tbuckley/cabot-search huggingface dataset:
Abstract 12050: The CHA2DS2-VASc Score Predicts High Mortality in Hospitalized Heart Failure Patients
Authors: Shunsuke Watanabe, Akiomi Yoshihisa, Yuki Kanno, Mai Takiguchi, Shunsuke Miura, Akihiko Sato, Takeshi Shimizu, Yuichi Nakamura, Hiroyuki Yamauchi, Takashi Owada, Satoshi Abe, Satoshi Suzuki, Masayoshi Oikawa, Nobuo Sakamoto, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2015)

Background: Atrial fibrillation (AF) is common in patients with heart failure (HF). CHA2DS2-VASc score is an originally risk assessment tool for stroke in patients with AF. Recently, it has been reported that CHA2DS2-VASc score is associated with mortality in patients with acute coronary syndrome with or without AF. We aimed to examine the value of the CHA2DS2-VASc score as a risk assessment tool in patients with HF. Methods and Results: Consecutive 1011 patients admitted for treatment of HF were divided into three groups based on CHA2DS2-VASc score: low score group (CHA2DS2-VASc score 1-3, n=316), moderate score group (CHA2DS2-VASc score 4-6, n=549) and high score group (CHA2DS2-VASc score 7-9, n=145). Of 1011 HF patients, 387 (38.3%, mean age 70.5 years, male 247) had AF. We compared patient characteristics and prospectively followed all-cause mortality among the three groups. The high score group, as compared to low and moderate score groups, had higher cardio-ankle vascular index (9.0 vs. 8.5, 7.9, P=0.001), lower levels of hemoglobin (11.2 vs. 12.1, 13.4 g/dl, P&lt;0.001), sodium (138.5 vs. 138.4, 139.4 mEq/l, P=0.002) and estimated GFR (40.0 vs. 52.7, 64.3 ml/min/1.73m 2 , p&lt;0.001). In contrast, left ventricular ejection fraction was similar among the three groups. Importantly, all-cause mortality was higher in high score group than in low and moderate score groups (P&lt;0.001). In the multivariable Cox proportional hazard analyses, CHA2DS2-VASc score was an independent predictor of all-cause mortality (all patients: HR 1.203, P&lt;0.001; AF patients: HR 1.152, P=0.009; non-AF patients: HR 1.228, P&lt;0.001). Conclusions: The CHA2DS2-VASc score was an independent predictor of all-cause mortality in HF patients with or without AF. CHA2DS2-VASc score may help to identify patients at high risk for mortality and need for optimization of risk-reducing treatment in HF patients.
Abstract 17041: Effect of Sodium-glucose Cotransporter 2 Inhibitor on Vascular Endothelial Function and Diastolic Function in Patients With Heart Failure With Preserved Ejection Fraction (hfpef)
Authors: Takaaki Sakai, Shinichiro Miura
Journal: Circulation (2017)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a common disease with high incidence and increasing prevalence. The sodium-glucose cotransporter 2 (SGLT2) inhibitors are a n...
FRI0028 Suppression of experimental arthritis by treatment with a novel dmard, smp-114
Authors: F Nishikaku, S Tagashira, K Hagi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> A more promising therapeutic approach to rheumatoid arthritis would be to maintain joint function. Our studies have been performed with the above goal in mind and showed that some azole compounds meet these requirements. SMP-114, a novel isoxazole derivative, was selected from them and characterised as a compound with antiarthritic activity and without any cyclooxgenase inhibitory activity. <h3>Objectives</h3> The objective of these studies was to evaluate the effect of SMP-114 on joint oedema, bone resorption and ankylosis in experimental models of rheumatoid arthritis. <h3>Methods</h3> Adjuvant arthritis was induced in Lewis rats by a single injection of Mycobacterium butyricum in the plantar surface of right hindpaw on day 0, and animals were treated therapeutically (days 10–24 or days 17–21) with SMP-114. Anti-inflammatory activity was determined by measurements of paw swelling. The protective effect on joint integrity was determined by measuring radiographic and histological changes. Collagen-induced arthritis was induced in DBA/1J mice. Animals were immunised intradermally at the base of the tail with type II collagen (day 0 and day 21). SMP-114 was administered orally (days 0–49). Efficacy was assessed clinically, histologically and radiographically. <h3>Results</h3> Treatment (days 10–24) of adjuvant arthritis with SMP-114 significantly reduced paw oedema with a minimum effective dose of 10 mg/kg. This was accompanied by a more extensive reduction in bone and cartilage destruction around the metatarsal-phalangeal joint, as assessed by histologic and radiographic examinations. SMP-114 was also able to significantly ameliorate full-blown adjuvant arthritis. When daily administration of SMp-114 began on day 17, well into the chronic destructive phase, the agent produced a dose-response effect on paw oedema, with a minimum effective dose of less than 2.5 mg/kg. The compound (range 20 80 mg/kg) demonstrated a capacity for ameliorating joint inflammation (paw oedema) and protecting joint structure coincident with a decrease in the number of osteoclasts in articular lesions in mice with collagen-induced arthritis. SMP-114 also showed anti-fibroblastic effect and, as a result, reduced a frequency of development of ankylosis in these models. This profile of activity was not shared by nonsteroidal anti-inflammatory drugs such as indomethacin. <h3>Conclusion</h3> Our studies show that SMP-114 has remarkable protective effects on the joint of adjuvant arthritic rats and collagen-induced arthritic mice. These data suggest that SMP-114 will show greater benefit in slowing joint destruction and disease progression in rheumatoid arthritis in humans.
Prevalence of potentially inappropriate prescribing in older people in primary care and its association with hospital admission: longitudinal study
Authors: Teresa Pérez, Frank Moriarty, Emma Wallace, Ronald McDowell, Patrick Redmond, Tom Fahey
Journal: BMJ (2018)

