tbuckley/cabot-search huggingface dataset:
Abstract 300: Predominant Effect of Conventional Bystander CPR Without Dispatcher-Assisted Instruction on Survival from Out-of-Hospital Cardiac Arrests in Remote Time-Distance Region
Authors: Yutaka Takei, Taiki Nishi, Takahisa Kamikura, Hiroki Matsubara, Yukihiro Wato, Keisuke Ohta, Hideo Inaba
Journal: Circulation (2014)

Aim:  To identify the factors associated with survival from bystander-witnessed out-of-hospital cardiac arrests (OHCAs) in remote time-distance region.   Methods:  Cleaned data for 193,914 bystander-witnessed OHCAs without any prehospital physician involvement were extracted from those for 716,608 OHCAs collected prospectively between 2007 and 2012 in Japan. Of these OHCAs, 17,209 cases having a response time (call[[Unable to Display Character: ‒]]arrival) interval of >13 min were defined as OHCAs in remote region and analyzed for factors associated with one-month neurologically favorable survival.   Results:  The rates of bystander CPR (BCPR) and dispatcher-assisted CPR (DA-CPR) in the remote region (52.2 and 45.3%, respectively) were slightly higher than those in the other regions (45.9 and 44.2%). However, the survival rate in this region (1.1%, odds ratio; 95% CI, 0.24; 0.21-0.28) was much lower than that in other regions (4.3%, reference). When BCPR was classified into five groups, the survival rate in remote region was 0.6, 1.0, 1.6, 1.6 and 2.9% for no BCPR (N=8,231), compression-only BCPR following DA-CPR (N=4.321), conventional (compression + ventilation) BCPR following DA-CPR (N=1,492), compression-only BCPR without DA-CPR (N=1.990) and conventional BCPR without DA-CPR (N=1,175), respectively. After adjustment for other factors associated with outcomes, odds ratio (95% confidence interval) for survival with the conventional BCPR without DA-CPR group as reference was 0.25 (0.16[[Unable to Display Character: ‒]]0.40), 0.33 (0.21[[Unable to Display Character: ‒]]0.54), 0.54 (0.31[[Unable to Display Character: ‒]]0.92) and 0.51 (0.30[[Unable to Display Character: ‒]]0.85) for no BCPR, compression-only BCPR following DA-CPR, conventional BCPR following DA-CPR, compression-only BCPR without DA-CPR group, respectively.   Conclusions:  Conventional BCPR on bystander’s own initiative (without DA-CPR) has predominant effect on survival from OHCAs in remote time-distance region.
Ifosfamide plus doxorubicin in metastatic adult sarcomas: a multi-institutional phase II trial.
Authors: P J Loehrer, G W Sledge, C Nicaise, J Usakewicz, J D Hainsworth, O J Martelo, G Omura, T J Braun
Journal: Journal of Clinical Oncology (1989)

Between April 1986 and March 1987, 42 patients with advanced sarcoma were entered in this multi-institutional trial evaluating ifosfamide plus doxorubicin. The majority of patients had leiomyosarcoma and malignant fibrous histiocytoma although two patients with sarcomas of osseous origin were included. Doxorubicin was administered at a dosage of 60 mg/m2 by continuous push and ifosfamide 5.0 g/m2 by continuous infusion over 24 hours with mesna (7.5 g2 over 36 hours) with courses repeated every 3 weeks until progression, toxicity cumulative doxorubicin dosage of 450 mg/m2. Overall, 15 (36%) patients demonstrated objective remissions including three complete and 12 partial remissions (95% confidence limits, 21.5% to 52.0%). The median duration of remission was 7.0 months and the median survival time for all eligible patients was 8.0 months. Toxicity was predominantly hematologic with the median leukocyte nadir being 1,300 per microliter of blood and documented sepsis in six patients. These data support activity for ifosfamide plus doxorubicin in patients with advanced sarcoma, but the actual contribution of ifosfamide needs to be evaluated through prospective randomized trials which are currently underway.
Effect of the addition of rituximab to front line therapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) on the remission rate and time to treatment failure (TTF) compared to CHOP alone in mantle cell lymphoma (MCL): Results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG)
Authors: W. Hiddemann, M. Dreyling, M. Unterhalt, R. Repp, S. Hermann, A. Haenel, B. Metzner, C. Pott, F. Hartmann, R. Parwaresch
Journal: Journal of Clinical Oncology (2004)

