tbuckley/cabot-search huggingface dataset:
Abstract 16000: Patient Characteristics and Outcomes Associated With Troponin Testing
Authors: Yissela Escobedo, Travis Haneke, Sarah Payne, Clinton Jones, Patrick McGrade, Bright Izekor, Kendall Hammonds, Jeffrey Michel, Robert J Widmer
Journal: Circulation (2020)

Introduction: Troponin I (TnI) is a principal biomarker in diagnosing acute myocardial infarction (AMI). However, large numbers of hospitalized patients are tested for TnI in whom AMI is unlikely or not expected. Hypothesis: We hypothesized the baseline comorbidities of those undergoing troponin testing differ from those not tested and that troponin testing is associated with outcomes. Methods: In total, 54,039 inpatient admissions from a 9-hospital system in Texas were reviewed over a 24-month period (2017-2018). Data were collected on primary international classification of disease (ICD-10) diagnoses, TnI, risk factors, and death during hospitalization or readmission within 30 days. Odds ratios were calculated for all patients adjusted for demographic differences in the population. Bivariate analysis was performed on the baseline risk factors for both troponin testing and troponin positivity. Results: TnI testing occurred in 30,173/54,039 (55.8%) individual hospital admissions. Of those, 19.9% had at least one elevated TnI value &gt;99th% (0.1 ng/ml). Tested patients were older (70.1 [IQR 59.5, 80.9] vs 63.7 [IQR 53.4, 73.1] years), more likely to be male (14,497/30,173 (48.1%) vs 10,845/23,866 (45.4%)) and had a greater burden of cardiovascular disease and risk factors including: gender, race, smoking, hypertension, hyperlipidemia, type 2 diabetes mellitus, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, prior cerebrovascular accident, and prior AMI. Troponin testing was associated with death during hospitalization (OR 3.11, 95% CI 2.63, 3.71, p&lt;0.0001), and an elevated troponin was found to be associated with mortality (OR 4.06, 95% CI 3.49, 4.72, p&lt;0.0001). Conclusions: Troponin testing is associated with death during index hospitalization. Troponin values &gt;99th% were associated only with increased mortality. This data suggest that selection plays a role in identifying patients at risk for in-hospital death.
Pre-existing immune status associated with response to combination of sipuleucel-T and ipilimumab in patients with metastatic castration-resistant prostate cancer
Authors: Meenal Sinha, Li Zhang, Sumit Subudhi, Brandon Chen, Jaqueline Marquez, Eric V Liu, Kate Allaire, Alexander Cheung, Sharon Ng, Christopher Nguyen, Terence W Friedlander, Rahul Aggarwal, Matthew Spitzer, James P Allison, Eric J Small, Padmanee Sharma, Lawrence Fong
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Sipuleucel-T is a US Food and Drug Administration-approved autologous cellular immunotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We examined whether administering ipilimumab after sipuleucel-T could modify immune and/or clinical responses to this treatment. Methods A total of 50 patients with mCRPC were enrolled into a clinical trial ( NCT01804465 , ClinicalTrials.gov) where they received ipilimumab either immediately or delayed 3 weeks following completion of sipuleucel-T treatment. Blood was collected at various timepoints of the study. Luminex assay for anti-prostatic acid phosphatase (PAP) and anti-PA2024-specific serum immunoglobulin G (IgG) and ELISpot for interferon-γ (IFN-γ) production against PAP and PA2024 were used to assess antigen-specific B and T cell responses, respectively. Clinical response was defined as &gt;30% reduction in serum prostate-specific antigen levels compared with pretreatment levels. The frequency and state of circulating immune cells were determined by mass cytometry by time-of-flight and statistical scaffold analysis. Results We found the combination to be well tolerated with no unexpected adverse events occurring. The timing of ipilimumab did not significantly alter the rates of antigen-specific B and T cell responses, the primary endpoint of the clinical trial. Clinical responses were observed in 6 of 50 patients, with 3 having responses lasting longer than 3 months. The timing of ipilimumab did not significantly associate with clinical response or toxicity. The combination treatment did induce CD4 and CD8 T cell activation that was most pronounced with the immediate schedule. Lower frequencies of CTLA-4 positive circulating T cells, even prior to treatment, were associated with better clinical outcomes. Interestingly, these differences in CTLA-4 expression were associated with prior localized radiation therapy (RT) to the prostate or prostatic fossa. Prior radiation treatment was also associated with improved radiographic progression-free survival. Conclusion Combining CTLA-4 blockade with sipuleucel-T resulted in modest clinical activity. The timing of CTLA-4 blockade following sipuleucel-T did not alter antigen-specific responses. Clinical responses were associated with both lower baseline frequencies of CTLA-4 expressing T cells and a history of RT. Prior cancer therapy may therefore result in long-lasting immune changes that influence responsiveness to immunotherapy with sipuleucel-T and anti-CTLA-4.
Abstract 15192: Effectiveness and Safety of Reduced Dose of Dabigatran for High Bleeding Risk Patient Subgroups With Atrial Fibrillation
Authors: Jaejin An, Zoe Bider, Tiffany Luong, T Craig Cheetham, Daniel T Lang, Ming-Sum Lee, Kristi Reynolds
Journal: Circulation (2020)

