Status Of Transplantation Research Articles

Impact of solid organ transplant status on outcomes of hospitalized patients with COVID-19 infection.

BackgroundThe COVID‐19 pandemic has caused significant morbidity and mortality in solid organ transplant (SOT) recipients. However, it remains unclear whether the risk factor for SOT patients is the immunosuppression inherent to transplantation versus patient comorbidities.MethodsWe reviewed outcomes in a cohort of SOT (n = 129) and non‐SOT (NSOT) patients (n = 708) admitted to the University of California, Los Angeles for COVID‐19 infection. Data analyses utilized multivariate logistic regression to evaluate the impact of patient demographics, comorbidities, and transplant status on outcomes. SOT patients were analyzed by kidney SOT (KSOT) versus nonkidney SOT (NKSOT) groups.ResultsSOT and NSOT patients with COVID‐19 infection differed in terms of patient age, ethnicity, and comorbidities. NKSOT patients were the most likely to experience death, with a mortality rate of 16.2% compared with 1.8% for KSOT and 8.3% for NSOT patients (p = .013). Multivariable analysis of hospitalized patients revealed that patient age (odds ratio [OR] 2.79, p = .001) and neurologic condition (OR 2.66, p < .001) were significantly associated with mortality. Analysis of ICU patients revealed a 2.98‐fold increased odds of death in NKSOT compared with NSOT patients (p = .013).ConclusionsThis study demonstrates the importance of transplant status in predicting adverse clinical outcomes in patients hospitalized or admitted to the ICU with COVID‐19, especially for NKSOT patients. Transplant status and comorbidities, including age, could be used to risk stratify patients with COVID‐19. This data suggests that immunosuppression contributes to COVID‐19 disease severity and mortality and may have implications for managing immunosuppression, especially for critically ill patients admitted to the ICU.

Israeli Medical Experts’ Knowledge, Attitudes, and Preferences in Allocating Donor Organs for Transplantation

Medical advancement has increased the confidence in successful organ transplants in end-stage patients. As the waitlist of organ demand is multiplying, the organ allocation process is becoming more crucial. In this situation, a transparent and efficient organ allocation policy is required. This study evaluates the preferences of medical experts to substantial factors for allocating organs in different hypothetical scenarios. Twenty-five medical professionals with a significant role in organ allocation were interviewed individually. The interview questionnaire comprised demographic information, organ donation status, important organ allocation factors, public preference knowledge, and experts’ preferences in different hypothetical scenarios. Most medical experts rated the waiting time and prognosis as the most important, while the next of kin donor status and care and contribution to the well-being of others were the least important factors for organ allocation. In expert opinion, medical experts significantly considered public preferences for organ allocation in making their decisions. Altogether, experts prioritized waiting time over successful transplant, age, and donor status in the hypothetical scenarios. In parallel, less chance of finding another organ, donor status, and successful transplant were prioritized over age. Medical experts are the key stakeholders; therefore, their opinions are substantial in formulating an organ allocation policy.

