Citations

Abstract Aims The aim of this study is to evaluate the contemporary use of a pulmonary artery catheter (PAC) in acute myocardial infarction-cardiogenic shock (AMI-CS). Methods and results A retrospective cohort of AMI-CS admissions using the National Inpatient Sample (2000–2014) was identified. Admissions with concomitant cardiac surgery or non-AMI aetiology for cardiogenic shock were excluded. The outcomes of interest were in-hospital mortality, resource utilization, and temporal trends in cohorts with and without PAC use. In the non-PAC cohort, the use and outcomes of right heart catheterization was evaluated. Multivariable regression and propensity matching was used to adjust for confounding. During 2000–2014, 364 001 admissions with AMI-CS were included. PAC was used in 8.1% with a 75% decrease during over the study period (13.9% to 5.4%). Greater proportion of admissions to urban teaching hospitals received PACs (9.5%) compared with urban non-teaching (7.1%) and rural hospitals (5.4%); P < 0.001. Younger age, male sex, white race, higher comorbidity, noncardiac organ failure, use of mechanical circulatory support, and noncardiac support were independent predictors of PAC use. The PAC cohort had higher in-hospital mortality (adjusted odds ratio 1.07 [95% confidence interval 1.04–1.10]), longer length of stay (10.9 ± 10.9 vs. 8.2 ± 9.3 days), higher hospitalization costs ($128 247 ± 138 181 vs. $96 509 ± 116 060), and lesser discharges to home (36.3% vs. 46.4%) (all P < 0.001). In 6200 propensity-matched pairs, in-hospital mortality was comparable between the two cohorts (odds ratio 1.01 [95% confidence interval 0.94–1.08]). Right heart catheterization was used in 12.5% of non-PAC admissions and was a marker of greater severity but did not indicate worse outcomes. Conclusions In AMI-CS, there was a 75% decrease in PAC use between 2000 and 2014. Admissions receiving a PAC were a higher risk cohort with worse clinical outcomes.

BackgroundPretreatment determination of renal cell carcinoma aggressiveness may help to guide clinical decision‐making.PurposeTo evaluate the efficacy of residual convolutional neural network using routine MRI in differentiating low‐grade (grade I–II) from high‐grade (grade III–IV) in stage I and II renal cell carcinoma.Study TypeRetrospective.PopulationIn all, 376 patients with 430 renal cell carcinoma lesions from 2008–2019 in a multicenter cohort were acquired. The 353 Fuhrman‐graded renal cell carcinomas were divided into a training, validation, and test set with a 7:2:1 split. The 77 WHO/ISUP graded renal cell carcinomas were used as a separate WHO/ISUP test set.Field Strength/Sequence1.5T and 3.0T/T2‐weighted and T1 contrast‐enhanced sequences.AssessmentThe accuracy, sensitivity, and specificity of the final model were assessed. The receiver operating characteristic (ROC) curve and precision‐recall curve were plotted to measure the performance of the binary classifier. A confusion matrix was drawn to show the true positive, true negative, false positive, and false negative of the model.Statistical TestsMann–Whitney U‐test for continuous data and the chi‐square test or Fisher's exact test for categorical data were used to compare the difference of clinicopathologic characteristics between the low‐ and high‐grade groups. The adjusted Wald method was used to calculate the 95% confidence interval (CI) of accuracy, sensitivity, and specificity.ResultsThe final deep‐learning model achieved a test accuracy of 0.88 (95% CI: 0.73–0.96), sensitivity of 0.89 (95% CI: 0.74–0.96), and specificity of 0.88 (95% CI: 0.73–0.96) in the Fuhrman test set and a test accuracy of 0.83 (95% CI: 0.73–0.90), sensitivity of 0.92 (95% CI: 0.84–0.97), and specificity of 0.78 (95% CI: 0.68–0.86) in the WHO/ISUP test set.Data ConclusionDeep learning can noninvasively predict the histological grade of stage I and II renal cell carcinoma using conventional MRI in a multiinstitutional dataset with high accuracy.Level of Evidence3Technical Efficacy Stage2

