tbuckley/cabot-search huggingface dataset:
Abstract 14710: Prognostic Impact of Coronary Revascularization Therapy in Patients With Ischemic Heart Failure
Authors: Jun Takahashi, Yasuhiko Sakata, Kotaro Nochioka, Masanobu Miura, Tsuyoshi Takada, Satoshi Miyata, Hiroaki Shimokawa
Journal: Circulation (2013)

Background:  Coronary revascularization therapy, including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), is indicated to improve ventricular function and long-term prognosis of patients with ischemic heart failure (IHF). However, it remains to be examined which strategy is more useful in IHF patients, especially with a reference to diabetes mellitus (DM).   Methods and Results:  We examined 2,232 consecutive IHF patients with stage C/D HF (73±11[SD] years, M/F 1,749/483) in our CHART-2 Registry, where 754 (34%) had DM. Their BNP levels and eGFR were 179±285 pg/ml and 59±25 ml/min/1.73m 2 , respectively. Before the enrollment, PCI and CABG had been performed in 1,294 (58%) and 430 (19%), respectively, while the remaining 508 (23%) had no history of revascularization. During the 3.1±1.2 years of follow-up, Kaplan-Meier analysis revealed that in the non-DM patients, crude all-cause mortality of the PCI group was significantly lower compared with the CABG or the non-revascularization group (log-rank test; PCI vs. CABG, P Figure  ). Cox hazard model adjusted by age, sex, comorbidities (hypertension, hyperlipidemia), hemoglobin, eGFR, BNP, LVEF and medications (ACE inhibitor/ARB, β-blocker, statin) demonstrated that in the non-DM patients, only PCI was an independent positive predictor for all-cause mortality (PCI: HR[95%CI] 0.68[0.49-0.96], CABG: 0.88[0.59-1.32]), whereas in the DM patients, no superiority of PCI or CABG was noted to non-revascularization (PCI: HR[95%CI] 0.84[0.49-1.42], CABG: 0.96[0.51-1.83]).   Conclusions:  These results indicate the different prognostic impact of revascularization therapy in stage C/D IHF patients, depending on the revascularization mode and the presence or absence of DM.
Phase II study of dual phosphoinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma (TCC).
Authors: Emmanuel Seront, Sylvie Rottey, Bertrand Filleul, Phillipe Glorieux, Jean Charles. Goeminne, Jean-Marie Vandenbulcke, Brieuc Sautois, Petra Boegner, Vincent Verschaeve, Aline Gillain, Aline Van Maanen, Jean-Pascal H. Machiels
Journal: Journal of Clinical Oncology (2015)

e15535 Background: Excessive activation of the PI3K/Akt/mTOR pathway is frequently observed in TCC, due to loss of PTEN and/or activating mutation of PIK3CA.We previously showed in a phase II trial that the mTOR inhibitor everolimus resulted in modest efficacy in advanced TCC with a disease control rate (DCR) of 27% (Seront et al, Annals Oncology 2012). However, following this study, we demonstrated in different TCC cell lines that PI3K inhibition enhanced efficacy of mTOR inhibitor with a synergistic effect observed mainly in cells with PI3K/Akt/mTOR pathway alterations (Seront et al. Br J Cancer 2013). In this phase II study, we assessed the safety and efficacy of BEZ235, an oral pan-class I PI3K and mTOR Complex1/2 inhibitor in locally advanced or metastatic TCC after failure of platinum-based therapy. Methods: Patients with locally advanced or metastatic TCC progressing after platinum-therapy were prospectively stratified by PI3K/Akt/mTOR pathway alteration defined as PTEN loss and PI3KCA mutation and all received BEZ235 until progressive disease (PD) or unacceptable toxicity. The primary end point was the progression free survival (PFS) rate at 8 weeks, using modified Simon Minimax Two-stage testing procedure (alpha 0.1, beta 0.1, P0 20%, P1 40%). However, this study closed prematurely due the arrest of BEZ235 development. Results: 20 patients (18 without and 2 with PI3K/Akt/mTOR alteration) were enrolled and received BEZ235. One partial response (5%) and 2 stable diseases (10%) were observed, all in patients without PI3K/mTOR pathway alteration. The PFS rate at 8 weeks was 10%; the median PFS was 1.8 month (CI 95% 1.35-3.32) and median overall survival reached only 3.8 months (CI 95% 1.5-7.4). Forty percents of patients presented grade 3-4 adverse events including mucositis (10%), asthenia (15%), nausea/diarrhea (10%), anemia (10%), pneumonitis (5%) and hypertension (5%). Conclusions: BEZ235 showed modest clinical activity and unfavorable toxicity profile in patients with advanced TCC. Despite a complete blockade of the PI3K/mTOR axis, BEZ235 does not seem promising in monotherapy in pretreated TCC. Clinical trial information: NCT01856101.
Abstract P136: Healthier Personal Habits Of Primary Care Physicians Increase The Likelihood Of Their Recommending Lifestyle Modifications For Their Hypertensive Patients That Are Consistent With The National Guidelines
Authors: Olivia Y Hung, Nora L Keenan, Jing Fang
Journal: Circulation (2012)

