TPA Reagent Pack. Malaria was tested by pan malaria card, monoclonal anti-pan specific parasite lactate dehydrogenase antibody conjugated to colloidal gold, and another monoclonal anti-pan specific parasite lactate dehydrogenase antibody immobilized on a nitrocellulose strip in a thin line. Results: Out of 16413 blood donors 342(2.1%) were found to be seropositive and 16071 (97.9%) were found to be seronegative. The total number of donors, who were found positive for HBsAg/Anti HCV was 1 (0.3%). Out of the seropositive cases, HBsAg, HCV, HIV, and Syphilis infections constituted 28.9%, 27.5, 14.6, and 28.7% cases respectively. Conclusions: There is a need for the development and implementation of stringent donor selection and sensitive screening tests to reduce the risk of acquiring transfusion-transmitted illnesses.

Research points way on how to stem decline in donors, volunteerism

A new report from the Generosity Commission, a coalition of businesses, philanthropists and civil society groups focused on generosity in America, highlights a series of actions that funders and grantmakers of all stripes can take to help reverse one of the most important trends in philanthropy in recent years — a continuing decline in the number of donors and volunteer rates.

Does old-to-young kidney transplantation rejuvenate old donor kidneys?

The number of older organ donors is increasing due to the aging population. Aged kidneys often face problems such as delayed graft function but previous murine experiments suggested the possibilities of rejuvenation, for example, in a parabiosis setting between old and young mice. To investigate kidney-graft rejuvenation, we compared an old-to-young (O-Y) patient transplantation group and a transplantation group with donors/recipients of approx. the same age (SA) with the renal senescence marker p16 in kidney biopsy samples at baseline and one year post-transplantation. We retrospectively analyzed our hospital's 32 cases of living-donor ABO-compatible transplants performed between 2013-2020. Both the baseline and one-year biopsy (n=9) or only the baseline biopsy (n=32) were analyzed. We divided the nine cases into an O-Y group (donors' median age 68 yrs, recipients 41, difference -27) and an SA group (donors' median age 53 yrs, recipients 51.5, difference -3.5). p16 was stained with the clones JC8 and E6H4 to determine the precise p16-positive rate. The 32 baseline biopsies' p16-positive rate was weakly related to donor age, suggesting that the p16-positive rate can help evaluate kidney senescence. The (n=5) O-Y group's p16-positive rates were at baseline 0.08 and one year 0.12; the (n=4) SA group's rate was 0.03 at both baseline and one year. No kidney rejuvenation was observed, even when old donor kidneys went to young recipients.

Icelike water molecules with single hydrogen bond donor on the surface of nano anatase and rutile particles by IR spectroscopy

The hydration behavior of TiO2 nanoparticles was studied by molecular dynamics simulations and a novel IR ratio spectroscopy method. It was found that the hydration water at the titanium dioxide interface contains molecules with a large number of single hydrogen bond donors, and approximately five water layers were confined within the nano-grooves of the nanoparticles. The confinement effect was observed to enhance the strength of the hydrogen bonds and to slow down the movement of the water molecules around the surface of the nanoparticles.

International review of blood donation screening for anti-HBc and occult hepatitis B virus infection.

Hepatitis B core antibody (anti-HBc) screening has been implemented in many blood establishments to help prevent transmission of hepatitis B virus (HBV), including from donors with occult HBV infection (OBI). We review HBV screening algorithms across blood establishments globally and their potential effectiveness in reducing transmission risk. A questionnaire on HBV screening and follow-up strategies was distributed to members of the International Society of Blood Transfusion working party on transfusion-transmitted infectious diseases. Screening data from 2022 were assimilated and analyzed. A total of 30 unique responses were received from 25 countries. Sixteen respondents screened all donations for anti-HBc, with 14 also screening all donations for HBV DNA. Anti-HBc prevalence was 0.42% in all blood donors and 1.19% in new donors in low-endemic countries; however, only 44% of respondents performed additional anti-HBc testing to exclude false reactivity. 0.68% of anti-HBc positive, HBsAg-negative donors had detectable HBV DNA. Ten respondents did universal HBV DNA screening without anti-HBc, whereas four respondents did not screen for either. Deferral strategies for anti-HBc positive donors were highly variable. One transfusion-transmission from an anti-HBc negative donor was reported. Anti-HBc screening identifies donors with OBI but also results in the unnecessary deferral of a significant number of donors with resolved HBV infection and donors with false-reactive anti-HBc results. Whilst confirmation of anti-HBc results could be improved to reduce donor deferral, transmission risks associated with anti-HBc negative OBI donors must be considered. In high-endemic areas, highly sensitive HBV DNA testing is required to identify infectious donors.

