tbuckley/cabot-search huggingface dataset:
mFOLFOX-bevacizumab or XELOX-bevacizumab then bevacizumab (B) alone or with erlotinib (E) in first-line treatment of patients with metastatic colorectal cancer (mCRC): Interim safety analysis of DREAM study
Authors: C. Tournigand, B. Samson, W. Scheithauer, C. Louvet, T. Andre, G. Lledo, J. Latreille, F. Viret, B. Chibaudel, A. de Gramont
Journal: Journal of Clinical Oncology (2009)

4077 Background: Anti-VEGF or EGFR inhibitors demonstrated clinical activity in combination with chemotherapy (CT) in mCRC. The DREAM trial compares, after an induction CT of 6 cy of FOLFOX-B or XELOX-B, a maintenance with B ± E. We report here a pre-planned safety analysis of induction (I) and maintenance (M) phase for the first 200 patients. Methods: Patients (pts) with untreated mCRC were randomly assigned to 2 arms (I): mFOLFOX+B (n=100), or mXELOX+B (n=100). mFOLFOX-B: LV 400 mg/m 2 , Oxaliplatin (ox) 100 mg/m 2 , B 5 mg/kg d1, 5FU ci 2.4g/m 2 46h, q2w, mXELOX-B: Ox 100 mg/m 2 d1, capecitabine 2.5 g/m 2 d1–7, B 5mg/kg, q2w. To date, 117 pts with a disease control after 6 cy have had a 2 nd randomisation (M): B alone (7.5 mg/kg q3w, n=56) or B+E 150 mg/d (n=61) until PD. Results: Pts characteristics were: sex: 124M/76F, median age: 62.4 years (26–80), primary tumors: colon 152, rectum 53, synchronous metastases: 150 pts, &gt; 1 metastase site: 115, PS 0/1: 134/66, Alk. Ph.&gt;UNL: 87 pts, and LDH&gt;UNL: 88pts. For I, 92 pts in mFOLFOX-B and 93 in XELOX-B were evaluable for toxicity (tox). Tox (%) for mFOLFOX-B/XELOX-B were: any toxicity grade (gr) 3 or 4: 21/30; neutropenia gr 3 6/1, gr 4 0/2; febrile neutropenia gr 3 1/1, gr 4 0/1; thrombopenia gr 3 0/1, gr 4 0/2; anemia gr 2 8/15, gr 3 2/1; nausea gr 2 17/15, gr 3 4/6; vomiting gr 2 10/12, gr 3 2/5; mucositis gr 2 6/6, gr 3 0/4; diarrhea gr 2 8/12, gr 3 5/20, gr 4 0/1; neuropathy gr 2 23/17 gr 3 3/1; HFS gr 2 0/7, gr 3 0/2; hypertension gr 2 2/3, gr 3 1/0; proteinuria gr 2 1/5; SAEs 14/25. For M, 56 pts in B and 61 pts in B+E were evaluable. Tox (% B/B+E) were: neutropenia gr 2 0/3; thrombopenia gr 2 2/0; nausea gr 2 2/2, gr 3 2/0; vomiting gr 3 2/0; mucositis gr 2 2/3; diarrhea gr 2 0/6, gr 3 2/6; skin tox gr 1 9/31, gr 2 0/38, gr 3 0/16, gr 4 0/2; proteinuria gr 2 5/5; hypertension gr 1 9/15, gr 2 3/8, gr 3 3/0. Conclusions: This interim safety analysis demonstrated that induction with mFOLFOX-B or XELOX-B as well as maintenance with B or B + E appears to be well-tolerated, without unexpected side effects. The DREAM study is ongoing, with a prolonged induction phase of 6 months (3 mo with ox then 3 mo with fluoropyrimidines-B) before randomisation for maintenance therapy. [Table: see text]
Abstract MP70: Ten Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Robyn L McClelland, Neal Jorgensen, Diane Bild, Greg Burke, Wendy Post, Steve Shea, Kiang Liu, Karol Watson, Aaron Folsom, Matthew Budoff, J. Jeffrey Carr, Michael Blaha, Richard Kronmal
Journal: Circulation (2014)

