Survival Of Transplant Recipients Research Articles

Sonographic features of thoracoabdominal wall metastases of liver cancer after liver transplantation

ObjectiveSonographic features are not well-defined in thoracoabdominal wall metastases (TAWM) of liver cancer after liver transplantation (LT), which is one of the most important reasons affecting the long-term survival of transplant recipients. The purpose of this study was to analyze the sonographic features of TAWM from liver cancer after LT and to identify the role of ultrasound (US) in the differential diagnosis between TAWM and benign lesions of the thoracoabdominal wall after LT. MethodsThis retrospective study included 1,999 LT recipients between January 2008 and July 2021. Clinical characteristics and sonographic features of 32 patients with thoracoabdominal wall lesions were analyzed. The types of thoracoabdominal wall lesions were studied, and the US findings of benign and malignant lesions were compared. Whether TAWM from liver cancer after LT exhibited any distinctive sonographic appearance was evaluated. ResultsAll seven malignant cases were metastases from liver cancer. The benign group included 13 cases of thoracoabdominal wallencapsulated effusion/hematoma, nine of abdominal incisional hernia, and three of thoracoabdominal wall inflammatory mass. Sonographic features were significantly different between two groups. Compared with the benign group, metastases lesions were frequently located in the parietal peritoneum/pleura (4/7 vs 1/25, p = 0.009), fewer lesions were located at abdominal incisions (3/7 vs 23/25, p = 0.012), all metastatic lesions were hypoechoic (7/7 vs 5/25, p = 0.001), and most lesions had blood flow signals (4/7 vs 3/25, p = 0.026). Additionally, most metastatic cases had intrahepatic lesions (4/7 vs 1/25, p = 0.004) and multiple extrahepatic solid lesions in the abdomen (6/7 vs 0/25, p = 0.000). ConclusionsCompared with benign lesions, TAWM of liver cancer after LT exhibited unique sonographic features.

Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients.

Acute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR. Candidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort. We identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77). We have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients.

Body mass index percentage and survival in pediatric patients listed for lung transplantation: A modern-era multi-institutional analysis

Prior studies suggest that being underweight by body mass index percentiles (BMI%) or thinness grade did not affect post-transplant survival in pediatric lung transplant (LTx) recipients regardless of cystic fibrosis (CF) or non-CF diagnosis. Graft and overall survival from the time of listing was instead evaluated based on listing BMI%, the current standard of practice for BMI definitions in pediatrics, to ascertain the impact of a "severely low" subcategory. The UNOS registry was queried for children listed for LTx (aged 2 to <18 years) from January 1986 to March 2020. BMI% at listing and transplant were calculated per CDC guidelines according to age in years, sex, and reported BMI%. Patients were divided by listing BMI%: severely low (<3rd), low (3-<5th), normal (5-<85th), overweight (85-<95th), and obese (≥95th). Kaplan-Meier curves were generated to assess differences in overall survival since listing based on BMI% classes. Cox proportional-hazards models were developed to assess risk factors for overall and graft survival, including listing BMI%, transplant listing era (≥2005), and listing age, by reporting hazard ratios (HR). Listing BMI% was calculable for 1,876 patients. The proportion of patients with CF differed significantly between BMI% groups (p < 0.001). Patients listed with a non-CF diagnosis comprised 34% of those in the severely low category, and 88% of those listed with an obese BMI%. Compared to patients with a normal listing BMI%, the cohort with severely low BMI% had worse overall survival regardless of LTx (p=0.009) and graft survival (p=0.034). Compared to patients with a low BMI%, those with a severely low BMI% had significantly poorer graft survival as well (p=0.040). Mean graft survival was not significantly different between groups that remained at listing BMI% vs those that improved in category despite an overall small sample size. Independent predictors of poorer survival from the time of listing include severely low vs low-normal BMI% (HR=1.20) and listing age (HR=1.02). The proportion of children listed at severely low BMI% has steadily decreased with time, yet pediatric LTx candidates listed with a severely low BMI% had poorer graft and overall survival compared to those of normal BMI%. Severely low listing BMI% was an independent prognostic factor for higher mortality risk from the time of placement on the waitlist. BMI% may be a modifiable target for improving survival regardless of transplantation.

