tbuckley/cabot-search huggingface dataset:
Anticholinergic Medication Burden–Associated Cognitive Impairment in Schizophrenia
Authors: Yash B. Joshi, Michael L. Thomas, David L. Braff, Michael F. Green, Ruben C. Gur, Raquel E. Gur, Keith H. Nuechterlein, William S. Stone, Tiffany A. Greenwood, Laura C. Lazzeroni, Laura R. MacDonald, Juan L. Molina, John A. Nungaray, Allen D. Radant, Jeremy M. Silverman, Joyce Sprock, Catherine A. Sugar, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, Neal R. Swerdlow, Gregory A. Light
Journal: American Journal of Psychiatry (2021)

Objective: Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients. Methods: Cross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia−2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB). Results: ACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage. Conclusions: Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes–including psychotropics used in usual care–should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.
Abstract 13324: TRACP5b, a Marker of Osteoporosis, is Associated With Adverse Cardiac Events in Hospitalized Patients With Heart Failure
Authors: Yusuke KIMISHIMA, Akiomi YOSHIHISA, Satoshi Abe, Yasuhiro Ichijo, Koichiro Watanabe, Yu Hotuki, Tetsuro Yokokawa, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, ATSUSHI KOBAYASHI, Yasuchika Takeishi
Journal: Circulation (2020)

Introduction: Tarterate-resistant acid phosphatase type 5b (TRACP5b) is derived from osteoclast, and has been used as a maker of osteoporosis. Although heart failure (HF) is associated with catabolic bone remodeling, serum TRACP5b levels have not been rigorously examined in patients with HF. Methods and Results: We conducted a prospective observational study of 688 decompensated HF patients, and patients were divided into tertiles based on serum TRACP5b levels: 1 st (TRACP5b &lt;316 mU/dL, n = 229), 2 nd (316 ≤ TRACP5b &lt;490 mU/dL, n = 229), and 3 rd (490 mU/dL ≤ TRACP5b, n = 230) tertiles. We compared baseline patients’ characteristics and their post-discharge prognosis including cardiac mortality and cardiac events such as cardiac death and worsening HF. Age was significantly higher, and prevalence of female and anemia was significantly higher in the 3 rd tertile than in the 1 st and 2 nd tertiles (age, 71.9 vs. 64.2 and 67.3 years, P&lt;0.001; female, 50.4% vs. 35.4% and 43.2%, P=0.005; anemia, 54.8% vs. 41.9% and 46.7%, P=0.021). In contrast, left ventricular ejection fraction, prevalence of hypertension, diabetes, chronic kidney disease and atrial fibrillation did not differ among the tertiles. In the Kaplan-Meier analysis ( Figure , mean follow up of 426 days), cardiac mortality and cardiac event rates progressively increased from the 1 st to the 3 rd tertiles (cardiac mortality, 3.1%, 5.2% and 8.7%, log-rank P =0.024; cardiac event rates, 10.9%, 14.0% and 20.4%, log-rank P=0.010). In the multivariable Cox proportional hazard analysis, the 3 rd tertile was found to be an independent predictor of cardiac mortality and cardiac events (cardiac mortality, hazard ratio 1.381, P=0.035; cardiac events, hazard ratio 1.664, P=0.044). Conclusion: High serum levels of TRACP5b, a marker of osteoporosis, is associated with adverse prognosis in HF patients.
Abstract 15615: Association of Covid-19 With QTc Prolongation: A Need for Routine Ecg Screening
Authors: Adarsh S Vangala, Michelle S Harkins, Gregory J Mertz, Ishan R Shah, Madhura Myla, Mark W Sheldon, Alexander Nihart, Veena Raizada
Journal: Circulation (2020)

