tbuckley/cabot-search huggingface dataset:
Core Outcomes for Colorectal Cancer Surgery: A Consensus Study
Authors: Angus G. K. McNair, Robert N. Whistance, Rachael O. Forsythe, Rhiannon Macefield, Jonathan Rees, Anne M. Pullyblank, Kerry N. L. Avery, Sara T. Brookes, Michael G. Thomas, Paul A. Sylvester, Ann Russell, Alfred Oliver, Dion Morton, Robin Kennedy, David G. Jayne, Richard Huxtable, Roland Hackett, Susan J. Dutton, Mark G. Coleman, Mia Card, Julia Brown, Jane M. Blazeby
Journal: PLoS Medicine (2016)

Background Colorectal cancer (CRC) is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs); however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard “core” set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery. Methods and Findings The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals) from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods). Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78%) centers, including 90 professionals, and 97 out of 267 (35%) patients. Second round response rates were high for all stakeholders (>80%). Analysis of responses lead to 45 and 23 outcome domains being retained after the first and second surveys, respectively. Consensus meetings generated agreement on a 12 domain COS. This constituted five perioperative outcome domains (including anastomotic leak), four quality of life outcome domains (including fecal urgency and incontinence), and three oncological outcome domains (including long-term survival). Conclusion This study used robust consensus methodology to develop a core outcome set for use in colorectal cancer surgical trials. It is now necessary to validate the use of this set in research practice.
When is the spread of a cultural trait due to cultural group selection? The case of religious syncretism
Authors: Carlos Santana, Raj Patel, Shereen Chang, Michael Weisberg
Journal: Behavioral and Brain Sciences (2016)

Abstract The reproduction of cultural systems in cases where cultural group selection may occur is typically incomplete, with only certain cultural traits being adopted by less successful cultural groups. Why a particular trait and not another is transmitted might not be explained by cultural group selection. We explore this issue through the case of religious syncretism.
Trends in neoadjuvant chemotherapy (NAC) use for muscle-invasive bladder cancer (MIBC): An updated report using the National Cancer Database (NCDB).
Authors: Paulo Gustavo Bergerot, Guru Sonpavde, Rebecca A. Nelson, Neeraj Agarwal, Caroline Nadai Costa, JoAnn Hsu, Toni K. Choueiri, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2016)

4540 Background: NAC is a standard of care for MIBC. A report from the NCDB cites increasing use during a 5-yr timeframe (2006-2010; Reardon et al Eur Urol 2015). We examine trends over a 10-yr span and include unique populations (cT1 or N+) who receive this modality. Methods: Patients (pts) with MIBC (ICD-O-3 8120/8130) diagnosed from 2004 to 2013 were identified who had (1) received cystectomy, (2) no prior radiotherapy, and (3) complete clinicopathologic data. Univariate and multivariate analyses were conducted to determine whether demographic or clinicopathologic criteria were associated with use or non-use of NAC. Trend analyses were conducted to assess cumulative use of NAC, segregating pts with cT2-4/N0 disease. Results: 17,180 pts were included in the analysis, 2,622 of whom received NAC. From 2004 to 2013, an increase in NAC use from 14.8% to 40.0% was seen overall, with an increase from 8.4% to 35.5% in pts with cT2-4/N0 disease. Rates of NAC use for cT2-4/N0 disease rose in parallel to use for cT1 and N+ disease. While rates of NAC rose over this 10-year span, use of adjuvant chemotherapy was stable, ranging from 6.9% to 12.1%. On multivariate analysis, increasing age, non-White race, lower income, treatment in a community setting, high Charlson Index Group risk, and a lack of private insurance were associated with decreasing utilization of NAC (P < 0.01 for each). Conclusions: A broader longitudinal analysis of the NCDB highlights a more profound increase in NAC use over the past decade and also implies use in patients with cT1 and N+ disease. Use of adjuvant chemotherapy showed no substantial change over this 10-year span. Our study also highlights socioeconomic barriers to NAC use, such as income level, race and treatment setting. Interventions to improve NAC use in these settings should be considered.
Phase II trial of combination thalidomide (thal) plus temozolomide (TMZ [TT]), in patients with metastatic malignant melanoma (MMM): Southwest Oncology Group S0508
Authors: J. Clark, J. Moon, L. F. Hutchins, J. A. Sosman, W. M. Kast, D. Da Silva, P. Y. Liu, J. A. Thompson, V. K. Sondak
Journal: Journal of Clinical Oncology (2008)

