Heart Transplant Immunosuppression Strategies at Cedars-Sinai Medical Center.
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ABSTRACT:
SUBMITTER: Chang DH
PROVIDER: S-EPMC9536714 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Heart Transplant Immunosuppression Strategies at Cedars-Sinai Medical Center.
Chang David H DH Youn Jong-Chan JC Dilibero Deanna D Patel Jignesh K JK Kobashigawa Jon A JA
International journal of heart failure 20200929 1
Heart transplant is the optimal treatment for selected patients with end-stage heart failure. Immunosuppression after heart transplantation has significantly reduced the incidence of rejection and improved patient outcomes with the routine use of calcineurin inhibitors. Antimetabolites and proliferation signal inhibitors add to the improvement in patient outcomes as well. The goal of induction therapy is to provide intense immunosuppression when the risk of allograft rejection is highest. Most m ...[more]
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Project description:BackgroundCOVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear.MethodsWe included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression, adjusting for age and time since transplant.ResultsThe median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea, oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor, antimetabolite, and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy.ConclusionsWe present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients.
| S-EPMC8131557 | biostudies-literature
Project description:We use a Master Regular-based precision cancer medicine framework to predict drug sensitivity to tumors.
2022-09-06 | GSE212377 | GEO
Project description:ImportanceIn the United States, the number of deceased donor hearts available for transplant is limited. As a proxy for medical urgency, the US heart allocation system ranks heart transplant candidates largely according to the supportive therapy prescribed by transplant centers.ObjectiveTo determine if there is a significant association between transplant center and survival benefit in the US heart allocation system.Design, setting, and participantsObservational study of 29 199 adult candidates for heart transplant listed on the national transplant registry from January 2006 through December 2015 with follow-up complete through August 2018.ExposuresTransplant center.Main outcomes and measuresThe survival benefit associated with heart transplant as defined by the difference between survival after heart transplant and waiting list survival without transplant at 5 years. Each transplant center's mean survival benefit was estimated using a mixed-effects proportional hazards model with transplant as a time-dependent covariate, adjusted for year of transplant, donor quality, ischemic time, and candidate status.ResultsOf 29 199 candidates (mean age, 52 years; 26% women) on the transplant waiting list at 113 centers, 19 815 (68%) underwent heart transplant. Among heart transplant recipients, 5389 (27%) died or underwent another transplant operation during the study period. Of the 9384 candidates who did not undergo heart transplant, 5669 (60%) died (2644 while on the waiting list and 3025 after being delisted). Estimated 5-year survival was 77% (interquartile range [IQR], 74% to 80%) among transplant recipients and 33% (IQR, 17% to 51%) among those who did not undergo heart transplant, which is a survival benefit of 44% (IQR, 27% to 59%). Survival benefit ranged from 30% to 55% across centers and 31 centers (27%) had significantly higher survival benefit than the mean and 30 centers (27%) had significantly lower survival benefit than the mean. Compared with low survival benefit centers, high survival benefit centers performed heart transplant for patients with lower estimated expected waiting list survival without transplant (29% at high survival benefit centers vs 39% at low survival benefit centers; survival difference, -10% [95% CI, -12% to -8.1%]), although the adjusted 5-year survival after transplant was not significantly different between high and low survival benefit centers (77.6% vs 77.1%, respectively; survival difference, 0.5% [95% CI, -1.3% to 2.3%]). Overall, for every 10% decrease in estimated transplant candidate waiting list survival at a given center, there was an increase of 6.2% (95% CI, 5.2% to 7.3%) in the 5-year survival benefit associated with heart transplant.Conclusions and relevanceIn this registry-based study of US heart transplant candidates, transplant center was associated with the survival benefit of transplant. Although the adjusted 5-year survival after transplant was not significantly different between high and low survival benefit centers, compared with centers with survival benefit significantly below the mean, centers with survival benefit significantly above the mean performed heart transplant for recipients who had significantly lower estimated expected 5-year waiting list survival without transplant.
| S-EPMC6865773 | biostudies-literature
Project description:BackgroundVariation in the use of immunosuppression regimens after liver transplant has not been well described.MethodsImmunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice.ResultsIn the first 6 months after transplant, triple immunosuppression (tacrolimus, antimetabolite, corticosteroids) was the most common regimen (42.9%). By months 7 to 12, immunosuppression regimens were more commonly antimetabolite sparing (33.7%) or steroid sparing (26.9%), followed by triple (14.4%), mammalian target of rapamycin inhibitor (mTORi)-based (12.1%), or cyclosporine-based (9.2%). Based on intraclass correlation analysis, clinical characteristics explained less than 10% of the variation in immunosuppression choice, whereas program preference/practice explained 23% of steroid sparing, 26% of antimetabolite sparing, 28% of mTORi, and 21% of cyclosporine-based regimen use. Although case factors were not dominant practice drivers, triple immunosuppression in months 7 to 12 was more common among retransplant recipients and those with prior acute rejection. Hepatocellular carcinoma as cause of liver failure (adjusted odds ratio [aOR], 2.15; P<0.001), cancer within 6 months (aOR, 6.07; P<0.001), and 6-month estimated glomerular filtration rate less than 30 mL/min per 1.3 m2 (aOR, 1.98; P<0.001) were associated with mTORi use compared with triple immunosuppression in months 7 to 12, whereas acute rejection predicted lower use (aOR, 0.72; P=0.003).ConclusionsLiver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.
