Recipient Age Research Articles

Donor fat-to-muscle ratio and kidney transplant outcomes: Aproposition of metabolic memory.

The impact of donor abdominal fat-to-muscle ratio (FMR) on kidney transplant (KT) outcomes was assessed. Given the transient nature of the donor's metabolic environment in transplant recipients, this study investigated the capacity of body composition to induce metabolic memory effects. KT patients (n=895) who received allografts from living donors (2003-2013) were included. Donor fat and muscle were quantified using pre-KT abdominal computed tomography scans. Patients were categorised into donor FMR tertiles and followed up for graft outcomes. Additionally, genome-wide DNA methylation analysis was performed on 28 kidney graft samples from KT patients in the low- and high-FMR groups. Mean recipient age was 42.9±11.4years and 60.9% were males. Donor FMR averaged 1.67±0.79. Over a median of 120.9±42.5months, graft failure (n=127) and death-censored graft failure (n=109) were more frequent in the higher FMR tertiles. Adjusted hazard ratios for the highest versus lowest FMR tertile were 1.71 (95% CI, 1.06-2.75) for overall graft failure and 1.90 (95% CI, 1.13-3.20) for death-censored graft failure. Genome-wide DNA methylation analysis identified 58 differentially methylated regions (p<0.05, |Δβ|>0.2) and 35 genes showed differential methylation between the high- (FMR >1.91) and low-FMR (FMR <1.27) groups. Donors with increased fat and reduced muscle composition may negatively impact kidney allograft survival in recipients, possibly through the transmission of epigenetic changes, implying a body-composition-related metabolic memory effect.

Living-Donor Uterus Transplantation: A Clinical Review

Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. More than 90 uterus transplantations have been performed worldwide, mostly from living donors. Living-donor (LD) UTx is a challenging surgical procedure since it poses ethical issues, and it is a high-risk and invasive surgery with higher hysterectomy-related risks compared to conventional hysterectomy. A total of 59 living-donor hysterectomies have been reported in the literature, including 35 performed with a laparotomic approach, 20 with a robotic approach and 4 with a laparoscopic approach. The mean donor age was 45.6 ± 9.1 years, and 22 were unrelated with the recipients, 34 were emotionally related (27 mothers, 5 sisters, 2 mother’s sisters). The mean recipient age was 28.8 ± 4.5 years. Mayer–Rokitansky–Küster–Hauser syndrome was the most common indication for uterus transplant. Robotic living-donor hysterectomy had the longest operative time but resulted in a lower blood loss and postoperative stay compared to laparotomic and laparoscopic approaches. Twenty-nine births from LD-UTx have been reported, four after robotic living-donor hysterectomy and twenty-five after a laparotomic procedure. UTx is now an effective treatment for women with UFI. While living-donor UTx in some cases may be considered an experimental procedure, it offers the extraordinary possibility to give women the opportunity to have a pregnancy. Many efforts should be made to reduce the potential risks for donors, including the use of mini-invasive techniques, and the efficacy of UTx in the recipients, giving the potential harm of immunosuppression in a recipient of a non-life-saving organ.

Mapping the Caregiver Experience in a Canadian Province: Research Methodology for the Saskatchewan Caregiver Experience Study.

Policies and services for older adults are increasingly focused on living in the community, rather than relying on institutions. A total of 70-80% of community care for older adults is provided by family and friend caregivers. With Canada's aging population, the number of caregivers to older adults is growing. The purpose of this paper is to describe the research methodology that was employed in the Saskatchewan Caregiver Experience Study. The methodology was used to map the experiences and gather perspectives of caregivers in Saskatchewan and to identify their priority support needs. Qualitative description was the approach in this study. An online qualitative survey was administered via SurveyMonkey and distributed via Facebook and community newsletters. The survey collected caregiver demographics and asked three open-ended questions regarding: (1) the challenges that caregivers experience; (2) the positive aspects of caregiving; and (3) the support needs and priorities of Saskatchewan caregivers. A fourth question where caregivers could freely express any other experiences or perspectives was included. Content analysis was the method used for data analysis. 355 individuals met the inclusion criteria for this study. Participants were evenly distributed amongst urban-large, urban-small/medium, and rural settings in Saskatchewan. The average age of caregivers and care recipients were 61 and 83 respectively. This study has implications for research, practice, and policy. By gathering the full spectrum of the caregiver experience in Saskatchewan, this study can help to inform how communities, governments, and our healthcare system can best support caregivers in their role.