Introduction: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) recommended lifestyle interventions, either with or without pharmacologic treatment, for all patients with high blood pressure. The objective of this study is to determine the association of physicians’ personal habits with their attitudes and behaviors regarding JNC VII lifestyle modification guidelines. Hypothesis: Primary care physicians who have healthier habits, as defined by eating more cups of fruits and/or vegetables, exercising more frequently, and/or not smoking, would be more likely to recommend lifestyle interventions consistent with JNC VII than their counterparts who have less healthy habits. Methods: One thousand primary care physicians completed DocStyles 2010, a voluntary web-based survey designed to provide insight into physician attitudes and behaviors regarding various health issues. Results: The respondents’ average age was 45.3 years and 68.5% (685 of 1000) were male. In regards to physician behavior, 4.0% (40 of 1000) smoked at least once a week, 38.6% (386 of 1000) ate ≥5 cups of fruits and/or vegetables ≥5 days/week, and 27.4% (274 of 1000) exercised ≥5 days/week. When asked about specific types of advice offered to their hypertensive patients, physicians reported recommending that their patients eat a healthy diet (922 of 1000), or cut down on salt (961 of 1000), or attain or maintain a healthy weight (948 of 1000), or limit the use of alcohol (754 of 1000), or be physically active (944 of 1000). Collectively, 66.5% (665 of 1000) made all 5 lifestyle modification recommendations. Physicians who were between 40 - 49 years old were 1.6 times as likely of making all 5 lifestyle recommendations compared with those who were under 40 years. Additionally, those who exercised at least once per week or did not actively smoke were approximately twice as likely to recommend these interventions. Conclusions: The probability of recommending all five lifestyle modifications increased with both the physician exercising at least once per week and not having smoked.
CHA2DS2-VASc Score for Predicting Stroke and Thromboembolism in Patients With AF and Biological Valve Prosthesis
Authors: Raphael Philippart, Anne Brunet-Bernard, Nicolas Clementy, Thierry Bourguignon, Alain Mirza, Denis Angoulvant, Dominique Babuty, Gregory Y.H. Lip, Laurent Fauchier
Journal: Journal of the American College of Cardiology (2016)
Toxic Effects of Sorafenib in Patients With Differentiated Thyroid Carcinoma Compared With Other Cancers
Authors: Gary W. Jean, Rene M. Mani, Aliza Jaffry, Saad A. Khan
Journal: JAMA Oncology (2016)