Objectives: In the modern era existing risk scores are not well calibrated, and may overestimate or underestimate risk in different populations. Several studies have demonstrated the added value of coronary artery calcium (CAC) over and above traditional risk factors for risk prediction. Our goal was to develop a risk score to estimate 10-year CHD risk using CAC and traditional risk factors. Methods: The MESA study is a cohort of 6814 participants aged 45-84 and free of clinical heart disease at baseline (2000-2002) in which CAC (Agatston score) was measured. Incident coronary heart disease (CHD) events included myocardial infarction, CHD death, and angina when accompanied by revascularization. Penalized Cox regression models (“shrinkage” models) were used to perform variable selection and estimate the risk score coefficients. Covariates which were considered for inclusion in the risk score model were: age, gender, race/ethnicity, HDL and total cholesterol, lipid lowering medication use, systolic blood pressure (SBP), anti-hypertensive medication use, body mass index (BMI), current smoking, family history of heart attack, diabetes, and CAC. Pre-specified interactions considered included: age, gender, race/ethnicity and CAC with all other predictors; anti-hypertensive medications-by-SBP; and lipid lowering medications-by- total cholesterol. Bootstrapping was used to establish the internal validity of the model to avoid over-optimism. Results: Participants were followed for a median of 10.2 years, and 393 CHD events were observed. With the exception of BMI and diastolic blood pressure, all the risk factors were included in the risk score. The risk score demonstrates good discrimination and calibration, with survival adapted area under the ROC curve (AUC) of 0.81 and discrimination slope of 0.91. The model exhibits improved performance compared to existing risk scores, even after recalibration of traditional risk scores to the MESA population, which have yield an AUC for Framingham risk score of 0.72, and an AUC for traditional risk factors fit to MESA of 0.76. The improvement reflects both the addition of CAC and a tuning of the parameter estimates for the traditional risk factors. The MESA 10-year CHD risk calculator will be available online to facilitate clinical use. Conclusions: An accurate estimate of 10-year CHD risk can be obtained using traditional cardiovascular risk factors and CAC.
Outcome of phase II oncology clinical trial abstracts presented at annual meeting of the American Society of Clinical Oncology (ASCO)
Authors: R. T. Hoeg, J. A. Lee, M. A. Mathiason, K. Rokkones, S. L. Serck, K. L. Crampton, A. Emmel, A. J. Jumonville, E. A. Severson, R. S. Go
Journal: Journal of Clinical Oncology (2006)

6010 Background: Translation of evidence-based medicine into clinical practice depends on timely and full publication of clinical trials. Previous studies have shown that a substantial number of phase I and III trials presented at the annual meetings of ASCO remain unpublished more than 5 years after presentation. We investigated the outcome of phase II trials presented at ASCO. Methods: We searched for phase II trials using the 1997 ASCO Annual Meeting Proceedings. We excluded trials reporting only preliminary data or interim analyses. The following information were extracted from each study: type of presentation, country of origin, sample size, sponsor, treatment modality, novelty of treatment, and efficacy. A literature search was performed using the Medline and EMBASE databases up until January 2006 for full publications in peer-reviewed journals. If a trial was not found, the authors were contacted by E-mail. Results: We identified 124 phase II trials with 13.7%, 30.6%, and 55.6% presented orally, in poster, and in print, respectively. Most trials were either submitted from countries in North America (50.8%) or Europe (34.7%). Funding came from the pharmaceutical companies (24.2%), governments (20.2%), study institutions (15.3%), private foundations (9.7%), or was not specified (30.6%). The top 5 cancers studied were lung, breast, ovarian, gastric, and sarcoma. Treatment included mostly chemotherapy, either alone (87.1%) or in combination with other modalities (3.2%). To date only 70.2% of the trials have been published. The median time to publication for all abstracts was 23 months. The cumulative rates of publication were 12.9%, 34.7%, 51.6%, 64.5%, and 68.5% at 1, 2, 3, 5, and 7 years, respectively. None of the factors we analyzed, including type of presentation, country of origin, sample size, sponsor, novelty of treatment, and efficacy, influenced the likelihood of or time to publication. Conclusions: About a third of phase II oncology clinical trials initially presented as abstracts at the 1997 ASCO annual meeting have not been published almost a decade later. Similar to phase I and III trials, underreporting of phase II trials is an important problem with serious implications for clinical practice that needs to be addressed. No significant financial relationships to disclose.
Whether screening for ovarian cancer saves lives is still unclear despite large trial
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

