tbuckley/cabot-search huggingface dataset:
OCT–Defined Morphological Characteristics of Coronary Artery Spasm Sites in Vasospastic Angina
Authors: Eun-Seok Shin, Soe Hee Ann, Gillian Balbir Singh, Kyung Hun Lim, Hyuck-Jun Yoon, Seung-Ho Hur, Ae-Young Her, Bon-Kwon Koo, Takashi Akasaka
Journal: JACC. Cardiovascular imaging (2015)
Abstract #4695: Novel 2-thiazol or 2-thiophen-substituted quinazolinone derivatives with significant anti-tumor effects
Authors: Jennifer Carroll, Lisa Adams, Donna Rogers, John Clifford, Heather Kleiner, Tammy Dugas, Kenneth McMartin, Brian Latimer, Rajan Giri, Kamala Vasu, Anthony Giordano, Briana Williams
Journal: Cancer Research (2009)

Novel substitutions of thiazol or thiophen at the 2- position created a proprietary library of nearly 400 quinazolinone derivatives with potent anti-inflammatory properties in a rat paw edema model, which were subsequently tested for their molecular mechanism of action, potential anti-tumor activity, and structure-activity relationship (SAR). A primary screen for inhibition of NF\#954;B and AP-1 activity identified 16 compounds with IC 50  against NF\#954;B and/or AP-1 transcription factors which were then tested for differential effects on normal and tumor cell viability. Analytical methods were established to determine bioavailability and biodistribution of 3 lead compounds to guide SAR. All 3 compounds were delivered to animals by daily gavage, 10mg/kg to 50mg/kg with no limiting toxicity over 6 weeks of delivery. LS0300122, a dual NF\#954;B/AP-1 inhibitor, decreased tumor growth and angiogenesis in the PC-3 prostate cancer xenograft model and MDA-MB-231 breast cancer cell motility by 75% in Boyden chamber and wound-healing assays  in vitro . In addition, LS0300122-treated mice had significantly smaller tumors in the RM-1 murine prostate model, where modulation of pro-inflammatory and pro-angiogenic cytokines and increased expression of monocyte and macrophage recruiting cytokines were measured in blood. Kidney, liver, and total body weight were unaffected by daily administration of LS0300122 and there was minimal treatment-associated pathology. The PathwayFinder microarray (SA Biosciences) confirmed inhibition of NF\#954;B and AP-1 and various effectors in LS0300122-treated PC-3 cells. In addition, significant inhibition of p53 pathway members, including CDK2, p21 Waf1/Cip1 , PlG3, and TrailR/DR5 was seen. The AP-1 inhibitor, LS0300012, was also effective in various assays, inhibiting PC-3 tumor volume and angiogenesis, inhibiting breast cancer motility, and reducing tumor volume in a squamous cell carcinoma model, with no effect on body or organ weight. The NF\#954;B inhibitor, LS0300187, effectively inhibited PC-3 tumor volume and angiogenesis, inhibited breast cancer motility, and significantly inhibited p65 expression in tumors from the squamous cell carcinoma model. Interestingly, LS0300187 caused a rapid increase in body weight with a slight increase in kidney weight and no effect on liver weight. In all, the substitution of either thiazol or thiophen residues at the 2- position can generate novel quinazolinone derivatives with significant anti-inflammatory and anti-cancer effects and low toxicity.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4695.
Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up
Authors: K.A. Papp, C.E.M. Griffiths, K. Gordon, M. Lebwohl, P.O. Szapary, Y. Wasfi, D. Chan, M.-C. Hsu, V. Ho, P.D. Ghislain, B. Strober, K. Reich
Journal: British Journal of Dermatology (2013)