Off-label reduced dosing of direct oral anticoagulants is common among patients at high bleeding risk with atrial fibrillation (AF), however, outcomes data of reduced dosing are limited. We evaluated the effectiveness and safety of reduced dose of dabigatran [110 mg twice daily (BID)] vs. standard dose [150 mg BID] in high bleeding risk subgroups with AF. We identified adult patients with AF who initiated dabigatran (index date) with creatinine clearance (CrCl) ≥30 mL/min between 2012-2018 from Kaiser Permanente Southern California. Three high bleeding risk subgroups were identified: 1) patients aged ≥80 years; 2) patients with moderate renal impairment (CrCl 30-49 mL/min) regardless of age; or 3) patients with bleeding within 12 months prior to the index date or HAS-BLED score ≥3. Patients were followed through December 2018 for stroke or systemic embolism, major bleeding requiring hospitalization, and all-cause mortality. Cause-specific hazard regression models were used to investigate associations between dabigatran dose and clinical outcomes adjusting for covariates and considering competing risks of death. Among high bleeding risk patients with AF [3,749 aged ≥80 years; 1,716 with moderate renal impairment; 3,051 with recent bleed or high HAS-BLED score], 34% received reduced dose of dabigatran. Patients who received reduced dose were older, had reduced renal function, and had more comorbidities. Compared with standard dose, reduced dose of dabigatran was not associated with an increased risk of stroke or systemic embolism but was associated with lower risk of major bleed in patients aged ≥80 years ( Table ). Reduced dose of dabigatran was also associated with lower risk of mortality among patients aged ≥80 years and patients with moderate renal impairment. A lower risk of bleeds and mortality associated with reduced vs standard dose of dabigatran in high-risk patients with AF suggest a better dosing strategy for these risk groups.
Abstract 14196: Prognostic Importance of Platelet Dysfunction for Thrombosis-Related Adverse Events During Cardiopulmonary Bypass
Authors: Loretta Tsui San Ho, Mark McVey, Martin Lenihan, Keyvan Karkouti
Journal: Circulation (2018)

Introduction: Hemostatic activation induced by cardiopulmonary bypass (CPB) may lead to the formation of micro-thrombi and thereby contribute to thromboembolic adverse events. CPB-induced platelet ...
Abstract 14892: Mobile Technology Improves Adherence to Cardiac Rehabilitation: A Propensity Score-matched Study
Authors: Tasnim F Imran, Na Wang, Stephanie Zombeck, Gary J Balady
Journal: Circulation (2020)