Brain Development in Children With Early Onset Liver Disease

AimsBiliary Atresia (BA) is a progressive inflammatory liver disease and the most frequent indication for pediatric liver transplant. There is a strong association between BA in adulthood and reduced cognitive abilities, however, data on neurodevelopmental outcomes at an early age are scarce, with small participant numbers. Hence, the neurodevelopmental difficulties in BA are poorly understood in childhood even though the brain development and maturation occur in parallel with the time-course of BA. This study aimed to characterize the cognitive and behavioral phenotype within BA infants from the age of 14 months to 4 years and investigate the extent to which this group deviates from children of typical development.Methods42 infants with BA that were diagnosed and treated at Kings College Hospital were recruited into this study. These infants ranged from 14 months to 4 years (mean age = 3 Years, 1 month). Out of the 42 infants, 19 had received a liver transplant, 22 were stable on their native liver, and 1 was on the transplant waiting list. 36 Mullens Scale of Early Learning assessments and 42 Vineland Adaptive Behavior Scale Interviews were collected. 42 typically developing infants (TD) were also recruited into the study, matched for age and gender to the BA population. First, we compared the whole group with BA to TD; then we compared children with BA on their native liver to those with a transplant.ResultsAcross the cohort with BA, infants scored significantly lower on the Vineland Summary T-Score compared to age-matched TD control children (t(82) = −5.05, p &lt; .001) and across all domains of the Vineland. They also scored significantly lower than TD children on the Mullens Development Assessment (t(66) = −6.52, p &lt; .001), and this was also across all domains. BA children on their native liver scored lower on both instruments than children who had received a liver transplant, however, this difference did not reach significance.ConclusionIndividuals with Biliary Atresia, regardless of their transplant status, show lower levels of development across all aspects, suggesting a global delay. These findings suggest that all of these young children remain at significant risk for neurodevelopmental difficulties. These findings emphasize that special attention to neurodevelopment needs to be given as part of a holistic approach to care in a serious life-long illness. Work is ongoing to understand the trajectory of brain maturation in these children to ensure neurodevelopmental needs are addressed alongside physical health.

Organ donation in a developing Caribbean country: a single centre experience in Trinidad and Tobago

ABSTRACT Objectives The National Organ Transplant Unit was established in 2006 with the aim of providing renal and corneal transplants services. This study assessed the current state of the National Organ Transplant Unit and the organ donation experience at a single centre intensive care unit in Trinidad. Methods A review of legal, human and material resources and a retrospective chart review of the current status of organ donation and transplantation in Trinidad and Tobago was conducted. Data were collected from medical records of deceased donors for the period January 2006 to December 2020. The organ donor experience in the Adult Intensive Care Unit at a tertiary care hospital in Trinidad was also evaluated. Data were collected from medical records of all patients in the adult intensive care unit for the period October 2016 to December 2016. Results Trinidad and Tobago has four donor hospitals, one transplant centre, and one surgical team consisting of three surgeons, approximately 100 trained Transplant Procurement Managers and one trained laboratory technician. The deceased donation rate was 0.77 donor per million population in 2006, peaked in 2014 at 3.85 and then remained at 0.77. Donor potentiality for the adult intensive care unit was 66.7% with a donation rate of 5.3%. Conclusions Organ donation in Trinidad and Tobago mostly relies on living donors. Despite increases in organ donation and conversion rates, the country has not yet achieved self-sufficiency. The implementation of a taskforce dedicated to developing action plans to improve organ donation services may assist the country in achieving self-sufficiency.

Pre-operative sarcopenia is predictive of recurrent gastrointestinal bleeding on left ventricular assist device support: A multicenter analysis.

Whether pre left ventricular assist device (LVAD) sarcopenia is associated with higher incidence of gastrointestinal bleeding (GIB) on LVAD support remains unknown. To study the association between preoperative sarcopenia and post LVAD GIB events, we performed a retrospective, multi-centered study including patients with chest CTs performed ≤ 3 months prior to LVAD implantation at the University of Minnesota (n=143) and Houston Methodist Hospital (n=133). To quantify sarcopenia, unilateral pectoralis muscle mass indexed to body surface area (PMI) and attenuation (approximated by mean Hounsfield units; PHUm) were measured on pre-operative chest CT scans. Negative binomial regression analyses were performed to determine the association between pectoralis muscle measures and number of GIB events to 2 years of LVAD support. The study cohort included 276 LVAD recipients with 43 % designated as bridge to transplant at the time of LVAD implantation. High pectoralis muscle mass and tissue attenuation were both protective against GIB events. Each 5 unit increase in PHUm was associated with an adjusted 19 % reduction in the incidence rate of GIB (95 % CI 7-29 %, p=0.002). Each unit increase in PMI was associated with an adjusted 17 % reduction in the incidence of GIB (95 % CI 1- 29 %, p=0.04). The models were adjusted for age, sex, INTERMACS profile, bridge to transplant status, creatinine, albumin and implanting center. Preoperative sarcopenia, as quantified by pectoralis muscle size and attenuation, was associated with the development of recurrent GI bleeding after LVAD implantation. These CT quantitative measures appear to predict not only early mortality but morbidity on LVAD as well.

