tbuckley/cabot-search huggingface dataset:
Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens
Authors: Anja Mottok, George Wright, Andreas Rosenwald, German Ott, Colleen Ramsower, Elias Campo, Rita M. Braziel, Jan Delabie, Dennis D. Weisenburger, Joo Y. Song, Wing C. Chan, James R. Cook, Kai Fu, Tim Greiner, Erlend Smeland, Harald Holte, Kerry J. Savage, Betty J. Glinsmann-Gibson, Randy D. Gascoyne, Louis M. Staudt, Elaine S. Jaffe, Joseph M. Connors, David W. Scott, Christian Steidl, Lisa M. Rimsza
Journal: Blood (2018)
An evaluation of shifting administration of high-cost chemotherapy from the inpatient to an outpatient setting.
Authors: David L. Crosby, Katie Karkowski, Catherine Rodriguez, Frederick Lansigan
Journal: Journal of Clinical Oncology (2018)

107 Background: Patients often require critical management during chemotherapy and may need constant monitoring during and post-treatment in an inpatient (IP) unit. However, many patients can receive safe and effective administration of chemotherapy in an outpatient (OP) infusion setting, which respects patient’s wishes to shorten hospitalization stays. Optimizing OP treatment can also result in better utilization of resources that require critical monitoring. Since IP chemotherapy is not reimbursed separately, it is often considered a financial loss. This study evaluated the opportunity to decrease length of stay (LOS), reduce costs for our hematology/oncology inpatient practice, and increase utilization of a new infusion suite adjacent to IP unit. Methods: Work followed a Lean Six Sigma methodology – Define, Measure, Analyze, Improve, and Control. Multi-disciplinary clinical teams worked with quality improvement subject matter experts to explore regimens associated with inpatient administration of high-cost medications. Rituximab-based regimens were identified as the greatest opportunity to optimize cost reduction in the IP unit. The team set a goal to deliver rituximab as an OP in the infusion suite following hospital discharge. Baseline utilization of rituximab in the IP unit, revenue of the new infusion suite, and mean LOS for patients receiving R-EPOCH, a rituximab based regimen, were determined. Results: Percentage of IP rituximab administration was reduced by 56% resulting in $355,506 of cost avoidance in the IP unit. Mean quarterly revenue in the OP infusion suite increased from $104,363 at baseline to $293,607 through the first nine months by shifting rituximab to the OP setting, which projects to an annualized improvement of $756,976. Median LOS for patients receiving R-EPOCH was reduced by 12 hours (p &lt; 0.001). Conclusions: Our intervention has resulted in decreased administration of high-cost chemotherapy in the IP unit, reduced LOS, and increased patient convenience. In addition, the significant revenue generated in the OP infusion suite will support improving patient services at our not-for-profit medical center.
Leveraging the electronic medical record (EMR) to improve sepsis care in cancer outpatients.
Authors: William A. Dunson, Emily Erickson, Chad Freckleton, Mahima Saseendran, Betsy Kissell, Kencee Graves, Devin Horton, Terrell Rohm, Donald Milligan, Dominik Ose
Journal: Journal of Clinical Oncology (2018)

319 Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated response to infection and a major healthcare problem in cancer patients. Patients with cancer are at increased risk of morbidity and mortality from sepsis. Approaches like the modified Early Warning Score (mEWS) could offer an opportunity to identify patients at risk for sepsis earlier and to prompt a timely evaluation. However, available evidence for cancer outpatient settings remains scarce. The aim of this presentation is to describe first results of the mEWS implementation at Huntsman Cancer Hospital (HCC) outpatient clinics. The question, whether patients with sepsis can be detected using this approach will be answered. Methods: In 2015, the University of Utah Healthcare implemented mEWS as prediction tool for sepsis. The automated calculation of mEWS is based on real-time data from the EMR. For this analysis, we extracted a cancer outpatient population from a 15-month time frame (from December 2016 to February 2018) within the EHR. We selected patients with a mEWS &gt; 4, grouped these patients according to the process of care after mEWS scoring (e.g., admitted to ICU) and analyzed subgroup based upon mEWS score, discharge disposition and sepsis diagnosis. Results: Within the analyzed time frame 502 cancer outpatients had a mEWS score of 4 or higher. 88 of these patients (17.5%) were diagnosed with sepsis after mEWS screening. Out of the patients with sepsis, 22 were admitted to ICU, 63 were admitted to a medical floor and 3 were treated at the Huntsman Acute Care Clinic. Out of the 414 without a diagnosis of sepsis, 13 patients were admitted to ICU, 72 patients were admitted to a medical floor (in each case for other reasons then sepsis) and 329 patients were sent to home. Conclusions: Sepsis is a serious problem in cancer outpatient care. In our analysis, one in six patients with a mEWS score of 4 and higher were diagnosed with sepsis. This analysis has shown that the implementation of a real-time, EMR based scoring system like mEWS can support the early detection and treatment of sepsis in this population.
Abstract 13473: Increased Blood Residence Time on Transcatheter Aortic Valve Leaflets as a Precursor Mechanism to Leaflet Thrombosis following Valve-in-Valve Procedure: A Patient-Specific Simulation Study
Authors: Koohyar Vahidkhah, Shahnaz Javani, Mostafa Abbasi, Peyman N Azadani, Anwar Tandar, Ali N Azadani
Journal: Circulation (2016)