Pretransplant malignancy in pediatrics is not a risk factor for renal graft failure.

In adults, pretransplant malignancy (PTM) negatively impacts patient survival due to immunosuppression regimens influencing post-transplantation tumor growth. Few reports investigate the outcomes of pediatric kidney transplantation with PTM. We compare transplant outcomes for pediatric patients with PTM to matched controls, including cancer types extending beyond Wilms tumor. The United Network of Organ Sharing Database was queried to identify pediatric transplant recipients with histories of PTM. All PTM patients were matched to non-PTM patients, at a 1:1 ratio, with 0.001 match tolerance. Matching variables included transplant year, recipient age, recipient gender, recipient race, donor type, and prior transplant. Death-censored graft and patient survival were analyzed. All statistics were reported with 95% confidence intervals (CI). After propensity matching, 285 PTM and 285 non-PTM patients were identified, with transplant dates from 1990 to 2020. Median Kidney Donor Profile Index values were comparable between cohorts, 17% and 12%, respectively (p = .065). Kaplan-Meier analysis revealed that PTM patients did not have a significantly different rate of death-censored graft failure, compared to the non-PTM group [HR 0.76; 95% CI (0.54-1.1)]. There was also no difference in the overall survival between the two groups of patients [HR 1.1; 95% CI (0.66-2.0)]. A history of pediatric malignancy has minimal independent effect on their post-transplant survival. Additionally, pediatric patients with PTM demonstrated equivalent rates of graft survival. Thus, in contrast to adults, renal failure in children with history of pediatric malignancies should not be considered a complicating factor for renal transplantation.

Supporting adult unpaid carers via an online dancing intervention: A feasibility/acceptability study.

Unpaid carers often experience poor mental and physical health linked to their caring role. Engagement in physical activity has been shown to alleviate these negative health outcomes, but it is harder for carers to find the time, energy and space to exercise. This qualitative study, based in the UK, explored the feasibility of an online, dance-based physical activity intervention with six female unpaid carers. Five themes resulted from the thematic analysis of the pre- and post-intervention interviews: Perceived physical health benefits of the intervention; Perceived mental health benefits of the intervention; Satisfactoriness of the dance classes; Impact of caring responsibilities on participation; and Suggestions for future classes. Further research is required to measure the effectiveness of the dance intervention in improving mental and physical wellbeing with larger samples including a wider mix of carers in terms of gender, age and health conditions of the care recipients, as well as international samples. Future research should also consider the barriers that some carers may face when accessing an online intervention, and alternative forms of exercise that may appeal to other groups of carers (e.g., male carers, older adult carers).

Challenges faced in establishing a pediatric liver transplant program in a lower-middle-income country with free healthcare service.

Liver transplant is the cure for children with liver failure. Sri Lanka is a lower-middle-income country with a predominant free, state health system. Pediatric liver transplant program in Sri Lanka is still in the budding state where the initial experience of the program is yet to be documented. A retrospective review was performed including the clinical characteristics of all pediatric liver transplant recipients of Colombo North Centre for Liver Diseases since the inception of the program from June 2020 to May 2023. There were 14 PLT performed in 3 years. The median recipient age and weight were 8 years (6 months-15 years) and 23.3 kg (6.4-49.2), respectively. The majority were boys (64%). All were from low-income backgrounds. Indications for LT were acute liver failure (5/14), decompensated chronic liver disease (5/14), and acute on chronic liver failure (4/14). Underlying liver diseases were Wilson disease (6/14), autoimmune liver disease (3/14), biliary atresia (2/14) and progressive familial intrahepatic cholestasis type 3 (1/14), and unknown etiology (2/14). The majority were living donor liver transplants (86%). Of the living donors, 42% (5/12) were Buddhist priests. There were three immediate deaths and two late deaths. The 3-month survival was 78%, and overall survival was 64%. Living donor transplants carried a higher success rate (92%) compared to diseased donor transplants (0%; 2/2). Initial experience of pediatric liver transplant program of Sri Lanka is promising despite being established in a free healthcare system amidst the crisis circumstances.