A trial of more than 200 000 UK women has provided no definite answer as to whether screening for ovarian cancer saves lives. Longer follow-up studies are needed to decide whether testing the general population is cost effective, the researchers said.1

Ovarian cancer continues to be diagnosed at an advanced stage, and 60% of patients die within five years of diagnosis. The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) tested the hypothesis that screening for ovarian cancer in the general population can reduce deaths from the disease without causing significant harm.

The researchers recruited 202 638 women aged 50-74 from 2001 to 2005 through 13 trial centres in England, Northern Ireland, and Wales and randomised them to …
The ‘Omics’ of Amyotrophic Lateral Sclerosis
Authors: Diana Caballero-Hernandez, Miguel G. Toscano, Marta Cejudo-Guillen, Maria L. Garcia-Martin, Soledad Lopez, Jaime M. Franco, Francisco J. Quintana, Cintia Roodveldt, David Pozo
Journal: Trends in Molecular Medicine (2015)
Massachusetts Medical Society
Authors: John Figgis Jewett
Journal: New England Journal of Medicine (1976)

A 21-year-old gravida 1, known to have disseminated lupus erythematosus for three years, was admitted to the hospital at 18 weeks' gestation.The patient had been doing well on prednisone, 40 mg per day, and hydroxychloroquine, but proteinuria, hematuria and hypertension prompted the diagnosis of lupus nephritis. She gave a history of easy bruising, nausea and vomiting for several days, and was uncomfortable and irritable. Her blood pressure was 150/90 mm Hg. Soft tissues under the left eye were swollen, and discoloration suggested bleeding into the lower lid and orbit, but pelvic examination now disclosed for the first time a . . .
Acid attack victims should have same rights as disabled people, Indian Supreme Court rules
Authors: Sanjeet Bagcchi
Journal: BMJ (2015)

<h3>Abstract</h3> Recent evidence suggest that our experience of time is directly and intrinsically computed within the motor system. Accordingly, a variety of studies have demonstrated that concurrent movement impacts the estimate of temporal duration, such that perceived time is shifted towards the duration of movement. In order to investigate the role of the motor system, we tested human subjects (n=40) on a novel task combining reaching and time perception. In this task, subjects were required to move a robotic manipulandum to one of two physical locations to categorize a concurrently timed suprasecond auditory stimulus as “long” or “short”, relative to a running average criterion. Critically, subjects were divided into two groups: one in which movement during the interval was unrestricted and subjects could move freely to their choice, and one in which they were restrained from moving until the stimulus interval had elapsed. Our results revealed a higher degree of precision for subjects in the free-moving group. By further decomposing choice and response time data with a drift diffusion model of decision making, we identified the source of this change to a shift in the response threshold for free-moving subjects. Analysis of movement parameters revealed that eventual choice could be determined by movement parameters (e.g. trajectory, force) before the response was made, and even before the interval had elapsed, and that the variability of these movements was lower in the unrestrained group. A further experiment (n=14) verified that these findings were not due to proximity to the target, counting strategies, bias, or movement length. Our findings suggest that perceptual timing may be instantiated within the motor system as an ongoing readout of timing judgment and confidence.
Investigating Ambrosia Pollen Episodes in Poland using Back-Trajectory Analysis
Authors: Matt Smith, C. Skjøth, D. Myszkowska, Alicja Stach, I. Kasprzyk
Journal: Allergy (2009)