Steric effects and electronic manipulation of multiple donors on S0/S1 transition of Dn-A emitters

Multiple donor-acceptor (D-A) combinations represent a promising category of thermally activated delayed fluorescence (TADF) materials, offering potential for superior efficiency and stability. However, current systems are predominantly composed of limited donor groups, primarily carbazole-based derivatives. In this work, we developed a series of D-A type materials incorporating helical π-expanded carbazole (CzNaph) and 7H-dinaphtho[1,8-bc:1′,8′-ef]azepine (AzNaph), alongside traditional carbazole, ranging from mono- to tetra-substituted configurations (Dn-A). Through systematic investigation of geometric and electronic structures, the number and positioning of multiple donors are confirmed with significant manipulations on charge transfer characteristics and the S1 state via steric effects. Density functional theory (DFT) calculations reveal that varying the number of π-extended donors within the acceptor framework produces emission colors from ultraviolet to red, providing a diverse range of emitters. Furthermore, the reduced reorganization energy of S1 observed in tetra-substituted Cz and CzNaph, as well as MonoAzN, indicates lower structural relaxation, highlighting these materials' potential as stable luminescent candidates. This study underscores the importance of diverse composing units in achieving efficient and stable TADF emitters with multiple and hetero-donor configurations.

Related Factors of Syphilis Positive Rate in Blood Donors During the COVID-19 Epidemic.

In Shenzhen of China, the continuous increase of syphilis infections threatens the safety of blood transfusion. In 2020, COVID-19 was discovered and spread rapidly around the world, and affected the prevalence of syphilis among blood donors. From 2013 to 2020, there were 839,161 blood samples collected in the Shenzhen Blood Center. Blood samples were screened by ELISA tests and confirmed by the TPPA (Treponema pallidum particle agglutination) tests and the TRUST (toluidine red unheated serum tests). All data was analyzed by the chi-square test. From 2013 to 2020, the positive rate of syphilis among blood donors varied significantly among individuals in different ages, educational backgrounds, regions, and blood donation histories (P<0.001). In 2020, It was the first time that there were more repeat blood donors than first-time blood donors and more blood donors with a higher education level than those with a lower education level, and the lowest reactive and positive rate of syphilis among blood donors was observed. Compared to 2019, the prevalence of syphilis among female and repeat blood donors decreased significantly in 2020 (P<0.01). The prevalence of syphilis in blood donors is related to the characteristics of blood donors (in addition to gender) and the COVID-19 epidemic. COVID-19 can affect the prevalence of syphilis among blood donors by influencing the composition of blood donors and the number of syphile-positive donors in certain blood donors, including female and repeat blood donors.

Antecedent Cardiac Arrest Status of Donation After Circulatory Determination of Death (DCDD) Kidney Donors and the Risk of Delayed Graft Function After Kidney Transplantation: A Cohort Study.

The number of donors from donation after circulatory determination of death (DCDD) has increased by at least 4-fold over the past decade. This study evaluated the association between the antecedent cardiac arrest status of controlled DCDD donors and the risk of delayed graft function (DGF). Using data from the Australia and New Zealand Dialysis and Transplant, the associations between antecedent cardiac arrest status of DCDD donors before withdrawal of cardiorespiratory support, DGF, posttransplant estimated glomerular filtration rate (eGFR), and allograft loss were examined using adjusted logistic, linear mixed modeling, and cox regression, respectively. Among donors who experienced cardiac arrest, we evaluated the association between duration and unwitnessed status of arrest and DGF. A total of 1173 kidney transplant recipients received DCDD kidneys from 646 donors in Australia between 2014 and 2019. Of these, 335 DCDD had antecedent cardiac arrest. Compared with recipients of kidneys from donors without antecedent cardiac arrest, the adjusted odds ratio (95% confidence interval) for DGF was 0.85 (0.65-1.11) among those with kidneys from donors with cardiac arrest. There was no association between antecedent cardiac arrest and posttransplant eGFR or allograft loss. The duration of cardiac arrest and unwitnessed status were not associated with DGF. This focused analysis in an Australian population showed that the allograft outcomes were similar whether DCDD donors had experienced a prior cardiac arrest, with no associations between duration or unwitnessed status of arrest and risk of DGF. This study thus provides important reassurance to transplant programs and the patients they counsel, to accept kidneys from donors through the DCDD pathway irrespective of a prior cardiac arrest.