Abstract Objective To determine whether hospital admission is associated with potentially inappropriate prescribing among older primary care patients (aged ≥65 years) and whether such prescribing was more likely after hospital admission than before. Design Longitudinal study of retrospectively extracted data from general practice records. Setting 44 general practices in Ireland in 2012-15. Participants Adults aged 65 years or over attending participating practices. Exposure Admission to hospital (any hospital admission versus none, and post-admission versus pre-admission). Main outcome measures Prevalence of potentially inappropriate prescribing assessed using 45 criteria from the Screening Tool for Older Persons’ Prescription (STOPP) version 2, analysed both as rate of distinct potentially inappropriate prescribing criteria met (stratified Cox regression) and binary presence of potentially inappropriate prescribing (logistic regression) and adjusted for patients’ characteristics. A sensitivity analysis used matching with propensity scores based on patients’ characteristics and diagnoses. Results Overall 38 229 patients were included, and during 2012 the mean age was 76.8 (SD 8.2) years and 43% (13 212) were male. Each year, 10.4-15.0% (3015/29 077 in 2015 to 4537/30 231 in 2014) of patients had at least one hospital admission. The overall prevalence of potentially inappropriate prescribing ranged from 45.3% (13 940/30 789) of patients in 2012 to 51.0% (14 823/29 077) in 2015. Independently of age, sex, number of prescription items, comorbidity, and health cover, hospital admission was associated with a higher rate of distinct potentially inappropriate prescribing criteria met; the adjusted hazard ratio for hospital admission was 1.24 (95% confidence interval 1.20 to 1.28). Among participants who were admitted to hospital, the likelihood of potentially inappropriate prescribing after admission was higher than before admission, independent of patients’ characteristics; the adjusted odds ratio for after hospital admission was 1.72 (1.63 to 1.84). Analysis of propensity score matched pairs showed a slight reduction in the hazard ratio for hospital admission to 1.22 (1.18 to 1.25). Conclusion Hospital admission was independently associated with potentially inappropriate prescribing. It is important to determine how hospital admission may affect appropriateness of prescribing for older people and how potential adverse consequences of admission can be minimised.
Reply to Jie Gu, Dongjie Li, and Xiaobo Zhang's Letter to the Editor re: Guido Giusti, Silvia Proietti, Moisés E. Rodríguez-Socarrás, et al. Simultaneous Bilateral Endoscopic Surgery (SBES) for Patients with Bilateral Upper Tract Urolithiasis: Technique and Outcomes. Eur Urol 2018;74:810–5
Authors: Silvia Proietti, Moisés E. Rodríguez-Socarrás, Brian H. Eisner, Guido Giusti
Journal: European Urology (2018)
Abstract 18672: Effects of Prolonged Space Flight on Cardiac Structure and Function
Authors: Shuaib M Abdullah, Jeffrey L Hastings, Shigeki Shibata, Steven H Platts, Douglas R Hamilton, James D Thomas, Douglas E Hughes, Michael W Bungo, Benjamin D Levine
Journal: Circulation (2013)