Long-term safety evaluations of biologics are needed to inform patient management decisions.To evaluate the safety of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years.Safety data were pooled from four studies of ustekinumab for psoriasis. Rates of adverse events (AEs), serious AEs (SAEs) and AEs of interest [infections, nonmelanoma skin cancers (NMSCs), other malignancies and major adverse cardiovascular events (MACE)] per 100 patient-years (PY) of follow-up were analysed by ustekinumab dose (45 or 90 mg) and by year of follow-up (years 1-5) to evaluate the dose response and impact of cumulative exposure. Observed rates of overall mortality and other malignancies were compared with those expected in the general U.S. population.Analyses included 3117 patients (8998 PY) who received one or more doses of ustekinumab, with 1482 patients treated for ≥4 years (including 838 patients ≥5 years). At year 5, event rates (45 mg, 90 mg, respectively) for overall AEs (242·6, 225·3), SAEs (7·0, 7·2), serious infections (0·98, 1·19), NMSCs (0·64, 0·44), other malignancies (0·59, 0·61) and MACE (0·56, 0·36) were comparable between dose groups. Year-to-year variability was observed, but no increasing trend was evident. Rates of overall mortality and other malignancies were comparable with those expected in the general U.S. population.No dose-related or cumulative toxicity was observed with increasing duration of ustekinumab exposure for up to 5 years. Rates of AEs reported in ustekinumab psoriasis trials are generally comparable with those reported for other biologics approved for the treatment of moderate-to-severe psoriasis.
Interferon versus interferon plus prednisone remission maintenance therapy for multiple myeloma: a Southwest Oncology Group Study.
Authors: S E Salmon, J J Crowley, S P Balcerzak, R W Roach, S A Taylor, S E Rivkin, W Samlowski
Journal: Journal of Clinical Oncology (1998)

PURPOSE We evaluated the vincristine, doxorubicin, and dexamethasone (VAD) regimen alone or with chemosensitizers for remission induction and interferon (IFN) versus IFN plus prednisone (IFN/P) for remission maintenance in previously untreated multiple myeloma. PATIENTS AND METHODS Two hundred thirty-three patients were registered for remission-induction therapy with VAD or VAD plus the chemosensitizers verapamil and quinine. Patients who achieved remission were randomized to maintenance therapy with IFNalpha 3 MU in the evening three times weekly or IFN plus 50 mg of prednisone (IFN/P) on the morning after IFN until relapse. RESULTS Two hundred twenty-nine patients were eligible for induction. Fatal toxicities in nine patients who received VAD plus verapamil and quinine led to closure of this arm after 47 registrations. Subsequently, all patients received VAD induction. Despite the high early mortality rate on VAD plus sensitizers, overall survival by induction arm did not differ for median or 5-year survival with approximately 40% of patients surviving 5 years. Eighty-nine eligible patients who achieved remission were randomized to maintenance. Patients who received IFN/P had improved progression-free survival (median, 19 v9 months for IFN; P = .008). After 48 months, progression-free survival on IFN/P was at the thirtieth percentile, whereas it was below the tenth percentile on IFN alone. Median survival from start of maintenance was long on both arms (57 months for IFN/P v 46 months for IFN; P = .36). CONCLUSION IFN/Pwas more effective than IFN alone. Improved relapse-free survival may be attributable to IFN/P or to the use of prednisone for maintenance. This latter alternative is currently being studied.
Statistics Notes: Diagnostic tests 2: predictive values
Authors: D. G Altman, J M. Bland
Journal: BMJ (1994)

The whole point of a diagnostic test is to use it to make a diagnosis, so we need to know the probability that the test will give the correct diagnosis. The sensitivity and specificity1 do not give us this information. Instead we must approach the data from the direction of the test results, using predictive values.

Positive predictive value is the proportion of patients with positive test results who are correctly diagnosed.

Negative predictive value is the proportion of patients with negative test results who are correctly diagnosed.

Using the same data as in the previous note,1 we know that 231 of 263 patients with abnormal liver scans had abnormal pathology, giving the proportion of correct diagnoses as 231/263 = 0.88. …
Abstract 9: The Effect of CPR Quality: A Potential Confounder of CPR Clinical Trials
Authors: Demetris Yannopoulos, Benjamin Abella, Sue Duval, Tom Aufderheide
Journal: Circulation (2014)