Longitudinal analysis of social and community factors effective in increasing the number of liver donors in the United States.

In this research, it was aimed to evaluate of social and community factors effective in increasing the number of liver donors. Descriptive and relational scanning models were used to conduct the research. Data on liver donors was gathered from the USA Health Resources & Services Administration's Organ Procurement and Transplantation Network between 1988 and 2023. The United States (USA) World Bank Country Reports provided the mortality rates. The data was analyzed using Spearman rho correlation, year-controlled partial correlation, and Generalized Linear Model-Logit analysis. Deceased donor numbers were significantly and negatively correlated with government health expenditure (r = -0.816; P < .01), current health expenditure (r = -0.768; P < .01), female education attainment (r = -0.804; P < .01) and Gini index (r = 0.434; P < .05). Living donor numbers were significantly and negatively correlated with government health expenditure (r = -0.731; P < .01), current health expenditure (r = -0.781; P < .01), male percentage (r = -0.786; P < .01), female education attainment (r = -0.640; P < .05), employment (r = 0.751; P < .01), GDP (r = -0.792; P < .01) and Gini index (r = -0.486; P < .01). Living donor numbers were significantly and positively correlated with age dependency (r = 0.815; P < .01). Generalized Linear Model-Logit (GLM-L) results showed that effect of female education attainment had significant contribution on deceased liver donor (B = -3290.605; P < .01). Effects of significantly correlated community factors on living liver donor numbers were found to be statistically insignificant (P > .05). Research findings reveal that among community factors, especially women's participation in education has a statistically significant effect on liver donors. These results show that the health expenditures made over the years do not provide any added value for liver donors, and role of women on liver donor is significantly dominant.

Investigation of the crystal structure, spectral properties, and interactions of N-(R-nitrophenylsulfonamido)benzoic acids with human serum albumin

This study introduced the synthesis of two novel compounds in the N-(R-nitrophenylsulfonamido)benzoic acids (NO2-SBA), designated as HL6 and HL8. Detailed structural information for HL6 and HL8 was acquired through the employment of various characterization techniques such as single-crystal and powder X-ray diffraction, FT-IR spectroscopy, 1H and 13C NMR spectroscopy, and elemental analysis. X-ray diffraction and Hirshfield surface analysis provides a comparative analysis of hydrogen bonding in HL6·H2O and HL8, revealing significant differences in their interaction patterns and resulting crystal structures. Although both molecules possess the same number of hydrogen bond donors and acceptors, the nature of these interactions and their orientations lead to distinct packing arrangements. In HL6·H₂O, the presence of water molecules introduces additional hydrogen bonding possibilities, which are absent in HL8, significantly affecting the overall structure. Additionally, interactions of all nine compounds in the NO2-SBA series [categorized as o-ABA: HL1–HL3, m-ABA: HL4–HL6, and p-ABA: HL7–HL9] with human serum albumin (HSA) were investigated to understand how structural characteristics influence binding mechanisms and affinity. Fluorescence spectroscopy was employed to further examine these interactions, providing a better understanding of their pharmacological properties. The compounds exhibited moderate affinity to HSA, with the o-ABA series displaying a binding constant (Kb) ten times stronger than the other series, underscoring the significant role of the N,R groups in binding interactions.

Detection of enterovirus RNA in pancreas and lymphoid tissues of organ donors with type 1 diabetes.

