Heart Transplantation for Pediatric and Congenital Cardiac Disease: A Comparison of Two Eras over 23 Years and 188 Transplants at a Single Institution

2021 ◽  
Vol 12 (1) ◽  
pp. 17-26
Author(s):  
Genevieve C. Tuite ◽  
James A. Quintessenza ◽  
Alfred Asante-Korang ◽  
Sharon R. Ghazarian ◽  
Bethany L. Wisotzkey ◽  
...  

Background: To assess changes in patterns of practice and outcomes over time, we reviewed all patients who underwent heart transplantation (HTx) at our institution and compared two consecutive eras with significantly different immunosuppressive protocols (cohort 1 [80 HTx, June 1995-June 2006]; cohort 2 [108 HTx, July 2006-September 2018]). Methods: Retrospective study of 180 patients undergoing 188 HTx (June 1995-September 2018; 176 first time HTx, 10 second HTx, and 2 third HTx). In 2006, we commenced pre-HTx desensitization for highly sensitized patients and started using tacrolimus as our primary postoperative immunosuppressive agent. The primary outcome was mortality. Survival was modeled by the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard models were created to identify prognostic factors for survival. Results: Our 188 HTx included 18 neonates, 85 infants, 83 children, and 2 adults (>18 years). Median age was 260.0 days (range: 5 days-23.8 years). Median weight was 7.5 kg (range: 2.2-113 kg). Patients in cohort 1 were less likely to have been immunosensitized preoperatively (12.5% vs 28.7%, P = .017). Nevertheless, Kaplan-Meier analysis suggested superior survival in cohort 2 ( P = .0045). Patients in cohort 2 were more likely to be alive one year, five years, and ten years after HTx. Multivariable analysis identified the earlier era (hazard ratio [HR] [95% confidence interval] for recent era = 0.32 [0.14-0.73]), transplantation after prior Norwood operation (HR = 4.44 [1.46-13.46]), and number of prior cardiac operations (HR = 1.33 [1.03-1.71]) as risk factors for mortality. Conclusions: Our analysis of 23 years of pediatric and congenital HTx reveals superior survival in the most recent 12-year era, despite the higher proportion of patients with elevated panel reactive antibody in the most recent era. This improvement was temporally associated with changes in our immunosuppressive strategy.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shahnawaz Amdani ◽  
Othman Aljohani ◽  
James K Kirklin ◽  
Ryan Cantor ◽  
Devin Koehl ◽  
...  

Introduction: Traditional weight & height ratios as measures of donor-recipient (D-R) matching have been challenged in adult heart transplantation (HT). The optimal metrics for D-R matching in pediatric HT remain unclear, and were evaluated in the present study. Methods: All primary pediatric HT recipients in the Pediatric Heart Transplant Society database transplanted from 1993-2019 were included. Multiple metrics of size matching - height, weight, body mass index (BMI), body surface area (BSA), predicted heart mass (PHM) and total cardiac volume (TCV) were assessed to identify the metrics that would best predict 1-year post-transplant (PTx) graft loss (death/re-transplant). Kaplan-Meier analyses (risk unadjusted) and multivariate Cox proportional hazard models (risk adjusted) were used to assess the effect of differences of various size matching metrics on survival. Results: Among 6903 D-R pairs, multivariable hazard modeling identified the following risk factors for PTx mortality: female sex, black race, bilirubin, ECMO, VAD, mechanical ventilation, ICU admission at the time of transplant, presence of congenital heart disease, early era of transplant, donor ischemic time and cardiopulmonary bypass time. After adjusting for all covariates, increasing size mismatch by height, BSA, or PHM was associated with increased 1-year PTx graft loss, with a disproportionately higher hazard for undersized donors than oversized donors (Figure). Weight, BMI and TCV were not predictive of 1-year PTx graft loss on multivariate analysis. Conclusions: In pediatric HT recipients, increasing size mismatch by height, BSA and PHM is associated with increased 1-year PTx graft loss. Undersizing donors appears to carry a higher risk than oversizing.


2011 ◽  
Vol 70 (4) ◽  
pp. 583-589 ◽  
Author(s):  
Moetaza M Soliman ◽  
Darren M Ashcroft ◽  
Kath D Watson ◽  
Mark Lunt ◽  
Deborah P M Symmons ◽  
...  