Access to kidney transplantation among pediatric candidates with prior solid organ transplants in the United States.

Pediatric kidney transplant candidates require timely access to transplant to optimize growth and neurodevelopmental outcomes. We studied access to transplant for pediatric candidates with prior organ transplants. We used US registry data to identify pediatric kidney transplant candidates added to the waiting list 2015-2019 and used competing risk regression to study the association between prior transplant status and probability of receiving a kidney transplant, treating wait-list removal and death as competing events. Of 4962 pediatric kidney transplant candidates included, 89% had no prior transplant and 11% had received a prior organ transplant (kidney 87%, liver 5%, heart 5%). Prior transplant recipients were older at listing (median 15 vs. 12 years) and more likely to have PRA≥98% (22% vs. 0.3%) (both p < .001). There was no significant difference in the proportion of candidates from each group who were preemptively wait-listed. Unadjusted competing risk regression showed a lower risk of kidney transplant after wait-listing among candidates with prior organ transplant (HR 0.52, 95%CI 0.47-0.59, p < .001). This association remained significant after adjusting for candidate characteristics (HR 0.73, 95%CI 0.63-0.83, p < .001). Among deceased donor kidney recipients, median KDPI was similar between groups, but recipients with prior transplants were more likely to receive kidneys from donors with hypertension (4% vs. 1%, p=.01) and donors after cardiac death (11% vs. 4%, p < .001). Pediatric kidney transplant candidates with prior organ transplants have reduced access to transplant after wait-listing. Allocation system changes are needed to improve timely access to transplant for this vulnerable group.

Assessing the treatment pattern, health care resource utilisation, and economic burden of multiple myeloma in France using the Système National des Données de Santé (SNDS) database: a retrospective cohort study

BackgroundReal-world data on health care resource utilisation (HCRU) and costs for French patients with multiple myeloma (MM) are limited due to the quickly evolving MM treatment landscape. This retrospective, national-level study quantified the MM economic burden in France.MethodsThe study included patients with newly diagnosed MM from the Système National des Données de Santé coverage claims database between 2013 and 2018 who received active treatment within 30 days of diagnosis. HCRU included hospitalisations, drugs, consultations, procedures, tests, devices, transport, and sick leave. Costs were annualized to 2019 prices. Drug treatments, reported by line of therapy (LOT), were algorithmically defined using drug regimen, duration of therapy, and gaps between treatments. Analyses were stratified by stem cell transplantation status and LOT.ResultsAmong 6413 eligible patients, 6229 (97.1%) received ≥ 1 identifiable LOT; most received 1 (39.8%) or 2 LOT (27.5%) during follow-up. Average annual hospitalisation was 6.3 episodes/patient/year (median duration: 11.6 days). The average annual cost/patient was €58.3 K. Key cost drivers were treatment (€28.2 K; 39.5% of total HCRU within one year of MM diagnosis) and hospitalisations (€22.2 K; 48.6% of total HCRU costs in first year). Monthly treatment-related costs increased from LOT1 (€2.447 K) and LOT5 + (€7.026 K); only 9% of patients received LOT5 + . At LOT4 + , 37 distinct regimens were identified. Hospitalisation costs were higher in patients with stem cell transplantation than total population, particularly in the first year.ConclusionsThis study showed a high economic burden of MM in France (€72.37 K/patient/year in the first year) and the diversity of regimens used in late-line treatments.

