tbuckley/cabot-search huggingface dataset:
Considerations for Amending SNAP Regulations—Reply
Authors: Lisa Harnack
Journal: JAMA Internal Medicine (2017)

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Abstract 206: Intramyocardial Lipid Dysregulation in End Stage Heart Failure
Authors: Kenneth C Bedi, Charles Lim, Clementina Mesaros, Moez K Aziz, Ian A Blair, Kenneth B Margulies, J. Eduardo Rame
Journal: Circulation Research (2013)

Background: Advanced heart failure (HF) is characterized by metabolic abnormalities but studies conflict about the nature of these defects. Methods: We investigated the presence or absence of toxic intramyocardial lipid species using carefully procured human myocardium from lean, non-diabetic end-stage heart failure patients. Left ventricular myocardial samples were obtained at the time of heart transplant. Cases included idiopathic dilated (n=5) and ischemic (n=2) cardiomyopathy (n=7), and brain-dead organ donors without any history of heart failure (n=12). The failing hearts were examined before and after support with a left ventricular assist device (LVAD, n=7). Frozen samples were evaluated by liquid chromatography and high-resolution mass spectrometry (LC-HRMS) to identify lipid species and further quantitate their abundance. Samples for LC-HRMS were prepared using the Folch extraction method, and the samples were normalized to protein concentration via BCA protein assay. We selected for masses with p-values less than or equal to (p= .005) and a fold change greater than or equal to 2.5 Results: Diacylglycerols (DAGs), ceramides, sphingosines, and cardiolipins (CLs) were lower in failing samples than in non failing. The figure below for L-Palmitoylcarnitine is representative of the quantitative changes in lipids observed between failing and non-failing groups. Conclusion: Excess intramycellular lipid accumulation is not present in advanced heart failure. A significant deficiency in cardiac lipid species has been identified in end stage non-diabetic heart failure. Future studies in diabetic and obese patients with advanced heart failure are warranted.
Value of central line care teaching for families of pediatric oncology patients.
Authors: Chris Ivette Wong Quiles, Marc A Schwartz, Riley M Mahan, Amy Billett
Journal: Journal of Clinical Oncology (2017)

60 Background: Pediatric oncology care depends on central lines (CLs) in both outpatient and inpatient settings. Although inpatient implementation of CL maintenance bundles has been achieved, little attention has focused on families who care for CLs at home. Families are expected to follow best practice, but most have no prior experience or medical background. We sought to understand the comfort level and knowledge of families caring for external CLs at home and the value of our program’s existing teaching strategies, prior to an improvement initiative. Methods: Families caring for children with new and existing external CLs at home from May 2015-May 2016 were eligible for a survey and approached during outpatient visits if their primary team agreed. Using Likert scales, families were asked to assess their current comfort level with CL care, evaluate existing teaching strategies (instructional sheets; hands-on teaching by program nurses, and by home health nurses), and comment on other potentially helpful strategies. Five content questions regarding CL care were included to evaluate knowledge. Results: 80 of 82 (97.6%) families approached completed the survey. 70% had a CL in place for &gt; 60 days. 46.3% felt "very comfortable" performing CL care, 42.5% were "comfortable", and 11.2% were "sort of or not comfortable". Only 17.5% of families found instruction sheets indispensable. Hands-on teaching was indispensable for 51.3% of families; 1.3% responded that teaching was not performed. 27.5% of families found hands-on teaching by home health nurses indispensable, but 22.5% had not received this. 98% of content questions were answered correctly. Other helpful strategies concentrated on 3 themes: standardization of educational content, increased opportunity for hands-on practice, and cognitive aids (e.g. a checklist) for CL care. Conclusions: A minority of families feel the highest level of comfort with CL care at home even after months of experience. Improvement opportunities and gaps in CL care teaching strategies are prevalent. To help support families caring for CLs at home and ensure adherence to best practice, programs should engage families to better understand their needs and develop solutions to meet them.
Zebrafish Behavior: Opportunities and Challenges
Authors: Michael B. Orger, Gonzalo G. de Polavieja
Journal: Annual Review of Neuroscience (2017)

A great challenge in neuroscience is understanding how activity in the brain gives rise to behavior. The zebrafish is an ideal vertebrate model to address this challenge, thanks to the capacity, at the larval stage, for precise behavioral measurements, genetic manipulations, and recording and manipulation of neural activity noninvasively and at single-neuron resolution throughout the whole brain. These techniques are being further developed for application in freely moving animals and juvenile stages to study more complex behaviors including learning, decision making, and social interactions. We review some of the approaches that have been used to study the behavior of zebrafish and point to opportunities and challenges that lie ahead.
How Would You Manage Opioid Use in These Three Patients?
Authors: Daniel P. Alford, Marc L. Cohen, Eileen E. Reynolds
Journal: Annals of Internal Medicine (2017)