Preconditioning Frailty Phenotype Influences Survival and Relapse for Older Allogeneic Transplantation Recipients

Hematologic malignancies disproportionately affect older adults. Hematopoietic cell transplantation (HCT) is potentially curative, but poor overall survival (OS) has limited its use in older adults. Fried's frailty phenotype (FFP) is a geriatric assessment tool that combines objective and subjective performance measures: gait speed, grip strength, activity level, exhaustion, and weight loss. People meeting ≥3 criteria are classified as frail; 1 or 2 criteria, as pre-frail; and 0 criteria, as fit. To evaluate the association of pre-HCT FFP with post-HCT outcomes, we assessed FFP prior to conditioning for 280 HCT recipients age ≥60 years with acute leukemia or a myeloid neoplasm at 3 institutions. When analyzing survival by age group, patients age ≥70 years had inferior OS compared to patients age 60 to 69 years (P = .002), with corresponding OS estimates of 38.9% (95% confidence interval [CI], 27.8% to 49.9%) and 59.3% (95% CI, 51.9% to 65.9%). Nonrelapse mortality (NRM) also was significantly higher in the older patients (P = .0005); the 2-year cumulative incidences of NRM were 38.5% (95% CI, 27.5% to 49.2%) and 17.2% (95% CI, 12.3% to 22.8%), for older and younger recipients, respectively. The cumulative incidences of relapse did not differ by age group (P = .3435). Roughly one-third (35.5%) of the patients were fit, 57.5% were pre-frail, and 7.5% were frail, with corresponding 2-year OS estimates of 68.4% (95% CI, 57.9% to 76.8%), 45.5% (95% CI, 37.4% to 53.2%), and 45.8% (95% CI, 23.4% to 65.8%) (P = .013). FFP was not significantly associated with NRM, but being frail or pre-frail was associated with a higher rate of disease-related deaths (33.3% and 27.3%, respectively, compared with 17.4% for fit patients; P = .043). In univariate modeling of restricted mean survival time with a 3-year horizon (RMST_3y), the factors that were significantly associated were FFP, age, Karnofsky Performance Status (KPS), Disease Risk Index (DRI), and HCT-specific Comorbidity Index (HCT-CI). Of those factors, only FFP (P = .006), age (P = .006), KPS (P = .004), and DRI (P = .005) were significantly associated in multivariate modeling of RMST_3y. Estimates of RMST_3y were computed and 5 risk-groups were created with survival ranging from 31.4 months for those who were age 60 to 69 years, fit, had KPS 90 to 100, and low/intermediate-risk DRI compared to 10.5 months for those who had high-risk features for all the evaluated factors. In univariate and multivariate analyses for restricted mean time to relapse with a 3-year horizon (RMRT_3y), FFP (pre-frail versus fit, P = .007; frail versus fit, P = .061) and DRI (P = .001) were the only significant factors. Predicted RMRT_3y was longest (30.6 months) for those who were fit and had low/intermediate-risk DRI scores and shortest (19.1 months) for those who were frail and had high-risk or very high-risk DRI scores. Both age and FFP impact survival after HCT. Incorporation of FFP into pre-HCT evaluations may improve decision-making and counseling regarding HCT risk for older adults. Our findings support future trials designed to reverse frailty, such as pre-HCT supervised exercise programs, and correlative analyses to unravel the connection of frailty and relapse to generate future targets for intervention. Finally, exploration of novel HCT platforms to reduce relapse in pre-frail and frail patients, as well as reduce NRM in adults age >70 years, are warranted.