Patients with transplantation have reduced mortality in bacteraemia: Analysis of data from a randomised trial

ObjectivesInfection remains a major complication of organ transplantation. Paradoxically, epidemiological studies suggest better survival from serious infection. We analysed the relationship between organ transplantation and short -term mortality of patients with bloodstream infection. MethodsData on transplantation status was extracted from a large prospective, multi-centre clinical trial in bloodstream infection. Logistic regression for 28-day mortality was performed on the whole cohort and a propensity-matched cohort (3:1). Infective pathogen, focus of infection, and clinical variables were included in the model. Mediation analysis was performed on clinical variables to explore causation. Results4,178 participants were included in the full cohort, with 868 in the matched cohort, of which 217 received an organ transplant. Haematopoietic stem cell transplants (HSCT) were the most common transplant (n = 99), followed by kidney (n = 70). The most common pathogens were staphylococci and Enterobacterales. Transplantation status was associated with a reduced mortality in both the whole (Odds Ratio, OR 0.53; 95% CI 0.28, 0.77) and matched (OR 0.55, 95% CI 0.34, 0.90) cohort, while steroid use was robustly associated with increased mortality OR 4.4 (95% CI 3.12, 6.20) in the whole cohort and OR 5.24 (95% CI 2.79, 9.84) in the matched cohort. There was no interaction between steroid use and transplant status, so transplant patients on steroids generally had increased mortality relative to those without either. ConclusionsOrgan transplantation is associated with a near halving of short term mortality in bloodstream infection, including a cohort matched for comorbidities, infective pathogen and focus. Steroid usage is associated with increased mortality regardless of transplant status. Understanding the mechanism and causation of this mortality benefit should be a focus of future research.

Cystic fibrosis-related liver disease is an independent risk factor for mortality and increased health care resource utilization in hospitalized pediatric patients with cystic fibrosis.

Cystic fibrosis-related liver disease (CFLD) is more prevalent in recent decades due to the increasing life expectancy of patients with cystic fibrosis (CF). There is paucity of population-level data on the impact of CFLD on hospital outcomes. We interrogated nonoverlapping years (2003-2016) of the National Inpatient Sample and Kids' Inpatient Database to include all hospitalized patients <21 years of age with a primary diagnosis of CF within the United States. A concomitant diagnosis of cirrhosis, liver fibrosis, chronic liver disease, portal hypertension, hepatomegaly, splenomegaly, hypersplenism, and liver transplant status was considered as surrogates for the diagnosis of CFLD and was compared with CF-related hospitalizations without these diagnoses (controls) for demographics, comorbid conditions, in-hospital mortality, length-of-stay, and hospital charges. We evaluated 94,374 CF-related hospitalizations. The prevalence of CFLD was 5.8%. The prevalence increased from 3.1% (2003) to a peak of 7.3% (2014) with an overall increasing trend, p < 0.001. Hospitalizations with CFLD had an increased prevalence of significant comorbidities: respiratory failure,lung transplant, pulmonary hypertension, diabetes mellitus, malnutrition, Clostridioides difficile infection, cholelithiasis, anemia, and need for parenteral nutrition, p < 0.001. Multivariate regression models showed CFLD as independently associated with 2.1 (95% confidence interval [CI]: 1.5 to 2.8) times increased risk of inpatient mortality, contributed to 1.1 (95% CI: 0.89 to 1.37) additional days of hospitalization, and incurring $14,852 (95% CI: 12,204 to 17,501) excess hospital charges, p < 0.001. CFLD is associated with multiple comorbidities and is independently associated with increased risk of mortality and increased health care resource utilization in pediatric CF-related hospitalizations.

COVID-19 vaccines in patients with decompensated cirrhosis: a retrospective cohort on safety data and risk factors associated with unvaccinated status