Abstract Background: Growing evidence supports the critical role of preexisting immune response in triple negative breast cancer (TNBC). However, there are limitations with current evaluation approaches: inability to functionally assess the type of immune infiltration with traditional pathologic evaluation and loss of spatial distribution in conventional high-plex gene or protein expression analyses from the whole tumor section. Here, we report the initial analysis of immune protein expression as a function of spatial distribution and clinical outcomes in TNBC samples. Methods: NanoString GeoMxTM Digital Spatial Profiling (DSP) was used to quantify 39 immune-related proteins in stromal and tumor segments from 44 TNBC samples from the FinXX trial. Samples were matched for patient characteristics, treatment arm (capecitabine vs. 5-fluorouracil), and outcome based on recurrence-free survival (RFS) with 22 samples from patients who recurred and 22 samples from patients with durable RFS. Regions of interest (ROIs) were selected based on expression of cytokeratin (tumor), CD45 (leukocytes), or CD68 (macrophages). Each ROI was segmented into tumor (pancytokeratin-positive area) and stroma (pancytokeratin-negative/nuclear SYTO13-positive area). The general linear model was used for statistical analysis of differential expression with RFS as a categorical variable (recur yes or no). Results: A total of 950 tumor and stroma segments were included in this initial analysis. In both tumor and stroma segments, over-expression of T cell activation markers (CD137, GITR) was associated with better outcome, whereas T cell markers (CD3, CD4, CD8) were not significantly associated with outcome. In tumor segments alone, improved outcome was significantly associated with increased protein expression [> 2-fold change (FC) at p<0.001] of CD56, PD-L2, HLA-DR, CD137, GITR, and CD40. In CD45-enriched stroma, improved outcome was associated with elevated expression (FC>2.0, p<0.001) of PD-L2; whereas durable RFS was associated with elevated PD-L2 and IDO1 expression in CD68-enriched stroma. In contrast, macrophage/dendritic cell markers CD68 and CD11c were not associated with outcome. In tumor cells adjacent to CD45-enriched stroma, durable RFS was associated with increased abundance (FC>2.0, p<0.001) of PD-L2, CD56, CD27, GITR, CD20, HLA-DR, and IDO1. Similarly, in tumor segment associated with CD68-enriched stroma, proteins associated with RFS included PD-L2, HLA-DR, CD56, GITR, and CD137. Among 39 immune function proteins, only elevated CTLA4 expression in CD68-enriched stroma was associated with recurrence (FC=0.55, p<0.001), whereas tumor-segment CTLA4 was associated with RFS. Conclusions: Using an in-depth analysis to precisely quantify the abundance of multiple immune function proteins in a spatially defined manner, we observed that PD-L2, IDO1, and T cell activation markers were robustly associated with durable RFS in both tumor and stromal segments. In contrast, MHC components (HLA-DR, beta-2-microglobulin), B cell markers (CD20), and NK cell markers (CD56) were strongly associated with favorable outcome in tumor but not in stromal segments. Our study highlights the conclusion that the immune landscape of TNBC is far too complex to be encompassed by any single molecular marker, and more detailed analyses of the DSP data reported here are ongoing with a view towards using quantitative multiplex analyses to refine our understanding of how therapeutic outcome is influenced by interactions among immune cells and between immune and tumor cells. Acknowledgements: Supported by the Breast Cancer Research Foundation (BCRF18-161), Bankhead Coley (6BC05 Florida Department of Health), 26.2 with Donna Foundation, US National Cancer Institute (CA15083), and the Canadian Cancer Center Citation Format: Saranya Chumsri, Douglas Hinerfeld, Jennifer M. Kachergus, Yaohua Ma, Heather A Brauer, Sarah Warren, Xue Wang, Torsten O. Nielsen, Karama Asleh, Heikki Joensuu, Edith A. Perez, E. A. Thompson. Digital spatial mapping of the immune landscape of triple negative breast cancer reveals novel features of immune-tumor cell interaction [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD5-06.