Background: The Resuscitation Outcomes Consortium (ROC)-PRIMED clinical trial evaluated an active inspiratory impedance threshold device (ITD) during standard CPR (intended to improve CPR hemodynamics) on survival to hospital discharge with favorable neurological outcome (modified Rankin Score [mRS] ≤3) in adults with out-of-hospital cardiac arrest and found no benefit. CPR quality varied widely in the trial. We hypothesized the quality of CPR provided would have a significant interaction with the intervention. Methods: We used the NIH public access ROC-PRIMED database. A large proportion of patients had CPR quality parameters (compression rate, depth and fraction) collected. “Quality CPR” was considered delivered if simultaneous provision of the following occurred: a compression rate of 80-120, depth of 4-6 cm and fraction of &gt;50%, consistent with American Heart Association guidelines at the time of the study. We assessed for interaction between each individual parameter of “quality CPR” and their combinations with the active and sham ITD for survival with mRS≤3. Interaction was considered to be significant when p&lt;0.1. Results: Overall, a total of 848 and 827 patients in the active and sham ITD groups had documented “quality CPR” performed. Including all presenting rhythms, use of an active ITD increased survival to hospital discharge with MRS ≤3 compared to sham (61/848 [7.2%] versus 34/827 [4.1%], respectively; p=0.006, OR: 1.8, 95% CI: 1.17, 2.78). There was significant interaction between the active and sham ITD and compression rate, depth and fraction as well as their combinations. (Table 1) Conclusion: When “quality CPR” was delivered, the active ITD improved survival with mRS≤3 by an absolute 3.1%. CPR quality parameters showed significant interaction with the active and sham ITD. The quality of CPR delivered is a potential confounder of CPR clinical trials and should be appropriately controlled.
Abstract P011: Heart Failure and the Obesity Paradox Among Participants in the in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Raegan W Durant, Todd M Brown, Emily B Levitan, Joshua S Richman, Nicole Redmond, Stephen Glasser, Monika M Safford
Journal: Circulation (2013)

Background: Overweight and obese adults living with heart failure (HF) have lower mortality compared to those of normal weight. However, the specific relationships of overall weight status and central adiposity with mortality among those with HF are less well-defined. We examined the relationships among body mass index (BMI), waist circumference (WC) and mortality among patients hospitalized for HF in the REGARDS Study. Methods: REGARDS is a national cohort of US community-dwelling adults aged &gt;45 recruited from 2003 to 2007. We measured all-cause mortality rates among 565 participants hospitalized with HF who were normal weight (BMI 18.5-24.9 kg/m 2 ), overweight (BMI 25.0-29.9 kg/m 2 ), or obese (BMI &gt; 30.0 kg/m 2 ) at baseline. Underweight participants (BMI &lt; 18.5 kg/m 2 ) were excluded. Baseline WC, weight, and height were measured during an in-home exam. Index HF hospitalizations during follow-up were adjudicated by a panel of experts. Vital status was determined using the Social Security Death Index or the National Death Index. Cox proportional models estimated hazard ratios for all-cause mortality following the index HF hospitalization. Models were sequentially adjusted for WC, sociodemographics, HF severity (EF and BNP during HF hospitalization, prior history of HF, prior history of diastolic dysfunction), comorbidities, and health behaviors. Results: Among 565 participants hospitalized for HF, 116 (21%) were normal weight, 209 (37%) overweight, and 240 (42%) obese at baseline. Over a mean follow-up of 2.5 years, 253 deaths occurred. In multivariable analyses, overweight was associated with lower all-cause mortality in all models (Table). Each 1-cm increase in WC was associated with higher risk of all-cause mortality, but the relationship was not statistically significant after health behaviors were added in the final model. . Conclusions: Among adults hospitalized for HF, overweight as assessed by BMI may be associated with lower risk for mortality. However, central adiposity may confer higher risk of mortality.
Abstract 1555: Parasympathetic Response of the Heart is Attenuated in Sterol Response Element Binding Protein Knockout Mice
Authors: Ho-Jin Park, Serban P Georgescu, Chuang Du, Yali Zhang, Mark Aronovitz, Charles M Welzig, Bo Wang, Ronglih Liao, Hitoshi Shimano, Robert O Blaustein, Richard Karas, Jonas B Galper
Journal: Circulation (2006)
Abstract 13537: Early Increase in Serum Fatty Acid Binding Protein 4 Levels in Patients with Acute Myocardial Infarction: Lipolysis as a Novel Marker for Myocardial Ischemia
Authors: Hiroaki Sunaga, Yoshiaki Ohyama, Masaru Obokata, Tatsuya Iso, Tomoka Kawaguchi, Norimichi Koitabashi, Ryuichi Funada, Noriaki Takama, Mas Rizky A Syamsunarno, Hiroki Matsui, Tomoyuki Yokoyama, Masahiko Kurabayashi
Journal: Circulation (2014)