ObjectiveTo evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in patients with rheumatoid arthritis (RA).MethodThis analysis included 10 396 patients with RA registered with the British Society for Rheumatology Biologics Register, a prospective observational cohort study, who were starting their first anti-TNF therapy and were receiving one of the following DMARD treatments at baseline: no DMARD (n=3339), methotrexate (MTX) (n=4418), leflunomide (LEF) (n=610), sulfasalazine (SSZ) (n=308), MTX+SSZ (n=902), MTX+ hydroxychloroquine (HCQ) (n=401) or MTX+SSZ+HCQ (n=418). Kaplan–Meier survival analysis was used to study the persistence with anti-TNF therapy in each DMARD subgroup up to 5 years. Multivariate Cox proportional hazard models, stratified by anti-TNF used and start year and adjusted for a number of potential confounders, were used to compare treatment persistence overall and according to the reason for discontinuation between each of the DMARD subgroups, using MTX as reference.ResultsOne-year drug survival (95% CI) for the first anti-TNF therapy was 71% (71% to 72%) but this dropped to 42% (41% to 43%) at 5 years. Compared with MTX, patients receiving no DMARD, LEF or SSZ were more likely to discontinue their first anti-TNF therapy while patients receiving MTX in combination with other DMARDs showed better treatment persistence.ConclusionsThese results support the continued use of background DMARD combinations which include MTX. Consideration should be given to the discontinuation of LEF and SSZ monotherapy at the time anti-TNF therapies are started, with the possible exception of the SSZ+ETN combination.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Tao Ran ◽  
ZhiJi Chen ◽  
LiWen Zhao ◽  
Wei Ran ◽  
JinYu Fan ◽  
...  

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.


2020 ◽  
Author(s):  
Antonio Dono ◽  
Victor Lopez-Rivera ◽  
Ankush Chandra ◽  
Cole T Lewis ◽  
Rania Abdelkhaleq ◽  
...  

Abstract Background Pleomorphic xanthoastrocytomas (PXA) are circumscribed gliomas that typically have a favorable prognosis. Limited studies have revealed factors affecting survival outcomes in PXA. Here, we analyzed the largest PXA dataset in the literature and identify factors associated with outcomes. Methods Using the Surveillance, Epidemiology, and End Results (SEER) 18 Registries database, we identified histologically confirmed PXA patients between 1994 and 2016. Overall survival (OS) was analyzed using Kaplan-Meier survival and multivariable Cox proportional hazard models. Results In total, 470 patients were diagnosed with PXA (males = 53%; median age = 23 years [14-39 years]), the majority were Caucasian (n = 367; 78%). The estimated mean OS was 193 months [95% CI: 179-206]. Multivariate analysis revealed that greater age at diagnosis (≥39 years) (3.78 [2.16-6.59], P < .0001), larger tumor size (≥30 mm) (1.97 [1.05-3.71], P = .034), and postoperative radiotherapy (RT) (2.20 [1.31-3.69], P = .003) were independent predictors of poor OS. Pediatric PXA patients had improved survival outcomes compared to their adult counterparts, in which chemotherapy (CT) was associated with worse OS. Meanwhile, in adults, females and patients with temporal lobe tumors had an improved survival; conversely, tumor size ≥30 mm and postoperative RT were associated with poor OS. Conclusions In PXA, older age and larger tumor size at diagnosis are risk factors for poor OS, while pediatric patients have remarkably improved survival. Postoperative RT and CT appear to be ineffective treatment strategies while achieving GTR confer an improved survival in male patients and remains the cornerstone of treatment. These findings can help optimize PXA treatment while minimizing side effects. However, further studies of PXAs with molecular characterization are needed.


2020 ◽  
Author(s):  
Daniel C McFarland ◽  
Rebecca M. Saracino ◽  
Andrew H. Miller ◽  
William Breitbart ◽  
Barry Rosenfeld ◽  
...  

Background: Lung cancer-related inflammation is associated with depression. Both elevated inflammation and depression are associated with worse survival. However, outcomes of patients with concomitant depression and elevated inflammation are not known. Materials & methods: Patients with metastatic lung cancer (n = 123) were evaluated for depression and inflammation. Kaplan–Meier plots and Cox proportional hazard models provided survival estimations. Results: Estimated survival was 515 days for the cohort and 323 days for patients with depression (hazard ratio: 1.12; 95% CI: 1.05–1.179), 356 days for patients with elevated inflammation (hazard ratio: 2.85, 95% CI: 1.856–4.388), and 307 days with both (χ2 = 12.546; p < 0.001]). Conclusion: Depression and inflammation are independently associated with inferior survival. Survival worsened by inflammation is mediated by depression-a treatable risk factor.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mesnad Alyabsi ◽  
Fouad Sabatin ◽  
Majed Ramadan ◽  
Abdul Rahman Jazieh

