tbuckley/cabot-search huggingface dataset:
Use of Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation Who Have a History of Intracranial Hemorrhage
Authors: Tze-Fan Chao, Chia-Jen Liu, Jo-Nan Liao, Kang-Ling Wang, Yenn-Jiang Lin, Shih-Lin Chang, Li-Wei Lo, Yu-Feng Hu, Ta-Chuan Tuan, Fa-Po Chung, Tzeng-Ji Chen, Gregory Y. H. Lip, Shih-Ann Chen
Journal: Circulation (2016)

Background— The risk of further intracranial hemorrhage (ICH) and the benefit of stroke risk reduction with the use of oral anticoagulants for patients who have atrial fibrillation with a history of ICH remain unclear. We aimed to investigate the risks and benefits in patients who have atrial fibrillation with a previous ICH treated with warfarin or antiplatelet drugs in comparison with no antithrombotic therapies. Methods and Results— This study used the National Health Insurance Research Database in Taiwan. Among 307 640 patients who have atrial fibrillation with a CHA 2 DS 2 -VASc score ≧2, 12 917 patients with a history of ICH were identified and were assigned to 1 of 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Among patients with previous ICH, the rate of ICH and ischemic stroke in untreated patients was 4.2 and 5.8 per 100 person-years, respectively. The annual ICH and ischemic stroke rates in warfarin users were 5.9% and 3.4%, respectively. Among users of antiplatelet agents, the rates were 5.3% per year and 5.2% per year, respectively. The number needed to treat for preventing 1 ischemic stroke was lower than the number needed to harm for producing 1 ICH with warfarin use for patients with a CHA 2 DS 2 -VASc score ≧6 (37 versus 56). The number needed to treat was higher than the number needed to harm for patients with a CHA 2 DS 2 -VASc score &lt;6 (63 versus 53). Conclusions— Warfarin use may be beneficial for patients who have atrial fibrillation with a previous ICH having a CHA 2 DS 2 -VASc score ≧6. Whether the use of non–vitamin K antagonist oral anticoagulants could lower the threshold for treatment deserves further study.
Abstract 1208: Glutamine modulates cellular NAD+/NADH homeostasis thereby regulating cancer metastasis, drug sensitivity in cancer cells
Authors: Lifeng Yang, Abhinav Achreja, Tyler Moss, Joelle Baddour, Katherine Stilles, Lisa Chiba, Sun Hye Kim, Josh Morse, Juan Marini, Anil K. Sood, Prahlad T. Ram, Deepak Nagrath
Journal: Cancer Research (2015)

Abstract Glutamine can play a critical role in cellular growth in multiple cancers. Glutamine-addicted cancer cells are dependent on glutamine for viability, and their metabolism is reprogrammed for glutamine utilization through the tricarboxylic acid (TCA) cycle. Recently, we uncovered a missing link between cancer invasiveness and glutamine dependence. Using isotope tracer and bioenergetic analysis, we found that low-invasive ovarian cancer (OVCA) cells are glutamine independent, whereas high-invasive OVCA cells are markedly glutamine dependent. Consistent with our findings, OVCA patients’ microarray data suggest that glutaminolysis correlates with poor survival. Notably, the ratio of gene expression associated with glutamine anabolism versus catabolism has emerged as a novel biomarker for patient prognosis. Significantly, we found that glutamine regulates the cellular NAD+/NADH homeostasis, which mediates cancer metastasis and progression. On the other hand, the overexpression of NAD+ biosynthesis pathway enhances glutamine's entry into TCA cycle for cancer metastasis, as well as chemo-drug resistance. Our findings suggest that a combined approach of targeting high-invasive OVCA cells by blocking glutamine's entry into the TCA cycle, along with targeting NAD+ biosynthesis pathway may lead to potential therapeutic approaches for treating OVCAs. Our insights will present a unique opportunity for overcoming the drug resistance limitation in clinical trials in ovarian cancers. Citation Format: Lifeng Yang, Abhinav Achreja, Tyler Moss, Joelle Baddour, Katherine Stilles, Lisa Chiba, Sun Hye Kim, Josh Morse, Juan Marini, Anil K. Sood, Prahlad T. Ram, Deepak Nagrath. Glutamine modulates cellular NAD+/NADH homeostasis thereby regulating cancer metastasis, drug sensitivity in cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1208. doi:10.1158/1538-7445.AM2015-1208
Authors’ reply to Perry
Authors: Darrel P Francis, Graham D Cole
Journal: BMJ (2016)