The Kidney Not Taken: Single-Kidney Use in Deceased Donors.

The nonuse rate for kidneys recovered from deceased donors is increasing, rising to 27% in 2023. In 10% of these cases, 1 kidney is transplanted but the mate kidney is not. We conducted a retrospective, single-center cohort study from December 2001 to May 2023 comparing single kidneys transplanted at our center (where the contralateral kidney was not used) to kidneys where both were transplanted separately, at least 1 of which was at our center. We performed 395 single deceased-donor kidney transplants in which the mate kidney was not transplanted. Primary reasons for mate kidney nonuse were as follows: no recipient located or list exhausted (33.4%), kidney trauma or injury or anatomic abnormalities (18.7%), biopsy findings (16.7%), and poor renal function (13.7%). Mean donor and recipient ages were 51.5 ± 14.2 and 60 ± 12.6 years, respectively. Mean kidney donor profile index was 73% ± 22%, and 104 donors (26.3%) had kidney donor profile index >85%. Mean cold ischemia was 25.6 ± 7.4 hours, and 280 kidneys (70.7%) were imported. Compared with 2,303 concurrent control transplants performed at our center, primary nonfunction or thrombosis (5.1% single vs 2.8% control) and delayed graft function (35.4% single vs 30.1% control) were greater with single-kidney use (both p < 0.05). Median patient and death-censored graft survival were shorter in the single group (11.6 vs 13.5 years, p = 0.03 and 11.6 vs 19 years, p = 0.003), although the former was at least double median survival on the waiting list. In patients with functioning grafts in the single-kidney group, 1-year mean serum creatinine was 1.77 ± 0.8 mg/dL and estimated glomerular filtration rate was 44.8 ± 20 mL/min/1.73 m 2 . These findings suggest that many mate kidneys are being inappropriately rejected, given the acceptable outcomes that can be achieved by transplanting the single kidney in appropriately selected recipients.

Family caregiver experiences and needs across health conditions, relationships, and the lifespan: a Qualitative analysis

ABSTRACT Purpose The purpose of this study was to understand the lived experiences of family caregivers who provide care to individuals across a broad range of ages, caregiving relationships, and health conditions and/or disabilities. Family caregiver research is typically siloed by health condition or by caregiving relationship, leaving gaps in understanding similarities and differences among caregivers. Methods We hosted three virtual focus groups with diverse family caregivers (n = 26) caring for an individual with a long-term disability and/or health condition(s). We conducted a qualitative thematic analysis using an iterative, inductive process. Results Participants primarily expressed shared experiences, despite having unique caregiving situations. We identified themes among a) caregiver experiences: Trying to Do It All, Balancing Complex Emotions, Managing Expectations, and Adjusting to Changes Over Time and b) caregiver needs: Longing for Breaks and Self-Care; Lacking Help, Support and Resources; and Desiring Understanding and Recognition. Conclusions These findings emphasize that many elements of the caregiving experience transcend care recipient age, condition, and relationship and are applicable to clinicians, researchers, and policy makers. The evidence of shared caregiver experiences can guide efficiencies in policy and practice (e.g., pooling of existing resources, expansion of interventions) to meet the needs of a broader population of caregivers.

Disparities in Cytomegalovirus Infection Rates by Race and Ethnicity among Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients at a Single Center

