tbuckley/cabot-search huggingface dataset:
Serum-transforming growth factor-α (TGF-α) and response to lapatinib plus capecitabine in HER2-positive (HER2+) metastatic breast cancer (MBC).
Authors: J. Rhee, S. Han, Y. Cha, H. Kim, D. Oh, S. Im, J. Ro, Y. Im, Y. Bang, T. Kim
Journal: Journal of Clinical Oncology (2010)

1102 Background: Although lapatinib plus capecitabine is effective in trastuzumab-resistant HER2+ MBC, predictive biomarker of the treatment has not been identified. We investigated biomarkers from serum of patients receiving lapatinib and capecitabine. Methods: Patients received lapatinib 1,250 mg once daily and capecitabine 2,000 mg/m2/day, day 1 to 14, every 3 weeks. Serum samples were obtained prior to treatment initiation. Levels of TGF-α, EGF, EGFR-extracellular domain (ECD) and HER2-ECD were measured by ELISA. We analyzed the association between the serum levels and response to the treatment. Besides, the effect of TGF-α on in vitro sensitivity of SK-BR-3 cells to lapatinib was investigated. Results: A total of 64 women were enrolled. All patients had HER2+ MBC and had progressed after trastuzumab containing regimen. The overall response rate was 31.3% and median TTP was 4.5 months in the study population. Among the serum markers, serum TGF-α level was significantly lower in responders (PR) compared to nonresponders (SD or PD) (median, 3.5 vs. 8.2 pg/mL; p=0.005). The EGFR-ECD level tended to be lower in responders than nonresponders (median, 21.9 vs. 24.9 ng/mL; p=0.190). The response rate was significantly higher in patients with low (≤3.75 pg/mL) than high TGF-α [61.1% (11/18) vs. 19.6% (9/46), respectively; p=0.001]. The response rate was also significantly higher in patients with low (≤22.2 ng/mL) than high EGFR-ECD [50.0% (11/22) vs. 21.4% (9/42), respectively; p=0.019]. In multivariate analysis adjusting for baseline characteristics, low serum TGF-α (adjusted OR, 17.1; 95% CI, 3.19 - 91.7) and low EGFR-ECD (adjusted OR, 10.7; 95% CI, 2.07 - 55.1) were independent predictive factors for response. Patients with low TGF-α tended to have longer TTP than those with high TGF-α [median, 6.5 (95% CI, 6.1-6.8) vs. 3.8 months (95% CI, 2.3-5.4); p=.067]. We confirmed that TGF-α diminished the sensitivity of SK-BR-3 cell to lapatinib in vitro, which was restored by cetuximab. Conclusions: These data suggest that TGF-α plays a role in resistance to lapatinib and capecitabine in HER2+ MBC. No significant financial relationships to disclose.
Abstract 13456: Depression is Associated with Cardiovascular Disease Risk in Prison Inmates
Authors: Misook L Chung, Terry A Lennie, Alison Connell, Alison L Bailey, Debra K Moser
Journal: Circulation (2011)

Background: Cardiovascular disease is the leading cause of death in prison inmates. Depression is a known predictor of cardiovascular disease in the general population. Inmates who are incarcerated...
Effects of Nesiritide and Predictors of Urine Output in Acute Decompensated Heart Failure
Authors: Stephen S. Gottlieb, Amanda Stebbins, Adriaan A. Voors, Vic Hasselblad, Justin A. Ezekowitz, Robert M. Califf, Christopher M. O'Connor, Randall C. Starling, Adrian F. Hernandez
Journal: Journal of the American College of Cardiology (2013)
Abstract 19486: Younger Age at Time of Pacemaker Implantation is Associated With Worse Survival
Authors: Douglas Elder, Ben Szwejkowski, Rohan jain, Alison Cook, Chim Lang, Alan Struthers, Anna Maria Choy
Journal: Circulation (2010)

Background: Pacemakers are the mainstay treatment for symptomatic bradycardia but pacing from the right ventricle apex can cause deleterious ventricular dysynchrony and lead to heart failure and in...
Abstract 21615: Disparities in Access to Revascularization After Acute Myocardial Infarction (MI) Before and After the 2002 IOM Report
Authors: Oluwaseyi B Bolorunduro, Adekunle Kiladejo, Kayode J Bello, Muhammad Amer, Olakunle O Akinboboye
Journal: Circulation (2010)