Abstract Background Colorectal cancer (CRC) is the most diagnosed cancer among males and third among females in Saudi Arabia, with up to two-third diagnosed at advanced stage. The objective of our study was to estimate CRC survival and determine prognostic factors. Methods Ministry of National Guard- Health Affairs (MNG-HA) registry data was utilized to identify patients diagnosed with CRC between 2009 and 2017. Cases were followed until December 30th, 2017 to assess their one-, three-, and five-year CRC-specific survivals. Kaplan-Meier method and Cox proportional hazard models were used to assess survival from CRC. Results A total of 1012 CRC patients were diagnosed during 2009–2017. Nearly, one-fourth of the patients presented with rectal tumor, 42.89% with left colon and 33.41% of the cases were diagnosed at distant metastasis stage. The overall one-, three-, and five-year survival were 83, 65 and 52.0%, respectively. The five-year survival was 79.85% for localized stage, 63.25% for regional stage and 20.31% for distant metastasis. Multivariate analyses showed that age, diagnosis period, stage, nationality, basis of diagnosis, morphology and location of tumor were associated with survival. Conclusions Findings reveal poor survival compared to Surveillance, Epidemiology, and End Results (SEER) population. Diagnoses at late stage and no surgical and/or perioperative chemotherapy were associated with increased risk of death. Population-based screening in this population should be considered.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Eric S Weiss ◽  
Nishant D Patel ◽  
Stuart D Russell ◽  
William A Baumgartner ◽  
Ashish S Shah ◽  
...  

Introduction : Single institution series have suggested that donor-recipient gender matching may be an important factor influencing survival following orthotopic heart transplantation (OHT). The United Network for Organ Sharing (UNOS) database provides a unique and novel opportunity to address this issue by examining outcomes based on gender pairing for a large cohort of OHT patients. Methods : We retrospectively reviewed the UNOS dataset to identify 18,240 patients receiving first time OHT between the years 1998 and 2007. Stratification was by both donor and recipient gender so that 4 separate groups were created (male donor with male recipient, female donor with male recipient, male donor with female recipient, and female donor with female recipient). The primary endpoint of all cause mortality was compared between groups using a Cox proportional hazard regression model. Secondary outcomes (thirty day and one year mortality and rejection during the first year) were examined with multiple logistic regression. Post transplant survival was modeled via the Kaplan Meier method. Results : Of 18,240 patients, 12,951 (71%) were matched by gender to their donor (77% for male recipients, n= 10,750 and 51% for female recipients n= 2,201). A total of 4,543 patients died during the study period (25%). Donor-recipient gender matching resulted in a reduction in the risk of adjusted cumulative mortality (Hz ratio 0.86 [0.78–0.95], p= 0.003) and the greatest risk for cumulative mortality occurred when pairing a male donor with a female recipient (Hz ratio 1.2 [1.04–1.37], p= 0.01). Thirty day and one year mortality were also significantly decreased by gender pairing (OR 0.75 [0.61–0.95], p= 0.02 for 30 day mortality, and OR 0.8 [0.68–0.93], p= 0.005 for one year mortality). Gender pairing resulted in a 13% decrease in the risk of graft rejection within the first year (OR 0.87 [0.79–0.98], p= 0.02]. Kaplan Meier survival modeling revealed that the greatest cumulative survival occurred when a male recipient received an organ from a male donor (Figure) Conclusions : The UNOS dataset has provided a large sample examining donor recipient gender pairing in OHT. Recipients who receive organs for same sex donors have significantly improved short and long term survival.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jacob P Kelly ◽  
Brad G Hammill ◽  
Jacob A Doll ◽  
G. Michael Felker ◽  
Paul A Heidenreich ◽  
...  

Background: In February 2014, coverage for cardiac rehabilitation (CR) was expanded by Centers for Medicare & Medicaid to include patients with chronic symptomatic heart failure (HF) on optimal medical therapy with ejection fraction <35%. Thus, we sought to characterize the patient population newly eligible for CR based on the expanded criteria and their associated outcomes. Methods: We analyzed the Get With The Guidelines-HF registry linked to Medicare claims data from 2008-2012 to assess three groups of patients age 65 or older: previously eligible (due to prior MI, CABG, stable angina, heart valve surgery, or PCI in the previous 12 months), newly eligible, and ineligible for CR. Ineligible patients met neither criteria. Incidence rate was calculated with Kaplan-Meier estimates and Cox proportional hazard models were used to determine the association of events. Results: Among 51,665 HF patients discharged alive, 27.2% (n=14,053) were newly eligible and 14.5% were previously eligible for CR (n=7477). Newly eligible patients were more likely to be black, have atrial fibrillation and EF < 35%, while having fewer previous hospitalizations than patients previously eligible for CR. Newly eligible and ineligible patients had similar risk for 1-year mortality compared with those previously eligible (adjusted Hazard Ratio [HR] 0.95, 95% Confidence Interval [CI] 0.88-1.02, p-value=0.13 and [HR] 1.05, 95% [CI] 0.98-1.13, p-value=0.17, respectively). However, newly eligible and ineligible patients had lower risk for 1-year readmission compared with those previously eligible (adjusted [HR] 0.89, 95% [CI] 0.85-0.93, p-value<0.001 and [HR] 0.94, 95% [CI] 0.90- 0.98, p-value<0.001). Conclusions: The extension of coverage for cardiac rehabilitation has tripled the potentially eligible HF population. As these newly eligible patients are at high risk for adverse outcomes, cardiac rehabilitation should be considered.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11559-11559
Author(s):  
Lawson Eng ◽  
Jie Su ◽  
Steven Habbous ◽  
Katrina Hueniken ◽  
M. Catherine Brown ◽  
...  

