tbuckley/cabot-search huggingface dataset:
Abstract 14618: Fasting Glucose, NT-proBNP, Treatment With Glycoprotein IIb/IIIa Inhibitors, and Outcomes in Non-ST-Segment Elevation Acute Coronary Syndromes: An Analysis From EARLY ACS
Authors: Serdar Farhan, Robert M Clare, Rudolf Jarai, L. Kristin Newby, David Morrow, Robert P Giugliano, Yuliya Lokhnygina, Robert M Califf, Robert A Harrington, Kurt Huber
Journal: Circulation (2013)
Abstract P302: Baseline Measures of Adiponectin, Systolic Blood Pressure and Drinking Alcohol are Associated with More Aortic Stiffness Progression among Men: The ERA JUMP Study
Authors: Samar R El Khoudary, Emma Barinas-Mitchell, J. David Curb, Chol Shin, Hirotsugu Ueshima, Kamal Masaki, Rhobert W Evans, Katsuyuki Miura, Daniel Edmundowicz, Lewis H Kuller, Kim Sutton-Tyrrell, Akira Sekikawa
Journal: Circulation (2012)

Objective: Aortic stiffness, a significant marker of vascular aging, is independently associated with CVD and all-cause mortality. Limited data are available about risk factors for the progression of aortic stiffness in healthy population. We examined several baseline risk factors as possible independent predictors of aortic stiffness progression among US men. Design: Participants were a population-based sample of black and white men aged 40–49 from the Pittsburgh site of the ERA JUMP Study, who were free of CVD at baseline. Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer at baseline and after 4.6±0.21(mean±SD) years of follow-up. Progression of cfPWV was evaluated as: 1) occurrence of progression (defined as ≥ 75th percentile of the change in cfPWV since baseline (≥ 118.5 cm/s increase); and 2) severity of progression as the difference between the natural-log cfPWV at follow-up and the natural-log cfPWV at baseline. Systolic BP (SBP), BMI, visceral adiposity, lipids, glucose, insulin, adiponectin, PAI-1, fibrinogen, CRP, alcohol drinking, and smoking status at baseline were evaluated as possible risk factors for occurrence and severity of cfPWV progression. Stepwise logistic and linear regression models were utilized as appropriate. In univariate analysis, risk factors found to be associated with cfPWV progression at a P value ≤ 0.25 were eligible for stepwise regression analysis. Variables were dropped from models at a P value &gt; 0.1. Age at baseline, follow-up time, race, heart rate, and medication use were forced in all models. Results: A total of 240 men (White:82.5%, Black:17.5%) who were 45.0±2.9 years old at baseline, were included in this analysis. During follow-up, cfPWV progressed in 125 participants (52.0%) with a median increase of 113.5 cm/s (Q1=46.0, Q3=204.5). Final models revealed that independent predictors of the occurrence of cfPWV progression were lower levels of adiponectin (OR: 0.46, 95%CI: 0.23, 0.95, P=0.04), higher levels of SBP (OR: 1.03, 95%CI: 1.002, 1.06, P=0.04) and drinking alcohol ≥ 2 times/week (OR: 1.92, 95%CI: 1.01, 3.64, P=0.046) at baseline. Similarly, adiponectin (β=−0.097(SE=0.04), P=0.02) and drinking alcohol ≥ 2times/week (β=0.084(SE=0.04), P=0.02) were also independent predictors of severity of cfPWV progression. No significant interactions were found between these predictors and race. Conclusions: Independent of age at baseline, follow-up time, race, heart rate and medication use, lower levels of adiponectin, higher levels of SBP and drinking alcohol ≥2 times/week at baseline are associated with greater progression in aortic stiffness among relatively young middle-aged US men.
Quantitative dynamic contrast-enhanced MRI of the lung in asthma
Authors: Wei-juan Zhang, Robert Niven, Simon Young, Yu-zhen Liu, Geoffrey Parker, Josephine Naish
Journal: European Respiratory Journal (2014)