Introduction: Leaflet thrombosis following valve-in-valve (ViV) procedures has been increasingly recognized. Nevertheless, the underlying mechanisms are not well-addressed and remained unclear. Hypothesis: Unlike surgical bioprostheses, the aortic portion of the transcatheter aortic valve (TAV) frame is circumferentially surrounded by degenerated bioprostheses in ViV (Fig 1 a-b). The geometric confinement of the TAV leaflets increases the blood residence time (BRT) on the leaflets. This acts as a precursor mechanism to the thrombus formation. Methods: A patient-specific geometry of the left ventricle, aorta, and coronary arteries was reconstructed from computed tomographic angiography (CTA) images using Simpleware software (Fig 1c). Two computational models representing a surgical bioprosthesis and a TAV in ViV setting were developed in the patient-specific geometry. 3D flow fields were obtained via a one-way fluid-solid interaction modeling approach. Thereafter, a particle tracking procedure was applied to calculate BRT on the leaflets. Finally, statistical analysis was performed to compare the BRT values between the two models. Results: Tracking of the blood particles in close proximity of the leaflets demonstrated significantly longer BRT on the aortic side of the leaflets in the ViV setting than surgical bioprosthesis (Fig 1d). During systole and diastole, the amount by which the mean BRT was higher for ViV than surgical valve was 341% and 90%, respectively (p&lt;0.001). Conclusions: The results of this study show that geometric confinement of TAV in ViV disrupts flow between the leaflets and the aortic sinuses, and increases the likelihood of thrombogenesis.
Exploiting MCL1 Dependency with Combination MEK + MCL1 Inhibitors Leads to Induction of Apoptosis and Tumor Regression in <i>KRAS</i>-Mutant Non–Small Cell Lung Cancer
Authors: Varuna Nangia, Faria M. Siddiqui, Sean Caenepeel, Daria Timonina, Samantha J. Bilton, Nicole Phan, Maria Gomez-Caraballo, Hannah L. Archibald, Chendi Li, Cameron Fraser, Diamanda Rigas, Kristof Vajda, Lorin A. Ferris, Michael Lanuti, Cameron D. Wright, Kevin A. Raskin, Daniel P. Cahill, John H. Shin, Colleen Keyes, Lecia V. Sequist, Zofia Piotrowska, Anna F. Farago, Christopher G. Azzoli, Justin F. Gainor, Kristopher A. Sarosiek, Sean P. Brown, Angela Coxon, Cyril H. Benes, Paul E. Hughes, Aaron N. Hata
Journal: Cancer Discovery (2018)

Abstract BH3 mimetic drugs, which inhibit prosurvival BCL2 family proteins, have limited single-agent activity in solid tumor models. The potential of BH3 mimetics for these cancers may depend on their ability to potentiate the apoptotic response to chemotherapy and targeted therapies. Using a novel class of potent and selective MCL1 inhibitors, we demonstrate that concurrent MEK + MCL1 inhibition induces apoptosis and tumor regression in KRAS-mutant non–small cell lung cancer (NSCLC) models, which respond poorly to MEK inhibition alone. Susceptibility to BH3 mimetics that target either MCL1 or BCL-xL was determined by the differential binding of proapoptotic BCL2 proteins to MCL1 or BCL-xL, respectively. The efficacy of dual MEK + MCL1 blockade was augmented by prior transient exposure to BCL-xL inhibitors, which promotes the binding of proapoptotic BCL2 proteins to MCL1. This suggests a novel strategy for integrating BH3 mimetics that target different BCL2 family proteins for KRAS-mutant NSCLC. Significance: Defining the molecular basis for MCL1 versus BCL-xL dependency will be essential for effective prioritization of BH3 mimetic combination therapies in the clinic. We discover a novel strategy for integrating BCL-xL and MCL1 inhibitors to drive and subsequently exploit apoptotic dependencies of KRAS-mutant NSCLCs treated with MEK inhibitors. See related commentary by Leber et al., p. 1511. This article is highlighted in the In This Issue feature, p. 1494
Race and Sex Differences in Post–Myocardial Infarction Angina Frequency and Risk of 1-Year Unplanned Rehospitalization
Authors: Connie N. Hess, Lisa A. Kaltenbach, Jacob A. Doll, David J. Cohen, Eric D. Peterson, Tracy Y. Wang
Journal: Circulation (2017)