The Institute of Medicine (IOM) report published in 2002 showed that Blacks were less likely to receive coronary revascularization such as CABG and stents even after controlling for insurance, income and age. It recommended that increased awareness of disparities among health professionals is needed to reduce this.We hypothesized that increased awareness of ethnic disparities since this report would have translated to reduction in disparities in coronary revascularization.   Methods:  A retrospective analysis was conducted using data from the AHRQ9s National Inpatient Sample (NIS) 1998–2007(10 years). All patients with acute myocardial infarction during this period were identified. The proportion that received percutaneous intervention (PCI) during the incident admission was compared in different ethnicities over the time period. Multivariate regression for each year was conducted using Poisson regression with robust variances to account for the relatively high rates of revascularizations. The analysis controlled for gender, insurance status, co-morbidities and hospital characteristics.   Results:  Based on the database, about 2.04 million patients were managed for acute MI from 1998–2007. The primary revascularization rate during the incident admission among Whites was 23%, Blacks−17.6% and Hispanics−21.4% [P   Conclusions:  Ethnic disparities in coronary revascularization persist despite the 2002 IOM report. More definitive measures need to be effected to reduce these disparities.
Abstract 10022: Effects of Therapeutic Lifestyle Change Diets High and Low in Dietary Fish-Derived Fatty Acids on Apolipoprotein B Metabolism in Moderately Hypercholesterolemic Middle-Aged and Older Subjects
Authors: Esther M Ooi, Alice H Lichtenstein, John S Millar, Margaret R Diffenderfer, Stefania Lamon-Fava, Helen Rasmussen, Francine K Welty, P Hugh R Barrett, Ernst J Schaefer
Journal: Circulation (2011)

Introduction: Nutritional and lifestyle modifications are the cornerstones of therapy for the treatment of dyslipidemia to prevent and treat coronary heart disease. Hypotheses: We hypothesized that the Therapeutic Lifestyle Change (TLC) diets, low (2 meals/wk) and high (8 meals/wk) in dietary fish intake, would increase the catabolism of apolipoprotein (apo) B containing lipoproteins and that the TLC high-fish diet would confer added benefits by decreasing the production of these lipoproteins. Methods: 20 subjects (mean ± SEM; age 66 ± 2 yr, BMI 26 ± 0.5 kg/m2) were provided with a Western diet for 6 wk and then with one of two TLC diets for 24 wk (10/group). At the end of each diet phase, subjects received a primed, constant infusion of d3-leucine for 15 h with hourly feeding. Very low-density lipoprotein (VLDL), intermediate-density lipoprotein and low-density lipoprotein (LDL) apoB-100, and triglyceride-rich lipoprotein (TRL) apoB-48 kinetics were determined using gas chromatography mass spectrometry a...
Abstract 2418: Complement Deposition in Endomyocardial Biopsy Is Predictive of Antibody-Mediated Rejection in Cardiac Transplantation
Authors: George G Sokos, E R Rodriguez, Carmela D Tan, Diane J Pidwell, Wilfried Mullens, Christina J Haire, David O Taylor, Randall C Starling
Journal: Circulation (2008)

Controversy exists regarding the criteria used for the diagnosis of Antibody-mediated rejection (AMR) and a consensus has not been reached regarding the most appropriate criteria for the diagnosis. Recent data have suggested the use of Immunohistochemistry for the presence of C4d as being adequate for the diagnosis but has not been uniformly accepted. The added utility of C3d staining in addition to C4d is unknown. METHODS: We evaluated endomyocardial biopsies from consecutive patients collected over a 14 month period. Biopsies were screened for the presence of complement deposition, specifically C4d and C3d. Electronic medical records were reviewed retrospectively for the clinical data and the diagnosis of clinically relevant AMR. RESULTS: A total of 1511 endomyocardial biopsies were performed on 330 consecutive patients. Eighteen patients were found to have evidence of C4d complement staining and 18 patients with both C4d and C3d staining. Mortality was significantly higher (28% vs 0%, p &lt; 0.05) in the patients with both C4d and C3d staining compared to C4d alone. Patients with both C4d and C3d received more treatment (corticosteroids, plasmapheresis), were hospitalized more frequently, and illness was associated with frank hemodynamic compromise including reduced EF and cardiac index (Table 1 ). CONCLUSION: Complement deposition with both C4d and C3d on endomyocardial biopsy is more commonly associated with reduced EF, hemodynamic compromise, and mortality. C4d alone, although common, is often not associated with morbidity. Statregies for the management and follow up of AMR should be a priority for research. TABLE 1: Clinical Outcomes
Abstract 2426: Relationship Indicators of Carotid and Left Main Coronary Artery Atherosclerosis by Ultrasound and the Number of Coronary Artery Disease
Authors: Hiroaki Takeshita, Toru Kataoka, Yoshiki Kobayashi, Takeshi Hozumi, Shinichi Iwata, Keitaro Ogawa, Hiroki Nishioka, Yoshihisa Shimada, Hajime Yamashita, Shoichi Ehara, Junichi Yoshikawa, Minoru Yoshiyama
Journal: Circulation (2006)
Causes of death need confirmation
Authors: K A Jellinger
Journal: BMJ (1996)