Sorafenib is approved by the US Food and Drug Administration for metastatic, radioactive iodine-refractory differentiated thyroid cancer. However, adverse effects common to the tyrosine kinase inhibitor class occur at a noticeably higher rate with sorafenib use in thyroid cancer patients. The mechanism for this increase in toxic effects is unknown.To provide an overview of the adverse effect profile of sorafenib in differentiated thyroid cancer and summarizes the literature regarding the frequency and etiology of selected adverse effects, with particular emphasis on the hand-foot skin reaction.A PubMed database search for relevant literature on this topic published within the last 15 years was conducted. Publications dealing with sorafenib and any of its common adverse effects were considered; this included randomized trials, observational studies, case reports or case series, and pertinent review articles. Given the lack of widespread literature on the topic, articles were generally not excluded from consideration unless there were serious flaws in study design.The DECISION trial of sorafenib in patients with differentiated thyroid cancer demonstrated significantly higher rates of common adverse effects, most notably hand-foot skin reaction, diarrhea, and hypertension, compared with sorafenib experience in renal or hepatocellular cancer. Other phase 2 and 3 trials have also consistently shown these differences. This review details the putative mechanisms behind the increase in toxic effects, but further work is needed to fully explain the toxic effects differential seen when using the same drug in different cancers.There is a distinct increase in the rate of occurrence of adverse effects of sorafenib when used in differentiated thyroid cancer compared with renal and hepatocellular cancer. While many theoretical explanations have been proposed, the exact mechanism for this differential in toxic effects remains unclear.
Comparison of two chemotherapeutic regimens − mitomycin + vindesine 4-cisplatin (MVP) vs. mitomycin + ifosfamide + cisplatin (MIP) − in advanced non-small-cell lung cancer
Authors: M González Barón, J Feliu, E Espinosa, C García Girón, E Blanco, P Garrido, A Colmenarejo, A Ordóñez, A Moyano, I de la Gándara
Journal: Annals of Oncology (1994)
Radiotherapy with or without temozolomide in elderly glioblastoma patients: Treatment results and prognostic factors.
Authors: A. Dirier, M. U. Abacioglu, S. Okkan, Y. Pak, Y. Yukselen Guney, G. Aksu, S. Soyuer, O. B. Oksuzoglu, A. D. Meydan, S. B. Zincircioglu
Journal: Journal of Clinical Oncology (2010)

2048 Background: Optimal treatment for elderly patients with glioblastoma (GBM) is controversial. We performed a retrospective analysis from 10 centers to investigate the role of adding temozolomide (TMZ) chemoterapy to radiotherapy (RT) in patients ≥ 60 years old. Methods: 305 newly diagnosed GBM patients (Group 1 = 60-69 years 215 patients; Group 2 = 70-82 years 90 patients) were eligible. 59% were male, median KPS score was 70 (range 30-100). Resection was total in 41%, subtotal in 40% and biopsy in 19%. Median RT dose was 60 Gy. 44% of Group 1 and 31% of Group 2 patients received concomitant and/or adjuvant TMZ. 19 patients received concomitant only, 13 adjuvant only and 90 received both. Univariate and multivariate analysis were performed to determine the prognostic factors. Results: The median overall survival (OS) was 9 months (8.11-9.89 %95 CI) for the all cohort. 6-month, 1-year and 2-year survival rates were 69%, 31% and 6%, respectively. Median OS for RT and RT+TMZ patients were 8 and 12 months (p < 0.001) in the whole group; 8 and 13 months in Group 1 (p < 0.001); 7 and 12 months in Group 2 (p = 0.001). Median OS for patients with total, subtotal resection and biopsy were 12, 9 and 6 months, respectively (p < 0.001). Lower age (p = 0.022) and higher KPS score (p < 0.001) linearly correlated with better OS. Multivariate analysis revealed resection type (p = 0.002), KPS score (p < 0.001) and addition of TMZ (p < 0.001) as independent prognostic factors for OS. Hematologic toxicities were grade 1-2 in 16% and > 2 in 11%, liver enzyme elevation Gr 1-2 in 3%. Conclusions: Age was not an independent variable for OS in our patient population. Patients over 70 years with good KPS may also benefit from addition of TMZ to RT with acceptable morbidity. Prospective trials in elderly population are needed to demonstrate this efficacy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Schering-Plough
Polymorphism and divergence at the prune locus in Drosophila melanogaster and D. simulans.
Authors: G M Simmons, W Kwok, P Matulonis, T Venkatesh
Journal: Molecular Biology and Evolution (1994)

The prune locus of Drosophila melanogaster lies at the tip of the X chromosome, in a region of reduced recombination in which nearby loci show reduced variation relative to evolutionary divergence from D. simulans. DNA sequencing of prune alleles from D. melanogaster and D. simulans reveals extremely low variation in D. melanogaster but greater variation in D. simulans. Divergence between the two species is not reduced. This pattern may be explained by either positive selection leading to hitchhiking of neutral variation or background selection against deleterious mutations. The pattern of silent versus replacement polymorphism and divergence at prune is consistent with either a model of weakly deleterious selection against amino acid substitutions or balancing selection.
15-year outcomes following conservative management among patients with screen-detected localized prostate cancer.
Authors: Grace L. Lu-Yao, Peter C. Albertsen, Dirk Moore, Yong Lin, Robert S. DiPaola, Siu-Long Yao
Journal: Journal of Clinical Oncology (2014)