Purpose: To assess the ability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to quantify pulmonary capillary permeability, leakage space and blood volume in asthmatic patients.  Methods: Consenting volunteers (10 healthy, 20 asthmatic) underwent pulmonary function tests and DCE-MRI at 1.5 Tesla within 7 days. The extended Kety model was fitted to the contrast agent concentration-time curves to extract transfer constant (K trans ), fractional leakage volume (v e ) and the fractional blood plasma volume (v p ). Parameters were summarized using median values over the lungs.  Results: Median v e  was significantly higher in asthmatics (0.30 ± 0.06 ml/ml tissue) than in healthy subjects (0.23 ± 0.02 ml/ml tissue, P = 0.001) but was not different between mild and severe asthmatics, indicating the increased extravascular leakage space in asthmatic lungs. While median K trans  did not differ between patients and healthy subjects, there was a difference between mild and severe asthmatics (0.19 ± 0.07 vs 0.28 ± 0.07 ml/min/ml tissue, P = 0.040), implying increased vascular permeability and/or blood flow in more severe disease. Median v p  was not different between groups.  Conclusion: Quantitative DCE-MRI parameters are promising biomarkers of pulmonary inflammation in asthma, with v e  sensitive to the presence of asthma and K trans  sensitive to asthma severity.  Acknowledgement: Dorothy Hodgkin Postgraduate Award from AstraZeneca and RCUK for funds.
Risk of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after adjuvant chemotherapy (CT) for early breast cancer (BC) in the community setting.
Authors: Neelima Denduluri, Janet L. Espirito, Brian Turnwald, Yunfei Wang, Lina Asmar, J. Russell Hoverman, Marcus A. Neubauer, Linda D. Bosserman, Leslie T. Busby, Barry Don Brooks, Thomas H. Cartwright, Mark A. Sitarik, Ian D. Schnadig, William E. Winter, Jody S. Garey, Kimberly A. Bergstrom, Roy A. Beveridge, Debra A. Patt
Journal: Journal of Clinical Oncology (2012)

62 Background: AML and MDS complicate adjuvant CT in BC. Incidence Rates of MDS/AML with pegfilgrastim (PGCSF) use and newer adjuvant regimens in large patient (pt) populations are not widely characterized. Methods: We queried the iKnowMed electronic health record from a large network of community oncology practices for pts diagnosed with stage I-III BC from 2007-2010 with at least 5 visits and follow up (f/u) through 2/2012 for our retrospective study. We stratified pts by adjuvant CT utilization (yes/no), regimen type, PGCSF use, age, and characterized the incidence of MDS/AML captured as a secondary diagnosis. Fisher’s exact test and student t-test were used for categorical and continuous variables, respectively; Cox proportional hazard model was used to estimate hazard ratios (HR) for risk factors associated with AML/MDS development. Results: We identified 20,900 pts with median f/u of 2.8 years (yrs) (1.2-5.2 yrs). 11,295 pts (54%) received CT, 41% of whom received anthracyclines (A); 9,605 (46%) did not receive CT. Median age of diagnosis in the CT and non-CT arms was 54 and 64 yrs, respectively (p &lt; 0.01). Among the CT-treated group, 12 pts or 0.11% (95% CI, 0.06-0.19) developed AML/MDS with median time to onset of 1.8 yrs and median f/u of 2.7 yrs. Of these 12 pts, 8 received A and 11 PGCSF. In the non-CT group, 18 pts or 0.19% (95% CI, 0.11-0.30) developed AML/MDS with median time to onset of 2.2 yrs and median f/u of 3 yrs (p=NS). Multivariate analysis of pts who received CT revealed pts ≥70 vs. &lt;70 yrs and those that received A-containing vs. alternate regimens were more likely to develop AML/MDS. Conclusions: Adjuvant CT did not increase risk of AML/MDS compared with those that did not receive CT. However, our findings confirm that increased age and A-containing CT regimens are associated with increased risk. The low event rate in our study population may be due to short f/u, younger age in the CT treated arm, and high utilization of non-A CT. Association with PGCSF warrants further evaluation. [Table: see text]
Spontaneous Regression of Friend Virus-Induced Erythroleukemia. II. Regression of Friend Murine Leukemia Virus-Induced Lymphocytic Leukemia2
Authors: Michael Dietz, Clifford Longley, Susan P. Fouchey, LaVonne Hall, Marvin A. Rich, Philip Furmanski
Journal: JNCI Journal of the National Cancer Institute (1977)

We characterized several aspects of spontaneous regression of lymphocytic leukemia in mice. The disease, induced by the helper murine leukemia virus (MuLV) component obtained from the regressing Friend virus complex (RFV), was characterized by spleen and lymph node enlargement, thymus involvement, and anemia. Leukemia regression occurred in about 25% of infected mice and resulted in the return of lymphoid organs to near-normal weight and normal histology and the recovery from anemia. A tenfold to 1,000-fold decrease in virus titer was seen in those mice in which leukemia regressed when compared to leukemic animals, although infectious virus was still recoverable from apparently normal spleens. The sera of mice in which leukemia regressed contained potent virus-neutralizing activity that was associated mainly with immunoglobulins. These studies firmly supported the evidence that the regressing phenotype of RFV was due to its helper MuLV component (MuLV-RF).
Docetaxel and capecitabine in metastatic androgen independent prostate cancer (AIPC): Phase II trial to detect clinical efficacy of a synergistic combination
Authors: U. N. Vaishampayan, L. Heilbrun, J. Eliason, E. Pontes, I. Powell, J. Forman
Journal: Journal of Clinical Oncology (2005)

