Development and validation of a simple web-based tool for early prediction of COVID-19-associated death in kidney transplant recipients.

This analysis, using data from the Brazilian kidney transplant (KT) COVID-19 study, seeks to develop a prediction score to assist in COVID-19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28-day fatality after the COVID-19 diagnosis, assessed by the area under the ROC curve (AUC-ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28-day fatality rate was 17% (n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID-19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC-ROC of 0.767 (95% CI 0.698-0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non-hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776.

Organ donation during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly changing circumstance with dramatic policy changes and universal efforts to deal with the initial crisis and minimize its consequences. To identify changes to organ donation and transplantation during this time, an anonymous web-based survey was distributed to 19 select organ procurement organizations (OPOs) throughout the United States comparing 90-day activity during March-May 2020 and March-May 2019. Seventeen OPOs responded to the survey (response rate of 89.5%). Organ authorization decreased by 11% during the current pandemic (n = 1379 vs n = 1552, P = .0001). Organ recovery for transplantation fell by 17% (P = .0001) with a further 18% decrease in the number of organs transplanted (P = .0001). Donor cause of death demonstrated a 4.5% decline in trauma but a 35% increase in substance abuse cases during the COVID-19 period. All OPOs reported significant modifications in response to the pandemic, limiting the onsite presence of staff and transitioning to telephonic approaches for donor family correspondence. Organ donation during the current climate has seen significant changes and the long-term implications of such shifts remain unclear. These trends during the COVID-19 era warrant further investigation to address unmet needs, plan for a proportionate response to the virus and mitigate the collateral impact.

Epipericardial fat necrosis as cause of chest pain in patient after heart transplantation.

Epipericardial fat necrosis is an uncommon clinical condition of unknown etiology. It typically presents as acute pleuritic chest pain and should be differentiated from acute pulmonary embolism and acute coronary syndrome. This condition is diagnosed by characteristic chest computed tomography findings of an ovoid mediastinal fatty lesion with intrinsic and surrounding soft-tissue stranding. Treatment of epipericardial fat necrosis includes the administration of anti-inflammatory agents, and symptoms usually resolve within a few days after treatment initiation. This disease entity has rarely been reported since it was first described in 1957. Most current knowledge of epipericardial fat necrosis is based on case reports that describe this condition in previously healthy individuals. We present the case of a 39-year-old woman with a history of heart transplant, who presented with chest pain secondary to epipericardial fat necrosis. Serial computed tomography revealed lesion resolution after appropriate treatment.

Epidemiology of end-stage renal failure among twins and diagnosis, management, and current outcomes of kidney transplantation between identical twins.

The aim of the study is to provide a comprehensive overview of identical twin kidney transplantation in the modern era. We provide epidemiologic trends in the US twin population from 1959 to 2000, current methods to identify zygosity, outcomes for identical twin transplants, and a comprehensive management strategy for identical twin kidney transplantation. By 2019, we project that 433 010 dizygotic and monozygotic twins will be alive and at risk for developing ESRF. Monozygosity between a donor-recipient pair can be confirmed by concordance in sex, blood type, and HLA antigen match with precision testing using 13/17 Short Tandem Repeat sequencing to a likelihood of nearly 100%. Among identical twin transplants from 2001 to 2017, excellent patient and kidney graft survival rates were noted. Approximately 50% of kidney transplant recipients of identical twins transplant did not receive maintenance immunosuppression, and no differences in graft survival were noted among patients with and without immunosuppression at 6 and 12 months (P = .8 and .7). Patients with glomerulonephritis as the cause of ESRF had lower graft survival (P = .06) suggesting that recurrent glomerulonephritis as a likely cause of graft loss among these recipients.

Discovery and cross-validation of peripheral blood and renal biopsy gene expression signatures from ethnically diverse kidney transplant populations.