9007 Background: In single institution phase II studies, combination TT has yielded response rates (RR) up to 32% in the treatment of MMM, leading to the use of TT as a standard therapy by some. We conducted a large multi-center phase II trial in an effort to better define the clinical efficacy of TT and the immune modulatory effects of thal, when combined with TMZ, in patients (pts) with MMM. Methods: Pts must have had biopsy proven cutaneous MMM, no active brain metastases, Zubrod PS 0–1, up to 1 prior systemic therapy for MMM excluding thal, TMZ or DTIC, adequate organ function, and give informed consent. The primary endpoint was 6-month progression-free survival (PFS). Study design: if 6-month PFS = 10% then not of interest, if 25% or more then warrants further study, with alpha = .04 and power = 0.92. Secondary endpoints included RR, survival (OS), toxicities, and assess relationship between immunologic biomarkers and clinical outcomes. Pts received thal (200mg/d escalated to 400mg/d for pts < 70, or 100mg/d escalated to 250mg/d for pts ≥ 70) plus concomitant TMZ (75mg/m2/d x 6 weeks with a 2-week rest between cycles). Treatment was continued until unacceptable toxicity or disease progression. No anticoagulation was required. Results: 64 pts were enrolled, 2 were ineligible and 2 refused treatment. The 6-month PFS = 15% (95% CI: 6%-24%); 1-year OS = 36% (95% CI: 24%-49%). 51 pts had measurable disease by RECIST and are evaluable for response. RR = 14% (95% CI: 6%-26%), all partial. One treatment-related death occurred due to MI; 3 other grade 4 events occurred including one case each of PE, neutropenia and CNS ischemia. 21 grade 3 events occurred, of which fatigue was the most common. Immunologic biomarkers were obtained at baseline, 5, 9 and 13 weeks, including (a) PBMC as a percentage and as an absolute count of CD4+/CD25+/CD69+ and CD16+/CD56+ cells; and (b) ELISPOT reactivity to a recall pool of antigens and will be presented. Conclusion: TT has little clinically meaningful activity above TMZ alone in MMM. When compared with a meta-analysis on systemic therapy of MMM, TT compares poorly. This regimen should not be considered a standard treatment for MMM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough Schering-Plough Celgene
The Potential Impact of Expanding Cardiac Rehabilitation in Heart Failure
Authors: Jacob P. Kelly, Bradley G. Hammill, Jacob A. Doll, G. Michael Felker, Paul A. Heidenreich, Deepak L. Bhatt, Clyde W. Yancy, Gregg C. Fonarow, Adrian F. Hernandez
Journal: Journal of the American College of Cardiology (2016)
P6 Fluticasone Propionate/Formoterol Fumarate Combination Therapy Has an Efficacy Profile Similar to That of Its Individual Components Administered Concurrently: Abstract P6 Table 1
Authors: T McIver, B Grothe, M Jain, S Dissanayake
Journal: Thorax (2012)

