tbuckley/cabot-search huggingface dataset:
Abstract 18933: Partners Together in Health (PaTH) Intervention to Reduce Cardiovascular Risk
Authors: Bernice Yates, Jane L Meza, Joe Norman, Kaye Stanek Krogstrand, Karen Schumacher
Journal: Circulation (2012)

Despite proven efficacy of cardiac rehabilitation (CR) in initiating lifestyle changes, less than 50% of coronary artery bypass graft (CABG) patients maintain changes 6 month later. The objective of this feasibility study was to test the Partners Together in Health (PaTH) Intervention versus usual care in improving physical activity and healthy eating behaviors in CABG patients and spouses. We used an experimental, two-group (n=17 couples/group), repeated measures design. CABG patients in both groups participated in CR. Spouses in the PaTH group attended CR with the patient and made the same healthy eating and physical activity changes as patients. Spouses in the control group attended educational classes with the patient which is the standard of care in CR. It was hypothesized that “two persons would be better than one" at making changes and sticking with them long-term. Eating behavior was measured using 3-day food records. Physical activity was measured using the Actiheart accelerometer. Data were collected at baseline (entrance in CR), 3-months (post-CR), and 6-months. Although healthy eating was similar between patient groups at the end of CR, by 6 months, there was a trend (p&lt;.10) for patients in the PaTH group to report better eating behavior than the control group on 3 dietary components: % fat calories (26.4% vs. 32.4%), % saturated fat calories (8.1% vs. 11.1%), and cholesterol (209.8 mg vs. 233.8 mg), respectively. Similar findings were obtained for PaTH vs. control spouses at 6-months: % fat calories (30.6% vs. 36.7%), % saturated fat calories (9.4% vs. 11.3%), and cholesterol (204.7 mg vs. 260.8 mg), respectively. No differences were found between patient groups at 3 or 6-months in the # of minutes/week of physical activity. Although patients were above the national guidelines for PA recommendations (&gt;150 min/week at &gt;3 METs) at 3- and 6-months, they were only participating in 162 min/week (PaTH group) vs. 182 min/week (control group) at 6-months. In contrast, spouses were engaged in approximately twice as much weekly physical activity as patients: 300 min/week (PaTH group) vs. 257.6 min/week (control group) at 6 months. Long-term maintenance of lifestyle changes is essential to positively influence health outcomes for both patients and spouses.
Induction chemotherapy with docetaxel, cisplatin, fluorouracil, and leucovorin for squamous cell carcinoma of the head and neck: a phase I/II trial.
Authors: A D Colevas, P M Busse, C M Norris, M Fried, R B Tishler, M Poulin, R L Fabian, T J Fitzgerald, A Dreyfuss, E S Peters, S Adak, R Costello, J J Barton, M R Posner
Journal: Journal of Clinical Oncology (1998)