BackgroundSafety data reported from the large-scale clinical trials of the coronavirus disease 2019 (COVID-19) vaccine are extremely limited in patients with decompensated cirrhosis. The vaccination campaign in this specific population could be difficult due to uncertainty about the adverse events following vaccination. We aimed to assessed the COVID-19 vaccination rate, factors associated with unvaccinated status, and the adverse events following vaccination in patients with decompensated cirrhosis.MethodsThis is a retrospective study from Ruijin Hospial (Shanghai, China) on an ongoing prospective cohort designed for long-term survival analysis of decompensated cirrhotic patients who recovered from decompensating events or acute-on-chronic liver failure (ACLF) between 2016 and 2018. We assessed the COVID-19 vaccination rate, the number of doses, type of vaccine, safety data, patient-reported reasons for remaining unvaccinated, factors associated with unvaccinated status, and the adverse events of COVID-19 vaccine. Binary logistic regression was used for identifying factors associated with unvaccinated status.ResultsA total of 229 patients with decompensated cirrhosis without previous SARS-CoV-2 infection participated (mean age, 56 ± 12.2 years, 75% male, 65% viral-related cirrhosis). Mode of decompensation were grade II‒III ascites (82.5%), gastroesophageal varices bleeding (7.9%), hepatic encephalopathy (7.9%). Eighty-five participants (37.1%) received at least one dose of vaccination (1 dose: n = 1, 2 doses: n = 65, 3 doses: n = 19) while 62.9% remained unvaccinated. Patient-reported reasons for remaining unvaccinated were mainly fear of adverse events (37.5%) and lack of positive advice from healthcare providers (52.1%). The experience of hepatic encephalopathy (OR = 5.61, 95% CI: 1.24–25.4) or ACLF (OR = 3.13, 95% CI: 1.12–8.69) and post-liver transplantation status (OR = 2.47, 95% CI: 1.06–5.76) were risk factors of remaining unvaccinated independent of residential areas. The safety analysis demonstrated that 75.3% had no adverse events, 23.6% had non-severe reactions (20% injection-site pain, 1.2% fatigue, 2.4% rash) and 1.2% had a severe event (development of acute decompensation requiring hospitalization).ConclusionsPatients with decompensated cirrhosis in eastern China are largely remained at unvaccinated status, particularly those with previous episodes of ACLF or hepatic encephalopathy and liver transplantation recipients. Vaccination against COVID-19 in this population is safe.Graphical

MO1021: Long-Term Outcomes After Conversion to a Belatacept-Based Immunosuppression in Kidney Transplant: A Matched Cohort Study

Abstract BACKGROUND AND AIMS Conversion to a belatacept regimen after transplant seems to be safe. However, no studies have reported the long-term efficacy and safety outcomes after conversion to a belatacept regimen and compared it with patients treated with a CNI-based regimen in kidney transplantation. This study aims to investigate the long-term outcomes of patients converted to a belatacept regimen compared with matched patients under a CNI regimen. METHOD Kidney transplant recipients transplanted between 1998 and 2019 from two French academic transplant canters were recruited. We used a propensity score to match with a 1:1 ratio of patients at the time of the biopsy, which indicates the conversion to a belatacept regimen to control patients under a CNI regimen with a biopsy after transplant. We used 11 parameters associated with graft survival for the matching, 4 baseline transplant characteristics (recipient age, prior transplant status, donor type and dgf) and 7 at time of the biopsy (time after transplant, eGFR, proteinuria, DSA and Banff scores cv, ah, IFTA). Transplant outcomes defined by graft and patient survival, as well as safety outcomes, were compared between the matched patients. RESULTS From 3215 kidney transplant recipients transplanted during the study period with the inclusion criteria (311 patients under belatacept and 2904 patients under CNI). A total of 243 patients under belatacept were matched with 243 controls under CNI. All prognostic parameters were well-balanced before conversion between the two groups, with a mean age of 54.7 ± 15.1 years (P = .4543), a mean time of 2.2 ± 3.2 years after transplant (P = .586), a mean eGFR of 33.0 ± 13.3 mL/min/1.73 m2 (P = .976), a median proteinuria of 0.23 (0.12–0.50) g/g (P = .278) and 30.9% of positive anti-HLA DSA (P = 1.0) in the belatacept group. After a mean follow-up time after conversion of 4.4 ± 2.5 years, 36 (14.8%) patients lost their grafts and 39 (16.0%) patients died in the belatacept cohort. After conversion to a belatacept regimen, the graft survival was significantly improved when we compared with the matched patients’ under CNI P &amp;lt; .0001 (Fig. 1). Patients converted to Belatacept showed a lower death rate of 16.0% compared with 30.0% for the CNI treated patients (P &amp;lt; .001). The safety outcomes showed a similar rate of biopsy proven rejection (P = .08), major adverse cardiovascular events and cancer between the two groups, while a significant higher rate of CMV disease was observed among the belatacept treated patients P &amp;lt; .01). CONCLUSION This study confirms that conversion to belatacept post-transplant is associated with improved long-term graft outcome and acceptable safety. Conversion to belatacept after transplant should be considered as a valuable therapeutic option for kidney recipients.