| S-EPMC6056277 | biostudies-literature
Project description:ImportanceWide state-level variability in waiting list outcomes have been noted for patients listed for heart transplant in the US, but little is known regarding center-level transplant rates since the heart allocation policy change.ObjectiveTo evaluate center-level transplant rates following the recent allocation policy change for heart transplant.Design, setting, and participantsThis cohort study used data from the United Network for Organ Sharing database from October 18, 2015, to March 1, 2020, for a nationwide analysis of transplant centers in the US. Transplant candidates were stratified into 2 time cohorts, with era 1 denoting the 3-year period before the policy change (October 18, 2018), and era 2 representing the 500-day period after the policy change but before the beginning of the COVID-19 pandemic. Data were analyzed from May to June 2021.ExposureThe heart allocation policy change enacted on October 18, 2018.Main outcomes and measuresCompeting risk regression for waiting list outcomes was performed to calculate adjusted era 1 and era 2 center-level transplant rates. Rates were compared across regions and states, as well as within organ procurement organizations. Pearson correlation coefficient was used to assess center-level factors associated with era 2 transplant rates.ResultsOf 15 940 transplant candidates included for analysis, 5063 (median [IQR] age, 56 [45-63] years; 1385 women [27.4%]) comprised the era 2 cohort. The proportion of patients with temporary mechanical circulatory support increased between era 1 and era 2 (extracorporeal membrane oxygenation, 2.00% vs 3.42%; percutaneous ventricular assist device, 0.66% vs 1.86%; intra-aortic balloon pump, 5.21% vs 13.10%). The adjusted mean center-level likelihood of transplant increased after the rule change (from 48.1% in era 1 to 78.0% in era 2). Significant variation in transplant rates was observed across regions and states even among centers with shared organ procurement organizations. The largest absolute difference in transplant rates was 27.1% for 2 centers belonging to the same organ procurement organization. Centers with higher transplant volumes in era 2 and with a greater proportion of candidates with intra-aortic balloon pump were observed to have higher transplant rates.Conclusions and relevanceDespite sharing organ supply and having a small geographical distance, these findings suggest that intercenter disparities in the likelihood of transplant have persisted following the heart allocation policy change. Further work is necessary to ensure equitable allocation of organs in heart transplant.
| S-EPMC8771429 | biostudies-literature
Project description:ImportanceUnder the current Centers for Medicare & Medicaid Services guidelines, there is incentivization to optimize posttransplant outcomes regardless of mortality among patients on the waitlist and transplant rates; few data exist with regard to transplant center acceptance practices and survival to heart transplant.ObjectivesTo evaluate the extent of variability in organ acceptance practices in the US and whether this center-level behavior is associated with heart transplant candidate survival.Design, setting, and participantsIn this retrospective cohort study, the US National Transplant Registry was queried for all match runs of adult candidates listed for isolated heart transplant between May 1, 2007, and March 31, 2017. Data analysis was conducted from October 30, 2018, to May 1, 2019. The final cohort included 93 transplant centers, 19 703 donors, and 9628 candidates.Main outcomes and measuresCenter acceptance rates for heart allografts offered to the highest-priority candidates, association between center acceptance rate and mortality among patients on the waitlist, and posttransplant outcomes between candidates who accepted their first-rank offers vs those who accepted previously declined offers.ResultsAmong 19 703 unique organ offers, 6302 hearts (32.0%) were accepted for first-rank candidates. After adjustment for donor, candidate, and geographic covariates, transplant centers varied in acceptance rates (12.3%-61.5%) of offers made to first-rank candidates. Higher acceptance rates were associated with lower cumulative incidence of 1-year mortality among patients on the waitlist. For every 10% increase in adjusted center acceptance rate, the risk of mortality decreased by 27% (subdistribution hazard ratio, 0.73; 95% CI, 0.67-0.80). No statistically significant difference was observed in 5-year adjusted posttransplant patient survival (adjusted hazard ratio, 1.02; 95% CI, 0.94-1.11) and graft failure (subdistribution hazard ratio; 0.95; 95% CI, 0.83-1.09) between hearts accepted at the first-rank compared with lower-rank positions.Conclusions and relevanceVariability in heart allograft acceptance rates appears to exist among transplant centers, with candidates listed at lower acceptance rate centers being more likely to experience mortality while on the waitlist. Comparable posttransplant survival suggests that allografts that were declined as a first offer perform as well as those that were accepted at their first offer. These findings suggest that organ acceptance rate or time to transplant from being added to the waitlist may be an additional measure of heart transplant program performance.