Background: The pollen grains of Ambrosia spp. are considered to be important aeroallergens. Previous studies have shown that the long-range transport of Ambrosia pollen to Poland is intermittent and mainly related to the passage of air masses over the Carpathian and Sudetes mountains from sources to the south, e.g. the Czech Republic, Slovakia and Hungary. In this study, Ambrosia pollen counts and back-trajectories from specific episodes in 1999 and 2002 have been analysed with the aim of identifying possible new sources of Ambrosia pollen arriving at three sites in Poland.
Method: The combination of Ambrosia pollen measurements (daily average and bi-hourly concentrations) and air mass trajectory calculations were used to investigate two Ambrosia pollen episodes recorded at Rzeszow, Krakow and Poznan on the 4th and 5th September 1999 and 3rd September 2002.  Ambrosia pollen counts were recorded by volumetric spore traps of the Hirst design. Trajectories were calculated using the transport model within the Lagrangian air pollution model, ACDEP (Atmospheric Chemistry and Deposition).
Results: The collective results of pollen measurements and back-trajectory analysis indicate plumes of Ambrosia pollen travelling up through Poland from the southeast during the investigated episodes. In 1999, the plume was first recorded at Rzeszow in Southeastern Poland during the morning of the 4th September. Its route can be followed as it passed Krakow during the afternoon of the 4th, and later on the 4th and 5th September at Poznan. Similarly, back-trajectories calculated during the morning and afternoon from Krakow and Rzeszow on the 3rd September 2002 indicates that the air masses arrived at these sites from the East or Southeast.
Conclusion: This study shows the progress of Ambrosia plumes into Poland from the southeast. Ambrosia pollen release occurs mainly during the day and so a midday peak in Ambrosia pollen concentrations may indicate a local source. However, if the plume of Ambrosia pollen tracked along its northwesterly path over Poland during investigated episodes did not originate from inside Poland, then it is likely that it came from the Ukraine. This identifies a possible new source of ragweed pollen for Poland. Trajectory analysis can only show the path along which an air mass travels, not the specific source area. Further investigation could therefore include source based transport models such as 3D Eulerian atmospheric transport models.
Species identification of dermatophytes in paraffin-embedded biopsies with a new polymerase chain reaction assay targeting the internal transcribed spacer 2 region and comparison with histopathological features
Authors: J.C. Eckert, B. Ertas, T.M. Falk, D. Metze, A. Böer-Auer
Journal: British Journal of Dermatology (2015)

Dermatophytosis is a very common skin infection with a broad clinical spectrum. Biopsies are often used to confirm the diagnosis, especially when the clinical presentation is unusual. Not uncommonly, organisms are hard to find even with periodic acid-Schiff stains. Polymerase chain reaction (PCR) for dermatophytes can be used in such cases.To test a new PCR assay allowing species identification of dermatophytes on paraffin-embedded biopsies, and to reassess histopathological criteria for diagnosis of dermatophytosis.In total, 121 biopsies of 92 patients with clinical suspicion of tinea were included. In 42 samples the clinical diagnosis had been confirmed histopathologically, and in 79 no fungal elements had been identified. PCRs targeting the internal transcribed spacer (ITS)2 region of dermatophytes were performed on the biopsies with subsequent sequencing. Sections were reassessed for the presence/absence of hyphae/spores, pattern and composition of infiltrate, and epidermal/follicular changes. Patient charts were reviewed for clinical data.The new ITS2 PCR assay detected 94% of the dermatophyte infections (compared with 79% identified by microscopy). Trichophyton rubrum was the dominant species (89%), and other species identified were Trichophyton verrucosum (2%), Microsporum canis (4%), Epidermophyton floccosum (2%) and Trichophyton interdigitale (4%). In particular, infections with T. interdigitale and manifestations with prominent spongiosis were not diagnosed histologically. Intracorneal neutrophils, which have been emphasized as a histopathological clue to dermatophytosis, were present in only 46% of PCR-positive samples.Molecular species identification of dermatophytes via ITS2 PCR can easily be implemented in a routine dermatopathology setting. It is fast and highly specific and improves the sensitivity of histopathological diagnosis of dermatophytosis.
Abstract 18920: In vivo Pathophysiology of Hypertrophic Cardiomyopathy in a Highly Prevalent 25 bp Deletion Mutation in MYBPC3
Authors: Diederik D Kuster, David Barefield, Suresh Govindan, Sivaguru Mayandi, Kyounghwan Lee, Roger Craig, Sakthivel Sadayappan
Journal: Circulation (2014)