Race and sex disparities in in-hospital treatment and outcomes of patients with acute myocardial infarction (MI) have been described, but little is known about race and sex differences in post-MI angina and long-term risk of unplanned rehospitalization. We examined race and sex differences in post-MI angina frequency and 1-year unplanned rehospitalization to identify factors associated with unplanned rehospitalization, testing for whether race and sex modify these relationships.Using TRANSLATE-ACS (Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome) data, we examined 6-week and 1-year angina frequency and 1-year unplanned rehospitalization stratified by race and sex among MI patients treated with percutaneous coronary intervention. We used multivariable logistic regression to assess factors associated with unplanned rehospitalization and tested for interactions among angina frequency, race, and sex.A total of 11 595 MI patients survived to 1 year postdischarge; there were 66.6% white male patients, 24.3% white female patients, 5.3% black male patients, and 3.8% black female patients. Overall, 29.7% had angina at 6 weeks, and 20.6% had angina at 1 year postdischarge. Relative to white patients, black patients were more likely to have angina at 6 weeks (female: 44.2% versus 31.8%; male: 33.5% versus 27.1%; both P<0.0001) and 1 year (female: 49.4% versus 38.9%; male: 46.3% versus 31.1%; both P<0.0001). Rates of 1-year unplanned rehospitalization were highest among black female patients (44.1%), followed by white female patients (38.4%), black male patients (36.4%), and white male patients (30.2%, P<0.0001). In the multivariable model, 6-week angina was most strongly associated with unplanned rehospitalization (hazard ratio, 1.49; 95% confidence interval, 1.36-1.62; P<0.0001); this relationship was not modified by race or sex (adjusted 3-way Pinteraction=0.41).One-fifth of MI patients treated with percutaneous coronary intervention report 1-year postdischarge angina, with black and female patients more likely to have angina and to be rehospitalized. Better treatment of post-MI angina may improve patient quality of life and quality of care and help to lower rates of rehospitalization overall and particularly among black and female patients, given their high prevalence of post-MI angina.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01088503.
Cost of care for patients with metastatic castration-resistant prostate cancer initiating on docetaxel versus oral targeted therapies in the United States.
Authors: Bingcao Wu, Sophia Li, Ozgur Tunceli, Ji Song, Chris Pericone, Zhijie Ding, Ajay S. Behl, Ayush Srivastava, Nancy Ann Dawson
Journal: Journal of Clinical Oncology (2018)

88 Background: Abiraterone acetate + prednisone and enzalutamide are approved oral targeted therapies (OTT) for metastatic castration-resistant prostate cancer (mCRPC) which have significant clinical benefit. However, their impact on healthcare cost relative to docetaxel (DOC) is not well understood. Methods: This retrospective cohort study used combined claims data from Truven MarketScan Commercial and Medicare Supplement Plan databases. Males ≥18 years with ≥1 prostate cancer diagnosis and a subsequent metastasis diagnosis were indexed on the first claim date of DOC or OTT between 1/1/2012 and 12/31/2016. ≥1 claim for an androgen deprivation therapy during the 12-month continuous enrollment period prior to metastasis was required; patients with end stage renal disease or other primary cancer were excluded. All-cause per patient per year (PPPY) costs were estimated in 2016 US dollars. A generalized linear model was used to compare adjusted costs between DOC and OTT cohorts. Results: A total of 1,159 and 200 mCRPC patients initiated on OTT and DOC, respectively. Mean follow up time for both cohorts was 1.2 years. Mean age of OTT patients was 75.1 (Standard Deviation = 10.7) years and mean Quan-Charlson Comorbidity Index (QCI) was 3.2 (1.9). Mean age of DOC patients was 65.9 (9.1) years; mean QCI was 2.9 (1.8). 21% of OTT and 56% of DOC patients were commercially insured. Following treatment initiation, total mean unadjusted all-cause PPPY costs were $144,350 ($80,606) and $137,814 ($84,405) for OTT and DOC cohort, respectively. The primary cost drivers were utilization of treatments indicated for mCRPC, outpatient encounters and inpatient hospitalizations. Total adjusted PPPY costs were higher for OTT than DOC patients ($141,008 vs. $125,318, p = 0.0012), mainly due to higher costs of treatments indicated for mCRPC ($80,443 vs. $55,820, p &lt; .0001). Medical costs (excluding mCRPC treatment) for OTT initiated patients were lower ($54,570 vs. $64,614, p = 0.0128). Conclusions: In a real-world setting, initiation on OTT was associated with higher overall cost of care for mCRPC compared with DOC. However, the cost of medical services was significantly lower when initiated on OTT.
Safety and clinical efficacy of programmed cell death 1 antibodies (PD-1 Ab) in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Doran Ksienski, Elaine Wai, Nicole Croteau, Mary Lesperance
Journal: Journal of Clinical Oncology (2018)