Previous literature has reported cytomegalovirus (CMV) infection rate disparities among racial/ethnic groups of hematopoietic cell transplantation (HCT) recipients. Because race and ethnicity categorizations are social constructs unlikely to affect biological systems, it is likely there are covariates on the pathway to CMV detection, known as mediators, that can explain the observed disparity. Recent developments in mediation analysis methods enable the analysis of time-to-event outcomes, allowing an investigation of these disparities to also consider the timing of CMV infection detection relative to HCT. This study aimed to explore whether racial and ethnic CMV infection disparities existed within a population of HCT recipients at our center, and whether clinical covariates explained any observed association. The study cohort included all recipients of allogeneic HCT performed at the Children's Hospital of Philadelphia between January 2004 and April 2017 who were CMV PCR-negative pretransplantation, had known donor/recipient CMV serology, and were under blood CMV PCR surveillance. Subjects were followed for 100 days post-HCT. Accelerated failure time models using subject's reported race/ethnicity, dichotomized into non-Hispanic White (NHW) and non-NHW, and exposure and time to CMV detection as outcomes examined whether selected clinical factors-donor/recipient CMV serostatus, recipient age, indication for HCT, hematopoietic cell source, match quality-mediated any identified exposure-outcome association. The analysis included 348 HCTs performed in 335 subjects, with 86 episodes (24.7%) in which CMV was detected via PCR analysis. The accelerated failure time model without mediators estimated that non-NHW subjects had fewer CMV-free survival days (time ratio, .21; 95% confidence interval, .10 to .44). Any hypothesized mediator mediated at most 5% of the total association between race/ethnicity and time to CMV detection. Non-NHW HCT recipients had fewer CMV-free survival days than NHW recipients; none of the clinical factors hypothesized to mediate this association accounted for a significant component of total association. Further research should focus on nonclinical factors influenced by systemic racism to better understand their effect on CMV infection among HCT recipients.

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

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

Development of an umbilical cord blood transplantation–specific nonrelapse mortality risk assessment score

AbstractHigher rate of nonrelapse mortality (NRM) remains yet to be resolved in umbilical cord blood transplantation (UCBT). Considering that UCBT has some unique features compared with allogeneic hematopoietic cell transplantation from other graft sources, a UCBT-specific NRM risk assessment system is required. Thus, in this study, we sought to develop a UCBT-specific NRM Risk Assessment (CoBRA) score. Using a nationwide registry database, we retrospectively analyzed 4437 recipients who had received their first single-unit UCBT. Using the backward elimination method, we constructed the CoBRA score in a training cohort (n = 2687), which consisted of recipients age ≥55 years (score 2), hematopoietic cell transplantation–specific comorbidity index ≥3 (score 2), male recipient, graft-versus-host disease prophylaxis other than tacrolimus in combination with methotrexate, performance status (PS) 2 to 4, HLA allele mismatch ≥ 2, refined Disease Risk Index high risk, myeloablative conditioning, and CD34+ cell doses < 0.82 × 105/kg (score 1 in each). The recipients were categorized into 3 groups: low (0-4 points), intermediate (5-7 points), and high (8-11 points) groups according to the CoBRA score. In the validation cohort (n = 1750), the cumulative incidence of NRM at 2 years was 14.9%, 25.5%, and 47.1% (P < .001), and 2-year overall survival (OS) was 74.2%, 52.7%, and 26.3% (P < .001) in the low, intermediate, and high groups, respectively. In summary, the CoBRA score could predict the NRM risk as well as OS after UCBT. Further external validation will be needed to confirm the significance of the CoBRA score.

Comparison of Kidney Graft Function and Survival in an Emulated Trial With Living Donors and Brain-Dead Donors.

Living donation (LD) transplantation is the preferred treatment for kidney failure as compared to donation after brain death (DBD), but age may play a role. We compared the 1-year estimated glomerular filtration rate (eGFR) after kidney transplantation for recipients of LD and DBD stratified by recipient and donor age between 2015 and 2018 in a matched cohort. The strength of the association between donation type and 1-year eGFR differed by recipient age (P interaction < 0.0001). For LD recipients aged 40-54years versus same-aged DBD recipients, the adjusted odds ratio (aOR) for eGFR ≥60mL/min/1.73m2 was 1.48 (95% CI: 1.16-1.90). For DBD recipients aged ≥ 60years, the aOR was 0.18 (95% CI: 0.12-0.29) versus DBD recipients aged 40-54years but was 0.91 (95% CI: 0.67-1.24) versus LD recipients aged ≥60years. In the matched cohort, 4-year graft and patient survival differed by donor age and type. As compared with DBD grafts, LD grafts increased the proportion of recipients with 1-year eGFR ≥60mL/min/1.73m2. Recipients aged ≥60years benefited most from LD transplantation, even if the donor was aged ≥60years. For younger recipients, large age differences between donor and recipient could also be addressed with a paired exchange program.