6501 Background: MCL is a disease of higher age and carries a bad prognosis with a median survival of only 3 to 4 years. New treatment modalities are therefore warranted. Based on the highly encouraging results of combining Rituximab with the Fludarabine, Cyclophosphamide, Mitoxantrone (FCM) regimen for salvage therapy of relapsed MCL, the GLSG embarked on a prospective randomised trial comparing CHOP versus Rituximab plus CHOP (R-CHOP) for first line therapy. Methods: 122 consecutive patients with newly diagnosed MCL of stages III and IV were randomised between CHOP versus R-CHOP. Results: Of the 122 patients 60 were randomised to CHOP and 62 to R-CHOP. A significantly higher rate of CR of 34% vs. 7% (p=0.00024) and of CR + PR of 94% versus 75% (p=0.005) was achieved for R-CHOP vs. CHOP treated patients. In addition, TTF was significantly longer (p=0.0131) while the time to progression was not statistically different. No differences were observed either within the two postremission strategies between R-CHOP or CHOP treated cases. Treatment associated side effects comprised predominantly myelosuppression and granulocytopenia in particular. Grade III and IV granulocytopenia was more frequent after R-CHOP (63% versus 53%, p=0.01). This was clinically not of major relevance, however, since severe infections were observed after 5% and 7% of courses, only. Conclusions: R-CHOP induces remissions in almost all patients with previously untreated MCL and prolongs the time to treatment failure significantly over CHOP alone. R-CHOP is a highly effective, well tolerated regimen for front line therapy of MCL. No significant financial relationships to disclose.
Prevention and treatment trials need different recruitment strategies: Experience from the IBIS 1 prevention trial in Australia and New Zealand
Authors: J. F. Forbes, M. A. Seccombe
Journal: Journal of Clinical Oncology (2004)

1030 Background: IBIS 1 is a double-blind, randomised, placebo-controlled trial to evaluate tamoxifen (20 mg, o, daily, 5 years) in preventing breast cancer (BC) in healthy women aged 35–70 at increased risk of BC. Risk was based on family history (most) and high risk benign pathology. It was anticipated that recruitment needed to go beyond conventional medical sources. The trial was conducted by the ANZ BCTG in Australia and New Zealand. Methods: : A national Recruitment Coordinator developed strategies involving print and electronic media, medical sources (GP's, breast clinics, high-risk clinics and screening) and ‘word-of-mouth’ (BC patients, relatives). Monthly print media releases or Community Service Announcements (CSA's) on radio or TV were sent widely in Australia and New Zealand. A free call number was established for enquiries which were forwarded weekly to Study Coordinators (SC's) at 19 IBIS 1 centres. SC's responded to enquiries and determined eligibility. Results: Accrual targets were exceeded with 2,674 women recruited in Australia and New Zealand, 37% of the international accrual. The ANZ BCTG participation rate per capita was one of the highest in the world for a tamoxifen breast cancer prevention trial. Annual enquiries increased from 2,155 in 1996 to 5,646 in 2000. Of women randomised, initial contact was by media 66%, medical sources 20%, friends and relatives 8% (other methods 5%). Randomisation rate varied widely amongst centres and this affected total recruitment; e.g. for Canberra Hospital, 33% of enquiries were eligible, 45% of these women were randomised (15% of initial enquiries). Factors affecting randomisation were time available for recruitment, personal contact versus mailing and distance to travel to an IBIS centre. Conclusions: Recruitment to BC prevention trials cannot rely on conventional medical sources. A coordinated media program is essential. Key factors affecting recruitment were infrastructure, coordination of publicity and centre performance. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Phase II trial of every 2 weeks dosing of irofulven (IROF) in patients (pts) with unresectable hepatocellular carcinoma (HCC): preliminary results
Authors: S. Falcon-Lizaraso, J. Leon Chong, F. Perazzo, F. Goldwasser, A. Cohn, C. Kahatt, G. Weems, S. G. Eckhardt
Journal: Journal of Clinical Oncology (2004)