Background: There are limited data on complications in acute myocardial infarction (AMI) admissions receiving extracorporeal membrane oxygenation (ECMO). Methods: Adult (>18 years) admissions with AMI receiving ECMO support were identified from the National Inpatient Sample database between 2000 and 2016. Complications were classified as vascular, lower limb amputation, hematologic, and neurologic. Outcomes of interest included temporal trends, in-hospital mortality, hospitalization costs, and length of stay. Results: In this 17-year period, in ~10 million AMI admissions, ECMO support was used in 4608 admissions (<0.01%)—mean age 59.5 ± 11.0 years, 75.7% men, 58.9% white race. Median time to ECMO placement was 1 (interquartile range [IQR] 0–3) day. Complications were noted in 2571 (55.8%) admissions—vascular 6.1%, lower limb amputations 1.1%, hematologic 49.3%, and neurologic 9.9%. There was a steady increase in overall complications during the study period (21.1% in 2000 vs. 70.5% in 2016). The cohort with complications, compared to those without complications, had comparable adjusted in-hospital mortality (60.7% vs. 54.0%; adjusted odds ratio 0.89 [95% confidence interval 0.77–1.02]; p = 0.10) but longer median hospital stay (12 [IQR 5–24] vs. 7 [IQR 3–21] days), higher median hospitalization costs ($458,954 [IQR 260,522–737,871] vs. 302,255 [IQR 173,033–623,660]), fewer discharges to home (14.7% vs. 17.9%), and higher discharges to skilled nursing facilities (44.1% vs. 33.9%) (all p < 0.001). Conclusions: Over half of all AMI admissions receiving ECMO support develop one or more severe complications. Complications were associated with higher resource utilization during and after the index hospitalization.

11615 Background: Deficiencies and barriers exist to delivering comprehensive and affordable cancer care. Understanding the variation in organizational commitment, existing programs, and expected outcomes for screening and management of financial distress is needed. Methods: Representatives from 17 of 27 NCCN Member Institutions (63%) completed an online survey in November 2018 conducted by the NCCN Best Practices Committee. Centers were classified based on number of unique patients seen per year, as large ( > 10,000) (76%), or small ( < 10,000) (34%). The survey focused on institutions’ screening and management practices for patient financial distress, perceived barriers in implementation, and leadership attitudes. Results: Routine screening for financial distress was reported by 77% of centers, and most used social worker assessments (94%). 56% screened patients throughout the cancer journey. Help with drug costs, meal or gas vouchers and payment plans were offered by 100% of centers. Formal pre-authorization programs and assistance with claims and denials was offered by 81%. Charity care for medical costs was provided by 100% of the large centers compared to only 33% of small centers (p = 0.03). Median number of social workers (24 vs. 3; p = 0.01) and pharmacy representatives (6 vs. 2; p = 0.02) was also different between large and small centers. 76% evaluated the impact of financial advocacy services through number of patients assisted (85%), bad debt and charity write-offs (85%) or patient satisfaction surveys (54%). 6% and 12% reported overall effectiveness of institutional practice for screening and management of financial distress as poor/ very poor respectively. Inadequate staffing and real time resources (69%), limited institutional budget (50%), lack of reimbursement (50%), and clinical time constraints (50%) were reported as potential barriers in provision of these services. 94% agreed about stronger integration of financial advocacy services into oncology practice and 84% felt that success of these services should be a quality metric. 31% of large centers vs. 100% of small centers plan to increase staffing in this area in the next 5 years. Conclusions: Majority of NCCN Member Institutions report screening and management programs for financial distress, though the actual practices and range of services vary widely. Information from this study can help centers benchmark their performance relative to similar cancer programs and identify best practices in this area.

Background and objectives: Calcium concentration is strictly regulated at both the cellular and systemic level, and changes in serum calcium levels can alter various physiological functions in various organs. This study aimed to assess the association between changes in calcium levels during hospitalization and mortality. Materials and Methods: We searched our patient database to identify all adult patients admitted to our hospital from January 1st, 2009 to December 31st, 2013. Patients with ≥2 serum calcium measurements during the hospitalization were included. The serum calcium changes during the hospitalization, defined as the absolute difference between the maximum and the minimum calcium levels, were categorized into five groups: 0–0.4, 0.5–0.9, 1.0–1.4, 1.5–1.9, and ≥2.0 mg/dL. Multivariable logistic regression was performed to assess the independent association between calcium changes and in-hospital mortality, using the change in calcium category of 0–0.4 mg/dL as the reference group. Results: Of 9868 patients included in analysis, 540 (5.4%) died during hospitalization. The in-hospital mortality progressively increased with higher calcium changes, from 3.4% in the group of 0–0.4 mg/dL to 14.5% in the group of ≥2.0 mg/dL (p < 0.001). When adjusted for age, sex, race, principal diagnosis, comorbidity, kidney function, acute kidney injury, number of measurements of serum calcium, and hospital length of stay, the serum calcium changes of 1.0–1.4, 1.5–1.9, and ≥2.0 mg/dL were significantly associated with increased in-hospital mortality with odds ratio (OR) of 1.55 (95% confidence interval (CI) 1.15–2.10), 1.90 (95% CI 1.32–2.74), and 3.23 (95% CI 2.39–4.38), respectively. The association remained statistically significant when further adjusted for either the lowest or highest serum calcium. Conclusion: Larger serum calcium changes in hospitalized patients were progressively associated with increased in-hospital mortality.