Center Volume Predicts Improved Early Outcomes in Multiorgan Heart Transplantation

Center volume is associated with improved survival after isolated heart transplant, but its impact on multiorgan heart transplant (MHT) outcomes is unknown. This study examines the impact of institutional MHT volume on MHT outcomes. Adult patients undergoing first time MHT from 2011 to 2021 were identified in the United Network for Organ Sharing database. Transplant centers were annually classified as low-, medium-, or high-volume if they performed <3, 3 to 5, or ≥6 MHTs that year, respectively. Graft failure was defined as death, failure, or re-transplantation of any allograft. A total of 1860 MHTs were performed at 104 centers, including 482 (26%) at low-, 601 (32%) at medium-, and 777 (42%) at high-MHT volume centers. Noncardiac allografts included kidney (83%), liver (16%), and lung (2%). The proportion of MHTs performed at high-volume centers increased from 10% in 2011 to 62% in 2021. Recipient age, race, and body mass index did not vary by center volume (all P > .05). Patients at high-volume centers were more likely to be in the intensive care unit pre-transplant (58% vs 44%, P < .001) and have shorter waitlist times (47 vs 92 days, P < .001) than those at low-volume centers. 30-day graft survival was higher in combined medium- and high-volume compared with low-volume centers (95% vs 92%, P = .004). Increasing center MHT volume was protective against 30-day graft failure (adjusted hazard ratio 0.93 [0.88-0.98]) on multivariate Cox regression. Higher MHT volume is associated with improved early graft survival after MHT, which may justify centralizing the performance of MHTs to high-volume centers.

Seroprevalence of binding and neutralizing antibodies against 18 adeno-associated virus types in patients with neuromuscular disorders.

High levels of pre-existing antibodies are a major challenge for the application of viral vectors since they can severely limit their efficacy. To identify promising candidates among adeno-associated virus (AAV) based vectors for future gene therapies for the treatment of hereditary neuromuscular disorders (NMDs), we investigated the antibody levels in sera from patients with NMDs against 18 AAV types, including 11 AAVs with wild-type capsids, 5 AAVs with peptide-modified capsids and 2 AAVs with shuffled capsids. With regard to the wild-type capsid AAVs, the lowest binding antibody levels were detected against AAV6, AAV5, AAV12 and AAV9, whereas the highest binding antibody levels were detected against AAV10, AAV8, AAV1, and AAV2. The lowest neutralizing antibody levels against wild-type AAVs were detected against AAV12, AAV5, AAV9, AAV7, AAV8 and AAV10, and the highest neutralizing antibody levels were detected against AAV13, AAV2 and AAV3. Interestingly, the influence of peptide modifications or shuffling of AAV capsids on antibody binding and AAV neutralization seemed to depend on the parental AAV. While the sex of the serum donors had no significant impact on binding or neutralizing antibody levels, we observed a trend to higher binding antibodies in older serum donors against some AAV types and a clear positive correlation of neutralizing antibody titers with the age of the serum donors. The disease status on the other hand did not have a meaningful impact on antibody levels, with no changes in AAV neutralization. Our data indicate that several wild-type or peptide-modified AAV may be good candidates for therapeutic application due to low pre-existing antibody levels, and that the age of potential recipients rather than their health status with regard to NMDs has the biggest impact on vector applicability.