We determined peripheral blood (PB) and biopsy (Bx) RNA expression signatures in a Brazilian and US cohort of kidney transplant patients. Phenotypes assigned by precise histology were: acute rejection (AR), interstitial fibrosis/tubular atrophy/chronic rejection (CR), excellent functioning transplants (TX), and glomerulonephritis recurrence (GN). Samples were analyzed on microarrays and profiles from each cohort were cross-validated on the other cohort with similar phenotypes. We discovered signatures for each tissue: (1) AR vs TX, (2) CR vs TX, and (3) GN vs TX using the Random Forests algorithm. We validated biopsies signatures of AR vs TX (area under the curve [AUC] 0.97) and CR vs TX (AUC 0.87). We also validated both PB and Bx signatures of AR vs TX and CR vs TX with varying degrees of accuracy. Several biological pathways were shared between AR and CR, suggesting similar rejection mechanisms in these 2 clinical phenotypes. Thus, we identified gene expression signatures for AR and CR in transplant patients and validated them in independent cohorts of significantly different racial/ethnic backgrounds. These results reveal that there are strong unifying immune mechanisms driving transplant diseases and identified in the signatures discovered in each cohort, suggesting that molecular diagnostics across populations are feasible despite ethnic and environmental differences.

Influence of epidemiology, immunosuppressive regimens, clinical presentation, and treatment on kidney transplant outcomes of patients diagnosed with tuberculosis: A retrospective cohort analysis.

Tuberculosis (TB) mortality is high among kidney transplant (KT) recipients. Although local epidemiology is an important factor, diagnostic/therapeutic challenges and immunosuppressive therapy (ISS) may influence outcomes. We analyzed the cumulative incidence (CumI) of TB in KT recipients receiving a variety of ISS with long-term follow-up. Our retrospective single-center cohort study included all KT procedures performed between January 1, 1998, and August 31, 2014, with follow-up until August 31, 2014. Induction therapy was based on perceived immunological risk; maintenance ISS included prednisone and calcineurin inhibitor (CNI) plus azathioprine (AZA), and mycophenolic acid (MPA) or mechanistic target of rapamycin inhibitor (mTORi). Thirty-four patients received belatacept/MPA. KT was performed on 11 453 patients and followed for 1989 (IQR 932 to 3632) days. Among these, 152 patients were diagnosed with TB (CumI 1.32%). Median time from KT to TB was 18.8 (IQR 7.2 to 60) months, with 59% of patients diagnosed after the first year. Unadjusted analysis revealed an increasing confidence interval (CI) of TB (0.94% CNI/AZA vs 1.6% CNI/MPA [HR = 1.62, 95% CI = 1.13 to 2.34, P = .009] vs 2.85% CNI/mTORi [HR = 2.45, 95% CI = 1.49 to 4.32, P < .001] vs 14.7% belatacept/MPA [HR = 13.14, 95% CI = 5.27 to 32.79, P < .001]). Thirty-seven (24%) patients died, and 39 (25.6%) patients experienced graft loss. Cytomegalovirus infection (P = .02) and definitive ISS discontinuation (P < .001) were associated with death. Rejection (P = .018) and ISS discontinuation (P = .005) occurred with graft loss. TB occurred at any time after KT and was influenced by ISS.

Long-term outcomes of transmesenteric portal vein recanalization for the treatment of chronic portal vein thrombosis after pediatric liver transplantation.

Portal vein thrombosis (PVT) may occur at any time following liver transplantation. We describe our experience with portal vein recanalization in cases of thrombosis after liver transplantation. Twenty-eight children (5%) out of 566 liver transplant recipients underwent portal vein recanalization using a transmesenteric approach. All children received left hepatic segments, developed PVT, and had symptoms or signs of portal hypertension. Portal vein recanalization was performed via the transmesenteric route in all cases. Twenty-two (78.6%) patients underwent successful recanalization and stent placement. They received oral anticoagulants after the procedure, and clinical symptoms subsided. Symptoms recurred due to portal vein restenosis/thrombosis in seven patients. On an intention-to-treat basis, the success rate of the proposed treatment was 60.7%. Only 17 out of 28 children with posttransplant chronic PVT retained stent patency (primary + assisted) at the end of the study period. In cases of portal vein obstruction, the transmesenteric approach via minilaparotomy is technically feasible with good clinical and hemodynamic results. It is an alternative procedure to reestablish the portal flow to the liver graft that can be performed in selected cases and a therapeutic addition to other treatment strategies currently used to treat chronic PVT.