Background and objectives: Goodpasture’s syndrome (GS) is a rare, life-threatening autoimmune disease. Although the coexistence of anti-neutrophil cytoplasmic antibody (ANCA) with Goodpasture’s syndrome has been recognized, the impacts of ANCA vasculitis on mortality and resource utilization among patients with GS are unclear. Materials and Methods: We used the National Inpatient Sample to identify hospitalized patients with a principal diagnosis of GS from 2003 to 2014 in the database. The predictor of interest was the presence of ANCA-associated vasculitis. We tested the differences concerning in-hospital treatment and outcomes between GS patients with and without ANCA-associated vasculitis using logistic regression analysis with adjustment for other clinical characteristics. Results: A total of 964 patients were primarily admitted to hospital for GS. Of these, 84 (8.7%) had a concurrent diagnosis of ANCA-associated vasculitis. Hemoptysis was more prevalent in GS patients with ANCA-associated vasculitis. During hospitalization, GS patients with ANCA-associated required non-significantly more mechanical ventilation and non-invasive ventilation support, but non-significantly less renal replacement therapy and plasmapheresis than those with GS alone. There was no significant difference in in-hospital outcomes, including organ failure and mortality, between GS patients with and without ANCA-associated vasculitis. Conclusions: Our study demonstrated no significant differences between resource utilization and in-hospital mortality among hospitalized patients with coexistence of ANCA vasculitis and GS, compared to those with GS alone.

AbstractBackgroundPrevious studies indicate there may be psychological consequences of being unable to serve as a living donor, but these have not been explored in a large national cohort of low‐income individuals who initiated living donor evaluation in US transplant centers.MethodsUsing data from 6574 National Living Donor Assistance Center (NLDAC) participants (November 1, 2007‐December 31, 2018), we utilized a cross‐sectional study design to evaluate short‐term depressive symptoms and satisfaction with life in living donors and non‐donors (those who were declined or withdrew from evaluation) using the Satisfaction with Life Scale (SWLS) and the PHQ‐8, with and without risk adjustment using linear regression.ResultsNational Living Donor Assistance Center participants originated from 207 US transplant centers. 52% of NLDAC participants responded to the survey (n = 3423; donors = 2848 (58.6% of all donors), non‐donors = 575 (33.5% of all non‐donors); ncenters = 201)). Respondents were significantly older, more likely to be female, white, non‐Hispanic, married, more educated, more full‐time employed, and more likely to be unrelated to the recipient vs non‐respondents (all, P < .001). Among survey respondents, donors were significantly younger, more likely to be non‐Hispanic, employed, and related to the recipient compared to non‐donors (all, P < .05). Higher PHQ‐8 scores were correlated with lower SWL scores (r = −.32, P < .001). Both groups displayed high SWLS (donors vs non‐donors: 27.1 vs 26.3, P = .002). Both groups had low levels of depressive symptoms overall, but donors had more symptoms than non‐donors (3.5 vs 2.4, P < .001). After risk adjustment, non‐donors had significantly less depressive symptoms by PHQ‐8 (28% lower, P < .001), but had lower life satisfaction (1.2 points lower, P < .001).ConclusionsDonors and non‐donors have high global levels of overall life satisfaction and low levels of depressive symptoms at 8 weeks after donation or denial. While small effect sizes were observed between groups in these outcomes, being a non‐donor was an independent risk factor for lower life satisfaction, which warrants further evaluation.