PURPOSE A phase I/II trial of docetaxel, cisplatin, fluorouracil (5-FU), and leucovorin (TPFL5) induction chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Twenty-three previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status less than or equal to 2 were treated with TPFL5. Postchemotherapy home support included intravenous fluids, prophylactic antibiotics, and granulocyte colony-stimulating factor (G-CSF). Docetaxel dose was escalated to determine the maximum-tolerated dose (MTD). Fifteen patients were treated with three cycles of TPFL5 at MTD. Patients who achieved either a partial response (PR) or complete response (CR) to three cycles of TPFL5 then received definitive twice-daily radiation therapy. Toxicity and clinical and pathologic response to TPFL5 were assessed. RESULTS Twenty-three patients received a total of 69 cycles of TPFL5. The MTD was determined to be docetaxel 60 mg/m2. Dose-limiting toxicity (DLT) was neutropenia. Additional significant toxicities at MTD were nausea, mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The overall response rate to TPFL5 was 100%, which included 14 of 23 (61%) clinical CRs and nine of 23 (39%) clinical PRs. Primary-site clinical and pathologic CR rates were 19 of 22 (86%) CRs and 20 of 22 (91%) CRs, respectively. Eight patients had less than a CR in the neck to chemotherapy and, therefore, had postradiation neck dissections, four of which were positive for residual tumor. CONCLUSION TPFL5 is a tolerable induction regimen in patients with good performance status. The DLT is neutropenia with significant mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The high response rates to TPFL5 justify further evaluation of this combination of agents in the context of formal clinical trials.
Safety data of Montanide ISA 51 VG and Montanide ISA 720 VG, two adjuvants dedicated to human therapeutic vaccines
Authors: Stephane Ascarateil, Aude Puget, Marie-Eve Koziol
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Montanide ISA 51 VG and Montanide ISA 720 VG are two novel adjuvants dedicated to human therapeutic vaccines. They have been used in more than 200 clinical trials involving cancer, AIDS, malaria or autoimmune disease vaccines and involving an accrual of more than 20000 patients.
Postibrutinib outcomes in patients with mantle cell lymphoma
Authors: Peter Martin, Kami Maddocks, John P. Leonard, Jia Ruan, Andre Goy, Nina Wagner-Johnston, Simon Rule, Ranjana Advani, David Iberri, Tycel Phillips, Stephen Spurgeon, Eliana Kozin, Katherine Noto, Zhengming Chen, Wojciech Jurczak, Rebecca Auer, Ewa Chmielowska, Stephan Stilgenbauer, Johannes Bloehdorn, Craig Portell, Michael E. Williams, Martin Dreyling, Paul M. Barr, Selina Chen-Kiang, Maurizio DiLiberto, Richard R. Furman, Kristie A. Blum
Journal: Blood (2016)
Independent prognostic value of the rest/activity circadian rhythm on overall survival (OS) in patients (pts) with metastatic colorectal cancer (MCC) receiving first line chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin: A companion study to EORTC 05963
Authors: C. Garufi, G. A. Bjarnason, S. Giacchetti, P. Innominato, C. Focan, B. Coudert, N. Tubiana, J. M. Waterhouse, T. Gorlia, F. Levi
Journal: Journal of Clinical Oncology (2005)

3553 Background: In tumor bearing rodents, disruption of the rest/activity rhythm (RAR) results in faster tumor growth and a shorter OS (Cancer Res 64:7879, JNCI 94:690, Cell 111:41). In single institution prospective trials on pts with metastatic breast cancer (JNCI 92:994) and MCC (Clin Cancer Res 6:3038), a disrupted circadian rhythm also results in a shorter OS. In this multicenter prospective trial, we studied the prognostic value of the RAR in MCC patients receiving first line FOLFOX-2 vs. 4-day chronomodulated infusion of the same drugs. Methods: To assess the RAR, 130 pts out of 564 pts in 9 centers wore a wrist-watch (actigraph), which recorded the number of wrist movements per minute for 3 days before starting therapy. Two RAR parameters, validated in previous clinical studies, were calculated: the autocorrelation coefficient at 24h (r24), indicating the robustness of the activity pattern over a period of 24 hours, and the dichotomy index (I<O), quantifying the differences in activity distribution between the rest phase and the active phase. The prognostic values of r24 and I<O were assessed by the logistic regression model for response and toxicity and by the Cox Proportional Hazard model for OS. Results: RAR parameters were not predictive for response or toxicity. When RAR parameters were categorized into quartiles, r24 and I<O were detected as potential prognostic factors for OS in a univariate analysis. The relative risk of death was 1.31 fold larger in the lowest vs highest I<O quartile. In a Cox Proportional Hazard model, I<O was confirmed as an independent predictor of OS (p < 0.0003) along with CEA ≥ 50 ng/ml (p = <0.0001), WHO PS 1 or 2 (P = 0.0129) and number of metastatic sites ≥ 2 (p = 0.039). Using the bootstrap technique, I<O had a 70% probability of inclusion in the Cox model, making it one of the strongest prognostic factors for OS. Conclusions: This multicenter prospective study establishes the strong and independent prognostic value of the rest/activity circadian rhythm for the overall survival of patients with metastatic colorectal cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi research funding for the EORTC 05963 trial
Inclusion of RBC-Transfusion Dependency Can Improve the Prognostic Value of Revised-IPSS in MDS Patients
Authors: Devendra K Hiwase, Deepak Singhal, Rakchha Chhetri, Monika M Kutyna, Peter B Harrison, Shriram V. Nath, Nicholas Wickham, Chi-Hung Hui, James X Gray, David M Ross, Ian D Lewis, Peter Bardy, John Reynolds, Luen Bik To
Journal: Blood (2014)
Abstract 19326: Microrna Regulating Protein Bicc1 Causes Dilated Cardiomyopathy Through Modulation of Polycystin-2
Authors: Hisato Yagi, Xiaoqin Liu, Bishwanath Chatterjee, You Li, Ashok Srinivasan, Adrew Kim, Deborah Farkas, Richard Francis, Jacqueline Ho, Kimimasa Tobita, Cecilia W Lo
Journal: Circulation (2012)