Background: “Cardiovascular deconditioning” induced by bed rest, a model for spaceflight, causes cardiac atrophy of ~1%/wk in men and women. Data from small numbers of astronauts NOT performing any exercise countermeasures suggest the rate of atrophy for spaceflight may be even greater. However, cardiac morphology has not been assessed using high resolution techniques before and after prolonged space flight in the International Space Station (ISS) era. Methods: Cardiac magnetic resonance imaging (MRI) to assess left and right ventricular volumes and masses, and fibrosis by late gadolinium enhancement was performed within 2 months before and 3 days after 4-6 months in space aboard the ISS on 13 astronauts. Results: Eight men and 5 women (mean age 49.5 years) astronauts participated (mean ISS duration 153 days). All performed regular and intensive combined endurance and strength training countermeasures inflight, and most did so at a higher intensity than they did pre-flight. No significant differences in left ventricular or right ventricular end-diastolic and -systolic volumes were observed (Table). Both right and left ventricular mass was preserved, and supine stroke volume was maintained. No evidence of myocardial fibrosis was seen in 11 astronauts who had late gadolinium enhancement performed before and after space flight. Conclusions: No deleterious effects of prolonged space flight were seen on cardiac structure and function. These results suggest that an appropriate astronaut exercise regimen may counteract the effects of “cardiovascular deconditioning” during prolonged space flight up to 6 months duration.
Abstract 14115: Systemic Oxygen Consumption Trends in Post-Cardiac Arrest
Authors: Amy J Uber, Anne V Grossestreuer, Parth V Patel, Michael W Donnino, Katherine M Berg
Journal: Circulation (2017)

Introduction: Mitochondrial dysfunction is thought to be a driver of ischemia-reperfusion injury after cardiac arrest (CA). Prior work suggests low oxygen consumption (VO2), driven by decreased oxy...
Abstract 20760: Does Deeper Hypothermia Reduce the Risk of Acute Kidney Injury After Circulatory Arrest for Aortic Arch Surgery?
Authors: Babatunde A Yerokun, Jorn Karhausen, David N Ranney, Ehsan Benrashid, Hanghang Wang, Jeffrey Keenan, Jacob Schroder, Mani Daneshmand, Jeffrey G Gaca, G. Chad Hughes
Journal: Circulation (2017)

Introduction: The effect of hypothermic circulatory arrest temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between hypothermic cir...
Quantification of Residual Bone Marrow Plasma Cells By Eight-Color Flow Cytometry in Patients with Multiple Myeloma: Comparison between the Dura Clone RE PC Panel (Beckman Coulter) and the Euro Flow MM-MRD Panel (Cytognos)
Authors: Kentaro Narita, Takeshi Yoroidaka, Momoko Fujisawa, Hiroyuki Takamatsu, Shinji Nakao, Kosei Matsue
Journal: Blood (2018)
Acute Respiratory Failure in the Adult
Authors: H. Pontoppidan, B. Geffin, E. Lowenstein
Journal: New England Journal of Medicine (1972)

Assessment of Respiratory FunctionAssessment of respiratory function is indispensable for the provision of adequate respiratory care at all stages of treatment: early diagnosis of pulmonary complications; estimation of the efficacy of preventive measures; establishment of criteria for institution of tracheal intubation and artificial ventilation as well as discontinuance (weaning).Table 2 lists the respiratory-function tests that we consider useful in the management of ARF. Those used routinely are easily performed, sensitive, reproducible during both spontaneous and controlled ventilation, and generally applicable at the bedside, with a minimum of discomfort to the patient. Indications, methodology and interpretation in different types of respiratory . . .
Exaggeration of PFS by blinded, independent, central review (BICR)
Authors: A. Stone, V. Gebski, R. Davidson, R. Bloomfield, J.W. Bartlett, A. Sabin
Journal: Annals of Oncology (2018)

Recent published studies have shown meaningful discrepancies between local investigator and blinded, independent, central review (BICR) assessed median progression-free survival (PFS). When the local review but not BICR shows progression, generally, no further assessments are carried out and patients are censored in the BICR analysis, leading to violation of the statistical assumptions of independence between censoring and outcome used in survival analysis methods.
Researcher questions new study suggesting benefits of breast screening
Authors: Susan Mayor
Journal: BMJ (2018)

A leading researcher in breast cancer screening has questioned the validity of a new observational study from Sweden which found greater benefit with breast cancer treatment in women taking part in screening compared with those not screened.1

“The study compared women who attended screening and those who were invited but did not attend screening. This is problematic in many ways because, when you compare those who comply with those who do not, you are comparing apples and pears,” said Mette Kalager, associate professor with the Clinical Effectiveness Research Group, University of Oslo, Norway, and previously head of the Norwegian Breast Cancer Screening Program. She added that changes in breast cancer treatment and care over time may also have influenced outcomes.