The Current Status of Organ Donation and Transplantation in Poland. Poltransplant Activity

This article summarizes comprehensive information about the current status of organ donation and transplantation in Poland. Reported statistical data of solid organs and vascularized composite allograft donation and transplantation from both deceased and living donors in Poland in 2015-2020 (presented in tables according to selected variables) are based on the national transplant registries, gathering information on donation and transplantation activity in medical centers involved in donation and transplantation programs in Poland. In 2020 during the COVID-19 pandemic, 529 potential deceased donors were referred to the Polish Transplant Coordinating Centre Poltransplant; 1310 solid organs from 393 actual deceased donors (10.2 per million population) were procured, mostly kidneys (758), livers (285), and hearts (157). Eighty percent were multiorgan retrievals (314). In 2020, 1231 organs procured from deceased donors and 59 organs from living donors were transplanted to 1236 recipients. This overview indicates that donation and transplantation activity from deceased donors in Poland decreased about 20% in 2020 compared with 2019, which is comparable with worldwide rates. As the unprecedented pandemic situation affected donation and transplantation procedures, there are measures that must to be taken to return to prepandemic donation and transplantation rates in both deceased and living transplant programs and then continue to improve in the years to come.

Long-term outcomes of crossmatch positive simultaneous liver-kidney transplantations in the United States.

The long-term outcomes of positive crossmatch (+XM) simultaneous liver-kidney (SLK) transplantations are conflicting. We examined the association between crossmatch status and SLK outcomes in recipients discharged on tacrolimus and mycophenolate with or without steroids. We analyzed the Scientific Registry of Transplant Recipients for all primary SLK recipients between 2003 and 2020 with available crossmatch and induction data. We grouped recipients according to the crossmatch status: negative crossmatch (-XM; n=3040) and +XM (n=407). Kaplan-Meier curves were generated to examine recipient, death-censored liver, and death-censored kidney survival by crossmatch status. Cox proportional hazard models were used to investigate the association between crossmatch status and outcomes of interest with follow-up censored at 10 years. Models were adjusted for recipient age, sex, diabetes mellitus, Model for End-Stage Liver Disease score, duration on the liver waiting list, induction immunosuppression, steroid maintenance, hepatitis C infection, donor age and sex, local vs. shared organ, cold ischemia time, and previous liver transplantation status. In the univariable analysis, crossmatch status was not associated with recipient survival (log-rank p=0.63), death-censored liver graft survival (log-rank p=0.05), or death-censored kidney graft survival (log-rank p=0.11). Compared with -XM, +XM recipients had a similar 1-year liver rejection rate, but higher kidney rejection rate (4.6% vs. 8.9%, p=0.002). In the multivariable models, +XM status was not associated with deleterious long-term recipient, liver, or kidney grafts survival. -XM and +XM SLK transplantations have comparable long-term recipient, liver graft, and kidney survival with a slightly increased risk of early kidney allograft rejection in the +XM group. Crossmatch positivity in SLK transplantations should not influence the decision to use organs from a specific donor.

Current Status and Perspectives of Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia.