The nPOD-Virus group collaboratively applied innovative technologies to detect and sequence viral RNA in pancreas and other tissues from organ donors with type 1 diabetes. These analyses involved the largest number of pancreas samples collected to date. We analysed pancreas, spleen, pancreatic lymph nodes, and duodenum samples from the following donor groups: a) donors with type 1 diabetes (n=71), with (n=35) or without (n=36) insulin-containing islets, (b) donors with single or double islet autoantibody positivity without diabetes (n=22) and c) autoantibody-negative donors without diabetes (control donors) (n=74). Five research laboratories participated in this collaborative effort using approaches for unbiased discovery of RNA viruses (two RNA-Seq platforms), targeted detection of Enterovirus A-D species using RT-PCR, and tests for virus growth in cell-culture. Direct RNA-Seq did not detect virus signal in pancreas samples, whereas RT-PCR detected enterovirus RNA confirmed by sequencing in low amounts in pancreas samples in three of the five donor groups, namely donors with type 1 diabetes with insulin-containing islets, 16% (5/32) donors being positive, donors with single islet autoantibody positivity with 53% (8/15) donors being positive, and non-diabetic donors with 8% (4/49) being enterovirus RNA positive. Detection of enterovirus RNA was significantly more frequent in single islet autoantibody-positive donors compared to donors with type 1 diabetes with insulin-deficient islets (p-value <0.001) and control donors (p-value 0.004). In some donors, pancreatic lymph nodes were also positive. RT-PCR detected enterovirus RNA also in spleen of a small number of donors and virus enrichment in susceptible cell lines before RT-PCR resulted in much higher rate in spleen positivity, particularly in donors with type 1 diabetes. Interestingly, the enterovirus strains detected did not cause a typical lytic infection, possibly reflecting their persistence-prone nature. This was the largest coordinated effort to examine the presence of enterovirus RNA in pancreas of organ donors with type 1 diabetes, using a multitude of assays. These findings are consistent with the notion that both the subjects with type 1 diabetes and those with islet autoantibodies may carry a low-grade enterovirus infection in the pancreas and lymphoid tissues.

Long-term CXCR3 antagonist AMG487 mitigated acute graft-versus-host disease by inhibiting T cell activation in a murine model

BackgroundLymphocyte migration plays a key role in the development of acute graft-versus-host disease (aGVHD). Blocking lymphocyte migration by targeting chemokine receptors, such as CXCR3, may be a promising strategy for preventing and treating aGVHD. Our previous studies have shown that short-term CXCR3 antagonist treatment combined with cyclosporine A alleviated aGVHD. However, the effect of long-term AMG487 treatment on aGVHD survival has not been thoroughly investigated. MethodsA murine aGVHD model was used to examine the expression of CXCR3 in donor T cells. The effects of short- and long-term AMG487 treatment on aGVHD survival were assessed. The infiltration of donor T cells into the liver and spleen tissues and the activation of donor T cells in splenic tissues were also examined. ResultsCXCR3 was consistently highly expressed in donor T cells in a murine aGVHD model. Long-term AMG487 treatment, but not short-term, improved survival and aGVHD outcomes (p < 0.05). Furthermore, long-term AMG487 administration reduced the number of donor T cells in the liver but increased the number of donor T cells in the spleen (p < 0.05). Long-term AMG487 treatment also inhibited donor T cell activation in the spleen (p < 0.05). ConclusionThis study demonstrates that long-term AMG487 treatment has a potential therapeutic effect on aGVHD and could be used as a novel therapy.

Temporal trends in organ donation among cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation

AimsThis study explores the evolution of organ donation from patients treated with extracorporeal-cardiopulmonary-resuscitation (ECPR) for refractory out-of-hospital-cardiac-arrest (OHCA) and evaluates the public health benefits of a mature ECPR program. MethodsThis retrospective, single-center study included OHCA patients (2016–2023) who had mostly initial shockable rhythms and were treated with ECPR. Organ donation rates from non-survivors through these years were analyzed. The public health benefit of ECPR was determined by the ratio of the sum of survivors with Cerebral Performance Category 1–2 and non-survivors who donated at least 1 solid organ, to the total ECPR patients. Temporal trends were analyzed yearly using linear regression. ResultsOut of 419 ECPR patients presenting with refractory OHCA over the study period, 116 survived neurologically intact (27.7%). Among non-survivors (n = 303), families of 41 (13.5%) consented to organ donation (median age 51 years, 75.6% male) and organs from 38 patients were harvested, leading to 74 organ transplants to 73 recipients. The transplanted organs included 43 kidneys (58.1%), 27 livers (36.5%), 3 lungs (4%), and 1 heart (1.4%), averaging 2.4 ± 0.9 accepted organs/donor. The number of organ donors and successful transplants correlated positively with the years since the ECPR program’s initiation (ptrend = 0.009, ptrend = 0.01). Overall, 189 patients (116 survivors, 73 organ recipients) benefited from ECPR, achieving organ-failure-free survival. The cumulative public health benefit of ECPR, considering the 116 survivors and 38 donors was 36.8%. ConclusionThe public health benefits of an established ECPR program extend beyond individual ECPR patient survival, forming a new, previously under-recognized source of transplant donors.