EDITOR,—After 5.4 years of follow up the Parkinson's Disease Research Group reports a significantly higher mortality in patients with early, mild Parkinson's disease given levodopa plus selegiline (arm 2) than in those given levodopa alone (arm 1). Although the causes of the 60% increased mortality “remain to be elucidated,” the group concludes that the data “cast doubts on the chronic use of selegiline.”1 This conclusion seems conjectural.

Firstly, the suggested deleterious effects of selegiline on the cardiovascular system are disproved by …
Socioeconomic status of women attending an oncogenetic counseling clinic
Authors: A. von Wachenfeldt, Y. Brandberg, H. Johansson, T. Fornander
Journal: Journal of Clinical Oncology (2007)

1526 Background: In women with a family history (FH) of breast cancer the risk can be substantially increased and starts at an earlier age compared with the general population. Women with FH of breast cancer are not suggested oncogenetic counselling unless the subject is brought up in the contact with medical professionals. Consequently, a woman with FH for breast cancer has to have knowledge about the possibility of counselling to come into question for information, advice and special surveillance program. The aim of this study was to characterize women at an oncogenetic counselling clinic in terms of socioeconomic status (SES) and to compare these data with population based figures from the same catchment area. Methods: All healthy women who had, once or repeatedly, been visiting the oncogenetic clinic at the Department of Oncology, Karolinska University Hospital / Sodersjukhuset, between April, 1998 - June, 2004 were eligible for study. A total of 307 out of 378 consecutive women consented to participate (81%) in the survey by returning mailed questionnaires. SES data were compared with official data for all women aged 24 -75 year from the same catchment area (n= 277 783 women). Results: See table . Conclusions: Women visiting the oncogenetic counselling clinic were higher educated, more often married and had a better economic situation than comparable women from the same catchment area. These findings indicate that efforts should be elaborated to increase the knowledge about the possibility of genetic counselling among women with FH for breast cancers. [Table: see text] No significant financial relationships to disclose.
Early intervention in pertussis outbreak with high attack rate in cohort of adolescents with complete acellular pertussis vaccination in Valencia, Spain, April to May 2015
Authors: A Míguez Santiyán, R Ferrer Estrems, J L Chover Lara, J Alberola Enguídanos, J M Nogueira Coito, A Salazar Cifre
Journal: Eurosurveillance (2015)

Forty-three pertussis cases reported in May 2015 in Valencia were linked to a school outbreak where 90% of the students had been vaccinated. Cases were diagnosed upon paediatrician consultation and in hospital emergency units. Approximately half of the cases were students born in 2002, the first age cohort with complete shift to acellular pertussis vaccine. Public health intervention, visiting school premises to conduct interviews, sample collection and early antibiotic prophylaxis stopped further spread in the community.
Abstract 849: Aleglitazar, a Balanced Peroxisome Proliferator-Activated Receptor (PPAR){alpha}/{gamma} Agonist, Provides Beneficial Effects on Cardiovascular Markers of Inflammation and Clotting
Authors: Robert R Henry, A Michael Lincoff, Sunder Mudaliar, Cathy Chognot, Michael Rabbia, Matthias Herz
Journal: Circulation (2009)