5053 Background: An understanding of the natural history of screen-detected prostate cancer is essential for making appropriate treatment decisions; however, such data are few and far between Methods: We assembled a population-based cohort consisting of 12,271 men aged >65 years diagnosed with screened detected (T1c) localized prostate cancer during 1992 - 2009 who did not receive surgery, radiotherapy, or androgen deprivation therapy (ADT) within 6 months of diagnosis. Competing risk analyses were used to assess cancer-specific mortality and use of cancer-related interventions. Results: Compared to outcomes of pre-PSA era patients, 15-year survival has improved considerably for conservatively managed patients diagnosed in the PSA era. The 15-year risk of prostate cancer specific mortality for men aged 66-74 diagnosed with T1C Gleason 5-7 prostate cancer was 6.1% (95% CI 3.6-8.8% ) compared to 17 - 23% among men diagnosed in the pre-PSA era. Similarly, substantial improvement was observed for patients with T1c Gleason 8-10 prostate cancer: 15-year prostate cancer mortality was 21.4% (95% CI 11.9 – 44.2%) compared to 56-65% in the pre-PSA era. The 15-year prostate cancer mortality for patients aged 75+ was 9.8% (95% CI 7.7-12.1%) for Gleason 5-7 and 25.2% (95% CI 18.4-33.2%) for Gleason 8-10. Among patients aged 66-74 with T1c Gleason 5-7 cancer, 53.6% (95% CI 50.6 – 56.9%) received cancer therapy (42.3% attempted curative therapy, 22.5% ADT, 6.6% palliative therapy) within 15 years of cancer diagnosis. Among those who received attempted curative cancer therapy, the majority did so within the first 3 years of follow-up. Conclusions: To our knowledge, this is the largest US population-based long-term study on screen-detected prostate cancer initially treated with conservative management. Fifteen-year disease-specific mortality following conservative management among men with screen-detected cancer has decreased by more than 60% as compared with results from the pre-PSA era. The risk of death due to prostate cancer for men diagnosed with T1c Gleason 5-7 disease in the PSA era is low.
Transcranial Magnetic Stimulation for Chronic Tinnitus
Authors: Jay F. Piccirillo
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
A drug interaction study of sorafenib (S) and rapamycin (R) in patients with advanced malignancies
Authors: T. Gangadhar, E. E. Cohen, L. Janisch, L. K. House, S. D. Undevia, G. F. Fleming, M. L. Maitland, J. Ramirez, M. J. Ratain
Journal: Journal of Clinical Oncology (2008)

2545 Background: R inhibits the mammalian target of rapamycin (mTOR) and is active in preclinical tumor models. S inhibits multiple kinases. S and mTOR inhibitors have activity in similar tumor types and may be synergistic. Methods: Design: A drug-drug interaction study of oral S and R in patients with PS 0–2 and histologically confirmed solid tumors with progressive disease after standard therapy or for which no standard therapy exists. Patients were assigned to one of two treatment arms in sequence. Arm A: S 400 mg bid starting day (D) 1, then S + R 3 mg qd starting D15. Arm B: R 3 mg qd starting D1, then R + S 400 mg bid starting D15. Primary endpoint: determine whether a significant pharmacokinetic interaction exists between R and S. Samples for pharmacokinetic analysis were collected on D1, 14, 15 and 29 (A) or D1, 8, 15, 22 (B). Paired t tests were used to compare mean drug concentrations. Results: 20 patients were enrolled from 4/07–10/07. Median age 54 (range 36–74); 55% men; PS 0: 60%, 1: 40%. 58 4-week cycles were administered (median 2; range 1–8). Grade 3 toxicity (% patients): rash 15%, hypophosphatemia 10%, diarrhea 20%, hypertension 5%, bleeding 5%, vomiting 5%. 2 patients died: 1 from infection, the other by arrhythmia. Pharmacokinetics: 6 patients per arm were evaluable. Initiation of R caused no significant change in the mean concentration of S at similar timepoints on D14 vs. D15: (7664, 5704 ng/mL; p=0.20) or D15 vs. D29: (5704, 5350 ng/mL; p=0.68). Initiation of S caused no change in the mean concentration of R on D8 vs. D15 (14.6, 16.4 ng/mL; p=0.43) or D15 vs. D22: (16.4, 16.1 ng/mL; p=0.91). The mean concentration R 20 minutes after drug was lower on D22 vs. D15: (9.1, 15.1 ng/mL; p=0.01) but there was no difference at 5 hours. Best response was stable disease in 45% of patients enrolled. Conclusions: S lowered the concentration of R at 20 minutes, which may merit further study. No other interactions between R and S were observed. Combination therapy was well tolerated and may be active in advanced cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Onyx Bayer, Inc. Bayer, Inc.
Sphingosine-1-phosphate receptor expression and signalling in human airway smooth muscle cells
Authors: Elisabeth Stafflinger, Holly Foster, Katharina Mahn, Christopher Corrigan, Tak Lee, Grzegorz Woszczek
Journal: European Respiratory Journal (2011)