260 Background: In advanced NSCLC, clinical trials have shown significant benefits to pembrolizumab (P) and nivolumab (N). At BC Cancer, clinicians utilize protocol based algorithms to manage immune related adverse events (irAE). The incidence of irAE and efficacy of PD-1 Ab in everyday practice might differ from clinical trials. Methods: Advanced NSCLC patients (pts) treated with N or P between 11/2015 to 10/2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Gr, CTCAE v4.0) of irAE, were abstracted. Kaplan-Meier curves of median overall survival (OS) from initiation of PD-1 Ab were generated. Multivariable analysis (MVA) with 6-week landmark analysis was performed with Cox proportional hazard regression models. Results: Characteristics of cohort (230 N- and 41 P- treated): median age 64y (range 39-82), non-squamous histology 75%, ECOG PS &gt; 1 at start of PD-1 Ab 31%, brain metastases (mets) 13%, liver mets 12%, and median Charlson Comorbidity Index (CCI) score 6. One hundred sixteen pts experienced 169 separate irAE: Gr1(74), Gr2 (68), Gr3(13), Gr4(10), Gr 5(4). Pneumonitis (14.6% vs. 4.8%, p = 0.041) and arthralgias (12.2% vs. 3.5%, p = 0.044) were more common in P than N. Steroids were administered to 25.2% of N pts and 19.5% of P pts (p = 0.557). Median follow-up from initiation of PD-1 Ab was 8.1months (range 0.1-33.9); median OS (95% CI) for N was 9.2 months (7.75-12.4) and for P was 13.5 months (10.6-not reached). 6-week landmark MVA for whole cohort revealed that male sex (p = 0.051), CCI≥3 (p &lt; 0.001), ECOG PS &gt; 1 (p &lt; 0.001), liver mets (p = 0.017) and development of irAE &gt; Gr2 versus no irAE (p = 0.036) were associated with decreased OS. Age, smoking status, histology, brain mets, EGFR status, irAE Gr 1/2 versus no irAE, and type of PD-1 Ab were not significant. Conclusions: Severe irAE were rare; pneumonitis and arthralgias were more common in P- than N- treated patients. The association with CCI, ECOG PS, and liver mets with decreased OS are consistent with literature. Association of severe irAE with shorter OS might reflect the need for improved physician education in irAE treatment algorithms.
Daily bathing with 4% chlorhexidine gluconate in intensive care settings: a randomized controlled trial
Authors: C. Pallotto, M. Fiorio, V. De Angelis, A. Ripoli, E. Franciosini, L. Quondam Girolamo, F. Volpi, P. Iorio, D. Francisci, C. Tascini, F. Baldelli
Journal: Clinical Microbiology and Infection (2018)
Abstract 18400: Intravenous Ranolazine Relieves Ischemia by Increasing Myocardial Adenosine Levels
Authors: D. E Le, Catherine M Davis, Kevin S Wei, Kristin L Lyon Scott, Yan Zhao, Matthew Nugent, Sanijv Kaul
Journal: Circulation (2016)

Background: The mechanism by which ranolazine (RAN) reduces stress-induced myocardial ischemia is not fully understood. Hypothesis: RAN relieves myocardial ischemia through the cardioprotective eff...
Inverse relationship of serum albumin to the risk of venous thromboembolism among acutely ill hospitalized patients: Analysis from the APEX trial
Authors: Gerald Chi, C. Michael Gibson, Yuyin Liu, Adrian F. Hernandez, Russell D. Hull, Alexander T. Cohen, Robert A. Harrington, Samuel Z. Goldhaber
Journal: American Journal of Hematology (2018)