The effectiveness of breast cancer screening has traditionally been assessed by randomised trials of sending women screening invitations on breast cancer mortality. But the authors of the new study said …
Abstract #1397: Effects of exposure to metal-rich air particles on miR-146a, miR-222 and miR-21 in occupationally exposed subjects
Authors: Valentina Bollati, Barbara Marinelli, Pietro Apostoli, Matteo Bonzini, Valeria Pegoraro, Joel Schwartz, Letizia Tarantini, Pier Alberto Bertazzi, Andrea Baccarelli
Journal: Cancer Research (2009)

Background: Inhalation of air particles and their metal components has been associated with increased risk of lung cancer. MiRNAs are highly conserved, non-coding small RNAs that regulate gene expression at the post-transcriptional level. Changes in the expression of miR-146a have been implicated in both development of multiple cancers and negative regulation of inflammation induced via the innate immune response. miR-21 promotes cell transformation, tumor growth, as well as well as invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. miR-222 is linked to a cell cycle checkpoint that ensures cell survival by coordinating competency for initiation of S phase with growth factor signaling pathways that stimulate cell proliferation. Objective: To identify effects of exposure to metal-rich particulate on miR-21, miR-222 and miR-146a expression in workers of an electric furnace steel plant with well characterized exposure. Methods: We measured miR-21, miR-222 and miR-146a expression in blood RNA obtained from 63 workers on the first day of a workweek (baseline) and after three days of work (post exposure). The relative expression of miRNAs was measured by real-time PCR using RNU48 as endogenous controls. Relative quantification of miRNA expression was calculated using the 2-\#916;\#916;Ct method. We determined individual exposure to inhalable particles and metals for all subjects. Results: We found under-expression of miR-21 (\#916;mean=1.1; p=0.05) and miR-222 (\#916;mean=1.9; p=0.002), in post exposure measures when compared to baseline. This decrease was negatively associated with exposure to airborne lead level for miR222 expression (\#946;=-2.75, p=0.01) while no association between miR-21 and exposure to airborne particles and metals was observed. We found also an over-expression of miR-146a associated with exposure to airborne lead level (\#946;=5.28, p=0.005) and airborne cadmium level (\#946;=3.06, p=0.04) with no differences between pre and past axposure. Conclusions: Exposure to inhalable metal-rich particles modifies miR-21, miR-222 and miR146a expression.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1397.
Comparison of Anesthesia Times and Billing Patterns by Anesthesia Practitioners
Authors: Eric C. Sun, Richard P. Dutton, Anupam B. Jena
Journal: JAMA Network Open (2018)

Most physicians must exercise discretion in choosing billing details that determine payment for their services. Understanding the degree to which physicians inappropriately use this discretion has important implications for payment policies. However, separating higher case complexity from inappropriate billing has made this a challenging issue to study. Anesthesia offers a useful test case because practitioners are partly compensated by self-reported length of time (anesthesia time) spent on a case.To characterize the incidence and consequences of inappropriate billing practices among anesthesia practitioners.In this cross-sectional study of data from a large anesthesia registry, 6 261 955 procedures performed by 4221 anesthesia practitioners (physician anesthesiologists, nurse anesthetists, and anesthesiologist assistants) between January 1, 2010, and March 31, 2015, were studied. A total of 3047 practitioners practiced primarily in community hospitals, whereas 453 practiced primarily in university hospitals and 721 practiced in other settings (eg, specialty hospital).Practitioners with anomalous patterns were identified as those reporting an unusually high number of anesthesia times ending in a multiple of 5 minutes (eg, 65 minutes).Incidence of anomalous patterns among anesthesia practitioners and the increase in anesthesia times associated with these patterns.This study included 4221 practitioners who each performed at least 300 anesthetic procedures. Practitioners in the top fifth percentile reported anesthesia times ending in a multiple of 5 minutes a mean (SD) of 53.7% (13.7%) of the time (range, 36.8%-96.1%), whereas practitioners in the 6th to 10th percentiles reported anesthesia times ending in a multiple of 5 minutes a mean (SD) of 31.8% (2.0%) of the time (range, 29.2%-36.7%). Practitioners in the top fifth percentile submitted billing for anesthesia times that exceeded the expected time by a mean of 21.5 minutes (95% CI, 15.8-27.1 minutes).In this study, findings suggest that anesthesia practitioners with the highest tendency to report anesthesia times ending in a multiple of 5 minutes did so with high frequency, which reflects anomalous billing. These practitioners also sought payment for longer-than-expected anesthesia times, which would correspond to higher payment for their services.
Peptide-based PET quantifies target engagement of PD-L1 therapeutics
Authors: Dhiraj Kumar, Ala Lisok, Elyes Dahmane, Matthew McCoy, Sagar Shelake, Samit Chatterjee, Viola Allaj, Polina Sysa-Shah, Bryan Wharram, Wojciech G. Lesniak, Ellen Tully, Edward Gabrielson, Elizabeth M. Jaffee, John T. Poirier, Charles M. Rudin, Jogarao V.S. Gobburu, Martin G. Pomper, Sridhar Nimmagadda
Journal: Journal of Clinical Investigation (2018)