4083 Background: IROF (MGI 114), the first compound of the acylfulvene class to enter clinical trials, has demonstrated antitumor activity in a variety of chemoresistant tumors. Currently available chemotherapy offers limited benefit to HCC pts. A phase II trial of IROF 11 mg/m2 daily x 4 every 28 days reported confirmed partial responses (PR) in 2/23 pts (ASCO 2003, abst 1107). An every 2 weeks schedule has been developed (AACR-NCI-EORTC 2001, abst 214). Methods: A multicenter phase II trial was initiated to evaluate the objective response rate (RECIST) in HCC pts receiving 0.55 mg/kg IROF (total dose ≤50 mg), as a 30 min IV infusion, days 1 and 15 every 28 days. Eligibility criteria include unresectable HCC, ECOG PS 0–1, and ≤1 prior therapy (chemotherapy included); 29 evaluable pts were to be included in a first stage of accrual with a total of 38 evaluable pts if ≥1 responses were observed in the first stage (Simon design). Results: As of Dec 2003, 38 pts (7 centers) have been treated; 29 pts are evaluable to date. Median age is 60 years (range 19–77), and median baseline PS 1 (0–1). Ten pts received 1 prior therapy (systemic therapy in 3 pts), 15 pts had metastatic disease at baseline, 11 pts had cirrhosis, 26 pts had alpha-fetoprotein (AFP) >20. Hepatitis history was negative/B/C/unknown in 14/18/7/1 pts. \(\underline{\mathrm{Efficacy}}\): Two confirmed PR (7%), with 55%/ 51% reduction in tumor size, decrease in AFP from 204 to 3 and 54 to 28, and improvement of symptoms. 13 pts had stabilization for a median of 4 months (2.6–5.4); 4/13 SD pts had AFP decrease, 6 pts >30% decrease; overall, 52% of pts had clinical benefit (SD + PR). \(\underline{\mathrm{Safety}}\): Principal adverse events were thrombocytopenia (grade [gr] 3: 21% of pts), neutropenia (gr 3: 10%), nausea (gr 3: 7%), anemia (gr 4: 3%) and visual symptoms (gr 3: 10%). Toxicity led to discontinuation in 3 pts (thrombocytopenia, visual symptoms) and dose reduction in 5 pts. Conclusion: Antitumor activity and acceptable tolerance was observed with IROF every 2 weeks in HCC pts. Accrual is ongoing in the second stage. A phase II trial of IROF combined with CPT-11 in HCC pts has also been initiated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CAC, Kremlin-Bicetre, France; MGI Pharma, Inc. MGI Pharma Inc, Bloomington, MN MGI Pharma Inc, Bloomington, MN MGI Pharma Inc.
Aerobic Interval Training Reduces the Burden of Atrial Fibrillation in the Short Term
Authors: Vegard Malmo, Bjarne M. Nes, Brage H. Amundsen, Arnt-Erik Tjonna, Asbjorn Stoylen, Ole Rossvoll, Ulrik Wisloff, Jan P. Loennechen
Journal: Circulation (2016)

Exercise training is an effective treatment for important atrial fibrillation (AF) comorbidities. However, a high level of endurance exercise is associated with an increased AF prevalence. We assessed the effects of aerobic interval training (AIT) on time in AF, AF symptoms, cardiovascular health, and quality of life in AF patients.Fifty-one patients with nonpermanent AF were randomized to AIT (n=26) consisting of four 4-minute intervals at 85% to 95% of peak heart rate 3 times a week for 12 weeks or to a control group (n=25) continuing their regular exercise habits. An implanted loop recorder measured time in AF continuously from 4 weeks before to 4 weeks after the intervention period. Cardiac function, peak oxygen uptake (o2peak), lipid status, quality of life, and AF symptoms were evaluated before and after the 12-week intervention period. Mean time in AF increased from 10.4% to 14.6% in the control group and was reduced from 8.1% to 4.8% in the exercise group (P=0.001 between groups). AF symptom frequency (P=0.006) and AF symptom severity (P=0.009) were reduced after AIT. AIT improved o2peak, left atrial and ventricular ejection fraction, quality-of-life measures of general health and vitality, and lipid values compared with the control group. There was a trend toward fewer cardioversions and hospital admissions after AIT.AIT for 12 weeks reduces the time in AF in patients with nonpermanent AF. This is followed by a significant improvement in AF symptoms, o2peak, left atrial and ventricular function, lipid levels, and QoL.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01325675.
Abstract 15720: Synergistic Effect of Acetylation and Methylation Modifiers in Attenuating Lung Vascular Hyperpermeability in Endotoxemia-Induced Inflammatory Lung Injury
Authors: Johnson Rajasingh, Jayakumar Thangavel, Sheeja Rajasingh, Yu-Ting Xuan, Buddhadeb Dawn
Journal: Circulation (2014)