<h3>Background</h3> A new asthma therapy containing a combination of the inhaled steroid fluticasone propionate (FLUT) and the long-acting β<sub>2</sub> agonist (LABA) formoterol fumarate (FORM) in a metered-dose inhaler has been developed (FLUT/FORM; <i>flutiform</i>®). In a double-blind, double-dummy, randomised, multicentre, four arm parallel group study, the efficacy and safety of FLUT/FORM <i>vs.</i> FLUT and FORM administered concurrently (FLUT+FORM) was assessed. Here we present efficacy results of a posthoc subgroup analysis comparing FLUT/FORM 500/20 µg <i>vs.</i> FLUT+FORM 500 µg + 24 µg (both twicedaily) by baseline asthma severity. <h3>Methods</h3> In total, 620 patients were randomised 1:1:1:1 to receive FLUT/FORM 500/20 µg, FLUT/FORM 100/10 µg, FLUT+FORM 500 µg + 24 µg or FLUT 500 µg. Randomisation was stratified by percentage predicted FEV1 at baseline [≥40– ≤60% (‘severe asthma’; 52% of patients) <i>vs.</i> &gt;60% – ≤80% (‘moderate asthma’; 48% of patients)], allowing a post-hoc dichotomised analysis by baseline FEV1 severity of spirometric and symptom-based endpoints. <h3>Results</h3> Similar improvements in lung function (change in pre-dose FEV1 and change in 2-hour post-dose FEV1) were seen in the FLUT/FORM 500/20 µg treatment group and the FLUT+FORM 500 µg + 24 µg treatment group overall [treatment difference 0.079 (95% CI: –0.032, 0.190) <i>P</i>=0.164 and treatment difference 0.040 (95% CI –0.069, 0.149) <i>P</i>=0.471, respectively]. Both severe and moderate asthmatic subgroups demonstrated mean changes from baseline approximating or exceeding a minimally important improvement (200 mL)1 with similar efficacy in the FLUT/FORM 500/20 µg and the FLUT+FORM 500 µg + 24 µg moderate and severe subgroups (Table 1). There were no statistically significant or clinically relevant differences overall or in either of the subgroups between FLUT/FORM 500/20 µg and FLUT+FORM 500 µg + 24 µg for any symptom-based endpoints. These included asthma symptom scores, sleep disturbance scores, rescue medication use and asthma control days. <h3>Conclusion</h3> FLUT/FORM and FLUT+FORM demonstrated similar improvements in lung function (pre-dose and 2hour post dose FEV1) and symptom-based endpoints in the overall population, and in both subgroups.
Abstract 263: Defective Autophagy Plays a Role in the Development of Angiotensin-Induced Cardiac Hypertrophy
Authors: Simon C Johnson, Vy Nguyen, Anthony Castanza, Peter S Rabinovitch
Journal: Circulation Research (2012)

While activated autophagy is a well reported feature of cardiac disease, the exact role of autophagy in the etiology and progression of cardiac hypertrophy and dysfunction is unclear; activation of autophagy appears to play either pro-survival or pro-apoptotic functions depending on the context. Here we demonstrate that dysfunctional autophagy plays a role in the development of angiotensin II-induced cardiac hypertrophy. Using a live, ex-vivo tissue imaging technique and transgenic LC3-GFP expressing mice we found that after short term (1 week) treatment, autophagic markers accumulate in angiotensin treated mouse hearts and that in a small population of cells this accumulation reaches a critical level where normal cell organization, specifically mitochondrial localization and contractile unit structure, and tissue architecture are disrupted. These observations are reminiscent of genetic diseases associated with dysfunctional autophagy, such as inclusion body myositis, where autophagic vesicles fail to properly clear and lead to cell death and tissue degeneration. We suggest that failed autophagy contributes to pressure-overload induced hypertrophy and that the cell death associated with dramatically dysfunctional autophagy in a subset of cardiomyocytes precedes fibrosis. This work provides a clear role for dysfunctional autophagy in promoting hypertrophy and fibrosis, and supports the notion that the promotion of successful autophagy is a clinically relevant target for therapeutic intervention.
Building from the HIV Response toward Universal Health Coverage
Authors: Jonathan Jay, Kent Buse, Marielle Hart, David Wilson, Robert Marten, Scott Kellerman, Morolake Odetoyinbo, Jonathan D. Quick, Timothy Evans, Peter Piot, Mark Dybul, Agnes Binagwaho
Journal: PLoS Medicine (2016)

Jonathan Jay and colleagues draw lessons from the the global HIV response that could help guide the universal health coverage movement.
Atypical Ductal Hyperplasia
Authors: Marissa Howard-McNatt
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Psychiatrist struck off for repeated plagiarism
Authors: Clare Dyer
Journal: BMJ (2016)

A psychiatrist who assured a 2014 fitness to practise tribunal that she had “learned her lesson” after suspension for plagiarising written assignments has been struck off after cutting and pasting other clinicians’ patient notes into her NHS trust’s computer system.