Ex vivo intranodal administration of sirolimus

BackgroundImmune-mediated adverse effects of current systemic immunosuppression therapy compromise long-term survival of liver transplant recipients. Our recently observed results showed that intranodal delivery of sirolimus induced interleukin (IL)-10–driven CD4+ CD25+ Foxp3+ regulatory T cells. The present report investigated the feasibility of intra-nodal delivery of sirolimus ex vivo into a human liver common bile duct lymph node. MethodsWe used a discarded donor human liver to directly administer sirolimus into a distal common bile duct lymph node. Sirolimus was injected once using an ultrasound-guided method. ResultsThe porta hepatis and its lymph node along the distal common bile duct were exposed. A handheld ultrasound probe (L15-7io, Koninklijke Philips N.V.) with a layer of standoff Aquasonic 100 Ultrasound Transmission Gel (Parker Laboratories, Inc) was applied to the exposed lymph node. Using a 1.0-mL 25G hypodermic needle, 0.05 mL of sirolimus solution was injected directly into the exposed lymph node. ConclusionsUnder sonographic guidance, direct injection of sirolimus into a hepatic draining lymph node along the common bile duct is accomplished precisely and reliably. Direct administration of therapeutic agents into local lymph nodes is a viable approach for effective targeted immunotherapy.

Deceased-Donor Renal Transplantation: A Single-Center Experience from a Tertiary Care Hospital in North India

Introduction: Deceased-donor renal transplants can help cope up with the increasing demand of renal allografts in India. We evaluated the outcomes of deceased-donor renal transplantation at our center. Methods: This retrospective study analyzed the donor and recipient characteristics along with graft and patient survival in deceased-donor renal transplant recipients at our center between April 2011 and October 2021. Results: The mean age of recipients (n = 21) and deceased donors was 48 ± 9.4 and 39.3 ± 8.7 years, respectively. Male:female ratio among recipients was 1.6:1 while that in donors was 2:1. Chronic glomerulonephritis (71.4%) was the most common native kidney disease. Most patients received antithymocyte globulin (80.9%) as induction and tacrolimus-based triple-drug regimen (80.4%) as maintenance therapy. The median follow-up duration was 32.8 months. Graft dysfunction was reported in 57.1% (n = 12/21) patients; acute tubular necrosis was the most common reason (n = 5). Six patients died, and sepsis was the most common reason for death (n = 3/6; 50%); 66.7% (n = 4/6) deaths occurred within the first 6 months. The mean graft survival time was 106.2 months (95% confidence interval: 95.4–116.6). The cumulative proportion of graft survival was 95.2% (n = 20/21) at 3 and 5 years. The cumulative proportion of patient survival was 80.9% at 3 years and 76.2% at 5 years. Conclusion: Patient outcomes over 5 years follow-up were good and suggest that deceased-donor transplants should be encouraged along with living-donor transplants to cover the huge demand–supply mismatch in renal replacement therapy.

(96) Impact of Donor Age on Survival of Lung Transplant Recipients According to Their Primary Diagnosis

(96) Impact of Donor Age on Survival of Lung Transplant Recipients According to Their Primary Diagnosis

Non-Traditional Non-Immunological Risk Factors for Kidney Allograft Loss-Opinion.

Rates of late allograft loss have improved slowly in the last decades. Well described traditional risk factors that influence allograft survival include cardiovascular events, rejection, infections and post-transplant neoplasia. Here, we critically evaluate the influence of several non-immunological, non-traditional risk factors and describe their impact on allograft survival and cardiovascular health of kidney transplant recipients. We assessed the following risk factors: arterial stiffness, persistent arteriovenous access, mineral bone disease, immunosuppressive drugs residual levels variability, hypomagnesemia, glomerular pathological alterations not included in Banff criteria, persistent inflammation and metabolic acidosis.

Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation.

Antibody-mediated rejection (AMR) is one of the most important challenges in the context of renal transplantation, because the binding of de novo donor-specific antibodies (dnDSA) to the kidney graft triggers the activation of the complement, which in turn leads to loss of transplant. In this context, the objective of this study was to evaluate the association between complement-fixing dnDSA antibodies and graft loss as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients. Our study included a cohort of 245 transplant patients over a 5-year period at Virgen de las Nieves University Hospital (HUVN) in Granada, Spain. dnDSA was observed in 26 patients. Of these patients, 17 had non-complement-fixing dnDSA and 9 had complement-fixing dnDSA. Our study demonstrated a significant association between the frequency of rejection and renal graft loss and the presence of C1q-binding dnDSA. Our results show the importance of the individualization of dnDSA, classifying them according to their ability to activate the complement, and suggest that the detection of complement-binding capacity by dnDSA could be used as a prognostic marker to predict AMR outcome and graft survival in kidney transplant patients who develop dnDSA.

Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling.

Acute lymphoblastic and myeloblastic leukemias (ALL and AML) have been known to modify the bone marrow microenvironment and disrupt non-malignant hematopoiesis. However, the molecular mechanisms driving these alterations remain poorly defined. Using mouse models of ALL and AML, here we show that leukemic cells turn off lymphopoiesis and erythropoiesis shortly after colonizing the bone marrow. ALL and AML cells express lymphotoxin α1β2 and activate lymphotoxin beta receptor (LTβR) signaling in mesenchymal stem cells (MSCs), which turns off IL7 production and prevents non-malignant lymphopoiesis. We show that the DNA damage response pathway and CXCR4 signaling promote lymphotoxin α1β2 expression in leukemic cells. Genetic or pharmacological disruption of LTβR signaling in MSCs restores lymphopoiesis but not erythropoiesis, reduces leukemic cell growth, and significantly extends the survival of transplant recipients. Similarly, CXCR4 blocking also prevents leukemia-induced IL7 downregulation and inhibits leukemia growth. These studies demonstrate that acute leukemias exploit physiological mechanisms governing hematopoietic output as a strategy for gaining competitive advantage.

Single-drug immunosuppression is associated with noninferior medium-term survival in pediatric heart transplant recipients

Patients are usually maintained on at least 2 immunosuppressive drugs (ISDs) after the first year post heart transplant. Anecdotally, some children are switched to single-drug monotherapy (a single ISD) for various reasons and varying durations. Outcomes associated with differences in immunosuppression after heart transplantation are unknown for children. A priori we defined a noninferiority hypothesis for monotherapy compared to ≥2 ISDs. The primary outcome was graft failure, a composite of death and retransplantation. Secondary outcomes included rejection, infection, malignancy, cardiac allograft vasculopathy and dialysis. This international, multicenter, retrospective, observational cohort study used data from the Pediatric Heart Transplant Society. We included patients who underwent first-time heart transplant <18 years of age between 1999 and 2020 with ≥1 year of follow-up data available. Our analysis included 3493 patients with a median time post-transplant of 6.7 years. There were 893 patients (25.6%) switched to monotherapy at least once with the remaining 2600 patients always on ≥2 ISDs. The median time on monotherapy after the first year post-transplant was 2.8 years (range 1.1-5.9 years). We found an adjusted hazard ratio (HR) of 0.65 (95%CI: 0.47-0.88) favoring monotherapy compared to ≥2 ISDs (p=0.002). There were no meaningful differences in the incidence of secondary outcomes between groups, except for a lower rate of cardiac allograft vasculopathy in patients on monotherapy (HR 0.58, 95%CI: 0.45-0.74). For pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was noninferior to standard therapy with ≥2 ISDs in the medium term. Some children are switched to a single immunosuppressive drug (ISD) for various reasons after heart transplant, but outcomes associated with differences in immunosuppression are unknown for children. We assessed graft failure in children on a single ISD (monotherapy) compared to ≥2 ISDs in a cohort of 3493 children with a first heart transplant. We found an adjusted hazard ratio of 0.65 (95%CI: 0.47-0.88) favoring monotherapy. We concluded that for pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was non-inferior to standard therapy with ≥2 ISDs in the medium term.