We thank Perry for raising the interesting difference between research trials where both patients and staff are blinded to whether the tablet is really a statin and everyday practice where patients and doctors know whether a statin is being taken. 1 2 In the blinded trials, there are indeed reports of symptoms, but (in the published data) these are equivalent between statin and placebo.In everyday practice, there are reports of symptoms but no blinded comparator group.
THU0301 Outcome of Patients with Diffuse Alveolar Hemorrhage in Anca Associated Vasculitis
Authors: Y. Gon, K. Misaki, T. Nagamoto, H. Horiuchi, H. Yamada, R. Saito, Y. Nakamura, T. Yokota
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Antineutrophil cytoplasm antibody (ANCA) associated vasculitis can be life-threatening. Diffuse alveolar hemorrhage is one of the most serious complications in ANCA-associated vasculitis (AAV). Steroid pulse, cyclophosphamide (CY), and plasma exchange therapies are recommended for severe alveolar hemorrhage. However, the mortality of patients with pulmonary vasculitis remains high. <h3>Objectives</h3> We examined the outcome of patients with AAV complicated with diffuse alveolar hemorrhage. <h3>Methods</h3> We retrospectively reviewed the clinical records of patients with AAV admitted at our hospital between January 1st 2008 and September 30th 2013.We analyzed in respect to outcomes age, CRP, Hb, serum creatinine (sCr) disease activity (Birmingham vasculitis activity score: BVAS), and medical treatment method. <h3>Results</h3> AAV occurred in 70 patients (GPA17, MPA43, and EGPA10) and diffuse alveolar hemorrhage in 21 patients (30%). The average age was 66.8±22.6 years (MPA 71.8±18.9 years old, GPA 50.5±28.7 years old), and the sex ratio was male: female 7:10. Other severe comorbidities were progressive glomerulonephritis (4 of 6 patients died), and interstitial pneumonia (2 from 2 patients). Nine patients died and eight cases received remission maintenance therapy. The average BVAS was 21.0±5.48 in the death group, and 18.4±4.65 (<i>p =0.34</i>) in the survival group. The was no significant difference in disease activity between the survival and death groups. There were no significant differences in CRP, sCr, Hb levels and volumes of alveolar hemorrhage in CT. There was a significant difference in average age (survival groups 51.4±28.9 years old, death groups 77.1±6.25 years old, <i>p =0.02</i>). There was also a significant difference in five-factor score (FFS) between the two groups (survival group 1.6±0.29, death group 0.5±0.76, <i>p =0.02</i>). All the cases in the survival group were treated with CY. <h3>Conclusions</h3> Our study showed that early CY treatment decreased the mortality of diffuse alveolar hemorrhage in AAV, especially in younger patients. <h3>Disclosure of Interest</h3> None declared
Cardiovascular Effects of Tricyclic Antidepressants in Depressed Patients with Chronic Heart Disease
Authors: Richard C. Veith, Murray A. Raskind, James H. Caldwell, Robert F. Barnes, Gail Gumbrecht, James L. Ritchie
Journal: New England Journal of Medicine (1982)

Twenty-four depressed patients with heart disease were treated for four weeks in a double-blind trial of imipramine, doxepin, or placebo to assess the effects of tricyclic antidepressants on ventricular function and rhythm. The tricyclic antidepressants had no effect on left ventricular ejection fraction at rest or during maximal exercise, as measured by radionuclide ventriculograms obtained before and after treatment. Premature ventricular contractions were reduced by imipramine but were not consistently changed by doxepin or placebo. Treatment with imipramine and doxepin, but not placebo, was associated with significant improvement (P less than 0.001) in standard ratings of depression. Our findings underscore the need for a reappraisal of the cardiovascular risks of tricyclic antidepressants and suggest that in the absence of severe impairment of myocardial performance, depressed patients with preexisting heart disease can be effectively treated with these agents without an adverse effect on ventricular rhythm or hemodynamic function.
Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents
Authors: Chongwen Bi, Cheng Ye, Yinghong Li, Wuli Zhao, Rongguang Shao, Danqing Song
Journal: Acta Pharmaceutica Sinica B (2016)

Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3'-substituents at the 11-side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a-b, alkenes 7a-b and sophoridinic amines 14a-b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
Two Transplantable Uterine Adenocarcinomas in the Rat
Authors: Hiroshi Kobayashi, Kokichi Kikuchi, Tsuneo Maki, Iwao Nishiya
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Two Transplantable Uterine Adenocarcinomas in the Rat Get access Hiroshi Kobayashi, Hiroshi Kobayashi Institute of Cancer Immunopathology, Hokkaido University School of Medicine, Sapporo, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Kokichi Kikuchi, Kokichi Kikuchi Institute of Cancer Immunopathology, Hokkaido University School of Medicine, Sapporo, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Tsuneo Maki, Tsuneo Maki Institute of Cancer Immunopathology, Hokkaido University School of Medicine, Sapporo, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Iwao Nishiya Iwao Nishiya Institute of Cancer Immunopathology, Hokkaido University School of Medicine, Sapporo, Japan 2We thank Professor Katsuo Takeda, Hokkaido University, Sapporo, Japan, and Dr. Thelma B. Dunn, National Cancer Institute, Bethesda, Md., for valuable suggestions and encouragement. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 34, Issue 1, January 1965, Pages 13–20, https://doi.org/10.1093/jnci/34.1.13 Published: 01 January 1965 Article history Received: 28 January 1964 Revision received: 27 August 1964 Published: 01 January 1965
Regional variation in physicians’ awareness, understanding, and use of personalized medicine in the treatment of cancer and perception of patient (pt) education.
Authors: Fortunato Ciardiello, Thomas Seufferlein, Josep Tabernero, Julien Taieb, Vladimir Moiseyenko, Brigette Ma, Gustavo A. Lopez, Regina Esser, Richard A. Adams
Journal: Journal of Clinical Oncology (2015)