11559 Background: Continued smoking after a cancer diagnosis is associated with poorer outcomes. Tobacco retail availability is negatively associated with cessation in non-cancer patients (pts), but has not been explored in cancer survivors. We evaluated the impact of tobacco retail availability on cessation in lung and HN cancer pts. Methods: Lung and HN cancer pts (Princess Margaret Cancer Centre, Toronto) completed questionnaires evaluating changes in tobacco use with a median of 26 months apart. Validated tobacco retail location data were obtained from Ministry of Health and pt home addresses were geocoded using ArcGIS 10.6.1, which calculated walking time/distance to nearest vendor, and vendor density within 250 meters (m) and 500m from pts. Multivariable logistic regression and Cox proportional hazard models evaluated the impact of vendor availability on cessation and time to quitting after diagnosis respectively, adjusting for significant clinico-demographic and tobacco covariates. Results: 242/721 lung and 149/445 HN pts smoked at diagnosis; subsequent overall quit rates were 66% and 49% respectively. Mean distance and walking time to a vendor was 1 km (range 0-13) and 11 min (range 0-156). On average, there was one vendor (range 0-19) within 250m and four vendors (range 0-40) within 500m from pts; 37% and 61% of pts lived within 250m and 500m from at least one vendor respectively. Greater distance (aOR 1.18 per 1000m [95% CI 1.00-1.38] p = 0.05) and increased walking time (aOR 1.01 per minute [1.00-1.02] p = 0.05) were associated with quitting at one year. Living within 250m (aOR 0.52 [0.32-0.84] p = 0.008) or 500m (aOR 0.57 [0.35-0.92] p = 0.02) to at least one vendor reduced quitting at one year. Living near more vendors within 500m had an increasing dose effect on reducing cessation rates at one year (aOR 0.96 per vendor [0.93-1.00] p = 0.05). Living within 500m to a vendor reduced chance of quitting at any time (aHR 0.66 [0.48-0.91] p = 0.01). HN and lung subgroups revealed similar associations. Conclusions: Close access to tobacco retail outlets is associated with reduced cessation rates for lung and HN cancer survivors. Reducing density of tobacco vendors is a cessation strategy that can positively impact cancer pt outcomes.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 467-467 ◽  
Author(s):  
Vaibhav G. Patel ◽  
William K. Oh ◽  
Matt D. Galsky ◽  
Bobby Chi-Hung Liaw ◽  
Che-Kai Tsao

467 Background: Stress-induced adrenergic signaling suppresses the immune system. A pre-clinical mouse model has shown that pharmacologic beta-blockade can stimulate CD8+ T-cell activity, and as a result improve efficacy of checkpoint inhibitors (CPI) to inhibit growth in solid tumors. Herein, we investigate the effect of BB on outcomes of patients receiving immunotherapy in mUC and mRCC. Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer patients seen between 2010-2018, we identified patients with either UC or RCC that have received CTLA-4 and/or PD-1/PD-L1 blockade. Patients who received only 1 dose of CPI were excluded from this analysis. A descriptive analysis was performed to assess clinical characteristics and treatment response. Overall Survival (OS) was calculated with Kaplan-Meier curves and cox proportional hazard models. Results: We identified 34 evaluable patients with mUC and 14 with mRCC that received CPI (Table). The median age at initiation was 69 years (39–91 years) and 81.2% (39/48) received prior chemotherapy and/or molecular targeted therapies. The mean duration of therapy was longer in the BB group compared to non-BB group (10.6 vs. 4.0 mo). For patients with mUC, the overall response rate (ORR) was 62.5% vs. 12.5% in favor of the BB group. For the patients with mRCC, the ORR was 40.0% vs. 10.0% in favor of the BB group. There were more outstanding responders (>1 year) in the BB group when compared with the non-BB group (41.2% vs. 6.5%). Patients with BB use had significantly improved median OS (NR vs. 11.6 mo, p = 0.004) when compared to those who did not receive BB. Conclusions: In this single-center cohort, the concurrent use of BB receiving CPI therapy is associated with an improved ORR, duration of therapy, and OS. Although this is hypothesis generating, the addition of BB is a promising strategy to improve response of immunotherapy, and prospective validation of this approach will be needed. [Table: see text]


Sign in / Sign up

Export Citation Format

Share Document