Long-term Outcome of Pediatric Liver Transplant Recipients Who Have Reached Adulthood: A Single-center Experience.

As long-term survival of pediatric liver transplant recipients increases, the assessment of physical, psychological, and social well-being becomes more important. In this retrospective analysis, 120 young adult patients (age ≥18 y) who underwent liver transplantation in childhood were studied. Patients with ideal outcome were defined as patients with perfect graft function, with no complications from the immunosuppressive medication, no late retransplantation, and no steroid treatment. Also, the patients' drug adherence and their psychosocial situation were assessed. After a median follow-up of 19 y, only 16.7% of the patients (mean age: 26.5 y) were considered patients with ideal outcome. The main reasons precluding ideal outcome were chronic kidney disease (38.3%), elevated liver enzymes (33.3%), and arterial hypertension (31.7%). Ideal outcome decreased over time from 54% to 42%, 26%, and 8% at 10-, 15-, 20-, and 25-y follow-up, respectively. Reduced drug adherence was noted in 24.8% of patients and associated with a significantly higher prevalence of donor-specific antibodies class II ( P = 0.015), elevated transaminases ( P = 0.010), and chronic rejection ( P < 0.001). Also, 15% of patients had a psychiatric disease, mainly depression. The morbidity of young adults who underwent liver transplantation as children was high and increased over time. The majority developed complications from immunosuppression or chronic graft dysfunction. More than 1 in 7 patients had a psychiatric disease and 1 in 4 was not perfectly drug adherent. Therefore, immunosuppressive treatment and psychological care should be optimized for these particularly vulnerable patients.

Post-transplant outcomes among cystic fibrosis patients undergoing lung transplantation colonized by Burkholderia: A single center cohort study

Prior infection with Burkholderia cepacia complex (BCC) has been associated with poorer outcomes after lung transplantation, posing an important dilemma for cystic fibrosis (CF). Although current guidelines consider BCC infection to be a relative contraindication, some centers continue to offer lung transplantation to BCC-infected CF patients. We conducted a retrospective cohort study which included all consecutive CF-LTR between 2000 and 2019 to compare the postoperative survival of BCC-infected CF lung transplant recipients (CF-LTR) to BCC-uninfected patients. We used a Kaplan-Meier analysis to compare survival of BCC-infected to BCC-uninfected CF-LTR and fitted a multivariable Cox model, adjusted for age, sex, BMI and year of transplantation as potential confounders. As an exploratory analysis, Kaplan-Meier curves were also stratified by the presence of BCC and urgency of transplantation. A total of 205 patients were included with a mean age of 30.5 years. Seventeen patients (8%) were infected with BCC prior to LT. Patients were infected with the following species: B. multivorans5, B. vietnamiensis3, combined B. multivorans and B. vietnamiensis3 and others4. None of the patients were infected with B. cenocepacia. Three patients were infected with B. gladioli. One-year survival was 91.7% (188/205) for the entire cohort, 82.4% (14/17) among BCC-infected CF-LTR, and 92.5% (173/188) among BCC uninfected CF-LTR (crude HR=2.19; 95%CI 0.99-4.85; p=0.05). In the multivariable model, presence of BCC was not significantly associated with worse survival (adjusted HR 1.89; 95%CI 0.85-4.24; p=0.12). In the stratified analysis for both presence of BCC and urgency of transplantation, urgency of transplantation among BCC-infected CF-LTR appeared to be associated with poorer outcome (p=0.003 across the 4 subgroups). Our results suggest that non-cenocepacia BCC-infected CF-LTR have comparable survival rate to BCC-uninfected CF-LTR.