Objective: To examine whether mobile technology improves adherence to cardiac rehabilitation and other outcomes. Methods: We identified enrollees of the cardiac rehabilitation program at Boston Medical Center from 2016-2020 (n=830). Some enrollees used a mobile technology application (Wellframe.com) that provided a customized interactive list of educational content in a progressive manner, used the patient’s smart phone accelerometer to provide daily step counts, and served as a two-way messaging system between the patient and the program staff. Adherence to cardiac rehabilitation was defined as the number of attended prescribed sessions and completion of the program. To evaluate change in the following: exercise capacity, Beck Depression Index (BDI) scores, weight, quality of life scores and Rate Your Plate nutrition scores, we used the generalized estimating equation method. Results: After 2:1 propensity score matching for age, sex, race, education, smoking status, transportation time to cardiac rehabilitation center, qualifying diagnosis, and baseline BDI score, there were 121 enrollees in the group using the Wellframe application as a supplement to the rehabilitation program and 280 enrollees in the Standard rehabilitation group. Enrollees had a mean age of 59 years; 32% were women, and 42% were black. Those in the mobile technology group attended a higher number of prescribed sessions (mean 28 vs. 22), RR: 1.17 (95% CI: 1.04-1.32, p=0.009), were 1.8 times more likely to complete the cardiac rehabilitation program (p=0.01), and had a slightly greater weight loss (lbs) post rehabilitation: -1.71 (95% CI: -0.30, -3.11, p=0.02) as compared to those in the Standard group; other outcomes were similar between the groups (Table 1). Conclusion: In a propensity-matched, racially diverse population, we found that adjunctive use of mobile technology significantly improved adherence to cardiac rehabilitation and number of attended sessions.
CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer
Authors: Erin M. Bange, Nicholas A. Han, Paul Wileyto, Justin Y. Kim, Sigrid Gouma, James Robinson, Allison R. Greenplate, Madeline A. Hwee, Florence Porterfield, Olutosin Owoyemi, Karan Naik, Cathy Zheng, Michael Galantino, Ariel R. Weisman, Caroline A. G. Ittner, Emily M. Kugler, Amy E. Baxter, Olutwatosin Oniyide, Roseline S. Agyekum, Thomas G. Dunn, Tiffanie K. Jones, Heather M. Giannini, Madison E. Weirick, Christopher M. McAllister, N. Esther Babady, Anita Kumar, Adam J. Widman, Susan DeWolf, Sawsan R. Boutemine, Charlotte Roberts, Krista R. Budzik, Susan Tollett, Carla Wright, Tara Perloff, Lova Sun, Divij Mathew, Josephine R. Giles, Derek A. Oldridge, Jennifer E. Wu, Cécile Alanio, Sharon Adamski, Alfred L. Garfall, Laura A. Vella, Samuel J. Kerr, Justine V. Cohen, Randall A. Oyer, Ryan Massa, Ivan P. Maillard, Kara N. Maxwell, John P. Reilly, Peter G. Maslak, Robert H. Vonderheide, Jedd D. Wolchok, Scott E. Hensley, E. John Wherry, Nuala J. Meyer, Angela M. DeMichele, Santosha A. Vardhana, Ronac Mamtani, Alexander C. Huang
Journal: Nature Medicine (2021)

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.
シロリムス溶出ステント挿入後のネオアテローム性動脈硬化のin vivo評価:初期および後期フォローアップ間のシリアルOCT所見の比較
Authors: Kozuki Amane, Shite Junya, Shinke Toshiro, Otake Hiromasa, Nakagawa Masayuki, Nagoshi Ryoji, Inoue Takumi, Hariki Hirotoshi, Ohsue Tsuyoshi, Taniguchi Yu, Iwasaki Masamichi, Hiranuma Noritoshi, Nishio Ryo, Kinutani Hiroto, Konishi Akihide, Hirata Kenichi
Journal: Circulation (2012)
The maternal diet index in pregnancy is associated with offspring allergic diseases: the Healthy Start study
Authors: Carina Venter, Michaela P. Palumbo, Deborah H. Glueck, Katherine A. Sauder, Liam O'Mahony, David M. Fleischer, Miriam Ben‐Abdallah, Brandy M. Ringham, Dana Dabelea
Journal: Allergy (2021)

Abstract Background A systematic review showed limited associations between pregnancy diet and offspring allergy. We developed a maternal diet index during pregnancy that was associated with offspring allergy outcomes. Methods Data came from Healthy Start, a Colorado pre‐birth cohort of mother/offspring dyads. Food propensity questionnaires were completed during pregnancy. Offspring allergic rhinitis, atopic dermatitis, asthma, wheeze, and food allergy diagnosis up to age four were verified from electronic medical records. Data were randomized into test and replication sets. The index included the weighted combination of variables that best predicted a combined outcome of any allergy in the test set. Index utility was verified in the replication set. Separate adjusted and unadjusted logistic models estimated associations between the index and each offspring allergy diagnosis in the full sample. Results The index included weighted measures of intake of vegetables, yogurt, fried potatoes, rice/grains, red meats, pure fruit juice, and cold cereals. Vegetables and yogurt were associated with the prevention of any allergy, while other components were associated with increased disease. In adjusted models, a one‐unit increase in the index was significantly associated with reduced odds of offspring allergic rhinitis (odds ratio (CI) 0.82 [0.72–0.94]), atopic dermatitis (0.77 [0.69–0.86]), asthma (0.84 [0.74–0.96]), and wheeze (0.80 [0.71–0.90]), but not food allergy (0.84 [0.66–1.08]). Conclusions This is the first study that has shown associations between an index of maternal dietary intake during pregnancy and multiple offspring allergic diseases. The results give hope for prevention of allergic diseases in utero .
Abstract 17014: Cardiologist Assessment and Approval Was the Primary Predictor of Kidney Transplant Candidacy and Transplantation Among Patients With Reduced Left Ventricular Ejection Fraction
Authors: Michelle Madden, Rory Gallen, Lisa LeMond, D Eric Steidley, Mira Keddis
Journal: Circulation (2020)