Ureterocalicostomy with lower pole nephrectomy in a renal transplant: A case report.

As the number of kidney transplants continues to rise, so does the number and complexities of surgical-related complications, which may be associated with increased morbidity and potentially graft loss. Ureteral stenosis, the most prevalent urological complication, may require diverse techniques for surgical correction depending on several recipient and graft abnormalities. Here we report the surgical and clinical outcomes of a 62-year-old man with a posttransplant pyeloureterostomy stricture successfully treated with ureterocalicostomy after a lower pole nephrectomy. Although the resection of renal parenchyma may prevent a stenosis recurrence, surgeons can be reluctant to use this strategy due to the possible negative impact on renal function. We highlight some key steps of the surgical technique to prevent unnecessary allograft lesion and present short-term outcomes, suggesting that this rarely described procedure is a safe and effective alternative treatment for kidney transplant recipients with pyeloureterostomy stenosis.

Sustained Posttransplantation Diabetes Is Associated With Long-Term Major Cardiovascular Events Following Liver Transplantation.

Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long-term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow-up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20-3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.

Mechanical Ventilation and Extracorporeal Membrane Oxygenation as a Bridging Strategy to Lung Transplantation: Significant Gains in Survival.

Mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) are increasingly used to bridge patients to lung transplantation. We investigated the impact of using MV, with or without ECMO, before lung transplantation on survival after transplantation by performing a retrospective analysis of 826 patients who underwent transplantation at our high-volume center. Recipient characteristics and posttransplant outcomes were analyzed. Most lung transplant recipients (729 patients) did not require bridging; 194 of these patients were propensity matched with patients who were bridged using MV alone (48 patients) or MV and ECMO (49 patients). There was no difference in overall survival between the MV and MV+ECMO groups (p = 0.07). The MV+ECMO group had significantly higher survival conditioned on surviving to 1 year (median 1,811 days ([MV] vs. not reached ([MV+ECMO], p = 0.01). Recipients in the MV+ECMO group, however, were more likely to require ECMO after lung transplantation (16.7% MV vs. 57.1% MV+ECMO, p < 0.001). There were no differences in duration of postoperative MV, hospital stay, graft survival, or the incidence of acute rejection, renal failure, bleeding requiring reoperation, or airway complications. In this contemporary series, the combination of MV and ECMO was a viable bridging strategy to lung transplantation that led to acceptable patient outcomes.

Changing Metrics of Organ Procurement Organization Performance in Order to Increase Organ Donation Rates in the United States.

The shortage of deceased-donor organs is compounded by donation metrics that fail to account for the total pool of possible donors, leading to ambiguous donor statistics. We sought to assess potential metrics of organ procurement organizations (OPOs) utilizing data from the Nationwide Inpatient Sample (NIS) from 2009-2012 and State Inpatient Databases (SIDs) from 2008-2014. A possible donor was defined as a ventilated inpatient death ≤75 years of age, without multi-organ system failure, sepsis, or cancer, whose cause of death was consistent with organ donation. These estimates were compared to patient-level data from chart review from two large OPOs. Among 2,907,658 inpatient deaths from 2009-2012, 96,028 (3.3%) were a "possible deceased-organ donor." The two proposed metrics of OPO performance were: (1) donation percentage (percentage of possible deceased-donors who become actual donors; range: 20.0-57.0%); and (2) organs transplanted per possible donor (range: 0.52-1.74). These metrics allow for comparisons of OPO performance and geographic-level donation rates, and identify areas in greatest need of interventions to improve donation rates. We demonstrate that administrative data can be used to identify possible deceased donors in the US and could be a data source for CMS to implement new OPO performance metrics in a standardized fashion.