An ENU-induced mutation in the RNA binding protein Bicc1 was recovered in a mutant named Destro. Destro exhibits complex congenital cardiovascular defects (CHD) associated with heterotaxy, with some mutants also exhibiting kidney, biliary ductal and pancreatic cysts. The mutation was identified by whole genome sequencing as Bicc1c.606+2T&gt;C, which caused an 18 amino acid in-frame deletion in the K homology domain required for RNA recognition. Previous studies showed Bicc1 mutations can cause polycystic kidney disease (PKD) via its role in regulating microRNA-17 (miR-17) activity, and the altered expression of polycystin-2 (Pkd2), a known miR-17 target. Destro mutants without CHD or laterality defects are postnatal viable, but die prematurely at 4-5 months of age with severe runting, even in the absence of PKD. Transthoracic echocardiography showed cardiac function in such animals declined markedly with age. This was associated with increase in LV chamber size/body weight ratio and the elevated expression of heart failure markers such as Nppa, Nppb, and osteopontin. As Pkd2 was recently shown to interact with ryanodine receptor, RyR2 to modulate Ca(2+) signaling in cardiomyocytes, we propose Bicc1 mutation can cause cardiomyopathy independent of defects associated with the kidney. Consistent with this hypothesis, we noted all homozygous Bicc1 mutants surviving to adulthood succumb to heart failure associated with dilated cardiomyopathy, but yet show no evidence of PKD. Overall, these findings indicate a novel role for the RNA binding protein Bicc1 in cardiac pathology involving dilated cardiomyopathy. Experiments are underway to examine the role of microRNA regulation of Pkd2 on cardiac pathology in the Bicc1 mutants. Based on these observations, we suggest patients with PKD may have additional risk for cardiomyopathy of an independent etiology from any underlying kidney disease.
Mental Health Conditions Among Patients Seeking and Undergoing Bariatric Surgery
Authors: Aaron J. Dawes, Melinda Maggard-Gibbons, Alicia R. Maher, Marika J. Booth, Isomi Miake-Lye, Jessica M. Beroes, Paul G. Shekelle
Journal: JAMA (2016)

Bariatric surgery is associated with sustained weight loss and improved physical health status for severely obese individuals. Mental health conditions may be common among patients seeking bariatric surgery; however, the prevalence of these conditions and whether they are associated with postoperative outcomes remains unknown.To determine the prevalence of mental health conditions among bariatric surgery candidates and recipients, to evaluate the association between preoperative mental health conditions and health outcomes following bariatric surgery, and to evaluate the association between surgery and the clinical course of mental health conditions.We searched PubMed, MEDLINE on OVID, and PsycINFO for studies published between January 1988 and November 2015. Study quality was assessed using an adapted tool for risk of bias; quality of evidence was rated based on GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.We identified 68 publications meeting inclusion criteria: 59 reporting the prevalence of preoperative mental health conditions (65,363 patients) and 27 reporting associations between preoperative mental health conditions and postoperative outcomes (50,182 patients). Among patients seeking and undergoing bariatric surgery, the most common mental health conditions, based on random-effects estimates of prevalence, were depression (19% [95% CI, 14%-25%]) and binge eating disorder (17% [95% CI, 13%-21%]). There was conflicting evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Neither depression nor binge eating disorder was consistently associated with differences in weight outcomes. Bariatric surgery was, however, consistently associated with postoperative decreases in the prevalence of depression (7 studies; 8%-74% decrease) and the severity of depressive symptoms (6 studies; 40%-70% decrease).Mental health conditions are common among bariatric surgery patients-in particular, depression and binge eating disorder. There is inconsistent evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Moderate-quality evidence supports an association between bariatric surgery and lower rates of depression postoperatively.
Abstract 19269: Relations and Predictive Value of Post-load and Fasting Glucose for Incident Cardiovascular Disease and Mortality in Older Adults: the Cardiovascular Health Study
Authors: Erika Brutsaert, Sanyog Shitole, Mary Lou Biggs, Kenneth Mukamal, Ian De Boer, Evan Thacker, Joshua Barzilay, Luc Djousse, Joachim H Ix, Nicholas Smith, Robert Kaplan, David Siscovick, Bruce Psaty, Jorge Kizer
Journal: Circulation (2014)