Introduction: Coronavirus Disease 2019 (COVID-19) has a high risk of death due to respiratory and cardiac complications. Internalization of the virus in the heart may derange myocyte functions such as repolarization, manifesting as QT prolongation on surface electrocardiograms (ECGs). Long QT is associated with cardiac arrhythmias, including sudden arrhythmic death. Previous studies of corrected QT (QTc) in Covid-19 have not controlled for other QTc prolonging comorbidities. Hypothesis: This study investigates whether COVID-19 is associated with prolonged QTc independent of other causes of QTc prolongation. Methods: QTc values were taken from ECGs of 36 patients with COVID-19 admitted to intensive care and 70 healthy age- and gender-matched control subjects. Patients were excluded if they received QTc-prolonging drugs, had hypokalemia, hypocalcemia, or hypomagnesemia, or history of excessive alcohol use. QTc values of COVID-19 patients were compared against normal control subjects. Results: The COVID-19 group included 15 females and 21 males with hypertension (n=11) and diabetes mellitus (n=5) as the most common comorbidities. Electrolytes were normal (K, 3.97 ± 0.41 mEq/L; Mg, 2.41 ± 0.38 mg/dL; and corrected Ca, 10.60 ± 0.60 mg/dL). QTc (msec) was significantly prolonged in COVID-19 compared with control subjects (total 469 ± 36.1 vs 418 ± 17.8; females, 475±29.2 vs 424 ± 11.4, and males 465 ± 40.5 vs 416 ± 19.9; all p&lt;0.001). Conclusions: COVID-19 alone, without an associated QT prolonging etiology, is associated with QTc prolongation. Ventricular arrhythmias may be more likely to affect women with COVID-19 than men with the disease. Therefore, it is recommended that, in COVID-19 patients, electrolytes be maintained within normal limits and QT prolonging drugs be avoided.
Direct oral anticoagulants for myeloproliferative neoplasms: results from an international study on 442 patients
Authors: Tiziano Barbui, Valerio De Stefano, Alessandra Carobbio, Alessandra Iurlo, Alberto Alvarez-Larran, Beatriz Cuevas, Francisca Ferrer Marín, Alessandro M. Vannucchi, Francesca Palandri, Claire Harrison, Hassan Sibai, Martin Griesshammer, Massimiliano Bonifacio, Elena M. Elli, Chiara Trotti, Steffen Koschmieder, Giuseppe Carli, Giulia Benevolo, Jean-Christophe Ianotto, Swati Goel, Anna Falanga, Silvia Betti, Daniele Cattaneo, Eduardo Arellano-Rodrigo, Lara Mannelli, Nicola Vianelli, Andrew Doyle, Vikas Gupta, Kai Wille, Douglas Tremblay, John Mascarenhas
Journal: Leukemia (2021)
New Strategy in Tissue Engineered Valve: Development of Autologous Valved-Conduit with the Sinus of Valsalva (BIOVALVEs)
Authors: Yamanami Masashi, Yahata Yuki, Fujiwara Megumi, Ueda Hatsue, Tajikawa Tsutomu, Ohba Kenkichi, Watanabe Taiji, Kanda Keiichi, Uechi Masami, Yaku Hitoshi, Nakayama Yasuhide
Journal: Circulation (2010)
Bringing safe and effective therapies to premenopausal women with breast cancer: efforts to broaden eligibility criteria
Authors: J.J. Gao, D. Krol, P. Narayan, F. Cardoso, M.M. Regan, M.P. Goetz, S.A. Hurvitz, L. Mauro, C. Hodgdon, C.P. Miller, B. Booth, E. Bloomquist, G. Ison, C. Osgood, V. Bhatnagar, L. Fashoyin-Aje, R. Pazdur, L. Amiri-Kordestani, J.A. Beaver
Journal: Annals of Oncology (2021)
Expression of YKL-40 in Nipple Aspirate Fluid and Serum Is Altered in Breast Cancer: Preliminary Results
Authors: Wenyi Qin, Weizhu Zhu, John Hewett, Lisa Schlatter, Edward Sauter
Journal: Cancer Research (2006)