4703 Background: Docetaxel plus prednisone is the current therapeutic choice in the management of metastatic AIPC. Capecitabine is an oral prodrug of 5-fluorouracil which is selectively converted intratumorally to 5-flourouracil by thymidine phosphorylase (TP). Differential overexpression of TP is noted in tumors as compared to normal tissue. Docetaxel pretreatment when followed by capecitabine therapy has demonstrated synergy in preclinical studies with xenograft models. The purpose of this phase II trial was to evaluate the efficacy and safety of this combination in metastatic AIPC. Methods: Eligible patients had metastatic AIPC with no prior chemotherapy for metastatic disease. Other requirements included castrate levels of testosterone adequate renal, liver and marrow function and evidence of disease progression either by PSA, new metastatic sites, or progression of measurable disease sites. Docetaxel was administered intravenously on days 1, 8 and 15 of a 28 day cycle at a dose of 36 mg/m2. Capecitabine was administered at a dose of 1250 mg/m2/day in two divided doses orally from days 5 to 18 of each cycle. Results: 11 of 15 patients planned in the first stage have been enrolled to date. Baseline characteristics were, median age 73 years (range 38–78 years).;baseline PSA 131ng/ml (Range 8.9–3716ng/ml); three patients had progressive measurable disease, 5 patients had progression of bony metastases and 3 patients had PSA progression alone. 7 of the 8 evaluable patients demonstrated >50% decline in PSA and both of the measurable disease patients evaluated had a partial remission. 41 cycles of therapy (median 5 cycles) have been administered. Three patients required dose reduction. No grade 4/5 toxicities were noted. Only 1 patient had grade 3 neutropenia. No therapy related hospitalizations or deaths were observed. Conclusions: Preliminary data suggest that the combination of capecitabine and docetaxel is well tolerated and demonstrates promising activity in metastatic AIPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Roche Aventis
Prevalence and predictors of burnout among specialty palliative care clinicians in the United States: Results of a national survey.
Authors: Arif Kamal, Janet Bull, Steven Wolf, Greg Samsa, Katherine Ast, Keith Mark Swetz, Tait D. Shanafelt, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2014)

87 Background: The increasing demand for specialist palliative care (PC) in cancer care requires an available and responsive clinical workforce. But as the volume of work expands, PC providers face an increased risk of burnout, characterized by depersonalization and work-related emotional exhaustion. The prevalence and predictors of burnout among PC providers is poorly understood. Methods: Members of the American Academy of Hospice and Palliative Medicine (e.g. advanced practice provider, registered nurses, chaplains) completed the Maslach Burnout Inventory (MBI) via electronic survey in the second half of 2013; respondents were recruited via e-mail, blog and Facebook posts, and Twitter tweets. The MBI determine burnout severity across two domains, Emotional Exhaustion (EE) and Depersonalization (DP). Severity is reported as “low”, “moderate”, or “high”; “high” is consistent with burnout. Demographic and work-related variables associated with burnout in other studies were determined via stepwise logistic regression. Results: We received surveys from 1,241 clinicians. We estimated a response rate of 30%. 68% of respondents were physicians. Most respondents were over age 50 (57%), female (65%), were married or partnered (82%) and had worked in the field for less than 10 years (67%). 42% took overnight call regularly, 30% reported working 50 hours per week or more, and 57% had at least 4 colleagues. Regarding burnout, 24% reported high DP, 59% reported high EE, and 62% of reported high burnout symptoms on either EE or DP scales. In logistic regression, younger physicians, those working more than 50 hours per work, and those with fewer colleagues within their practice were at greatest risk of burnout (p&lt;0.02). Conclusions: PC clinicians report a burnout rate of 62%. Even with the limitations of our methods and potentially biased sampling, this prevalence is remarkable and higher than data reported in medical oncology (45%). Burnout severity is associated with working in isolation and working longer hours. Further studies on how burnout affects sustainability of the PC workforce are needed, especially since this workforce is so critical to the provision of high quality cancer care.
Advanced colorectal cancer treatment and outcome in the community oncology setting
Authors: J. M. Koeller, P. Kwan, T. McKibbin, J. Simon
Journal: Journal of Clinical Oncology (2006)