As in younger patients, allogeneic stem cell transplantation (alloHSCT) offers the best chance for durable remission in older patients (≥60 years) with acute myeloid leukemia (AML). However, defining the best treatment strategy (and in particular, whether or not to proceed to alloHSCT) for elderly patients with AML remains a difficult decision for the hematologist, since potential toxicity of conditioning regimens, risks of graft-versus-host disease, impaired immune reconstitution and the need for prolonged immunosuppression may be of major concern in these vulnerable patients with complex needs. Hopefully, significant progress has been made over the past decade in alloHSCT for elderly patients and current evidence suggests that chronological age per se (between 60 and 75) is not a reliable predictor of outcome after alloHSCT. Here, we review the current state of alloHSCT in elderly patients with AML and also discuss the different approaches currently being investigated to improve both accessibility to as well as success of alloHSCT in these patients.

Relationship Between High Organ Donation Rates and COVID-19 Vaccination Coverage.

BackgroundBesides attaining the goal of self-protection, the rollout of vaccination programs also encourages altruistic practices. Therefore, the progress in vaccination against coronavirus disease (COVID-19) in each country may be related to the prevalence of cooperative and altruistic practices in health care. I hypothesized that in countries where organ donation is popular, individuals would exhibit a greater tendency to become vaccinated.MethodsI examined the correlation between the level of progress of COVID-19 vaccination and the status of organ donation just before the pandemic in Organization for Economic Co-operation and Development (OECD) countries. Publicly available statistical information on the progress of immunization and organ donation was used. Univariate and multivariate analyses were conducted to examine common drivers of immunization and organ donation.ResultsIn OECD countries, progress in vaccination was found to be significantly correlated with the status of organ donation in each country. This relationship was stable after the summer (September 1: Pearson's r = 0.442, October 1: 0.457, November 1: 0.366). The results of the univariate and multivariate analyses showed that high trust in medical professionals was significantly correlated with both the “progress of vaccinations” and “organ donations.”ConclusionsProgress in COVID-19 vaccination and organ donation status for transplantation have similar trends, and both may involve people's trust in medical personnel and public health systems. Similar to the efforts to obtain organ donors, governments around the world need to take further steps to ensure that vaccination programs are supported by people's trust and sense of solidarity.

First US DCD Pediatric Heart Transplant Using Ex-Vivo Perfusion: Is It Time for a Clinical Trial?

<h3>Introduction</h3> Heart recovery via donation after circulatory death (DCD) with ex-vivo perfusion (EVP) may increase the heart donor pool for appropriately-sized pediatric patients. We report the first pediatric DCD heart transplant in the United States (US) using EVP. <h3>Case Report</h3> The recipient is a 14 year-old female with a history of 1p36 gene deletion syndrome and dilated cardiomyopathy requiring extracorporeal life support and subsequent left ventricular assist device placement. The recipient was listed for heart transplantation status 1A. She and her parents consented for use of the investigational Organ Care System (OCS; Transmedics, Andover, Mass) under a Compassionate Use exception granted by the US Food and Drug Administration since, as a minor, she was excluded from the OCS DCD Heart trial (ClinicalTrials.gov: NCT03831048). Approval was also granted by our Institutional Review Board. After 5 months on the waitlist, a matched donor was accepted: A 27-year-old female with irreversible brain injury secondary to status epilepticus. The donor body surface area (BSA) was 1.64 m² and the recipient BSA was 1.58 m². The heart was successfully perfused on OCS and transplanted (key time points are illustrated in Figure). At the conclusion of the transplant echocardiography demonstrated moderate biventricular dysfunction. Delayed sternal closure was performed on postoperative day 3. Extubation occurred on postoperative day 6 and inotropes were discontinued on postoperative day 9, at which time echocardiogram demonstrated normal biventricular function. <h3>Summary</h3> We describe the first pediatric DCD heart transplantation in the US using EVP. This case, together with positive European and Australian outcomes, provides support for the consideration of a US clinical trial of EVP for carefully selected pediatric donors and recipients, which could provide insights into the safety and efficacy of pediatric DCD heart transplantation and lead to expansion of the pediatric donor pool.