The increase in overdose deaths from prescription opioids and heroin in the United States over the past 20 years is believed to have resulted from increases in prescription of opioids for management of acute and chronic pain. Managing chronic pain is challenging for primary care clinicians for many reasons, including the lack of evidence to guide practice. The Centers for Disease Control and Prevention published a comprehensive guideline in 2016 to help clinicians with opioid prescribing for chronic pain. In this Grand Rounds, the guideline is reviewed and an expert discusses its application to 3 patients prescribed opioids to treat chronic pain.
Frequent use of complex surgeries and survival outcomes in ovarian cancer patients: A propensity score analysis from the Korean Gynecologic Oncology Group.
Authors: Sokbom Kang, Dae Chul Jung, Seung Cheol Kim, Jae Weon Kim, Joo-Hyun Nam, Sang Young Ryu, Seok Ju Seong, Byoung Gie Kim
Journal: Journal of Clinical Oncology (2014)

5537 Background: To develop an indicator representing the quality of ovarian cancer surgery and to determine its predictive role in a prognostic model. Methods: From January 2002 to December 2008, the clinical records and computed tomography (CT) data of epithelial ovarian cancer patients were reviewed from the KGOG-3022 dataset. A propensity score was developed from a multivariable logistic model and used as a stratification factor or co-variable in Cox models to balance the differences between the high- and low/intermediate-complexity surgery group. Results: Data for 331 patients from six specialized teaching hospitals were reviewed. Complex surgery, defined as a surgery with a surgical complexity score > 7, was more frequently performed in patients with an ‘upper abdominal extension’ pattern, ‘diffuse peritoneal spread’ pattern, and grade III disease (P < 0.001, 0.017, and 0.001, respectively). To balance the differences, a propensity score for complex surgery was developed. The use of complex surgery for greater than 25% of advanced cases at the institutional level was consistently associated with improved progression-free survival (PFS) when the score was used as a covariate (Hazard ratio [HR] = 0.69, P = 0.038) or as a stratification factor (HR = 0.68, P = 0.033). In contrast, the complexity of individual surgery showed no significant association with PFS regardless of the adjustment methods (P = 0.90 and 0.76, respectively). Conclusions: The institutions that perform complex surgeries for greater than 25% of advanced ovarian cancer patients were associated with an approximately 30% reduction in recurrence risk after primary treatment.
Phase II study of cisplatin, etoposide and concurrent thoracic radiotherapy (TRT) followed by irinotecan and cisplatin in patients with limited stage small-cell lung cancer (SCLC); updated results of WJTOG9902
Authors: S. Mitsuoka, S. Kudoh, Y. Takada, K. Matsui, K. Eguchi, Y. Ichinose, K. Nakagawa, M. Takada, H. Saito, Y. Ariyoshi
Journal: Journal of Clinical Oncology (2004)

7044 Background: Cisplatin (P) plus etoposide (E) with concurrent TRT is a standard treatment for limited stage (LD) SCLC. Irinotecan (I) is an active agent for SCLC and IP is superior to PE in extensive stage SCLC. We initially conducted a randomized phase II study to evaluate of PE with concurrent TRT followed by either IP or IPE in LD-SCLC. However, the study protocol was amended to evaluate PE with concurrent TRT followed by IP in a single-arm phase II study because of unacceptable toxicity in IPE regimen. Purpose: To evaluate the efficacy and the safety profile of PE with concurrent TRT followed by IP in LD-SCLC. Methods: Eligibility criteria included untreated LD-SCLC, age ≤70, ECOG performance status 0–2 and adequate organ functions. P 80 mg/m2 day (d) 1 and E 100 mg/m2 d1–3 with concurrent TRT (1.5 Gy/BID, a total dose of 45 Gy) followed by 3 cycles of I 60 mg/m2 d1, 8, 15 and P 60 mg/m2 d1. Results: We enrolled 51 patients (pts), median age of 62 (range 45–70); male/female, 42/9; PS 0/1/2, 22/28/1. Eight pts were removed from the study after PE/TRT. Response and toxicity was evaluated in 49 pts. Overall response rate and complete response rate were 87.8% and 40.8%, respectively. Grade 4 toxicity included neutropenia 84%, anemia 10%, thrombocytopenia 0%, diarrhea 2% and infection 2%. To date median survival time was not reached. One-year and 2-year survival rate was 86.4% and 50.7%, respectively. Conclusions: PE with concurrent TRT followed by IP is active in LD-SCLC. This regimen deserves further evaluation in a randomized phase III study to compare PE with concurrent TRT in LD-SCLC. No significant financial relationships to disclose.
Phase II study evaluating the effect of concomitant ramucirumab (IMC-1121B; RAM) on the pharmacokinetics (PK) of docetaxel (DOC) in patients (pts) with advanced malignant solid tumors.
Authors: Mark N. Stein, Laura Quan Man Chow, David C. Smith, Dale Randall Shepard, Ding Wang, John D. Powderly, Ling Gao, Yong Lin, Minori Koshiji
Journal: Journal of Clinical Oncology (2014)