652  Background: YKL-40 (cartilage gp-39), is a secreted protein and a growth factor for connective tissue that stimulates the migration of endothelial cells. Preliminary investigations of YKL-40 demonstrated its role in rheumatoid and osteoarthritis (RA and OA), and levels of YKL-40 in serum in RA and OA patients are significantly higher than healthy controls. YKL-40 is secreted by cancer cells and overexpressed in epithelial cancers and gliomas, although its function is unknown. Increased serum YKL-40 in women with breast cancer is associated with a worse prognosis. Nipple aspirate fluid (NAF) is a physiologic fluid secreted from the breast ductal system that contains concentrated proteins secreted from the ductal epithelium. NAF collection is safe, reliable and noninvasive. Our previous studies suggest that NAF analysis may provide a promising noninvasive approach to detect pre and invasive breast cancer. The aims of this study were to 1).compare the concentration of YKL-40 in NAF vs. serum, and 2) assess if expression of YKL-40 in NAF and/or serum was associated with the presence of breast cancer. Materials and Method: 101 NAF (47 from women with breast cancer, 54 without) and 66 (29 with cancer, 37 without cancer) matched serum specimens were analyzed using a commercial ELISA kit (QUIDEL Corporation, San Diego, CA) according to the manufacturer9s protocol. Results: Median YKL-40 levels in NAF were 17,770 and 40,893 ng/mL for subjects with and without breast cancer, respectively. Median serum YKL-40 levels were 67 and 42 ng/mL for subjects with and without breast cancer, respectively. NAF YKL-40 levels in women with cancer were lower (p=0.039) than in women without, whereas serum levels were not significantly different based on cancer status (p=0.10). Conclusion: We observed an inverse correlation between NAF YKL-40 and the presence of breast cancer, and a nonsignificant trend for a direct correlation between serum levels of YKL-40 and breast cancer. Mechanisms to explain this different association with an organ specific vs. a systemic bodily fluid requires further study, as does the possible usefulness of this marker in NAF to determine if a woman has breast cancer.
Synergistic Effects of Hepatic Lipase (HL) Promoter And CETP Promoter Polymorphism on Increased HDL-C Levels in Both Gender
Authors: Takata M, Inazu A, Katsuda S, Miwa K, Kawashiri M, Nohara A, Higashikata T, Kobayashi J, Koizumi J
Journal: Circulation (2005)
Abstract 15784: Left Ventricular Structural Remodeling and Cardiomyopathy in Duchenne Muscular Dystrophy Carriers
Authors: Hannah Lehrenbaum, Michinari Hieda, Daniel Cheeran, Yunbeen Bae, Colby Ayers, Faris Araj, Alpesh Amin, James A De Lemos, Mark H Drazner, Ronald M Peshock, Vlad G Zaha, Benjamin D LEVINE, Pradeep P Mammen
Journal: Circulation (2020)

Introduction: Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder. DMD-associated cardiomyopathy is the primary mode of premature death in the majority of male DMD patients, but the prevalence of cardiomyopathy and its clinical significance in female DMD carriers is less well characterized. Hypothesis: We hypothesized that a significant proportion of DMD carriers develop maladaptive left ventricular (LV) structural remodeling and cardiomyopathy over time. Methods: A cross-sectional study was undertaken comparing cardiac magnetic resonance imaging (cMRI) and cardiopulmonary stress test (CPX) parameters between DMD carriers and healthy age- and sex-matched controls from the Dallas Heart Study (DHS). Demographic data, cMRI parameters, and CPX parameters were collected retrospectively on 30 consecutive DMD carriers and 26 control DHS subjects. Results: Overall, DMD carriers had a significantly lower LVEF compared to DHS controls (58+8% vs 70+7%, p&lt; 0.0001). The overall prevalence of reduced LVEF in DMD carriers (defined as LVEF &lt;60%) was 63% compared to 8% in DHS controls. The volumetric variables indexed to body surface area (LVEDVi and LVESVi) were significantly higher in DMD carriers compared to control subjects (72+14 ml/m 2 vs 58+7, p&lt; 0.0001; 31+10 ml/m 2 vs 17+5, p&lt; 0.0001; respectively). LV concentricity was also significantly lower among all DMD carriers compared to DHS controls (3.10+0.65 g/mL 0.67 vs 3.73+0.79, p =0.002). LV concentricity was significantly lower in DMD carriers with reduced EF compared to controls (3.09+0.51 g/mL 0.67 vs 3.73+0.79, p = 0.012), while DMD carriers with preserved EF also had reduced concentricity compared to controls (3.12+0.86 vs 3.73+0.79, p = 0.054). Finally, peak VO 2 was lower in DMD carriers compared to DHS controls (23+6 ml/kg/min vs 25+4, p =0.076), though this difference did not reach statistical significance. Conclusions: Collectively, the data suggest that middle-aged female DMD carriers are at greater risk of developing left ventricular systolic dysfunction and cardiomyopathy associated with decreased exercise capacity. A possible mechanism driving the development of this cardiomyopathy is progressive, maladaptive left ventricular dilatation and cardiac atrophy.
Comment on “Nuclear receptor PXR targets AKR1B7 to protect mitochondrial metabolism and renal function in AKI”
Authors: Zhilin Luan, Wenhua Ming, Cong Zhang, Xiaoxiao Huo, Feng Zheng, Xiaoyan Zhang, Youfei Guan
Journal: Science Translational Medicine (2021)