Aleglitazar (ALE) is a balanced dual PPAR α / γ  agonist, designed to optimize glycemic and lipid benefits, and minimize PPAR-related adverse effects, including weight gain, and peripheral edema. The SYNCHRONY study demonstrated significant improvements in glycemic control and lipids with a 150  μ g dose of ALE in patients with type 2 diabetes (T2D), with no evidence of adverse cardiovascular safety. The current exploratory analysis of SYNCHRONY investigated the effects of ALE at a range of doses on cardiovascular markers, including high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), and fibrinogen. Following a 4- to 5-week placebo run-in period, 332 patients (drug-naive or pretreated with ≤2 oral antidiabetic agents) were randomized to 16 weeks’ double-blind treatment with ALE at 1 of 4 daily doses (50, 150, 300 or 600  μ g) or placebo, or to open-label pioglitazone (PIO) 45 mg/day. After 16 weeks’ treatment, a trend towards reduction in hsCRP was observed with ALE vs placebo, which appeared to be dose dependent. Reductions from baseline in hsCRP were similar for the ALE 150  μ g dose and 45 mg of PIO. Reductions from baseline in PAI-1 were significant vs placebo at the 300 and 600  μ g doses of ALE, and were numerically greater than with PIO, but not with the 150  μ g dose. Dose-dependent reductions from baseline fibrinogen were observed for ALE that were significant vs placebo at doses ≥150  μ g. The expected PPAR γ  effects on body weight and fluid retention were observed with ALE, but at the 150  μ g dose body weight gain was less than with PIO (0.52 vs 1.06 kg) and incidence of peripheral edema (2 cases) was similar to placebo (3 cases) and less than with PIO (4 cases).
Abstract 4925: Noninvasive Angiographic Follow-Up 18 Months after Bioabsorbable Everolimus-Eluting Stent Implantation Using 64-Slice Computed Tomography (ABSORB)
Authors: Koen Nieman, Annick Weustink, Yoshinobu Onuma, Nico Bruining, Piotr Klimeczek, Morten Bottcher, John A Ormiston, Dariusz Dudek, Leif Thuesen, Pim J De Feyter, Patrick W Serruys
Journal: Circulation (2008)

While assessment of metal stents by CT angiography is complicated by blooming artifacts, noninvasive follow-up should be possible after implantation of non-metal, radiolucent, bioabsorbable stents. In a multicenter, prospective, open-label study (ABSORB) 30 patients underwent implantation of a 3.0 ×12-mm (N=28) or 3.0 × 18-mm(N=2) bioabsorbable everolimus-eluting stent made of polylactic acid (Abbott Vascular, Santa Clara, CA). At 19.2 ±1.1 months 64-slice CT angiography (Siemens Somatom Definition, Germany; Philips Brilliance 64, The Netherlands; GE LightSpeed VCT, WI) was performed in 25 patients (65 ±11 years, 15 male). Five patients were lost due to target-lesion re-intervention (N=1), contrast allergy (N=1), withdrawn consent (N=3). Cross-sectional, in-stent lumen areas were measured at submillimeter intervals using quantitative CT software (Circulation®, Siemens). Minimal in-stent lumen area was compared to the reference lumen area, based on adjacent proximal and distal lumen areas. Motion artifacts excluded one CT study. Radiopaque indicators (figure ) at the egdes of the absorbed stent were the only visible remains: distance 11.4 ±0.5 mm (12-mm stents). All stents were patent. Mean lumen area 5.2 ±1.3 mm 2 (range 3.2 – 7.4 mm 2 ). Minimal lumen area 3.6 ±0.9 mm 2 (range 2.2 – 5.7 mm 2 ), compared to a reference lumen area of 5.5 ±1.0 mm 2 (range 3.3 – 7.6 mm 2 ), resulting in a lumen area stenosis of 31 ±15% (range -2 - 51%). One case showed local lumen enlargement (12.0 mm 2 ). CT angiography was feasible and demonstrated moderate in-stent lumen loss without significant obstruction after bioabsorbable stent implantation.
A fifth of suicides among mentally ill are preventable
Authors: Zosia Kmietowicz
Journal: BMJ (2001)

The health service is being called on to step up efforts to protect people with mental health problems from harming themselves or other people after a report published this week showed that more than a fifth of suicides among people with mental illness could have been prevented.

About a quarter of the United Kingdom's 6500 suicides each year occur among people with mental illness, some 12% of them while in hospital, usually by hanging from a curtain rail.