Introduction:  A polymorphic deletion of 25 base pair (bp) in the cardiac myosin binding protein-C (cMyBP-C) gene, resulted in a modified C10 domain (cMyBP-C C10MUT ) that associated with hypertrophic cardiomyopathy (HCM). The 25 bp deletion leads to the replacement of 65 amino acids with a novel sequence of 58 amino acids in the C10 domain at C’-region. Prevalence of this mutation was found to be very high, with >55 million carriers worldwide. However, the mechanism by which this mutation leads to HCM is unknown.   Hypothesis:  cMyBP-C C10MUT  expression causes contractile dysfunction and leads to the development of HCM.   Methods and Results:  Expression of cMyBP-C C10MUT  in cultured adult rat cardiomyocytes led to improper localization and contractile dysfunction including reduced fractional shortening and velocities of shortening and relaxation without affecting Ca 2+ , suggesting that cMyBP-C C10MUT  impairs contractile function. To further demonstrate that cMyBP-C C10MUT  is sufficient to cause HCM and contractile dysfunction in vivo, transgenic mice were generated in which the C10 domain of cMyBP-C was modified to cMyBP-C C10MUT . Transgenic lines (C57BL/6) with 50% mutant expression compared to endogenous cMyBP-C show significant increase in heart weight/body weight ratio in females only by 12 weeks of age, compared to non-transgenic (NTG) litter mates (4.41±0.09 mg/g NTG, 4.94±0.17 mg/g cMyBP-C C10MUT ). M-mode echo analysis showed hypercontractile hearts (EF: 53.8%±4.3% NTG, 66.4%±4.7% cMyBP-C C10MUT ), but early diastolic dysfunction (E/E’: 32.3±5.7 NTG, 46.3±8.4 cMyBP-C C10MUT ) indicating the presence of HCM phenotype. Histopathological analyses demonstrated that cMyBP-C C10MUT  hearts showed evidence of myofibrillar necrosis or ventricular fibrosis. Electron microscopic analysis revealed normal sarcomere structure in cMyBP-C C10MUT  hearts with weaker cMyBP-C stripes. Furthermore, in skinned cardiomyocytes from cMyBP-C C10MUT  mice preserved maximum force generation was observed and an increased Ca 2+ -sensitivity of force generation, compared to controls (EC50: 3.37±0.01μM NTG, 2.90±0.01μM cMyBP-C C10MUT .   Conclusion:  Expression of cMyBP-C C10MUT  protein is sufficient to cause contractile dysfunction and HCM.
Structural and Functional Recoupling of Atrial and Ventricular Myocardium
Authors: Peter Kohl
Journal: Journal of the American College of Cardiology (2014)

Conventional wisdom suggests: this should not be possible. You should not be able to successfully restore sequential activation of cardiac chambers in an adult animal with complete atrioventricular conduction block simply by gluing one end of a dish-grown tissue strand containing neonatal rodent
Warning signs are common in the days before cardiac arrest but are often ignored
Authors: Jacqui Wise
Journal: BMJ (2015)