Introduction: Emerging evidence indicates that circulating fatty acid binding protein 4 (FABP4), predominantly expressed in adipocytes, are released from the cells through undefined mechanisms and are associated with obesity, insulin resistance and cardiovascular events. We investigated the time course of circulating FABP4 levels as well as cardiac troponin T (TnT) and heart-type FABP (H-FABP), established makers for myocardial necrosis, in patients with acute myocardial infarction (AMI). Methods and Results: Serial blood samples were analyzed in 67 consecutive AMI patients (48 men, aged 68 ± 13 years). FABP4 concentrations were significantly increased on admission in AMI patients compared with patients with stable exertional angina [median (interquatile range); 25.1 (17.0 to 45.4) vs 11.2 (8.8 to 18.3) ng/ml] and declined over the time course of 7 days thereafter while TnT and H-FABP levels increased after admission and peaked after PCI. A FABP4 level > 15.9 ng/ml on admission can discriminate AMI from s...
Abstract 8976: Prognostic Value of Electrocardiographic Cornell product in Chronic Heart Failure Patients
Authors: Yoichiro Otaki, Hiroki Takahashi, Tetsu Watanabe, Shinpei Kadowaki, Taro Narumi, Shintaro Honda, Hiromasa Hasegawa, Akira Funayama, Shunsuke Netsu, Mitsunori Ishino, Satoshi Nishiyama, Takanori Arimoto, Tetsuro Shishido, Takehiko Miyashita, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2011)

Background ; Heart failure is the major and increasing health problem with a high mortality. Although electrocardiogram (ECG) is a valuable non-invasive procedures used routinely for the diagnosis of heart failure, few ECG parameters, which are related to cardiac prognosis in chronic heart failure (CHF), are known. Cornell product is one of the parameters for ECG left ventricular hypertrophy (LVH). However, clinical significance of Cornell product has not been studied in CHF patients. The purpose of present study is to examine whether Cornell product is related to cardiac function and can predict clinical outcomes in CHF patients. Methods and Results ; We examined a standard 12-lead ECG in 356 consecutive CHF patients and calculated Cornell product {(S v3 + R aVL + 0.6 in woman) × QRS duration}. Patients were prospectively followed during a median follow up period of 697 days, with the end points of cardiac death and cardiac events. There were 99 cardiac events, including 30 cardiac deaths and 69 re-admissions for worsening heart failure. In a simple linear regression analysis, Cornell product correlated with ejection fraction (EF) (r = 0.431, p &lt; 0.0001). Cornell product was higher in patients with cardiac events than those without. In the univariate Cox proportional hazard analysis, age, NYHA functional class, brain natriuretic peptide, EF, and Cornell product were significant risk factor for cardiac events. A multivariate Cox proportional hazard analysis revealed that Cornell product was independent predictor of cardiac events in CHF patients. Kaplan-Meier analysis demonstrated that cardiac event rate was higher in patients with high Cornell product than patients with low Cornell product. Conclusion ; Cornell product is a promising parameters to detect not only LVH but also cardiac systolic dysfunction in CHF patients. Cornell product can be a highly reliable non-invasive parameter for predicting cardiac prognosis in CHF patients.
Association Between High Levels of Physical Exertion, Anger, and Anxiety Immediately Before Myocardial Infarction With Mortality During 10-Year Follow-Up
Authors: Loes Smeijers, Elizabeth Mostofsky, Geoffrey H. Tofler, James E. Muller, Willem J. Kop, Murray A. Mittleman
Journal: Journal of the American College of Cardiology (2015)
Abstract 901: Plasma proteins characterize second-line therapy response in progressive renal cell carcinoma
Authors: Sebastian Hölters, Lothar Bergmann, Viktor Grünwald, Ulrich Keilholz, Carsten Ohlmann, Michael Staehler, Diana Schmerler, Kerstin Junker
Journal: Cancer Research (2014)