Introduction: Elders have a high prevalence of post-load hyperglycemia, which may go undetected with standard screening. Post-load glucose has shown more robust associations with cardiovascular disease (CVD) and death than fasting glucose, but data in advanced old age are sparse. Whether post-load glucose improves risk prediction for CVD and death after accounting for fasting glucose has not been examined. Methods: Fasting and 2-hour post-load glucose were measured at baseline (1989) and follow-up (1996) visits in a prospective study of community-dwelling adults initially ≥65 years old (Cardiovascular Health Study). To evaluate if previously reported associations of fasting and post-load glucose with incident CVD from the baseline visit persist later in life, and apply to mortality, we focused on the 1996 visit (n=2394). To determine the incremental value of post-load glucose for risk prediction, we examined whether it could significantly reclassify baseline (1989) participants (≤75 years) into cholesterol treatment categories based on recent guidelines (n=2542). Results: Among participants in the 1996 visit (mean age 77), there were 543 incident CVD events and 1698 deaths during median follow-up of 11.2 years. In fully adjusted models, both fasting and 2-hour glucose were associated with CVD (HR per SD, 1.13 [1.03-1.25] and 1.17 [1.07-1.28], respectively) and mortality (HR per SD, 1.12 [1.07-1.18] and 1.14 [1.08-1.20]). After mutual adjustment, however, the associations for fasting glucose with either outcome were abolished, but those for post-load glucose remained unchanged. Among subjects ≤75 years old in 1989, there were 416 CVD events and 740 deaths at 10-year follow-up. Post-load glucose did not enhance reclassification using the 7.5% 10-year risk threshold, nor did it improve the C-statistic. Conclusion: In adults surviving to advanced old age, post-load glucose was associated with CVD and mortality independently of fasting glucose, but not vice versa, although there was no associated improvement in risk prediction. These findings affirm the robust association of post-load glucose with CVD and death late in life, but do not support the value of routine oral glucose tolerance testing for prediction of these outcomes in older adults.
Abstract 16045: MitoQ, a Mitochondrial Targeted Antioxidant, Decreases Maximal Oxidative Phosphorylation and Worsens LV Function in Heart Failure
Authors: Kelly A OConnell, Erinne R Dabkowski, Rogerio F Ribeiro, Wenhong Xu, Tatiana Galvao, William Stanley
Journal: Circulation (2012)

Heart failure (HF) increases mitochondrial production of reactive oxygen species (ROS) and decreases the capacity for oxidative phosphorylation. It has been proposed that prevention of mitochondria...
Two genetic polymorphisms of EGFR as useful predictive biomarkers for NSCLC patients receiving EGFR TKIs.
Authors: Jin Hyoung Kang, Jung-Young Shin, Jeong-Oh Kim, Ji-Eun Oh, Xiang-Hua Zhang, Sook Hee Hong, Eun Kyoung Jeon, Eun Kyung Cho
Journal: Journal of Clinical Oncology (2012)