A medical practitioners’ tribunal also found that Aliveni Ramanujam had signed her name in the attendance book for a case presentation that she did not attend, dishonestly claiming a continuing professional development point. She also wrote a prescription when her supervisor, assigned to scrutinise and guide her work after her earlier suspension for dishonesty, had told her not to do so until he had reached an agreement with the General Medical Council about the level of prescribing allowed.

Ramanujam’s disciplinary problems began in 2009, when she was working to obtain a certificate in …
Integrated Behavioral and Primary Care
Authors: Thomas L. Schwenk
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Systemic delivery of siRNA via targeted nanoparticles in patients with cancer: Results from a first-in-class phase I clinical trial.
Authors: A. Ribas, L. Kalinoski, J. D. Heidel, J. Peterkin, D. B. Seligson, J. E. Zuckerman, C. Choi, Y. Yen, M. E. Davis, A. W. Tolcher
Journal: Journal of Clinical Oncology (2010)

3022 Background: Systemically delivered small interfering RNA (siRNA) would allow targeting oncogenic molecules beyond current approaches. We report on the first siRNA trial with a targeted nanoparticle delivery system. Methods: Open-label, dose- escalation trial in pts with solid refractory cancers receiving 4 i.v. infusions (30 min) on d 1, 3, 8, and 10 of 21-d cycles. CALAA-01 nanoparticles consisted of a cyclodextrin-based polymer, transferrin protein (hTf) targeting ligand, polyethylene glycol (PEG) for stability, and siRNA against ribonucleotide reductase M2 (RRM2). The 70 nm particles were designed to minimize renal clearance and allow tumor vasculature permeation with binding to tumor hTf receptors (TfR). Primary endpoints (safety, MTD determination) were based on the first cycle. Results: 15 pts accrued to 5 dose levels (3, 9, 18, 24, 30 mg/m2), median age 62 (range 53-85). Most common histologies: GI (4), melanoma (3). Dose escalation progressed with no DLTs. Most common treatment-related AEs: fatigue (47%), fever/chills (33%), allergic (33%), constipation (33%), nausea/vomiting (20%), all g1-2. 1 pt had g3 anemia and 2 pts had g2 thrombocytopenia, all shortly after CALAA-01 infusions with rapid recovery. 1 pt had possibly-related sinus bradycardia (g2). No objective tumor responses were seen; 1 pt at highest dose had stable metastatic melanoma for 4 mo, a change from prior course. Biopsies in 3 pts (melanoma) showed particles in tumors. At 30 mg/m2 RRM2 knockdown (mRNA and protein) was seen with confirmation of mechanism by specific cleavage sequence (RACE-PCR). TfR was not downregulated in cancer cells. Conclusions: Systemic delivery of siRNA via targeted nanoparticles is safe and can induce specific, siRNA-mediated gene silencing. This approach could be expanded to any currently undruggable cancer therapy target. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Calando Calando Calando Calando
SCIMLA, A general tool for measuring somatic mutation load in solid tissues: Dramatic inter-individual variation mutagen hypothesis of breast cancer
Authors: Kuan-Chun Huang, Wenying Zhang, Xiaoyan Ni, Ross S. Berkowitz, Samuel C. Mok, Shu-Wing Ng
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4210 