Introduction: End stage renal disease (ESRD) patients with concomitant heart failure (HF) are often denied kidney transplantation (KTx). The aims of this study were to explore factors predictive of suitability for KTx and to assess cardiovascular (CV) outcomes in patients with impaired left ventricular ejection fraction (LVEF) presenting for KTx evaluation. Methods: We evaluated 109 consecutive adults with LVEF≤40% at the time of initial KTx evaluation between 2013 and 2018. Post-transplant CV outcomes were defined as non-fatal MI, admission for HF, CV death and all-cause mortality. Results: Mean age was 58.2 years (SD11.9), 78% were male, 58% had diabetes, 70% had history of CV events and 42% had ischemic cardiomyopathy. Mean LVEF was 31.5% (SD 6.47). Eighty patients had nuclear stress imaging; 10% were positive for reversible ischemia and 43% for prior infarct. Mean VO2max was 14.4(SD 5.71)ml/kg/min (31 patients). A cardiologist evaluated 93% of patients and was present at 58% of selection committee meetings. Twenty-four patients (22%) were denied by a cardiologist for KTx and 59 (54%) were denied by the selection committee, of whom 43 were due to CV risk. On univariate analysis, the variables associated with denial for KTx were: cardiologist denial, denial due to CV risk, Native American race (6% of cohort), higher NT-pro-BNP, prior MI, coronary intervention, positive stress study, anemia, lower EF and lower VO2max (all p&lt;0.05). On multivariate analysis, cardiologist denial was the only significant predictor of denial for KTx (OR: 29.4, p=0.0007). At median follow-up of 15 months, 5 (5%) suffered non-fatal MI, 13 (12%) were hospitalized for HF exacerbation and 17 (16%) died. Only 22 (20%) underwent KTx. Post-KTx, there was one death, one non-fatal MI and 3 hospitalizations for HF. Mean LVEF improvement was 16% (SD12.9). Conclusions: Only 38% of ESRD patients with LVEF≤40% presenting for KTx evaluation were approved and of those, only 52% received KTx. Cardiologist approval was the primary predictor of suitability for KTx. Despite careful selection, prevalence of CV events and mortality after KTx was 23%. There is need for a consistent multidisciplinary approach during KTx evaluation, including cardiologist input, to improve CV outcomes.
Diabetes: BMI cut-offs designed to trigger action are too high for some ethnic populations, say researchers
Authors: Jacqui Wise
Journal: BMJ (2021)

Researchers have called on the National Institute for Health and Care Excellence (NICE) to revise its current guidance on body mass index (BMI) and the risk of developing type 2 diabetes, as they found that a “one size fits all approach” does not work for adults from ethnic minority backgrounds.1

A large, population based cohort study by the team found that Black Caribbean, South Asian, Chinese, and Arab populations living in England had an equivalent risk of type 2 diabetes at substantially lower BMI values than the current cut-offs for obesity.

In 1993 the World Health Organization defined obesity as a BMI of 30 or more. However, subsequent evidence showed that Asian people were susceptible to diabetes at lower BMIs than White people, and in 2013 NICE lowered the …
クラスリン依存的機序を介してADP/AMP分解酵素の内皮細胞表面発現制御により止血を調節するKindlin-2
Authors: Pluskota Elzbieta, Ma Yi, M Bledzka Kamila, Bialkowska Katarzyna, A Soloviev Dmitry, Szpak Dorota, A Podrez Eugene, L Fox Paul, L Hazen Stanley, J Dowling James, MA Yan-Qing, F Plow Edward
Journal: Blood (2013)
Abstract 12611: Preclinical in-vivo Testing and Early Clinical Experience With a Dilatable Expanded-polytetrafluoroethylene Cardiovascular Conduit
Authors: Arush Kalra, Alan W Nugent, Timothy Pirolli, Joseph M Forbess, Paul Tannous, Asad Qadir
Journal: Circulation (2020)