Introduction. Myeloid leukemia in children with Down syndrome (ML-DS) is a unique subtype of acute myeloid leukemia, distinguished by an earlier age of onset (under 4 years of age); somatic mutations of GATA1; hypersensitivity of leukemic blasts to cytarabine and other chemotherapeutic agents; lack of CNS involvement; and superior event-free survival (EFS, 85-90% at 5 years). Due to these excellent outcomes, successive protocols by the Children's Oncology Group (COG) have aimed for a reduction of treatment intensity but continue to include a course containing high-dose cytarabine (HD-AraC) for all patients, which is associated with the bulk of infectious toxicity. COG AAML1531 is the first study to evaluate differential treatment for ML-DS patients based on risk-stratification. We report the outcomes for patients with Standard Risk (SR) ML-DS enrolled on AAML1531, who were treated without inclusion of HD-AraC (https://clinicaltrials.gov/ct2/show/NCT02521493?term=AAML1531&rank=1). Methods. Patients older than 90 days and younger than 4 years of age with ML-DS were eligible, including those presenting with myelodysplastic syndrome (&lt; 20% blasts in the bone marrow) and trisomy 21 mosaicism. Pathological and cytogenetic data were reviewed centrally. All patients received the same first course of induction therapy (cytarabine 200 mg/m2/24h IV as continuous infusion, day 1-4; daunorubicin 20 mg/m2IV, day 1-4; thioguanine 50 mg/m2/dose PO twice daily, day 1-4; and a single dose of age-based intrathecal cytarabine on day 1). After this first course, measureable residual disease (MRD) in the bone marrow by multi-dimensional flow cytometry in a reference laboratory was used for risk stratification. Patients with negative MRD (&lt;0.05%) were assigned to Standard Risk (SR) therapy, which was modeled after the AAML0431 predecessor study, but with further reduction of treatment by omission of the course containing HD-AraC/E. coli asparaginase (Induction II of AAML0431). Courses #2 and #3 of SR therapy were identical to the first course except that no further intrathecal chemotherapy was administered. Courses #4 and #5 (cytarabine 100 mg/m2/24h IV as continuous infusion day 1-7; etoposide 125 mg/m2 IV, day 1-3) were identical to the corresponding courses of AAML0431. For patients younger than 36 months, chemotherapy doses were calculated based on weight. Use of dexrazoxane during anthracycline-containing courses was at the discretion of the treating center but was captured by the data collection of the study. Patients with positive MRD (&gt;0.05%) after the first course were assigned to the High Risk (HR) Arm and received intensified therapy (equivalent to that used for non-DS AML). Accrual to the HR arm is ongoing. Results. Interim analysis of SR therapy was performed after 50% of expected EFS events had occurred as of June 30, 2018. The observed EFS was 89.3 +/- 6.1% at 2 years from study entry and significantly lower than expected for comparable MRD-negative patients whose treatment in predecessor study AAML0431 included a course of HD-AraC/E. coliasparaginase (p=0.0002). OS at 2 years was 88.7 +/- 6.8%. Among a total of 114 SR ML-DS patients, 11 developed a relapse, all within the first year from study entry (range 136-327 days). OS at 1 year from relapse was 9.1 +/- 17.3%. Based on the results of interim analysis, the SR arm of AAML1531 was closed to accrual due to lack of efficacy. Cytogenetic analysis showed that complex karyotypes (defined as &gt;3 independent abnormalities including &gt;1 structural one) were significantly more frequent in SR patients who relapsed (40%, n=10) compared to SR patients who did not (9%; n=100; p=0.017). The most common abnormalities were trisomies (61% of cases) of chromosomes 3 and 8, and a gain of a fourth copy of chromosome 21. Monosomy 7 was present in 20% of relapsed vs. 5% of patients without a relapse (p=0.122). Conclusions. MRD measured by multi-dimensional flow cytometry is insufficient to identify a subset of ML-DS patients for whom HD-AraC/E.coliasparaginase can be eliminated from treatment. Cytogenetic profiling may aid in further refining risk-based subsets of ML-DS patients. Additional approaches to risk stratification of ML-DS should be pursued, which take into account the emerging genetic events that co-operate with mutant GATA1 in the development of ML-DS. At this time, HD-AraC/E.coli asparaginase should be included in the treatment of ML-DS, regardless of MRD. Disclosures Druley: Washington University: Employment; ArcherDX Inc.: Employment, Equity Ownership. Loken:Hematologics, Inc: Employment, Equity Ownership. Eidenschink Brodersen:Hematologics, Inc: Employment.