Cancer is a disease of mutations and most if not all mutagens are carcinogens. More rigorous analysis of the relationship between mutations and cancers would benefit from a general method of measuring of mutation load, i.e., mutation frequency, pattern and spectrum, in humans and animals. Single Cell Imunohistochemical Mutation Load Assay (SCIMLA) is a method to measure somatic mutation load from single cells. SCIMLA requires reporter genes in which missense mutations often cause protein accumulation. P53 is the prototype reporter gene; other reporter genes will be developed. For SCIMLA, single cells that stain positively for protein accumulation are microdissected from ethanol fixed and paraffin embedded tissues. The reporter gene is amplified from the single cell and sequenced for somatic mutations. SCIMLA was used to test a first prediction of the lipophilic hypothesis of breast cancer, i.e. mammary cells are uniquely sensitive to a diverse population of lipophilic mutagens in the diet due to the unique anatomy of breast tissue: many tiny islands of cancer-prone mammary cells surrounded by a sea of terminally differentiated fat cells that serve to concentrate lipophilic mutagens. Our observation of marked interindividual variation in mammary cell mutation pattern is consistent with the hypothesis that marked interindividual variation in mutation pattern could reflect dietary exposure to the mutagenic fingerprints of a diversity lipophilic mutagens. Based on these data, a mouse model is being used to examine directly the effect of dietary lipophilic mutagens on mutation frequency and pattern in mammary vs colon and lung epithelium. Conclusion: SCIMLA is a tool for making key and unprecedented measurements of somatic mutation from single cells in situ, which may clarify the relationship between mutations and cancer as well as other diseases. The dramatic interindividual variations observed in mammary tissues constitutes the first biological application of this novel technology.
A first-in-human (FIH) phase I study of SAR125844, a novel selective MET kinase inhibitor, in patients (pts) with advanced solid tumors: Dose escalation results.
Authors: Eric Angevin, Gianluca Spitaleri, Antoine Hollebecque, Tommaso De Pas, Jean-Charles Soria, Marzia Harnois, Florent Mazuir, Sylvie Assadourian, Filippo De Marinis
Journal: Journal of Clinical Oncology (2014)

2506 Background: SAR125844 (SAR) is a potent and highly selective MET kinase inhibitor (IC50= 4.2 nM; Ki = 2.8 nM) demonstrated to be effective in MET-driven tumors with a good safety and pharmacokinetics (PK) profiles in preclinical models. This FIH phase I study was designed to determine the maximum tolerated dose (MTD), assess tolerance, PK and pharmacodynamics of SAR. Methods: Escalating doses of SAR, using a standard 3+3 escalation scheme, were administered intravenously (IV) every week in solid tumor pts with either high membrane total-MET protein expression or cMET-gene amplification. Results: 33 heavily pre-treated pts were enrolled: 17M/16F, median age 56 [range 27-75], ECOG-PS 0/1:10/23 with a variety of solid tumors including 9 colorectal and 9 lung adenocarcinomas. A total of 434 infusions (median 10 [range 1-57]) of SAR was administered across 9 Dose Levels (DLs) ranging from 50 to 740 mg/m2. DLTs were observed in 2 pts during the first 4 weeks consisting in grade (Gr) 3 transaminase increase (TI): 1 pt at 740mg/m2 and 1 pt at 570mg/m2. Recovery was obtained with dose omission and dose reduction. A Gr2 creatinine increase in 1 pt at 740mg/m2 was also taken into account for dose selection. No dose-dependent adverse events (AE) were observed. No Gr≥3 related clinical toxicity was observed. Main drug-related Gr1-2 toxicities included: nausea/vomiting (33.3%), fatigue (18.2%), diarrhoea (15.2%), headache (12.1%), infusion site phlebitis (12.1%), pyrexia (9.1%). Blood exposure PK parameters (AUC and Cmax) increased in proportion with the dose, with a mean clearance of 32.2 L/h associated with a large volume of distribution (528L). Preliminary anti-tumor activity was observed at 570mg/m2 with one partial response among a cMET-gene amplification lung adenocarcinoma pt. Seven pts with tumors not harbouring cMET-gene amplification experienced a long lasting stabilization over 3 months. Conclusions: SAR is well tolerated with early evidence of activity. SAR 570 mg/m2is currently being confirmed in 2 extension cohorts. Clinical trial information: NCT01391533.