Impact of Culture-Positive Preservation Fluid on Early Morbidity and Mortality After Lung Transplantation.

The prevalence, risk factors and outcomes associated with culture-positive preservation fluid (PF) after lung transplantation (LT) are unknown. From January 2015 to December 2020, the microbiologic analyses of PF used to store the cold ischaemia-placed lung graft(s) of 271 lung transplant patients were retrospectively studied. Culture-positive PF was defined as the growth of any microorganism. Eighty-three (30.6%) patients were transplanted with lung grafts stored in a culture-positive PF. One-third of culture-positive PF were polymicrobial. Staphylococcus aureus and Escherichia coli were the most frequently isolated microorganisms. No risk factors for culture-positive PF based on donor characteristics were identified. Forty (40/83; 48.2%) patients had postoperative pneumonia on Day 0 and 2 (2/83; 2.4%) patients had pleural empyema with at least one identical bacteria isolated in culture-positive PF. The 30-day survival rate was lower for patients with culture-positive PF compared with patients with culture-negative PF (85.5% vs. 94.7%, p = 0.01). Culture-positive PF has a high prevalence and may decrease lung transplant recipient survival. Further studies are required to confirm these results and improve understanding of the pathogenesis of culture-positive PF and their management.

Impact of Post-Transplant Diabetes Mellitus on Survival and Cardiovascular Events in Kidney Transplant Recipients.

Post-transplant diabetes mellitus (PTDM) is a risk factor for poor outcomes after kidney transplantation (KT). However, the outcomes of KT have improved recently. Therefore, we investigated whether PTDM is still a risk factor for mortality, major atherosclerotic cardiovascular events (MACEs), and graft failure in KT recipients. We studied a retrospective cohort of KT recipients (between 1994 and 2017) at a single tertiary center, and compared the rates of death, MACEs, overall graft failure, and death-censored graft failure after KT between patients with and without PTDM using Kaplan-Meier analysis and a Cox proportional hazard model. Of 571 KT recipients, 153 (26.8%) were diagnosed with PTDM. The mean follow-up duration was 9.6 years. In the Kaplan- Meier analysis, the PTDM group did not have a significantly increased risk of death or four-point MACE compared with the non-diabetes mellitus group (log-rank test, P=0.957 and P=0.079, respectively). Multivariate Cox proportional hazard models showed that PTDM did not have a negative impact on death or four-point MACE (P=0.137 and P=0.181, respectively). In addition, PTDM was not significantly associated with overall or death-censored graft failure. However, patients with a long duration of PTDM had a higher incidence of four-point MACE. Patient survival and MACEs were comparable between groups with and without PTDM. However, PTDM patients with long duration diabetes were at higher risk of cardiovascular disease.

Does donor treatment with inotropes and/or vasopressors impact post-transplant outcomes?