e13539 Background: RAM is a human IgG1 monoclonal antibody that specifically targets the extracellular domain of vascular endothelial growth factor receptor-2. The primary objective of this study was to investigate the effect of concomitant RAM on the PK of DOC. Methods: Key eligibility criteria for this study included pts ≥18 years of age with metastatic or locally advanced malignant solid tumors resistant to standard therapy or for which no standard therapy is available and an Eastern Cooperative Oncology Group performance status of 0-2. Pts received DOC 75 mg/m2and RAM 10 mg/kg on day 1 of a 3-week cycle. In cycle 1, DOC was administered alone; in cycle 2 and subsequent cycles, RAM was administered followed by DOC. Blood was drawn immediately before and at regular intervals after infusions for cycles 1 and 2 to determine serum concentrations of DOC and RAM. Patients who completed cycle 1, day 1 and cycle 2, day 1 were included in the drug-drug interaction analysis. Results: DOC PK parameters were assessed in 18 pts. The dose-normalized AUC(0-∞) and Cmax of DOC in cycle 2 were similar to those when DOC was administered alone in cycle 1, with geometric LS means ratios of 0.97 (90% CI: 0.84, 1.10) for AUC(0-∞) and 1.14 (90% CI: 0.84, 1.55) for Cmax. The most commonly reported drug-related treatment-emergent adverse events (TEAEs) included neutropenia, fatigue, and decreased WBC count (each in 9 patients, 40.9%); nausea (7 patients, 31.8%); and alopecia and dysgeusia (each in 5 patients, 22.7%). The most commonly reported grade ≥3 drug-related TEAEs were neutropenia and leukopenia. Conclusions: Coadministration of RAM had no effect on the PK of DOC. The incidence and severity of TEAEs were consistent with the known safety profiles of DOC and RAM. Clinical trial information: NCT01567163.
Protein Array-Based Approaches for Biomarker Discovery in Cancer
Authors: Yi Huang, Heng Zhu
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract Biomarkers are deemed to be potential tools in early diagnosis, therapeutic monitoring, and prognosis evaluation for cancer, with simplicity as well as economic advantages compared with computed tomography and biopsy. However, most of the current cancer biomarkers present insufficient sensitivity as well as specificity. Therefore, there is urgent requirement for the discovery of biomarkers for cancer. As one of the most exciting emerging technologies, protein array provides a versatile and robust platform in cancer proteomics research because it shows tremendous advantages of miniaturized features, high throughput, and sensitive detections in last decades. Here, we will present a relatively complete picture on the characteristics and advance of different types of protein arrays in application for biomarker discovery in cancer, and give the future perspectives in this area of research.
Co-clinical Analysis of a Genetically Engineered Mouse Model and Human Prostate Cancer Reveals Significance of NKX3.1 Expression for Response to 5α-reductase Inhibition
Authors: Aditya Dutta, Sukanya Panja, Renu K. Virk, Jaime Yeji Kim, Roseann Zott, Serge Cremers, David M. Golombos, Deli Liu, Juan Miguel Mosquera, Elahe A. Mostaghel, Christopher E. Barbieri, Antonina Mitrofanova, Cory Abate-Shen
Journal: European Urology (2017)
Mitoxantrone plus gemcitabine in pretreated patients with advanced breast cancer
Authors: A. Onyenadum, P. Kosmidis, G. Aravantinos, D. Bafaloukos, H. Gogas, C. Bacoyiannis, E. Razis, C. Markopoulos, T. Makatsoris, H. P. Kalofonos
Journal: Journal of Clinical Oncology (2004)