Background: Migration of fluid and inflammatory cells across vascular endothelial barrier is crucial in pathogenesis of acute lung injury (ALI) in sepsis. Currently no treatment can effectively improve the profound dysregulation of lung endothelial barrier in ALI. Hypothesis: We hypothesized that combinatorial treatment with DNA methyl transferase inhibitor 5-Aza 2-deoxycytidine (Aza) and histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) would synergistically preserve lung microvascular endothelial barrier function. Methods and Results: The trans-endothelial electrical resistance (TER) and capillary filtration coefficient (K fc ) data show that in LPS-exposed endothelial cells and mice, therapy with Aza+TSA leads to a significant decrease in lung microvascular permeability as compared with either alone. The ChiP data show that the VE-cadherin promoter region was more acetylated at histone 3 in LPS-induced lung ECs treated with Aza+TSA than either alone. In an ALI mouse model, post-injury treatment with a single dose of Aza+TSA prevented lung injury and afforded a significantly higher survival rate (80%) as compared with mice treated with either Aza or TSA alone. These effects were mediated by a significant attenuation of adverse lung histopathological changes and preservation of endothelial barrier integrity. Aza+TSA also significantly reduced neutrophil infiltration in the ALI model. The RT-PCR array data revealed that 42 inflammation-related miRNAs were differentially expressed in LPS-induced endothelial cells, among which miRNA-92a, 125b, 133a, 146, 214, 222, and 424 were strongly upregulated. Importantly, Aza+TSA treatment significantly reduced the expression of these miRNAs. The protection was ascribed to inhibition of the eNOS-Cav1-MLC2 signaling pathway and enhanced acetylation of histone markers on the VE-cadherin promoter. Conclusions: These data for the first time show the efficacy of synergistic effect of Aza+TSA therapy in preventing ALI in LPS-induced endotoxemia, and raise the possibility of an essential role of DNMT and HDAC in pathogenesis of ALI. This novel combinatorial regimen may improve and prolong the lives of people with ALI.
Abstract 17868: Effect of Device Implantation on Stroke Outcomes in Patients with Patent Foramen Ovale
Authors: Kanhaiya L Poddar, Vijaiganesh Nagarajan, Navkaranbir S Bajaj, Hazem Bdair, Shikhar Agarwal, Sachin S Goel, Emin M Tuzcu, Samir R Kapadia
Journal: Circulation (2012)

Background: Data are lacking on the risk of stroke in patients with patent foramen ovale (PFO) and implantable intracardiac devices, either permanent pacemaker (PPM) or implantable cardioverter def...
Correlation of copy number aberrations with clinico-pathological criteria in paediatric glial tumours
Authors: Samantha Ward, Richard Hayward, William Harkness, Kim Phipps, Dominic Thompson, Brian Harding, Peter Wilkins, John L. Darling, David G. Thomas, Tracy Warr
Journal: Neuro-Oncology (2003)

Abstracts from Neuro-Oncology are provided here courtesy of Society for Neuro-Oncology and Duke University Press.
Effect of duloxetine on chemotherapy-induced painful peripheral neuropathy.
Authors: Yasuo Hirayama, Takeshi Terui, Kazuhiko Koike, Toshiro Kusakabe, Hiroto Horiguthi, Kunihiko Ishitani
Journal: Journal of Clinical Oncology (2014)