The purpose was to evaluate the effects of the most commonly used cardiac donor inotropes/vasopressors on subsequent post-heart transplant survival. Adult heart transplant recipients from January 2000 to June 2022 were identified in the United Network for Organ Sharing (UNOS) database. Exclusion criteria included: multiorgan transplants, donor age<15, and recipient age<18. Donors receiving vasoactive medications at the time of procurement were compared to donors not receiving these medications. Those on vasoactive medications were stratified by medication: phenylephrine, dopamine, dobutamine, norepinephrine and epinephrine, the combination of these agents, and the concomitant administration of vasopressin with any single agent alone or in combination. The primary area of interest was short-and-long-term survival. Survival at 30 days, 1 year, and long-term (Median=13.6 years) was compared using logistic and Cox models to quantify survival endpoints. A total of 45,198 donors met inclusion criteria and had data on the use of vasoactive agents available. Mean donor age was 32.3 years with 71% male. Vasoactive medications and potential combinations included phenylephrine in 8156 donors (18.0%), dopamine in 9550 (21.1%), dobutamine in 718 (1.6%), epinephrine in 332 (.73%), and norepinephrine in 4854 (10.7%). A total of 25,856 donors (57.2%) were receiving vasopressin at the time of procurement. There was no impact of donor inotropes on 30-day survival. Donors receiving one inotrope and no vasopressin were associated with increased 1 year mortality (OR 1.14; p=.021), as were donors receiving 2+ inotropes and no vasopressin (OR 1.26; p=.006). For individual agents, 1 year mortality was increased for dopamine (OR 1.11; p=.042) and epinephrine (OR 1.59; p=.004). There is no difference in heart transplant recipient survival at 30 days when the donor is receiving inotropes without vasopressin at the time of procurement. Inotropic support without vasopressin is associated with greater 1 year mortality. The impact of donor inotropic support on long term heart transplant survival, and the interaction with vasopressin warrants further study.

Alloimmunization Against RBC Antigens Is Not Associated With Decreased Survival in Liver Transplant Recipients.

Improvement of liver transplantation (LT) outcomes requires better understanding of factors affecting survival. The presence of RBC alloantibodies (RBCAs) on survival in LT recipients was evaluated. This study was a single-center, retrospective cohort study reviewing transfusion records and all-cause mortality between 2002 and 2021. Between 2002 and 2021, 2079 LTs were completed, 1,396 of which met inclusion criteria (1,305 RBCA negative; 91 RBCA positive [6.5%]). The cohorts were similar in age (mean [range], 55.8 [17-79] years vs 56.8 [25-73] years; P = .41, respectively) or sex (RBCA negative, 859 [65%] men and 446 [35%] women vs RBCA positive, 51 [56%] men and 40 [44%] women; P = .0684). Of 132 RBCAs detected, 10 were most common were to E (27.27%), Jka (15.91%), K (9.09%), C (8.33%), M (6.06%), D (5.3%), Fya (4.55%), e (2.27%), c (2.27%), and Jkb (2.27%). Twenty-seven patients (29.7%) had more than 1 RBCA; the most common combinations were C with Jka (7.4%) and E with Dia (7.4%). All-cause mortality was increased in men (men, 14.45 years vs women, 17.27 years; P = .0266) and patients 65 years of age and older (≥65 years of age, 10.21 years vs <64 years of age, 17.22 years; P < .0001). The presence of RBCA (≥1) did not affect all-cause mortality (RBCA negative, 14.17 years vs RBCA positive, 15.29 years; P = .4367). The top 5 causes of death were infection (11.9%), primary malignancy (solid) (10.8%), recurrent malignancy (10.5%), cardiovascular arrest (7.1%), and pulmonary insufficiency/respiratory failure (5.7%). Survival in RBCA-positive LT recipients is no different from that in RBCA-negative LT recipients.

Robert H. Rubin and infectious disease in transplantation.

Robert H. Rubin, M.D. was among the first physician-scientists to focus attention on the infectious diseases associated with immune suppression. A superb bedside clinician and teacher, he developed many of the concepts central to the care and improved survival of organ transplant and stem cell transplant recipients. These concepts have provided the basis of clinical investigation and basic research for multiple generations of infectious disease specialists, immunologists, and transplant surgeons.

Impact of Blood Pressure Control on Graft Survival in Kidney Transplant Recipients

Cardiovascular disease is the primary driver of morbidity and mortality in kidney transplant recipients. Hypertension is an important risk factor for development of cardiovascular disease in this population. Despite its important role in post-transplant outcomes, the blood pressure goals for kidney transplant recipients remain elusive. Current guidelines are based on observational data or data extrapolated from the chronic kidney disease population. We followed 5-year blood pressure control of 378 kidney-alone transplant recipients at a single center and evaluated patient survival, graft survival, proteinuria, and rate of decline of kidney graft function. We found that a mean systolic blood pressure (BP) of 121 to 130 mm Hg was associated with better graft survival, slower decline of kidney allograft function, and lower degree of proteinuria when compared with a mean systolic BP ≤120 or >130 mm Hg. This study provides evidence for strict blood pressure control, systolic BP between 121 and 130 mm Hg, and also cautions against intensive control of systolic BP <120 mm Hg in kidney transplant recipients.