The National Confidential Inquiry into Suicide and Homicide by People with Mental Illness showed that many people at risk of suicide are simply slipping through the net. …
Abstract 14026: Absence of Coronary Calcification in Patients at Low Risk for Future Cardiovascular Events Robustly Predicts Absence of Obstructive Coronary Artery Disease by Coronary CT Angiography
Authors: Jamal Rana, Rine Nakanishi, Heidi Gransar, Victor Cheng, Sean Hayes, Louise Thomson, John Friedman, Leslee J Shaw, James K Min, Daniel S Berman
Journal: Circulation (2011)

Objectives: There are conflicting results regarding the prevalence of presence of obstructive CAD as evaluated by coronary CT angiography (CCTA) in the absence of any coronary artery calcium (CAC)....
Abstract 036: The Association between Mid-Life Cardiorespiratory Fitness and Dementia in Later Life
Authors: Laura DeFina, Benjamin Willis, Ang Gao, Nina Radford, David Leonard, Jarett Berry
Journal: Circulation (2012)

Introduction: Prior literature suggests that higher levels of physical activity are associated with a lower risk for Alzheimer disease and related dementias (ADRD). However, the association between cardiorespiratory fitness (CRF) in healthy, middle aged adults and ADRD decades later in older age has not been studied. Methods: We included 20,195 participants (21.0% female, mean age 49.8 years, and free of vascular disease at baseline) enrolled in the Cooper Center Longitudinal Study (CCLS) between 1970 and 2009. CRF was measured by modified Balke protocol and treadmill time was used to estimate metabolic equivalents (METs) and to stratify CRF into low-, intermediate-, and high-fit categories. Baseline data from the CCLS were matched with Medicare administrative claims data from the Center for Medicare and Medicaid Services (CMS). The primary outcome variable was the diagnosis of ADRD as defined by CMS validated algorithms. We used a Cox proportional hazard model to estimate the association between midlife fitness and the development of ADRD in later life. All models were multivariable-adjusted for age, BMI, hypertension, diabetes, hyperlipidemia, and smoking. Results: After more than 120,000 person-years of Medicare exposure, there were 1964 ADRD cases. As expected, we observed marked differences in the age-related prevalence of ADRD (age 70 1.19% vs. age 90 15.68%). In both men and women, higher midlife fitness was associated with a lower risk (per MET) for ADRD decades later [HR 95% CI: 0.96 (0.93–0.99) in men; 0.91 (0.86–0.98) in women]. Findings were similar when fitness was examined according to categories (high vs. low) but with wider confidence intervals in women [0.81 (0.70–0.95) in men; 0.76 (0.57–1.03) in women]. The figure illustrates dementia-free survival by fitness level for men and women. Conclusions: Higher mid-life CRF was associated with a lower risk of developing ADRD decades later in older age.
Why care of the dying is still poor
Authors: A. Blackburn
Journal: BMJ (1994)

EDITOR,—Mina Mills and colleagues' descriptive analysis of the care of dying patients in four Scottish teaching hospitals highlights an area of medical ignorance or avoidance that still exists 11 years after the study.1 I believe that there are several reasons for this.

Firstly, palliative care is not generally taught in the undergraduate medical curriculum. Like many of their seniors who trained before palliative care became established as a specialty, junior doctors are often unaware of what can be …
Abstract 13917: A Pro-Inflammatory, Hyperinsulin State, Not Hyperglycemia, is Associated With Adverse Outcomes After Pediatric Heart Surgery
Authors: Alejandro A Floh, Cedric Manlhiot, Nadia A Clarizia, Michael-Alice Moga, Andrew N Redington, Brian W McCrindle, Gustavo La Rotta, Svetlana Khaikin, Christopher A Caldarone, Glen S Van Arsdell, Steven M Schwartz
Journal: Circulation (2011)

Introduction: Hyperglycemia following CPB for congenital heart disease (CHD) may be associated with poor outcomes. This may be due to an insulin resistant, pro-inflammatory state and not directly to hyperglycemia, but this has not been studied. Hypothesis: The combination of high insulin levels and a heightened inflammatory state is associated with impaired cardiac output and adverse clinical outcomes following CPB for CHD. Methods: Children undergoing CPB for CHD were prospectively enrolled. Plasma hormone and cytokine levels were measured for up to 72 hours following surgery and results were log transformed for analysis. A subset of children in the ICU had cardiac index (CI) measured by respiratory mass spectrometry. Data on standard clinical outcomes were recorded. Results: 157 children (mean age 3.6 years, IQR 0.33-4.44) were enrolled. 31% had peak glucose 180-270 mg/dL and 17% > 270 mg/dL. 22 subjects (14%) reached the composite adverse outcome consisting of shock, seizures, renal or hepatic dysfunct...
Effect of Common Bile Duct Obstruction on Susceptibility of Liver to Bacterial Infection
Authors: L R FREEDMAN
Journal: JAMA (1963)

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