Immune checkpoint therapies have shown tremendous promise in cancer therapy. However, tools to assess their target engagement, and hence the ability to predict their efficacy, have been lacking. Here, we show that target engagement and tumor-residence kinetics of antibody therapeutics targeting programmed death ligand-1 (PD-L1) can be quantified noninvasively. In computational docking studies, we observed that PD-L1–targeted monoclonal antibodies (atezolizumab, avelumab, and durvalumab) and a high-affinity PD-L1–binding peptide, WL12, have common interaction sites on PD-L1. Using the peptide radiotracer [64Cu]WL12 in vivo, we employed positron emission tomography (PET) imaging and biodistribution studies in multiple xenograft models and demonstrated that variable PD-L1 expression and its saturation by atezolizumab, avelumab, and durvalumab can be quantified independently of biophysical properties and pharmacokinetics of antibodies. Next, we used [64Cu]WL12 to evaluate the impact of time and dose on the unoccupied fraction of tumor PD-L1 during treatment. These quantitative measures enabled, by mathematical modeling, prediction of antibody doses needed to achieve therapeutically effective occupancy (defined as >90%). Thus, we show that peptide-based PET is a promising tool for optimizing dose and therapeutic regimens employing PD-L1 checkpoint antibodies, and can be used for improving therapeutic efficacy.
Human mutant p53 lung cancer cells respond differently to PRIMA-1 induced apoptosis
Authors: Li Gao, Wenrui Duan, Xin Wu, Gregory Otterson, Miguel Villalona-Calero
Journal: Cancer Research (2007)

4879  The tumor suppressor protein p53 is a key regulator of cell cycle control, apoptosis, and genomic stability in response to various cellular stresses. P53 mutations were reported in 50-60% of non-small cell lung cancers and in up to 90% of small cell lung tumors, thus p53 represent a common mutation in this malignancy. Mutant p53 proteins fail to bind DNA and transactivate p53 target genes that mediate cell cycle arrest or apoptosis. The frequent mutation of p53 and loss of p53 function in tumors make mutant p53 a prime target for pharmacological therapeutic intervention in cancers. Because mutant p53 is over expressed in tumor cells, one of the effective approaches is to restore the tumor suppressing function to mutant p53.  The compound p53-dependent reactivation and induction of massive apoptosis (PRIMA-1) has been shown to induce apoptosis in human tumor cells containing mutant p53 by restoration of tumor suppressor function of p53. This is believed to be mediated by a change in the conformation of mutated p53 protein, restoring DNA binding and activation of p53 target genes. We investigated the effects of PRIMA-1 in apoptosis using human lung cancer cell lines A549 (wild type p53), H1299 (p53 null), H23 (mutant p53, 246I), H211 (mutant p53, 248Q), and H1155 (mutant p53, 273H). Western blot analysis with PARP [poly(ADP-ribose) polymerase] and caspace-3 antibodies showed that this compound selectivelyinduced apoptosis in the H1155 and H211 cells, but was not toxic to the A549, H1299, and H23 cells.  These results suggest PRIMA-1 is a highly selective small molecule toxic to p53 mutantcells and may serve as a prototype for the development of newp53-targeting agents for therapy of lung cancers. However the efficiency of PRIMA-1 to restore mutant p53 proteins to wild-type conformation may be correlated to p53 mutational types and status. Further understanding the relationships between PRIMA-1 and p53 mutational types may lead to effective strategies for p53 related pharmacological therapeutic intervention in human lung cancers.