Comparison of Cytomegalovirus Reactivation in Children After Allogeneic Hematopoietic Cell Transplantation in 2 Transplant Eras

Reactivation of cytomegalovirus (CMV) is typically considered harmless as long as the immune system remains unaffected by medications or other factors. CMV reactivation may occur as a result of acute graft-versus-host disease of Grades II to IV. One possible factor contributing to this risk is the rise in the number of donors who lack genetic similarities or relationships. We hypothesized that the anti-CMV IgG level before transplantation could potentially serve as an indicator of the likelihood of CMV reactivation following hematopoietic cell transplantation. We examined a cohort of young individuals who underwent allogeneic HCT between 1998 and 2022 to evaluate the occurrence of CMV reactivation. The patients were divided into 2 time periods: 1998 to 2016 (comparison group) and 2017 to 2022 (intervention group). Between 1998 and 2016, 292 patients underwent hematopoietic HCT. Recipients from 2017 to 2022 experienced a slightly higher risk of CMV reactivation than those from 1998 to 2016. The comparison of prophylactic and preemptive medication showed no significant difference between the periods (P = .32). Patients treated from 1998 to 2016 experienced a 23% decrease in the risk of symptomatic CMV reactivation and related illnesses compared to those treated from 2017 to 2022 (P = .08 and .15, respectively). Our study showed that the intervention group had more symptomatic CMV reactivations. Various factors may contribute to this, including CD19-directed immunotherapy and the CMV status of the recipient before transplantation.

Predicting of hepatic steatosis in living liver donor via CT liver attenuation index (LAI) and fibroscan controlled attenuation parameter (CAP) correlation with biopsy result

BackgroundThe most prevalent persistent parenchymatous liver alterations in healthy individuals are thought to be hepatic steatosis. The liver biopsy is the most crucial procedure for the identification and measurement of hepatic steatosis. By identifying the liver attenuation index (LAI) at CT image with fibroscan controlled attenuation parameter (CAP), hepatic steatosis can be evaluated without the risk of liver resection.ObjectiveUsing liver biopsy histological analysis as a reference standard, to examine the precision of the CT liver attenuation index (LAI) and fibroscan controlled attenuation parameter (CAP) for quantitative evaluation of macrovesicular steatosis in living related liver donors.MethodsIn this cross-sectional study, comparing the CT liver attenuation index & fibroscan controlled attenuation parameter with liver biopsy result for the detection of the steatosis in subject's candidate for liver living donors, 50 subjects were conducted at Ain Shams Specialized Hospital and other private hospitals over about 2 years.ResultsOur study reported that liver attenuation index of 9 is the cutoff value in post-contrast CT images with sensitivity 100% and specificity 80% that make it a very good method to exclude donor to have steatosis ≥ 15%, which mean that if donor had LAI index < 9, we can safely do proceed do liver biopsy. Our study reported that CAP measurement had an AUROC OF 0.780, for detecting steatosis ≥ 15%, with sensitivity is only 60% with specificity as CT LAI of 80%, our results consider low compared to other studies, that could be due to small number of donors in our study with steatosis ≥ 15% (five cases from 50 donors) unlike the other studies.ConclusionWhen used to estimate the amount of liver fat in liver donors, the examined CAP and CT indices worked equally. But according to multivariate analysis, the only factor strongly linked with hepatic steatosis in a living donors was the CT LAI index. We contend that the combination of CT LS attenuation index and CAP allows for the detection of the degree of hepatic steatosis and can be used as an option to liver biopsy, reserving liver biopsy for those with positive steatosis donors.