Abstract Hypoalbuminemia is a common finding and independent predictor for unfavorable prognosis. The prognostic value of albumin measurement for short‐term VTE prediction in hospitalized patients remains unclear. In the APEX trial ( ClinicalTrials.gov identifier: NCT01583218), medical inpatients were randomized to receive either extended‐duration betrixaban or shorter‐duration enoxaparin and followed for 77 days. Baseline albumin concentrations were obtained in 7266 subjects with evaluable VTE endpoints. The association of baseline albumin to VTE was assessed, with adjustment for patient characteristics, thromboprophylaxis, and biomarkers for fibrinolysis and inflammation (ie, D‐dimer and C‐reactive protein [CRP]). VTE risk refinement was evaluated by incorporation of albumin to well‐validated risk assessment models. A stepwise increase in the risk of VTE ( P &lt; .0001) was observed with lower levels of albumin. Patients at the bottom albumin quartile (&lt;35 g/L) had a two‐fold greater odds for developing VTE compared with the top quartile (≥42 g/L) (OR = 2.119 [95% CI, 1.592‐2.820]; adjusted OR = 2.079 [1.485‐2.911]). The odds for VTE increased by 1.368 (95% CI, 1.240‐1.509) times per SD decrement of albumin (5.24 g/L). Compared with the propensity score‐matched pairs of patients with albumin ≥35 g/L, patients with albumin &lt;35 g/L had a greater risk of VTE (OR = 1.623 [1.260‐2.090]; adjusted OR = 1.658 [1.209‐2.272]). Albumin measurement also refined VTE risk discrimination and reclassification after inclusion in the risk assessment models. In conclusion, acutely ill hospitalized patients with low serum albumin had an increased VTE risk through 77 days. VTE risk assessment models for medical inpatients should consider incorporation of baseline albumin measurement.
Abstract 17117: In Vitro Monitoring of Microbubble Mediated Clot Dissolution Using Optical Coherence Tomography (OCT)
Authors: Jonathan E Leeman, Jong S Kim, Larry Kagemann, Francois Yu, Xucai Chen, John J Pacella, Joel S Schuman, Flordeliza S Villanueva, Kang Kim
Journal: Circulation (2011)

Background: Thrombolysis using ultrasound (US) induced destruction of systemically injected microbubbles (MBs) is a potential targeted treatment for acute myocardial infarction or ischemic stroke. The physical mechanisms underlying MB mediated clot lysis are incompletely elucidated, partly due to limitations in methods to characterize morphologic and volumetric changes in a thrombus resulting from MB destruction. Here, we explore possibilities for 3D quantitative assessment of sonothrombolysis using optical coherence tomography (OCT), a high resolution imaging modality. Methods: Thrombi were formed in polyethylene tubing (1.67 mm i.d.) from recalcified porcine blood using silk suture as a nidus for thrombosis. Lipid shell MBs suspended in saline and tissue plasminogen activator (rt-PA, 3 μ g/ml) were perfused through the tube (22 μ l/min, 2x107 MBs/ml) using a syringe pump while US pulses (1 MHz, 1.0 MPa, 100 cycles) were delivered over 30 min to the clot from a single element transducer every 5 sec to ensure MB replenishment between destructive pulses. 3D OCT images of clots were obtained before and after US treatment, rt-PA alone, or saline alone (n=3/condition). Clot volume was measured using clot boundary determination by thresholding pixel intensity of each cross-sectional OCT image. Results: Thrombi treated with US + MBs + rt-PA decreased in volume by 55.7% (0.02 mm3; p=0.02). rt-PA alone resulted in a 25.6% (0.009 mm3; p=0.39) decrease in volume and treatment with saline alone did not change clot volume (0.003 mm3; p=0.94). OCT images qualitatively showed greatest change in clot shape and volume in regions closest to the source of US (Fig 1). Conclusion: 3D OCT can quantify thrombolysis. As expected, the addition of US and MBs enhanced the lytic effect of rt-PA. OCT imaging may reveal the physical effects of contrast US on thrombus structure, thereby yielding insights into mechanisms of sonothrombolysis that can be used to optimize treatment regimens.
Rebel attacks and political scaremongering raise risk of Ebola spreading in the Congo
Authors: Sophie Arie
Journal: BMJ (2018)

The World Health Organization has warned that an Ebola outbreak in the Democratic Republic of Congo (DRC) could quickly spread because of a “perfect storm” of escalating problems, including rebel fighting and mistrust of international responders.

“We are now extremely concerned that several factors may be coming together to create a perfect storm,” WHO’s head of emergency response, Peter Salama, told a news conference in Geneva, Switzerland.

A rebel attack on the town of Beni, where WHO is based, interrupted the process of tracing and monitoring people infected with Ebola around the North Kivu province. Some 120 people have been infected …