Age-dependent trends in adverse reactions of SARS-CoV-2 vaccines: A narrative review

&lt;p&gt;Since the initiation of immunization against SARS-CoV-2, the adverse reactions of vaccines have remained a major contributor to vaccine hesitancy. Their occurrence has been attributed to the immune response against the administered antigen, which is affected by different factors including the age of the vaccine recipient. The trends of the adverse reactions of COVID-19 vaccines have shown a higher frequency in younger adults (18–64 years old) than in the older population (≥65 years). One of the potential reasons is the healthy and efficient immune systems of younger individuals, which provide a robust pro-inflammatory response upon antigen encounter. Their adaptive immune system has a diverse array of naïve T and B lymphocytes, which aids in antigen elimination with the development of a long-lasting immunological memory. Age-related changes in the immune system of the elderly are referred to as immunosenescence, which reduces its efficiency. The phenomenon of cellular senescence and inflammageing can lower the vaccine responses of older recipients. Thymic involution and ageing of the bone marrow can lead to decreased levels of naïve T-cells and memory B-cells. This could compromise the ability to either fight new infections or effectively respond to vaccines and develop a lasting immune memory. Along with clinical trials of senolytic drugs, lifestyle interventions are being studied to mitigate such age-related changes. Further insights into vaccine responses in the elderly population and the means to alleviate the hallmarks of immunosenescence are required.&lt;/p&gt;

An Emerging Issue: Carbapenem-Resistant Enterobacteriaceae in Solid-Organ Transplantation.

Bloodstream infections caused by carbapenem-resistant bacteria have increased globally. Solid-organ transplant recipients are more prone to these infections. This study aimed to compare the clinical courses of carbapenem-susceptible and carbapenem-resistant Enterobacteriaceae bloodstream infections and to identify risk factors for carbapenem resistance in solid-organ transplant recipients. For this retrospective descriptive study, data for solid-organ transplant recipients (age ≥18) treated from 2015 to 2022 were obtained from medical records. Enterobacteriaceaepositive blood culture was screened from laboratory data. Among 72 patients, there were 100 bacteremia episodes. Patients included 40 kidney (55.6%), 21 liver (29.2%), 7 heart (9.7%), and 4 combined liver and kidney (5.6%) transplant recipients. Fifty-seven bacteremia episodes were recorded between 2015 and 2020, and 43 bacteremia episodes were recorded between 2020 and 2022. Carbapenem resistance was reported in 15.8% of patients before 2020, whereas this rate increased to 39.5% after 2020 (P = .007). Pitt bacteremia score ≥4 (P < .001), Charlson comorbidity index ≥4 (P = .021), chronic liver disease (P = .015), septic shock at admission (P = .001), hypotension at admission (P = .006), bacteremia episodes 48 hours after hospitalization (P = .004), hospitalization in the past 3 months (P = .004), and prior invasive procedure (P = .043) were significant factors for carbapenem resistance. Logistic regression analysis showed that bacteremia 48 hours after hospitalization (P = .002) and hospitalization in the past 3 months (P = .006) were independent risk factors. Carbapenem resistance increased significantly over the years. Bacteremia 48 hours after hospitalization and hospitalization within the past 3 months were determined to be risk factors for carbapenem resistance. Carbapenem-resistant infections are still nosocomial infections. Patients should be hospitalized for as a short time as possible, and both patients and their physicians should follow infection control and prevention methods.

Liver transplantation program at the Burnasyan Federal Biophysical Center: experience in 500 procedures