e18050 Background: The EGFR mutation on particular exons has been known as a strong predictive biomarker to EGFR TKIs (tyrosine kinase inhibitors) in NSCLC pts. However, some pts having wild type EGFR do not infrequently show clinically favorable outcome to EGFR TKIs. Accordingly, we hypothesized that clinical outcome and skin toxicity to EGFR TKIs might be related to specific single nucleotide polymorphisms regulating the expression of EGFR gene as well as EGFR sensitive mutation. Methods: In 211 advanced or metastatic NSCLC pts receiving gefitinib or erlotinib, we assayed mutation status of EGFR in paraffin embedded tumor tissue using PNA clamping method and direct sequencing. Six different SNPs in genomic DNA extracted from peripheral blood were analyzed; promoter 191C&gt;A, 216 G&gt;T, CA repeat number, exon 13 R497K, exon 20 2607G&gt;A, and exon 25 D994D. Results: M:F ratio was 106:105 and mean age was 63.2 (35.0-82.0). Histological subtypes are as follows: 175 adenocarcinoma, 32 squamous cell ca. and 3 large cell ca. Objective response (CR+PR) was observed in 78 pts (36.9%) and SD in 69 pts (32.7%). Median PFS and OS were 8.7 ± 11.3 and 15.9 ± 14.8 months, respectively. Of 167 pts in whom EGFR mutation was analyzed, 68 pts (40.7%) had EGFR harboring sensitive mutation. In R497K, wild type (RR) was 35 (21.0%) and K alleles (RK + KK) were 132 (79.0%). In D994D, wild type (GG) was 76 (45.5%) and heterozygote and homozygote variants (GA+AA) were 91(54.5%). Statistically significant differences of PFS and OS were observed between wild and hetero-/homozygote variants of R497K (11.9 m vs. 36.2 m, p=0.037 and 23.7 m vs. 39.1 m, p=0.054, respectively) in the pts harboring mutant type EGFR. Meanwhile, in the pts harboring wild type EGFR, GA+ AA genotype of D994D demonstrated much longer PFS and OS compared with GG genotype (PFS: 18.5 vs. 3.7 m, p=0.013 and 37.6 vs. 15.2 m, p=0.035, respectively). In addition, skin rash showed statistically significant association with R497K polymorphism (P=0.031). Conclusions: Our data suggest that two germline genetic variations of EGFR gene, R497K and D994D, be useful pharmacogenetic biomarker to predict longer PFS and OS for EGFR TKIs in advanced NSCLC pts harboring mutant type and wild type EGFR, respectively.
Impact of Cell Therapy on Myocardial Perfusion and Cardiovascular Outcomes in Patients With Angina Refractory to Medical Therapy
Authors: Abdur Rahman Khan, Talha A. Farid, Asif Pathan, Avnish Tripathi, Shahab Ghafghazi, Marcin Wysoczynski, Roberto Bolli
Journal: Circulation Research (2016)

The effect of stem/progenitor cells on myocardial perfusion and clinical outcomes in patients with refractory angina remains unclear because studies published to date have been small phase I-II trials.We performed a meta-analysis of randomized controlled trials to evaluate the effect of cell-based therapy in patients with refractory angina who were ineligible for coronary revascularization.Several data sources were searched from inception to September 2015, which yielded 6 studies. The outcomes pooled were indices of angina (anginal episodes, Canadian Cardiovascular Society angina class, exercise tolerance, and antianginal medications), myocardial perfusion, and clinical end points. We combined the reported clinical outcomes (myocardial infarction, cardiac-related hospitalization, and mortality) into a composite end point (major adverse cardiac events). Mean difference (MD), standardized mean differences, or odds ratio were calculated to assess relevant outcomes. Our analysis shows an improvement in anginal episodes (MD, -7.81; 95% confidence interval [CI], -15.22 to -0.41), use of antianginal medications (standardized MD, -0.59; 95% CI, -1.03 to -0.14), Canadian Cardiovascular Society class (MD, -0.58; 95% CI, -1.00 to -0.16), exercise tolerance (standardized MD, 0.331; 95% CI, 0.08 to 0.55), and myocardial perfusion (standardized MD, -0.49; 95% CI, -0.76 to -0.21) and a decreased risk of major adverse cardiac events (odds ratio, 0.49; 95% CI, 0.25 to 0.98) and arrhythmias (odds ratio, 0.25; 95% CI, 0.06 to 0.98) in cell-treated patients when compared with patients on maximal medical therapy.The present meta-analysis indicates that cell-based therapies are not only safe but also lead to an improvement in indices of angina, relevant clinical outcomes, and myocardial perfusion in patients with refractory angina. These encouraging results suggest that larger, phase III randomized controlled trials are in order to conclusively determine the effect of stem/progenitor cells in refractory angina.
Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma
Authors: Toni K. Choueiri, Bernard Escudier, Thomas Powles, Paul N. Mainwaring, Brian I. Rini, Frede Donskov, Hans Hammers, Thomas E. Hutson, Jae-Lyun Lee, Katriina Peltola, Bruce J. Roth, Georg A. Bjarnason, Lajos Géczi, Bhumsuk Keam, Pablo Maroto, Daniel Y.C. Heng, Manuela Schmidinger, Philip W. Kantoff, Anne Borgman-Hagey, Colin Hessel, Christian Scheffold, Gisela M. Schwab, Nizar M. Tannir, Robert J. Motzer
Journal: New England Journal of Medicine (2015)

Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate.Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus.Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.).