The nuclear pregnane X receptor may not protect against ischemia/reperfusion-induced acute kidney injury in mice.
Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial
Authors: José Manuel Pérez-García, Geraldine Gebhart, Manuel Ruiz Borrego, Agostina Stradella, Begoña Bermejo, Peter Schmid, Frederik Marmé, Santiago Escrivá-de-Romani, Lourdes Calvo, Nuria Ribelles, Noelia Martinez, Cinta Albacar, Aleix Prat, Florence Dalenc, Khaldoun Kerrou, Marco Colleoni, Noemia Afonso, Serena Di Cosimo, Miguel Sampayo-Cordero, Andrea Malfettone, Javier Cortés, Antonio Llombart-Cussac
Journal: The Lancet Oncology (2021)
Abstract 15732: Transcatheter Aortic Valve Replacement as a Path to Transplant: Similar Short-term Outcomes in Liver and Renal Failure
Authors: Hope Caughron, Devang Parikh, Zev Allison, Vaikom Mahadevan
Journal: Circulation (2020)

Introduction: Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement in patients with predicted poor surgical outcomes due to end stage liver disease (ESLD) or end stage renal disease (ESRD), though there remains minimal data regarding outcomes and treatment strategy in this population. This study evaluates in-hospital, 30-day, and 1-year outcomes after TAVR in a cohort of patients with ESLD and/or ESRD compared to a cohort without these comorbidities. Methods: We retrospectively compared 317 consecutive patients (N=37 ESLD and ESRD, N=286 without ESLD or ESRD) age &gt;18 who underwent transfemoral or transssubclavian TAVR at University of California San Francisco Medical Center from August 1 st , 2014 to April 1 st , 2020. Results: The ESLD and ESRD group had younger patients (69.8±11.5 vs 79.1±9.8, p&lt;0.01), a higher incidence of diabetes mellitus (54.8% vs 28.3%, p&lt;0.01), and higher STS-PROM scores (7.8±6.5 vs 4.7±3.9, p&lt;0.01). Comparing the ESLD and ESRD to the control group, there were similar rates of in-hospital cerebrovascular events (3.2% vs 3.5%, p=0.94), vascular complications (6.5% vs 7.0%, p=0.91), and mortality (0.0%, vs 1.7%, p=0.46) with more bleeding events at discharge (9.7% vs 2.1%, p=0.01) and 1-year (29.2% vs 10.4%, p=0.01). Mortality rates were similar at 30-days (3.2% vs 2.1%, p=0.69) and 6-months (3.4% vs 2.8%, p=0.83), with a trend towards higher mortality in the ESLD and ESRD group at 1-year (16.7% vs 7.8%, p=0.15) from primarily noncardiac causes. Readmission rates were higher in the ESLD and ESRD cohort at 6-months (58.6% vs 27.2%, p&lt;0.01) and 1-year (66.7% vs 40.6%, p=0.02). One patient received dual kidney-liver transplant, 1 patient received a liver transplant, and 8 patients remain on the transplant wait-list. Conclusion: Patients with ESLD and ESRD who underwent TAVR had higher rates of bleeding events and noncardiovascular readmissions with similar rates of mortality at discharge, 30-days, and 6-months when compared to patients without these comorbidities. This study suggests that TAVR may be a safe path to transplant in patients with liver or renal failure and aortic valve pathology, though additional studies are necessary to confirm these findings.
Microvasculatures: Multiphoton‐Guided Creation of Complex Organ‐Specific Microvasculature (Adv. Healthcare Mater. 10/2021)
Authors: Samuel G. Rayner, Caitlin C. Howard, Christian J. Mandrycky, Stefan Stamenkovic, Jonathan Himmelfarb, Andy Y. Shih, Ying Zheng
Journal: Advanced Healthcare Materials (2021)
Abstract P140: Dynamic Relationships Between Body Fat And Circulating Adipokine Levels From Adolescence To Young Adulthood: The Santiago Longitudinal Study
Authors: Daeeun Kim, Annie Green Howard, Estela Blanco, Raquel Burrows, Paulina Correa, Cecilia Albala, José L Santos, Bárbara Angel, Betsy Lozoff, Anne E Justice, Sheila Gahagan, Kari E North
Journal: Circulation (2021)