Background: exGraft is an FDA cleared synthetic vascular conduit. A unique property observed is controllable expansion. Preclinical studies with post-implantation balloon dilation and initial use in infants with congenital heart disease (CHD) are described. Methods: Eight piglets (1.5 months (mo)) and 8 lambs (2.5 mo) were implanted with exGraft using an aortic interposition model. Follow up for average 2.5 mo and 3.5 mo respectively allowed somatic growth. Balloon dilation was performed with fluoroscopy and inflation rate was varied to understand optimal expansion method. 3 CHD neonates were implanted with exGraft as a Right Ventricle (RV) to Pulmonary Artery (PA) conduit. Percutaneous balloon dilation of the RV-PA conduit was performed in the interstage period (Table 1). Results: Dilation was achieved to 150% of the original size in 6 piglets and 5 lambs when balloons were inflated gradually up to 6 ATM with a 5 second hold at each ATM. Rapid inflation resulted in anastomotic dehiscence in 2 piglets and 3 lambs. Gradual percutaneous exGraft dilation in 3 neonates was to 150-175% of original diameter to increase pulmonary blood flow and reduce cyanosis. There were no adverse events. Final diameter was confirmed upon explant of conduit (Table 1). Conclusion: In preliminary pre-clinical and clinical experience, safe serial and gradual exGraft expansion has been demonstrated. Expansion of vascular conduits via catheterization expands the options for CHD management. Figure 1: Dilation of 6mm exGraft RV-PA conduit in Patient 1. (A) Baseline angiogram with predominantly proximal stenosis. (B) Fluoroscopy of maximum dilation to 9mm. (C) Final angiogram with increased diameter.
Abstract 16504: Low Disturbed Flow Induces Dynamic Immune Compartment Alterations in Atherogenesis as Revealed by Single Cell Rna-seq
Authors: Lili Qu, Chuan Li, Alyssa Matz, Annabelle Rodriguez-Oquendo, Anthony Vella, Patrick Murphy, Beiyan Zhou
Journal: Circulation (2020)

Low disturbed blood flow (LDF) is a critical contributing factor to atherogenesis but its direct impact on the immune compartment was not well-depict. To fill this knowledge gap, we adopted scRNA-seq to capture sheer-stress induced immune responses during atherogenesis. A partial carotid artery ligation (PCAL) model was selected for its paired comparison of carotid arteries with normal flow (NF) or LDF. Indeed, we observed drastic changes in both endothelial and immune compartment. Macrophages were the most significantly increased population induced by LDF (from 4% to 12% of CD45+ cells) with two well-separated subsets (Mac-c8, Mac-c9). MacSpectrum analyses revealed that Mac-c8 displayed higher inflammatory states than the lipid-laden Mac-c9. Interestingly, three T subtypes displayed unique flow-induced enrichment patterns that were selectively enriched in LDF but not in the NF condition. Furthermore, we created an original algorithms to evaluate the impact of sheer-stress on membrane protein-mediated cell-cell interaction among all cell types in the atheroma. Several pairs of molecular interactions were identified, including multiple APP-ligands interaction pairs and those in BAG2 Signaling. Moreover, signature genes identified in these LDF-induced T cells displayed high correlation to the plaque severity in human artery-aorta samples. Collectively, our study provided a high-resolution and focused analyses of sheer-stress induced immune cell action during atherogenesis. This is also the first identification of unique T subsets, to our knowledge, that are enriched in arterial wall exposed to low and disturbed flow. Further characterization of these cells will provide valuable information to understand and therapeutically treat atherogenesis.
Central Nervous System–Specific Outcomes of Phase 3 Randomized Clinical Trials in Patients With Advanced Breast Cancer, Lung Cancer, and Melanoma
Authors: Kathryn Corbett, Alisha Sharma, Gregory R. Pond, Priscilla K. Brastianos, Sunit Das, Arjun Sahgal, Katarzyna J. Jerzak
Journal: JAMA Oncology (2021)

This cohort study determines the proportion of phase 3 clinical trials for patients with metastatic breast cancer, lung cancer, and melanoma that included patients with brain metastases and/or evaluated central nervous system–specific end points.