574 Background: A multinational survey of oncologists was conducted to assess the awareness and use of biomarkers in clinical practice (Ciardiello et al, ESMO 2014). These data explore regional variations as well as perceived level of “cancer literacy” among pts. Methods: Ten-minute online interviews were conducted with practicing oncology specialists (3 to 35 years of experience, treating &gt; 15 pts/month) from 12 representative countries in Europe, South America, and Asia. Results: In total, 895 interviews were completed; numerous regional differences were observed. While most physicians use biomarkers (90%), there were marked regional variations. KRAS was the most frequent test. Among the 10% of physicians not using biomarkers, local availability of testing, speed of obtaining results, and cost were cited as the main reasons. The majority of Chinese doctors indicated that physician training (82%) and better biomarker information for pts (83%) would enable them to use biomarkers more often (global averages: 38% and 34%, respectively). Striking variation was seen in physicians’ assessment of pts’ knowledge of cancer biology, treatment options, use of biomarkers, and involvement in their own treatment plans. Only 38% of German physicians believed their pts know that tumors can be tested to help decide which treatment to give (global average: 73%). Only 21% of Saudi Arabian physicians believed the treatment decision process is shared between the doctor and/or multidisciplinary team and pt (global average: 82%). While physicians felt specialist nurses were the best source of information for pts, only 45% globally believed pts had access to these nurses (ranging from 19% in Russia to 83% in the UK). Conclusions: These data demonstrate wide global use of biomarkers but with regional variations reflecting cultural and local practice. Perception of pt cancer literacy and pt access to information also differs widely. Most physicians agree, however, that pts require more information to understand their disease better and become involved in treatment decisions.
AB0803 Obesity is Associated with Psoriatic Arthritis and Contributes to the Increased Use of Biologics
Authors: P. Cetin, M. Keser, D. Solmaz, G. Sen, B. Zengin, I. Sari, N. Akkoc, F. Onen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> An increased prevalence of obesity and metabolic syndrome (Mets) has been reported in psoriatic arthritis (PsA) as compared with the general population suggesting an association between the inflammation and atherosclerotic risk factors. Takayasu arteritis (TA) is a systemic inflammatory disease which affects mostly the aorta and its main branches. Increased atherosclerosis has also been reported in Takayasu patients. <h3>Objectives</h3> In this study, we aimed to investigate the prevalances of obesity and Mets in patients with PsA and to compare the results with those in patients with TA. <h3>Methods</h3> This cross-sectional study included patients with PsA and age matched control patients with TA who were followed in the Rheumatology out-patient clinic at Dokuz Eylul University. Patients with body mass index (BMI; kg/m<sup>2</sup>) between 25.0 and 29.99 were classified as overweight and those with ≥30 as obese. The NCEP-ACT III criteria were used to identify subjects with MetS. Disease activity was assessed in patients with PsA using the Composite Psoriatic Disease Activity Index (CPDAI), BASDAI and DAS28. HAQ and DLQI were used for the health assessment and BASFI for the functional status. <h3>Results</h3> There were 117 PsA patients (78 female; mean age: 47.2±12.0 years; disease duration: 8.0±8.4 years) who fulfilled the CASPAR criteria and 32 TA patients (29 female; mean age: 43.5±11.3 years; disease duration: 8.3±8.7 years) who fulfilled the ACR 1990 classification criteria for TA.The prevalence of obesity and overweight was found to be higher in PsA compared with TA (29.9% versus 18.8% and 40.2% versus 28.0%, respectively; p=0.03). The prevalence of MetS was 28.2% in PsA and 18.8% in TA (p0.05).In the further analysis of obese, overweight patients and patients with normal BMI, no differences were found regarding disease activity, functional status, health assessment, disease duration, and glucocorticoid and DMARD use (p0.05). However there was a higher frequency of biologic use in the obese and overweight patients compared with those with normal BMI (42.9% and 23.4%, respectively vs 11.4%, p0.05) <h3>Conclusions</h3> This study demonstrates a higher prevalence of obesity in PsA compared with TA. The increased use of biologics in obese patients suggests the association of obesity with worse disease severity in PsA. <h3>Disclosure of Interest</h3> None declared
Chemotherapy in very elderly cancer patients (85 years and over): A retrospective study
Authors: R. Bascioni, F. Giorgi, M. Safi, L. Giustini, G. De Signoribus, R. Silva
Journal: Journal of Clinical Oncology (2009)