16040 Background: The treatment of advanced (adv) colorectal cancer (CRC) is currently a moving target due to the availability of new agents and a multitude of clinical trials. It is of interest to see how community oncologists have responded to these changes, and what effect they have had on outcome (survival). We report the chemotherapy treatment (tx) of adv CRC in the community oncology setting. Methods: This is an IRB-approved retrospective study. All available patient (pt) records with adv CRC, treated with chemotherapy, and having expired between 2003 and 2005, or who were still alive at data capture were included. Results: Two hundred and seven pts (60% newly diagnosed; 40% recurred), from 4 clinics (FL, OH, NV, ME) receiving 2444 cycles (3% in 2002; 18% in 03; 40% in 04, 39% in 05) were identified. Fifty percent of pts were male, the mean age was 65 yo, and the ECOG P.S. were 21%-0; 49%-1; 25%-2; 5%-3. Pts received a mean of 12 cycles of tx. A large variation in regimen usage was seen. Forty-three percent of pts received only 1 line of tx including 20+ regimens (top 10: Folfox4; IFL; 5FU/leuc; CapeOx; Folfox6; Xeloda; Folfiri2; Folfox7; CPT-11, Folfiri1), 24% received 2 lines of tx including 18+ regimens 2nd line (top 10: Folfox4; CPT-11; CapeOx; IFL; Xeloda; 5FU/leuc; Folfiri2; Folfox6; Cetuximab; Folfiri1), 15% received 3 lines of tx including 16+ regimens 3rd line (top 10: Folfox4; CapeOx; CPT-11; Xeloda; 5FU/leuc; IFL; Cetuximab; Xeliri; Folfiri1; Bevacizumab). In addition, 9% of pts received 4 lines of tx and 5% received 5 or more lines of tx. Of interest, looking at 1st line tx, IFL decreased and Folfox4 increased over the study period. Biologics were found in 48% of cycles (bevacizumab 35%; cetuximab 13%). Seventy-seven percent of pts had significant toxicity. Toxicity defined as a dose or regimen change, toxic delay or a return visit was seen in 23% of cycles (combined endpoint). Survival was available for 74 pts (81% of deaths were reported in 2004/05). Overall median survival was 17 months (&lt;66 yo - 20.3 mo; &gt;65 yo - 11.5 mo; newly diagnosed - 19.0 mo; recurred - 14.3 mo). Conclusions: Community oncologists utilized a multitude of agents/regimens in the tx of adv CRC. This may be appropriate in light of all the recent changes in disease tx strategy. Although, survival rates are near those published in the literature. [Table: see text]
Disaster at Buffalo Creek. From chaos to responsibility
Authors: G M Stern
Journal: American Journal of Psychiatry (1976)

The litigation initiated by the 625 survivors of the Buffalo Creek flood who refused to settle with the coal company claims office was a landmark case. For the first time, individuals who were not present at the scene of a disaster were allowed to recover for mental injuries. Psychic impairment, the term coined for these injuries, was found in virtually all of the survivor-plaintiffs. In an out of court settlement, the survivors were awarded $13.5 million, $6 million of which was distributed on the basis of a point system as compensation for the psychological damages.
Randomized phase II study of erlotinib (E) or intercalated E with carboplatin/paclitaxel (CP) in chemotherapy-naive advanced NSCLC: Correlation of biomarker status and clinical benefit
Authors: F. R. Hirsch, R. Dziadziuszko, L. Varella-Garcia, W. Franklin, P. Bunn, F. Kabbinavar, B. Wacker, J. Rusk, K. Richardson, D. R. Camidge
Journal: Journal of Clinical Oncology (2009)