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database

BackgroundConsiderable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization. MethodsThe Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018. ResultsA total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment. ConclusionWe present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.

Hand Transplants, Daily Functioning, and the Human Capacity for Limb Regeneration.

Unlike some of our invertebrate and vertebrate cousins with the capacity to regenerate limbs after traumatic loss, humans do not have the ability to regrow arms or legs lost to injury or disease. For the millions of people worldwide who have lost a limb after birth, the primary route to regaining function and minimizing future complications is via rehabilitation, prosthetic devices, assistive aids, health system robustness, and social safety net structures. The majority of limbs lost are lower limbs (legs), with diabetes and vascular disorders being significant causal contributors. Upper limbs (arms) are lost primarily because of trauma; digits and hands are the most common levels of loss. Even if much of the arm remains intact, upper limb amputation significantly impacts function, largely due to the loss of the hand. Human hands are marvels of evolution and permit a dexterity that enables a wide variety of function not readily replaced by devices. It is not surprising, therefore, for some individuals, dissatisfaction with available prosthetic options coupled with remarkable advances in hand surgery techniques is resulting in patients undertaking the rigors of a hand transplantation. While not “regeneration” in the sense of the enviable ability with which Axolotls can replace a lost limb, hand transplants do require significant regeneration of tissues and nerves. Regaining sophisticated hand functions also depends on “reconnecting” the donated hand with the areas of the human brain responsible for the sensory and motor processing required for complex actions. Human hand transplants are not without controversy and raise interesting challenges regarding the human regenerative capacity and the status of transplants for enabling function. More investigation is needed to address medical and ethical questions prior to expansion of hand transplants to a wider patient population.

Bisphosphonates and bone mineral density in patients with end-stage kidney disease and renal transplants: A 15-year single-centre experience

Chronic Kidney Disease Stage 5 (CKD-5) imparts a 4-fold increase in minimal trauma fracture with a substantial increase in mortality following hip fracture. Bone disease in CKD is complex, characterised by abnormal levels of PTH, calcium, phosphate, ALP, and vitamin D, manifesting as a condition known as CKD-Mineral and Bone Disorder (CKD-MBD). While bisphosphonates (BPs) are widely used in the management of osteoporosis, their therapeutic role when end-stage renal function and bone disease co-exist remains unclear. This 15-year retrospective cohort study examines the long-term use of BPs in CKD-4 and -5 patients receiving no renal replacement therapy, haemodialysis and renal transplant in a tertiary centre in Sydney, Australia. In multivariate regression adjusting for age, baseline bone mineral density (BMD) and history of fracture, BP use was associated with net gain in lumbar spine bone density in renal transplant recipients over a mean treatment period of 3.5 years (net annual BMD gain of 0.039 g/cm2, p = 0.005). No such benefit was seen in hip BMD in CKD subjects. Regardless of transplant status, CKD patients treated with BPs had no improvement in hip BMD with a general decline in hip BMD across both groups during the study period (hip BMD: transplant recipients decline 0.024 ± 0.81 g/cm2, non-transplant CKD patients decline 0.055 ± 0.84 g/cm2). BP therapy did not result in significant changes in biochemical parameters (ALP, PTH, and phosphate) and no serious adverse effects were detected in association with BP use. In particular, kidney function was not affected by BPs post-transplant (eGFR = 43 ± 29 ml/min/1.73 m2, p = 0.80). BPs preserved lumbar spine bone density in kidney transplant recipients but did not prevent declines in hip bone mineral density in either transplant patients or those with CKD-4 and -5. SummaryThere remains a lack of clarity of the risks vs. benefits of bone-sparing pharmacotherapy in chronic kidney disease Stages 4 and 5. This single-centre 15-year retrospective data analysis showed that bisphosphonates are not associated with any detectable serious adverse effects in CKD-4 and -5 and effective at mitigating lumbar spine bone loss in kidney transplant patients.

OPTN/SRTR 2020 Annual Data Report: Introduction

OPTN/SRTR 2020 Annual Data Report: Introduction