181 Background: Approximately 20% to 40% of patients with cancer who receive neurotoxic chemotherapy will develop painful chemotherapy-induced peripheral neuropathy. Smith et. al firstly reported that duloxetine was effective on above neuropathy after taxanes and platinums (JAMA 2013), so we planed to evaluate the duloxetine effect in Japanese patients after above drugs and more expanding drugs include vinca alkaloids and bortezomib. Methods: Patients were randomized to receive either duloxetine followed by vitamin(V)B12 or VB12 by duloxetine. The initial treatment consisted of 20 mg of duloxetine or 1.5g VB12 for the first week and 40mg of duloxetine or VB12 daily for 3 additional weeks (an open label, randomized, crossover). Dose reduction by the adverse effects was permitted. The primary hypothesis was that duloxetine would be more effective than VB12 in decreasing chemotherapy-induced peripheral neuropathic pain. Numbness and Pain severity were assessed weekly using visual analogue scale (VAS). This research was approved by the Research Ethics Committee of Higashi Sapporo Hospital and University Hospital Medical Information Network (UMIN) Center in Japan.Thirty-four cases (Breast cancer: taxanes 2, gastric cancer: taxane 5, colon cancer: oxaliplatin 6, Malignant lymphoma: vincristine 13, multiple myeloma: bortezomib 8) were made an entry in our institution. Five cases dropped out because of the adverse effect with sleepy and general malaise. Results: Obvious improvements of VAS scores of numbness and pain were observed in duloxetine group. Significant differences of delta VAS (pre VAS scale – 4 weeks VAS after drug administration) were observed between duloxetine group and VB12 group in the aspect of numbness (p=0.02) and pain (p=0.03). Conclusions: Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with VB12 for 4 weeks resulted in a reduction in numbness and pain, but there are many cases with drop out by the adverse effects. Clinical trial information: 000011554.
HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients
Authors: Andrea Napolitano, Daniel J. Antoine, Laura Pellegrini, Francine Baumann, Ian Pagano, Sandra Pastorino, Chandra M. Goparaju, Kirill Prokrym, Claudia Canino, Harvey I. Pass, Michele Carbone, Haining Yang
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To determine whether serum levels of high mobility group box protein 1 (HMGB1) could differentiate malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls. Experimental Design: Hyperacetylated and nonacetylated HMGB1 (together referred to as total HMGB1) were blindly measured in blood collected from malignant mesothelioma patients (n = 22), individuals with verified chronic asbestos exposure (n = 20), patients with benign pleural effusions (n = 13) or malignant pleural effusions not due to malignant mesothelioma (n = 25), and healthy controls (n = 20). Blood levels of previously proposed malignant mesothelioma biomarkers fibulin-3, mesothelin, and osteopontin were also measured in nonhealthy individuals. Results: HMGB1 serum levels reliably distinguished malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls. Total HMGB1 was significantly higher in malignant mesothelioma patients and asbestos-exposed individuals compared with healthy controls. Hyperacetylated HMGB1 was significantly higher in malignant mesothelioma patients compared with asbestos-exposed individuals and healthy controls, and did not vary with tumor stage. At the cut-off value of 2.00 ng/mL, the sensitivity and specificity of serum hyperacetylated HMGB1 in differentiating malignant mesothelioma patients from asbestos-exposed individuals and healthy controls was 100%, outperforming other previously proposed biomarkers. Combining HMGB1 and fibulin-3 provided increased sensitivity and specificity in differentiating malignant mesothelioma patients from patients with cytologically benign or malignant non–mesothelioma pleural effusion. Conclusions: Our results are significant and clinically relevant as they provide the first biomarker of asbestos exposure and indicate that hyperacetylated HMGB1 is an accurate biomarker to differentiate malignant mesothelioma patients from individuals occupationally exposed to asbestos and unexposed controls. A trial to independently validate these findings will start soon. Clin Cancer Res; 22(12); 3087–96. ©2016 AACR.
Patients rescued by crossover to rubitecan in phase III study of rubitecan capsules versus 5-FU in pancreatic cancer
Authors: S. W. Papish, R. K. Ramanathan, J. Pincus, M. Hirmand, H. A. Burris
Journal: Journal of Clinical Oncology (2005)

4165 Background: Rubitecan (Orathecin) is a novel oral inhibitor of topoisomerase I in the camptothecin class. Methods: A Phase III randomized multinational open-label study of rubitecan versus 5-FU in pancreatic cancer patients who had progressive disease following gemcitabine treatment was undertaken. The primary endpoint was overall survival. Key patient eligibility criteria included pathologic diagnosis of pancreatic cancer, progressive disease on gemcitabine, Karnofsky Performance Status of ≥50 and life expectancy of ≥2 months. Rubitecan was administered at 1.5 mg/m2 orally 5 days/week. 5-FU was administered at 600 mg/m2 intravenously once weekly. Patients who progressed or experienced intolerable toxicity could crossover to the alternate treatment arm. Results: 93 of 224 (41%) 5-FU patients crossed over to rubitecan rescue. Only 1 of 224 rubitecan patients crossed over to 5-FU. Main reasons for rescue with rubitecan were radiologic (75%) and symptomatic (12%) progression on 5-FU. Median survival from randomized baseline was longer for patients who crossed over from 5-FU to rubitecan rescue compared to patients who did not crossover from 5-FU (184 versus 66 days). 35 of 93 (38%) patients had follow-up scans after the initiation of rubitecan rescue and were evaluable for tumor response assessment. 14 of 35 (40%) patients achieved tumor growth control (4 had objective tumor responses and 10 had disease stabilization). The most common Grade 3/4 adverse events with rubitecan were myelotoxicity (34%) and gastrointestinal (14%). All deaths on study were primarily related to disease progression. Conclusions: These results support that patients with refractory/resistant pancreatic cancer, who have progressed on gemcitabine and 5-FU, can derive benefit from rubitecan, an oral medication that can be taken at home with manageable toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration SuperGen SuperGen SuperGen SuperGen