Sphingosine-1-phosphate (S1P), a bioactive lipid and ligand for five G protein coupled receptors (S1P1-S1P5), is a key regulator of cell trafficking, cell differentiation and immune responses. Recently, increased concentrations of S1P have been detected in airways of asthmatic subjects and S1P has been shown to be a potent constrictor of human airway smooth muscle (HASM) cells. The aim of this study was to investigate the expression and signalling pathways of S1P receptors in HASM cells. HASMs have been grown from bronchial biopsies of healthy individuals. Real-time PCR has been used to determine gene expression. Intracellular signalling in response to S1P was measured using MAP kinase phosphorylation, intracellular calcium and cAMP assays. Three of the five known receptors are expressed in HASM cells at mRNA level: S1P1, S1P2, and S1P3. S1P potently activated intracellular calcium flux in a concentration-dependent manner, with EC50=4×10-9M. Using a range of selective agonists and antagonists, S1P1 and S1P3 were found to couple to Gi and inhibit forskolin induced cAMP generation, whereas S1P2 and S1P3 signalled through intracellular calcium mobilisation. S1P also induced phosphorylation of extracellular signal-regulated kinase (Erk) and increased expression of several genes, including interleukin-6. This study demonstrates that S1P receptors may signal effectively through multiple intracellular pathways in response to S1P and activate HASM cells.
Metastatic pulmonary calcification: ‘crazy paving’ pattern
Authors: Kay Por Yip
Journal: Thorax (2015)

A 60-year-old man was admitted under the cardiology team for increasing shortness of breath over the past two months. His medical history of note included stable renal transplant 8 years ago, previous parathyroidectomy due to uncontrolled tertiary hyperparathyroidism and hypertension. His echocardiogram showed a critical aortic stenosis and was thus worked up for an …
Cyclophosphamide versus 5-fluorouracil, doxorubicin, and mitomycin C (FAM') in the treatment of hormone-resistant metastatic carcinoma of the prostate: a preliminary report of a randomized trial.
Authors: B S Kasimis, J B Miller, C A Kaneshiro, K A Forbes, E M Moran, G E Metter
Journal: Journal of Clinical Oncology (1985)

There is no evidence that combination chemotherapy is superior to single agents in the treatment of advanced, hormone-resistant carcinoma of the prostate. We are reporting the preliminary results of a randomized trial comparing cyclophosphamide (CTX) with a combination of 5-fluorouracil, doxorubicin and mitomycin C (FAM'). Thirty-one patients were randomized and 30 of them were evaluable for response. Sixteen patients were treated with CTX and 14 with FAM'. On the CTX arm, eight (50%) of the patients had stable disease (SD) and eight (50%) had progressive disease (PD). On the FAM' arm, one (7%) patient had partial response (PR), five (36%) patients had SD and eight (57%) failed to respond. The difference in response rates between the two regimens was not significant (P greater than .72). The median time to progression (MTP) of all patients treated with CTX was six weeks and the MTP of patients treated with FAM' was 16 weeks (P less than .007). This difference in MTP could be explained in part by the unequal time to reevaluation between the two regimens. The MTP of the responders on CTX however, was 13 weeks, while for FAM' it was 33 weeks (P = .014). This difference suggests that FAM' has superior activity to CTX. Pain alleviation was seen in 25% of patients treated with CTX and in 64% of those treated with FAM' (P less than .01). Toxicity was tolerable on both regimens. We conclude that CTX and FAM' have similar response rates. Patients treated with FAM' enjoyed longer MTP and greater pain alleviation than those treated with CTX.