Mechanical Circulatory Support in the Treatment of Advanced Heart Failure.

According to the Centers for Disease Control, heart failure (HF) remains a pervasive condition with high morbidity and mortality, affecting 5.8 million people in the United States and 23 million worldwide. For patients with refractory end-stage HF, heart transplantation is the "gold standard" for definitive treatment. However, the demand for heart transplantation has consistently exceeded the availability of donor hearts, with approximately 2331 orthotopic heart transplantations performed in the United States in 2015 despite an estimated 100 000 to 250 000 patients with New York Heart Association class IIIB or IV symptoms that are refractory to medical treatment, making such patients potential transplant candidates. As such, the need for mechanical circulatory support (MCS) to treat patients with end-stage HF has become paramount. In this review, we focus on the history, advancements, and current use of durable MCS device therapy in the treatment of advanced heart failure.

Laparoscopic Biopsies in Pancreas Transplantation.

As there is no precise laboratory test or imaging study for detection of pancreas allograft rejection, there is increasing interest in obtaining pancreas tissue for diagnosis. Pancreas allograft biopsies are most commonly performed percutaneously, transcystoscopically, or endoscopically, yet pancreas transplant surgeons often lack the skills to perform these types of biopsies. We have performed 160 laparoscopic pancreas biopsies in 95 patients. There were 146 simultaneous kidney-pancreas biopsies and 14 pancreas-only biopsies due to pancreas alone, kidney loss, or extraperitoneal kidney. Biopsies were performed for graft dysfunction (89) or per protocol (71). In 13 cases, an additional laparoscopic procedure was performed at the same operation. The pancreas diagnostic tissue yield was 91.2%; however, the pancreas could not be visualized in eight cases (5%) and in 6 cases the tissue sample was nondiagnostic (3.8%). The kidney tissue yield was 98.6%. There were four patients with intraoperative complications requiring laparotomy (2.5%) with two additional postoperative complications. Half of all these complications were kidney related. There were no episodes of pancreatic enzyme leak and there were no graft losses related to the procedure. We conclude that laparoscopic kidney and pancreas allograft biopsies can be safely performed with very high tissue yields.

Hemodialysis Clinic Social Networks, Sex Differences, and Renal Transplantation.

This study describes patient social networks within a new hemodialysis clinic and models the association between social network participation and kidney transplantation. Survey and observational data collected between August 2012 and February 2015 were used to observe the formation of a social network of 46 hemodialysis patients in a newly opened clinic. Thirty-two (70%) patients formed a social network, discussing health (59%) and transplantation (44%) with other patients. While transplant-eligible women participated in the network less often than men (56% vs. 90%, p = 0.02), women who participated discussed their health more often than men (90% vs. 45.5%, p = 0.02). Patients in the social network completed a median of two steps toward transplantation compared with a median of 0 for socially isolated patients (p = 0.003). Patients also completed more steps if network members were closely connected (ß = 2.23, 95% confidence interval [CI] 0.16-4.29, p = 0.03) and if network members themselves completed more steps (ß = 2.84, 95% CI 0.11-5.57, p = 0.04). The hemodialysis clinic patient social network had a net positive effect on completion of transplant steps, and patients who interacted with each other completed a similar number of steps.

Proteasome Inhibitor Carfilzomib-Based Therapy for Antibody-Mediated Rejection of the Pulmonary Allograft: Use and Short-Term Findings.