| S-EPMC7160742 | biostudies-literature
Project description:BackgroundHeart transplant (HT) recipients may be at higher risk of acquiring SARS-CoV-2 infection and developing critical illness. The aim of this study is to describe characteristics and outcomes of HT recipients infected by SARS-COV-2, from a high-volume transplant center.MethodsWe have described data of all adult HT recipients with confirmed coronavirus disease 2019 by RT-PCR in nasopharyngeal samples from April 5, 2020, to January 5, 2021. Outcomes and follow-up were recorded until February 5, 2021.ResultsForty patients were included. Twenty-four patients (60%) were men; the median age was 53 (40-60) y old; median HT time was 34 mo; and median follow-up time 162 d. The majority needed hospitalization (83%). Immunosuppressive therapy was reduced/withdrawn in the majority of patients, except from steroids, which were maintained. Seventeen patients (42.5%) were classified as having severe disease according to the ordinal scale developed by the World Health Organization Committee. They tended to have lower absolute lymphocyte count (P < 0.001) during follow-up when compared with patients with mild disease. Thirty-day mortality was 12.5%. However, a longer follow-up revealed increased later mortality (27.5%), with median time to death around 35 d. Bacterial nosocomial infections were a leading cause of death. Cardiac allograft rejection (10%) and ventricular dysfunction (12.5%) were also not negligible.ConclusionsMajor findings of this study corroborate other cohorts' results, but it also reports significant rate of later events, suggesting that a strict midterm surveillance is advisable to HT recipients with coronavirus disease 2019.
| S-EPMC8862677 | biostudies-literature
Project description:Lung transplantation (LTx) has evolved significantly since its inception and the improvement in LTx outcomes over the last three decades has predominantly been driven by advances in immunosuppression management. Despite the lack of new classes of immunosuppression medications, immunosuppressive strategies have evolved significantly from a universal method to a more targeted approach, reflecting a greater understanding of the need for individualized therapy and careful consideration of all factors that are influenced by immunosuppression choice. This has become increasingly important as the demographics of lung transplant recipients have changed over time, with older and more medically complex candidates being accepted and undergoing LTx. Furthermore, improved survival post lung transplant has translated into more immunosuppression related comorbidities long-term, predominantly chronic kidney disease (CKD) and malignancy, which has required further nuanced management approaches. This review provides an update on current traditional lung transplant immunosuppression strategies, with modifications based on pre-existing recipient factors and comorbidities, peri-operative challenges and long term complications, balanced against the perpetual challenge of chronic lung allograft dysfunction (CLAD). As we continue to explore and understand the complexity of LTx immunology and the interplay of different factors, immunosuppression strategies will require ongoing critical evaluation and personalization in order to continue to improve lung transplant outcomes.
| S-EPMC8662512 | biostudies-literature
Project description:Reduction of preventable hospital readmissions that result from chronic or acute conditions like stroke, heart failure, myocardial infarction and pneumonia remains a significant challenge for improving the outcomes and decreasing the cost of healthcare delivery in the United States. Patient readmission rates are relatively high for conditions like heart failure (HF) despite the implementation of high-quality healthcare delivery operation guidelines created by regulatory authorities. Multiple predictive models are currently available to evaluate potential 30-day readmission rates of patients. Most of these models are hypothesis driven and repetitively assess the predictive abilities of the same set of biomarkers as predictive features. In this manuscript, we discuss our attempt to develop a data-driven, electronic-medical record-wide (EMR-wide) feature selection approach and subsequent machine learning to predict readmission probabilities. We have assessed a large repertoire of variables from electronic medical records of heart failure patients in a single center. The cohort included 1,068 patients with 178 patients were readmitted within a 30-day interval (16.66% readmission rate). A total of 4,205 variables were extracted from EMR including diagnosis codes (n=1,763), medications (n=1,028), laboratory measurements (n=846), surgical procedures (n=564) and vital signs (n=4). We designed a multistep modeling strategy using the Naïve Bayes algorithm. In the first step, we created individual models to classify the cases (readmitted) and controls (non-readmitted). In the second step, features contributing to predictive risk from independent models were combined into a composite model using a correlation-based feature selection (CFS) method. All models were trained and tested using a 5-fold cross-validation method, with 70% of the cohort used for training and the remaining 30% for testing. Compared to existing predictive models for HF readmission rates (AUCs in the range of 0.6-0.7), results from our EMR-wide predictive model (AUC=0.78; Accuracy=83.19%) and phenome-wide feature selection strategies are encouraging and reveal the utility of such datadriven machine learning. Fine tuning of the model, replication using multi-center cohorts and prospective clinical trial to evaluate the clinical utility would help the adoption of the model as a clinical decision system for evaluating readmission status.
| S-EPMC5362124 | biostudies-other
Project description:BackgroundKidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies.MethodsWe performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate.ResultsOf the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients.ConclusionsData from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.
| S-EPMC7454827 | biostudies-literature