Outcomes following heart or bilateral-lung transplantation from donors who died of drug toxicity in British Columbia, Canada.

The illicit drug toxicity (overdose) crisis has worsened across Canada; between 2016 and 2021, more than 28,000 individuals have died of drug toxicity. Organ donation from persons who experience drug toxicity death (DTD) has increased in recent years. This study examines whether survival after heart or bilateral-lung transplantation differed by donor cause of death. We studied transplant recipients in British Columbia who received heart (N=110) or bilateral-lung (N=223) transplantation from deceased donors aged 12-70 years between 2013 and 2019. Transplant recipient survival was compared by donor cause of death from drug toxicity or other. Five-year Kaplan-Meier estimates of survival and 3-year inverse probability treatment weighted Cox proportional hazards models were conducted. DTD donors made up 36% (40/110) of heart and 24% (54/223) of bilateral-lung transplantations. DTD donors were more likely to be young, white, and male. Unadjusted 5-year recipient survival was similar by donor cause of death (heart: 87% for DTD and 86% for non-DTD, p=.75; bilateral- lung: 80% for DTD and 76% for non-DTD, p=.65). Adjusted risk of mortality at 3-years post-transplant was similar between recipients of DTD and non-DTD donor heart (hazard ratio [HR]: .94, 95% confidence interval (CI): .22-4.07, p=.938) and bilateral-lung (HR: 1.06, 95% CI: .41-2.70, p=.908). Recipient survival after heart or bilateral-lung transplantation from DTD donors and non-DTD donors was similar. Donation from DTD donors is safe and should be considered more broadly to increase organ donation.

Hospitalization and survival of solid organ transplant recipients with coronavirus disease 2019: A propensity matched cohort study.

Solid organ transplant (SOT) recipients are predicted to have worse COVID-19 outcomes due to their compromised immunity. However, this association remains uncertain because published studies have had small sample sizes and variability in chronic comorbidity adjustment. In this retrospective cohort study conducted at a multihospital health system, we compared COVID-19 outcomes and survival up to 60 days following hospital admission in SOT recipients taking baseline immunosuppressants versus hospitalized control patients. The study included 4,562 patients who were hospitalized with COVID-19 (108 SOT recipients and 4,454 controls) from 03/2020 to 08/2020. Mortality at 60 days was higher for SOT recipients (17% SOT vs 10% control; unadjusted odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.04-2.91, P = 0.04). We then conducted a 1:5 propensity matched cohort analysis (100 SOT recipients; 500 controls) using age, sex, race, body mass index, hypertension, diabetes, chronic kidney disease, liver disease, admission month, and area deprivation index. Within 28 days of admission, SOT recipients had fewer hospital-free days (median; 17 SOT vs 21 control; OR = 0.64, 95%CI 0.46-0.90, P = 0.01) but had similar ICU-free days (OR = 1.20, 95%CI 0.72-2.00, P = 0.49) and ventilator-free days (OR = 0.91, 95%CI 0.53-1.57, P = 0.75). There was no statistically significant difference in 28-day mortality (9% SOT vs 12% control; OR = 0.76, 95%CI 0.36-1.57, P = 0.46) or 60-day mortality (16% SOT vs 14% control; OR = 1.15, 95%CI 0.64-2.08, P = 0.64). Hospitalized SOT recipients appear to need additional days of hospital care but can achieve short-term mortality outcomes from COVID-19 that are similar to non-SOT recipients in a propensity matched cohort study.