e20632 Background: Elderly cancer patients (pts) population is expanding due to demographic changes. Currently 2.4 % of Italian population is older than 85, with this group accounting ∼8 % of all cancer pts in our geographic area. Since very elderly (85 years and over) cancer pts are generally excluded from clinical trials, few data are available about tolerability of chemotherapy in this population. Methods: We conducted a retrospective analysis of cancer pts aged 85 years and over receiving chemotherapy for advanced disease in the years 2005–2007 in three Oncology Unit of the Regione Marche, Italy. Results: We identified 50 patients (26 males, 24 females) with a mean age of 86.4 (range 85–95), ECOG PS 0 (4 pts) 1 (25 pts) 2 (13 pts) 3 (8 pts). Type of cancer (pts): NSCLC (13), colorectal (11), breast (5), prostate (4), gastric (3), NHL (3), bladder (2), head-neck (2), ovarian (2), vulvar (1), skin (1), pancreas (1), GIST (1), UPT (1). Main co-morbidities included hypertension (18 pts), COPD (8 pts) and heart disease (6 pts). The median number of cycles in first line chemotherapy were 6 (1–44); 20 pts received 2 or more lines of chemotherapy (range 2–5). Dose reductions were planned in all pts: in 26 dose reduction was 30 %, in 22 was 50%, in 2 &gt; 50 %. Most used drugs were: vinorelbine os or iv (14 pts), capecitabine (9 pts), gemcitabine (7 pts). Target agents were used in 7 pts (5 erlotinib, 2 gefitinib, 2 rituximab, 1 sunitinib). Ten partial responses were observed; main toxicities were: grade 3–4 neutropenia (10 %), grade 3 diarrhea (5 %), and 1 pts had grade 3 hand-foot syndrome. No treatment related deaths were observed. Conclusions: Very elderly cancer pts (85 years and over) in good PS and few co-morbid conditions receiving dose reduced chemotherapy experienced acceptable toxic effects; a partial response was documented in 10 out of 50 pts. The expanding use of chemotherapy and target therapy in this clinical setting has profound influence on health care management and costs. Prospective studies specifically designed for this pts population could clarify the benefit, in terms of quality of life and survival, of an interventionist instead of a supportive care only approach. No significant financial relationships to disclose.
116PD: Short-course, high-dose image-guided radiotherapy in poor risk patients with very central non-small cell lung cancer
Authors: H. Tekatli, N. Haasbeek, M. Dahele, P. de Haan, W. Verbakel, E. Bongers, S. Hashemi, E. Nossent, B. Slotman, S. Senan
Journal: Journal of Thoracic Oncology (2016)
Abstract 578: Molecular subgroup analysis of clinical outcomes in a phase 3 study of gemcitabine and oxaliplatin with or without erlotinib in advanced biliary tract cancer
Authors: Seung T. Kim, Joon Park
Journal: Cancer Research (2015)

Abstract BACKGROUND. We previously reported that the addition of erlotinib to gemcitabine and oxaliplatin (GEMOX) resulted in greater antitumor activity and might be a treatment option for patients with biliary tract cancers. Molecular subgroup analysis of treatment outcomes in patients who had specimens available for analysis was undertaken. METHODS. EGFR, KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp reactions. Survival and response rates were analyzed according to the mutational status. 64 patients (48.1%) were available for mutational analysis in the chemotherapy alone group and 61 (45.1%) in the chemotherapy plus erlotinib group. RESULTS. 1.6% (2/116) harboured an EGFR mutation (2 patients; exon 20), 9.6% (12/121) harboured a KRAS mutation (12 patients; exon 2), and 9.6% (12/118) a PIK3CA mutation (10 patients; exon 9 and 2 patients; exon 20). The addition of erlotinib to GEMOX in patients with KRAS wild type disease (n = 109) resulted in significant improvements in overall response compared with GEMOX alone (30.2% vs. 12.5%, P = 0.024). In 95 patients with both wild type KRAS and PIK3CA, there was evidence of a benefit associated with the addition of erlotinib to GEMOX with respect to response rate (RR) as compared with GEMOX alone (P = 0.04). CONCLUSION. This study demonstrates that KRAS mutational status might be considered a predictive biomarker for the response to erlotinib in biliary tract cancers (BTCs). Additionally, the mutation status of PIK3CA may be a determinant for adding erlotinib to chemotherapy in KRAS wild type BTCs. Keywords: KRAS, PIK3CA, Erlotinib Citation Format: Seung T. Kim, Joon Park. Molecular subgroup analysis of clinical outcomes in a phase 3 study of gemcitabine and oxaliplatin with or without erlotinib in advanced biliary tract cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 578. doi:10.1158/1538-7445.AM2015-578
A Randomized Trial Comparing Fluconazole with Clotrimazole Troches for the Prevention of Fungal Infections in Patients with Advanced Human Immunodeficiency Virus Infection
Authors: William G. Powderly, Dianne M. Finkelstein, Judith Feinberg, Peter Frame, Weili He, Charles van der Horst, Susan L. Koletar, M. Elaine Eyster, John Carey, Hetty Waskin, Thomas M. Hooton, Newton Hyslop, Stephen A. Spector, Samuel A. Bozzette
Journal: New England Journal of Medicine (1995)

Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated.We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia.After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 years of follow-up in the fluconazole and clotrimazole groups, respectively; P < 0.001). Survival was similar in the two groups.Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.