8026 Background: E plus chemotherapy showed no additive effects in NSCLC but preclinical studies suggested that intercalation of E and chemotherapy could give synergy. Clinical studies suggested that EGFR mutations could aid in pt selection. KRAS mutation status of tumors was also evaluated. We conducted a randomized phase II study of E and E intercalated with CP in pts with chemonaive NSCLC. Methods: Stage IIIB/IV EGFR+ NSCLC pts were randomized to E 150 mg/d or CP d1 plus E days 2–15 q21 days (ECP). After 4 cycles, E continued until PD. Tumor tissue was evaluated by IHC (EGFR), FISH (EGFR gene copy number), and PCR amplification followed by DNA sequencing (EGFR and KRAS mutations). Results: Among 143 pts randomized 53% EGFR FISH+; 13% activating EGFR mutations and 8% non-activating EGFR mutations (evaluable samples=114); and 22% KRAS mutations (evaluable samples=130). No pt had both EGFR and KRAS mutations. EGFR-activating mutations were higher among females (19% vs 6% males), adenocarcinoma histology (17% vs 0% others), Asians (45% vs 7% non-Asian), and never smokers (29% vs 7% former and 0% current); KRAS mutations were higher in current smokers (41% vs 27% former and 0% never) and adenocarcinoma histology (22% vs 18% squamous). In the E arm, 6-mo PFS probability for the efficacy evaluable population (n=69) was significantly higher in pts with EGFR activating mutations vs no mutations (89% vs 25%, HR=0.17, P=0.001), numerically higher in pts with EGFR FISH+ vs FISH- (40% vs 22%, HR=0.61, P=0.07), and with KRAS wild type vs mutation+ (38% vs 12%, HR=0.56, P=0.10). Response rates, PFS and OS by type of EGFR/KRAS mutation will be presented. In the ECP arm, 6-mo PFS probability for the efficacy evaluable population (n=68) was numerically higher in pts with EGFR activating mutations (42% vs 29%, HR=0.72, P=0.53), numerically higher in pts with wild type KRAS (32% vs 9%, HR=0.57, P=0.08), and numerically lower in pts with EGFR FISH+ vs FISH- (23% vs 30%, HR=0.93, P=0.78). Conclusions: Activating EGFR mutations correlate with increased 6 mo PFS probability in 1 st line therapy with E. EGFR FISH + and absence of KRAS mutation trend towards increased 6 mo PFS rate with E. [Table: see text]
Human metapneumovirus involved in acute exacerbations in COPD patients
Authors: Marijke Vanspauwen, Frits Franssen, Cathrien Bruggeman, Emiel Wouters, Catharina Linssen
Journal: European Respiratory Journal (2011)

Introduction:  COPD is characterized by the occurrence of acute exacerbations (AE) which may be caused by several factors, including infections. Human metapneumovirus (hMPV) is an important cause of severe respiratory tract infections in young children, the elderly and immunocompromised subjects. This study evaluates the presence of hMPV and other respiratory viruses in stable sputum samples of patients with COPD and the relation with the occurrence of AE.   Material and methods:  From March 2009 until August 2010 sputum samples of COPD patients clinically rehabilitating at the centre of expertise for chronic organ failure (CIRO), were included. Patients were followed during an 8 week period and sputum samples were collected during the stable state and during an AE. Real-time PCR for respiratory viruses, including rhinovirus and hMPV, was performed.   Results:  A total of 498 sputum samples (218 patients) were included, 257 samples (52%) were collected during the stable phase. Viruses were detected in 64 (25%) of the stable samples. The most frequently isolated viruses in the stable samples were hMPV (12%) and rhinovirus (12%). A total of 74 patients experienced an AE in the weeks after stable sample collection, of which 12 (16%) had hMPV in the stable sample. Patients with hMPV in the stable phase experienced significantly more AEs in the first weeks after sample collection compared to patients without hMPV (or any other virus) (p=0.03).   Conclusion:  hMPV was one of the most isolated viruses in samples collected during the stable state. Patients with hMPV in the stable sample experienced more exacerbations compared to patients without any virus in the stable sample.
Fatal attraction: How macrophages participate in tumor metastases
Authors: Dmitry Gabrilovich
Journal: The Journal of Experimental Medicine (2015)

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Insight from Dmitry Gabrilovich



Macrophages are critically important for the regulation of tumor growth and metastases. They contribute to tumor angiogenesis, tumor cell extravasation, and survival at the sites of metastases. Now, [Kitamura et al.][2], using mouse models of
Optical Coherence Tomography Angiography of Asymptomatic Neovascularization in Intermediate Age-Related Macular Degeneration
Authors: Luiz Roisman, Qinqin Zhang, Ruikang K. Wang, Giovanni Gregori, Anqi Zhang, Chieh-Li Chen, Mary K. Durbin, Lin An, Paul F. Stetson, Gillian Robbins, Andrew Miller, Fang Zheng, Philip J. Rosenfeld
Journal: Ophthalmology (2016)
비알코올간질환과 비만 : 비알코올간질환과 비만에서의 약물요법
Authors: 조동혁
Journal: Clinical and Molecular Hepatology (2008)

Nonalcoholic fatty liver disease (NAFLD) is a common clinicopathological condition characterized by significant lipid deposition in the hepatocytes of the liver parenchyma. The clinicopathologic spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Associations between obesity, type 2 diabetes mellitus, and steatosis have long been recognized, as has the high prevalence of cirrhosis in diabetes. Although many treatment modalities have been used in patients with NASH, there is currently no proven effective treatment for NAFLD; however, a multimodal treatment plan that targets obesity, insulin resistance, hyperlipidemia, and hypertension might be the best option.