Introduction: Adipose tissue secretes adipokines such as adiponectin and leptin playing important roles in energy metabolism. Adiponectin has a protective effect against cardiometabolic diseases (CMD), whereas leptin increases risk of CMD. Although associations between plasma adipokines and body fat mass have been established, most have been cross-sectional, limiting causal inferences. Hypothesis: We hypothesize that 1. adipokines can affect body fat accumulation via the regulation of energy homeostasis and 2. adipose tissue can affect the amount of adipokines secreted. Thus, we assessed the associations between body fat percent (BF%) and adipokines during adolescence and 6 years later. Methods: Measurements for plasma leptin (N=622) and adiponectin (N=565) were available at age 16 and 22 in participants from the Santiago Longitudinal Study. BF% was measured by dual X-ray absorptiometry. Structural equation models were used to estimate longitudinal associations of BF% and adipokines at baseline and with 6-year changes in these values, adjusted for sex, time to follow-up, baseline age, physical activity, nutrition quality, smoking status, and alcohol consumption. Results: Effect estimates are shown in Figure 1 . We found evidence of association between baseline adipokine and BF% change and baseline BF% and adipokine change with the one notable exception a lack of association between baseline BF% and adiponectin change. Conclusions: Leptin and BF% were positively associated longitudinally, but the longitudinal associations between adiponectin and BF% were counterintuitive or non-significant. While there might be a close long-term relationship between leptin levels and body fat accumulation, the long-term relationship between adiponectin levels and body fat accumulation might develop after the adolescence and young adulthood transition.
Paroxysmal Nocturnal Hemoglobinuria Results from Initial Clonal PIG-a Mosaicism
Authors: Michael J. Clemente, Bartlomiej Przychodzen, Cassandra M. Hirsch, Bhumika J. Patel, Taha Bat, Yasunobu Nagata, Marcin W. Wlodarski, Hideki Makishima, Jaroslaw P. Maciejewski
Journal: Blood (2017)
58P Cost-effectiveness analysis of trastuzumab emtansine versus trastuzumab for Chinese patients with residual invasive HER2-positive early breast cancer
Authors: X. Guan, H-C. Li, Q-J. Chen, B. Hua, J-J. Li, F. Ma, Y-S. Wang, H. Xu, C. Liu, Q. Yang, A-X. Ma
Journal: Annals of Oncology (2021)
Abstract 12931: Myocardial Regeneration in End-stage Heart Failure After Left Ventricular Unloading
Authors: Tiberiu Pana, Ingrid Kepinski, Adam Fairbourn, Aneela Afzal, Jainy Savla, Pradeep P Mammen, Mark H Drazner, Rathan Subramaniam, Eric N Olson, Stavros G Drakos, Vlad G Zaha, Hesham A Sadek
Journal: Circulation (2020)

Introduction: Left Ventricular Assist Devices (LVAD) decrease cardiac mechanical work and metabolic demand and may decrease cardiomyocyte oxidative stress, followed by cell cycle re-entry and cell regeneration. We tested whether LVAD long-term support is associated with myocardial regeneration. Methods: Viability fluorodeoxyglucose (18FDG) - positron-emission tomography scans were performed &gt;3 months after LVAD implantation and every 6 months thereafter. 4 patients aged 18-70 with end-stage non-ischemic (NICM, n=3) or ischemic cardiomyopathy (ICM, n=1) were included. Low metabolic activity myocardial regions of interest (ROI) at &lt;15th percentile of relative 18FDG signal intensity were identified on the baseline scan. Global signal and co-registered low-intensity ROIs were analyzed on subsequent scans vs. baseline. Results: LV ejection fraction ranged 0-35% at baseline. Two patients (LVAD speed 2660 rotations per minute - RPM, output 3.4-4.1 and 5.6-5.9 liters per minute (LPM), respectively) underwent 2 scans before cardiac transplantation, exhibiting borderline increased global signal (1-4%) and significantly increased 18FDG signal in the baseline low-intensity ROI on the follow-up scan (67.7, 75.7%). The other 2 patients (LVAD parameters: 5600 RPM/ 4.6-5.8 LPM; 9200 RPM/ 4.3-4.8 LPM) exhibited decreased global 18FDG signal (10-16%) and increased signal in the co-registered baseline low-intensity ROIs (1.7-21.5%) (Figure). Conclusions: LVAD long-term support is associated with a global decrease in myocardial 18FDG uptake signal over time, and with increased viability signal in baseline low-intensity ROIs, suggestive of myocardial regeneration in metabolically inactive regions. Future research is required to identify patient subgroups that are most likely to exhibit high regeneration potential upon long-term LVAD support.
179P Discordance rates of clinicopathological features in bilateral breast cancer
Authors: A. Aranda-Gutierrez, A.S. Ferrigno, B.F. Vaca-Cartagena, F.A. Gonzalez-Mondellini, A. Becerril-Gaitán, M. Roman-Zamudio, M.A. Acosta-Sandoval, M. Torres-Leal, C.A. Treviño-Alanis, H. Diaz-Perez, S. Cardona, C. Villarreal-Garza
Journal: Annals of Oncology (2021)