To analyze the features and outcomes of 500 liver transplantations in adults over a 12-year period. The study included data on 500 liver transplantations between May 2010 and April 2023. We analyzed 483 adults who underwent transplantation and 438 candidates for this procedure. All data were obtained from local liver transplantation registry. Clinical outcomes were recorded as of June 1, 2023. Statistical analysis was performed using the Statistica 12 (StatSoft Inc., USA) and Jamovi version 2.3.21.0 software (Jamovi project). Among 438 patients in the waiting list between January 2012 and May 2023, liver transplantation was performed in 198 (45%) cases including 27 (6%) transplantations from living-related donors and 37 (8%) procedures in other centers. There were 109 (25%) deaths. The 1- and 3-year survival rates were 81% (95% CI 76-85%) and 50% (95% CI 42-59%), respectively. Organs from deceased donors (n=134, 27%) and living-related donors (n=366, 73%) were used for transplantations. Redo transplantations were necessary in 21 (4%) cases. The median age of recipients was 45 years (range 18-72), median MELD-Na score - 16 (range 6-43). The most common indications for transplantation were viral cirrhosis (37%), cholestatic liver disease (16%), and hepatocellular carcinoma (14%). Monotherapy with calcineurin inhibitors was performed in 39% of cases, combination of calcineurin inhibitors and glucocorticoids, antimetabolites or mTOR inhibitors - 52%, three-component schemes - 8% of cases. Annual, 5- and 7-year survival rates of recipients after primary transplantation were 87% (95% CI: 84-90%), 79% (95% CI: 75-83%) and 75% (95% CI: 70-80%), respectively. In case of liver transplantation from living-related donors, these values were 89% (95% CI: 86-92%), 84% (95% CI: 80-88%) and 80% (95% CI: 75-85%), after transplantation from deceased donors - 81% (95% CI: 74-88%), 66% (95% CI: 57-76%) and 58% (95% CI: 45-72%), respectively. Liver transplantation is highly effective for patients with diffuse and focal liver diseases. Living donors not only significantly improve availability of this technology, but also provide substantial advantages in outcomes compared to liver transplantation from deceased donors, reducing the likelihood of recipient mortality by 10% after one post-transplantation year and by more than 20% after five years.

Program Report: Expanding the Deceased Donor Pool in Manitoba With an Age-Targeted Kidney Transplant Program.

The ongoing shortage of organs for transplant combined with the highest prevalence of end-stage kidney disease (ESKD) in Canada has resulted in long wait times for a deceased donor transplant in Manitoba. Therefore, the Transplant Manitoba Adult Kidney Program has ongoing quality improvement initiatives to expand the deceased donor pool. This clinical transplant protocol describes an age-targeted program intended to increase the use of transplants with a kidney donor profile index (KDPI) >85 by allocating them to suitable pre-consented recipients age ≥65 with low wait times. The goal is to improve survival and quality of life for older recipients by maximizing a previously under-utilized donor pool. Scoping literature review; Transplant Manitoba deceased donor audit; and key stakeholder engagement with patient partners, inter-disciplinary health care providers, and health system leaders. The alternative donor pool criteria include deceased donor kidneys with KDPI 86-100 or another concern for graft longevity but are otherwise suitable for transplantation. Patients with no living donor, age ≥65, low wait times and otherwise eligible for transplant listing will be educated, and if suitable, pre-consented for the age-targeted program. All patients remain eligible for a standard criteria donor according to the local allocation criteria. The age-targeted program waitlist follows the same provincial allocation rules using wait time, panel reactive antibody (PRA), and human leukocyte antigen (HLA) match points for determining rank order. If an age-targeted recipient experiences early graft loss from a KDPI 86-100 kidney within 12 months from transplant, their cumulative wait time, including time with the transplant, will be reinstated upon relisting. Transplant Manitoba's provincial allocation rules do not permit bypassing top of the list recipients for kidney offers; therefore, transplant providers were previously reluctant to utilize KDPI 86-100 donor kidneys to top of the list recipients eligible for higher quality kidneys. This age-targeted program facilitates allocation of KDPI 86-100 kidneys to suitable older pre-consented recipients with low wait times, who may obtain a survival and quality of life benefit from these transplants. This approach expands the utilized deceased donor pool to benefit all Manitobans awaiting a deceased donor kidney transplant. This program was launched in January 2023, and there are no data reported on outcomes given the small numbers and abbreviated follow-up. The goal of this quality improvement project is to improve access to deceased donor kidney transplantation for Manitobans with ESKD. This program was developed with patient and provider feedback, including multimedia patient education materials which may be helpful for other programs. We anticipate this program is a safe and effective way to expand access to deceased donor kidney transplantation using a previously under-utilized donor pool.

Donor and recipient age matching improves outcomes after deceased donor liver transplantation

Donor and recipient age matching improves outcomes after deceased donor liver transplantation