OBJECTIVE: Osteoporosis (OP) is a well recognized complication of ankylosing spondylitis (AS), but there is no clear guidance to its appropriate management. To establish what might be considered as reasonable practice we surveyed the current practice of consultant rheumatologists in the United Kingdom. METHODS: A questionnaire comprising 14 questions relating to the management of OP in AS was sent to 449 British rheumatologists. Three hundred ten (69%) of the 449 questionnaires sent were returned. RESULTS: Only 98 respondents (31.6%) indicated that assessment of OP formed part of their routine management. Dual energy x-ray absorptiometry (DEXA) was the technique of choice for assessing bone mineral density (BMD) for 284 (91.6%). As general treatment, dietary advice was offered by 101 (32.6%) respondents, whereas 306 (98.7%) gave advice on exercise. Two case scenarios were presented and treatment choices recorded. When faced with a patient with osteopenia (-2.5 &lt; T score &lt; -1.0), 168 (54.2%) respondents would prescribe calcium and vitamin D supplements and 66 (21.3%) would prescribe a bisphosphonate. A second scenario featured a man with femoral neck T score of -2.80 and lumbar spine T score of -0.23. In this case 238 (76.8%) respondents would prescribe a bisphosphonate and 99 (31.9%) calcium and vitamin D, with some prescribing both. Thirty-eight (12.3%) would not prescribe calcium and vitamin D or a bisphosphonate. Two hundred twenty-seven (88.3%) rheumatologists indicated that they would repeat the BMD measurement in a patient with OP within 2 years. CONCLUSION: The majority of British rheumatologists do not routinely assess patients with AS for OP. Most would manage OP in AS in a similar way to postmenopausal OP, but many would not. It does not appear to be generally recognized that in AS, spinal BMD as measured by DEXA rises with advancing radiographic changes, so that hip BMD is the measurement of choice. A robust evidence base is required to clarify guidelines for the management of OP in AS.
Estrogen protection, oxidized LDL, endothelial dysfunction and vasorelaxation in cardiovascular disease: New insights into a complex issue
Authors: C SUBAHPACKER
Journal: Cardiovascular Research (2006)

See article by Monsalve et al.  [14]  (pages 66–72) in this issue. 

Pre-menopausal women have a lower risk of developing hypertension than men or post-menopausal women [1]. Estrogens may prevent or delay the onset of hypertension in pre-menopausal women. Similarly, animal models such as the spontaneously hypertensive rat (SHR) exhibit sexual dichotomy in development of essential hypertension, and estrogen reduces blood pressure in hypertensive female rats [2,3]. Such animal models are useful in the study of the protective effects of estrogen in the development of human essential hypertension [4–6].

Peripheral resistance is abnormally elevated at any given level of cardiac output in all forms of hypertension [7]. Resistance arteries are normally maintained in a state of partial constriction (vascular tone). Increased resistance may be due to altered contractility or relaxation of arterial smooth muscle. Diminished relaxation of blood vessels in SHR has been suggested to play a role in the mechanism of hypertension [8–11]. Impaired arterial muscle relaxation has been well documented in male SHR [9] and … 

*Tel.: +1 317 274 9765; fax: +1 317 274 3318. Email address: spacker1{at}iupui.edu
Superiority of dendritic cell vaccine vs tumor cell vaccine: survival by stratification subsets in MACVAC randomized Phase II trial of patient-specific vaccines utilizing antigens from autologous melanoma tumor cell lines
Authors: Robert O Dillman, Edward McClay, Thomas Amatruda, George Semeniuk, Clark Haskins, Robert Weber, David Burtzo, Carol DePriest, Denysha Carbonell, Andrew Cornforth
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts In a randomized Phase II trial conducted in patients with metastatic melanoma, superior overall survival (p=0.007) was observed for 18 patients treated with vaccines that consisted of autologous dendritic cells loaded with antigens from irradiated autologous melanoma stem cells, (