Abstract Introduction &amp; Objectives: For patients with metastatic renal cell carcinoma (mRCC) vascular endothelial growth factor (VEGF)-targeted therapy represents a promising first-line therapy after tumour nephrectomy. For patients who progress during first-line therapy, inhibitors of mammalian target of rapamycin (mTOR) represent an option for second-line therapy. Within the framework of the MARC-2 clinical trial, the aim of our study is the identification and validation of marker proteins associated with second-line therapy (Everolimus) response. Material &amp; Methods: We included blood plasma samples from 19 mRCC patients receiving Everolimus. Therapy response was defined as stable disease and partial remission. We analysed the samples by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS) using CM10 and Q10 arrays. For the identification of potential marker proteins, 2-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and antibody array screening are on-going. Results: We identified 20 mass peaks by SELDI-TOF MS with Q10 and 16 with CM10 chips for the discrimination between responders (defined as stable disease or partial remission after two month of therapy) and non-responders (defined as progressive disease after 2 month of therapy). With the Q10, but not with the CM10 chip, we obtained five peaks for the discrimination between both patient groups before the first drug application. These peaks could be useable to preselect patients for the second-line therapy with Everolimus. For therapy monitoring, we found seven mass peaks (four with Q10 and three with CM10 chips) after two weeks and 24 mass peaks (11 with Q10 and 13 with CM10 chips) after four weeks of therapy to differentiate between responders and non-responders. These mass peaks could be useful to estimate the therapy response for the patients. Conclusion/Outlook: Our preliminary results argue for the presence of blood plasma proteins which potentially predict therapy response to Everolimus before as well as during therapy. The confirmation and identification of the SELDI-TOF MS outcomes by 2-dimensional gel electrophoresis and MALDI-TOF MS is on-going as well as the antibody array screening for angiogenesis related proteins. Sponsored by: iOMEDICO AG Citation Format: Sebastian Hölters, Lothar Bergmann, Viktor Grünwald, Ulrich Keilholz, Carsten Ohlmann, Michael Staehler, Diana Schmerler, Kerstin Junker. Plasma proteins characterize second-line therapy response in progressive renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 901. doi:10.1158/1538-7445.AM2014-901
Abstract 14881: Shortened Telomere Length is Associated with Paroxysmal but Not Persistent/Permanent Atrial Fibrillation in Cardiovascular Patients Referred for Angiography
Authors: John F Carlquist, Stacey Knight, Richard M Cawthon, Benjamin D Horne, Jeffrey S Rollo, John A Huntinghouse, T J Bunch, Joseph B Muhlestein, Jeffrey L Anderson
Journal: Circulation (2014)

BACKGROUND: Telomeres are hexanucleotide repeats at chromosome ends that prevent chromosome degradation. Short telomere length (TL) correlates with biological ageing and is associated with risk for age-associated diseases. Atrial fibrillation (AF) can occur as paroxysmal (Px), persistent (Ps) or permanent (Pm). Progression from Px to Ps/Pm AF is accompanied by increased risk for AF-associated adverse events. We t found that short TL is associated with a history of AF; for the present study we examined TL in relationship to the types of AF. METHODS: Peripheral blood DNA was obtained from sequential consenting patients (pts) (n=3576) at angiography. TL was measured in triplicate by monochrome (SYBR Green I) multiplex quantitative PCR (Bio-Rad CFX384 Detection System) and normalized to a quantitatively-measured, single-copy gene (albumin). AF history was extracted from Intermountain Healthcare’s electronic records and AF type determined by chart review for 246 of 325 (75.7%) AF patients. Non-parametric tests were used. RESULTS: For the 246 subtyped AF pts, 66.3% were male, 94.3% Caucasian, mean age was 70 yrs. The leading AF type was Px (43.5%), followed by Pm (32.9%), and Ps (23.6%). Mean TL for non-AF pts was 0.954 ±0.325 and the mean TL for AF pts was 0.912±0.30. The mean Px TL (Table) was significantly shorter than for Ps or Pm AF. Ps and Pm TL did not differ. Adjusting for age, gender, prior CVA, PCI, statin use, disease severity; TL (per unit of decrease) was associated with Px AF compared to Ps/Pm AF (OR=6.64; CI 2.17, 20.32; p=0.0009). CONCLUSIONS: The association of shorter TL with Px AF but not Ps/Pm AF suggests that decreased TLs is associated with an etiologic AF subtype. No association between shortened TL and Ps/Pm AF may further suggest that TL measurement for pts with Px AF may have prognostic utility with respect to AF progression. Further study into the physiological basis of these observations is warranted.