We present this observational study of lung transplant recipients (LTR) treated with carfilzomib (CFZ)-based therapy for antibody-mediated rejection (AMR) of the lung. Patients were considered responders to CFZ if complement-1q (C1q)-fixing ability of their immunodominant (ID) donor-specific anti-human leukocyte antibody (DSA) was suppressed after treatment. Treatment consisted of CFZ plus plasma exchange and immunoglobulins. Fourteen LTRs underwent CFZ for 20 ID DSA AMR. Ten (71.4%) of LTRs responded to CFZ. DSA IgG mean fluorescence intensity (MFI) fell from 7664 (IQR 3230-11 874) to 1878 (653-7791) after therapy (p = 0.001) and to 1400 (850-8287) 2 weeks later (p = 0.001). DSA C1q MFI fell from 3596 (IQR 714-14 405) to <30 after therapy (p = 0.01) and <30 2 weeks later (p = 0.02). Forced expiratory volume in 1s ( FEV1 ) fell from mean 2.11 L pre-AMR to 1.92 L at AMR (p = 0.04). FEV1 was unchanged after CFZ (1.91 L) and subsequently rose to a maximum of 2.13 L (p = 0.01). Mean forced expiratory flow during mid forced vital capacity (25-75) (FEF25-75 ) fell from mean 2.5 L pre-AMR to 1.95 L at AMR (p = 0.01). FEF25-75 rose after CFZ to 2.54 L and reached a maximum of 2.91 L (p = 0.01). Responders had less chronic lung allograft dysfunction or progression versus nonresponders (25% vs. 83%, p = 0.04). No deaths occurred within 120 days and 7 patients died post CFZ therapy of allograft failure. Larger prospective interventional studies are needed to further describe the benefit of CFZ-based therapy for pulmonary AMR.

Long-Term Medical and Psychosocial Outcomes in Living Liver Donors.

Due to the enduring organ shortage, living donor liver transplantation has been a valuable treatment strategy for advanced liver disease patients for over 20 years. A variety of reviews have summarized the extensive data now available on medical and psychosocial risks to living donors in the aftermath of donation. However, evidence on donor medical and psychosocial outcomes beyond the first year postdonation has not been synthesized in any previous review. The evidence base on such "long-term" outcomes has been growing in recent years. A review of this evidence would therefore be timely and could serve as an important resource to assist transplant centers in their efforts to fully educate prospective donors and gain informed consent, as well as develop appropriate postdonation clinical care and surveillance plans. We reviewed recent literature on long-term donor outcomes, considering (a) medical outcomes, including mortality risk, rates of complications, abnormalities detected in laboratory testing, and the progress of liver regeneration; and (b) donor-reported psychosocial outcomes reflecting physical, emotional, and interpersonal/socioeconomic well-being, as well as overall health-related quality of life. We summarize limitations and gaps in available evidence, and we provide recommendations for future research and clinical care activities focused on long-term outcomes in liver donors.

Long-Term Follow-up of a Randomized Controlled Trial Evaluating a Mobile Health Intervention for Self-Management in Lung Transplant Recipients.

Mobile health interventions may help transplant recipients follow their complex medical regimens. Pocket Personal Assistant for Tracking Health (Pocket PATH) is one such intervention tailored for lung transplant recipients. A randomized controlled trial showed Pocket PATH's superiority to usual care for promoting the self-management behaviors of adherence, self-monitoring and communication with clinicians during posttransplant year 1. Its long-term impact was unknown. In this study, we examined associations between Pocket PATH exposure during year 1 and longer term clinical outcomes-mortality and bronchiolitis obliterans syndrome (BOS)-among 182 recipients who survived the original trial. Cox regression assessed whether (a) original group assignment and (b) performance of self-management behaviors during year 1 predicted time to outcomes. Median follow-up was 5.7 years after transplant (range 4.2-7.2 years). Pocket PATH exposure had no direct effect on outcomes (p-values >0.05). Self-monitoring was associated with reduced mortality risk (hazard ratio [HR] 0.45; 95% confidence interval [CI] 0.22-0.91; p = 0.027), and reporting abnormal health indicators to clinicians was associated with reduced risks of mortality (HR 0.15; 95% CI 0.04-0.65; p = 0.011) and BOS (HR 0.27; 95% CI 0.08-0.86; p = 0.026), regardless of intervention group assignment. Although Pocket PATH did not have a direct impact on long-term outcomes, early improvements in self-management facilitated by Pocket PATH may be associated with long-term clinical benefit.