829 Background: Gemcitabine and mitoxantrone have both been demonstrated significant antitumor activity in patients with breast cancer. The aim of the study was to evaluate the efficacy and safety of the combination as second or third line treatment in patients with advanced breast cancer (ABC). Methods: Fifty-six previously treated patients with ABC were enrolled from June 2000 to November 2002 and 46 were eligible. Mean age was 56 years (range 35–72) and ECOG performance status was <3. Sites of metastasis were as follows: liver 56%, bones 48%, lungs 46%, lymph nodes 17%. All patients received mitoxantrone 10mg/m2, D1 and gemcitabine 1000mg/m2, D1+8 every 21 days for 6 cycles. The relative dose intensity of mitoxantrone and gemcitabine was 0.76 and 0.77, respectively. A total of 211 cycles were delivered. Results: All patients were analyzed for toxicity for response. There were no complete responders. The objective response rate was 24% (95% confidence interval [CI] 12.6–38.8), 15 (33%) patients had stable disease, 15 (33%) had progressive disease and 4 (9%) were nonevaluable. At median follow up of 27.8 months overall survival was 13.3 months (range 0.6–33.8+) and the median time to disease progression was 4.4 months (range 0.2–33.8). Toxicities (grade III-IV) were as follows: leukopenia 18 (39%), neutropenia 19 (41%), thrombocytopenia 4 (8,5%), anemia 6 (13%) and alopecia 1 (2%). Febrile neutropenia was recorded in 2 (4%) patients. There were no treatment-related deaths. Conclusions: The combination of mitoxantrone and gemcitabine is an effective and well-tolerated regimen in pretreated patients with advanced breast cancer. No significant financial relationships to disclose.
Inulin prebiotic: is it all about bifidobacteria?
Authors: Sandrine Paule Claus
Journal: Gut (2017)

In this issue, Vandeputte et al 1 present a unique study exploring the effects of chicory-derived inulin on the human gut microbiota by combining Next Generation Sequencing and faecal metabolomics to gain new insights into the mechanisms of action underlying inulin's health-promoting effects. The study supports that inulin prebiotics stimulate growth of bifidobacteria while simultaneously driving a number of other modulations of the gut microbial ecosystem that may be associated with health-promoting effects.

Consumption of inulin-type fructans (ITFs) has been associated with a number of health benefits, including normalisation of GI function, regulation of body weight gain and energy metabolism.2 Some of the suggested mechanisms of action include regulation of the immune system, modulation of GI peptides, production of short chain fatty acids (SCFAs) and modulation of triglyceride metabolism.2–4 Down in the intestine, ITFs have long been known for their prebiotic activity targeted towards the enhancement of the genus Bifidobacterium.5 The latter is a well-known inhabitant of the human gut and one of the first micro-organism to colonise the infant's intestine at birth. Bifidobacteria are believed to promote health by producing some antimicrobial substances protecting the host from opportunistic pathogens, in addition to large amounts of lactic acid, which contribute to maintain a low pH in the colon, thereby limiting pathogen growth. Yet, inulin's prebiotic effects on human's gut microbial ecology have so far mostly been assessed using culture-based …
Matched-pair comparison of outcome of patients with clinical stage I non-small cell lung cancer treated with resection or stereotactic radiosurgery.
Authors: Julia Shelkey, Achilles Fakiris, Malcolm M. DeCamp, Laura Nyshel Medford-Davis, John Charles Flickinger, Abram Recht, Adam Liss, Chandra Prakash Belani, Jill Deluca, Neelabh Maheshwari, John M. Varlotto
Journal: Journal of Clinical Oncology (2012)

7040 Background: Stereotactic body radiotherapy (SBRT) is an alternative to surgery alone for certain patients with clinical stage I non-small cell lung cancer (NSCLC), but comparing their effectiveness is difficult because of differences in patient selection and staging. Methods: Two databases were combined which contained 132 patients treated by lobectomy (LR) and 48 by sublobar resection (SLR) and 137 patients managed with SBRT after negative staging between 1999-2009. We compared rates of overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) between patients treated with surgery and SBRT to each other and in relation to possible prognostic factors. We then performed a matched-pair analysis comparing surgery and SBRT results. Median follow-up for the entire study population was 25.8 months. Results: On univariate analysis, OS was significantly correlated with histology, the Charlson Comorbidity Index, tumor size, aspirin use, and use of SBRT; DFS was correlated only with histology; and no variable was significantly correlated with LRC. Multivariate analysis found improved OS in patients with adenocarcinoma and those undergoing surgical resection. The NSCLC “not otherwise specified” histology was associated with poorer DFS. Overall survival was significantly poorer for SBRT patients in the matched-pair analysis than for patients treated with surgery, but DFS and LRC were not significantly different between these groups. Conclusions: Our retrospective study has demonstrated similar LRC and DFS in patients treated with SBRT or surgery, but worse OS in the former group, when patients were matched for prognostic factors. Our investigation suggests that randomized trials are needed to eliminate selection bias in treatment assignment in order to accurately compare outcomes between these approaches.
Patient Reactions to Surgeon Recommendations About Contralateral Prophylactic Mastectomy for Treatment of Breast Cancer
Authors: Steven J. Katz, Nancy K. Janz, Paul Abrahamse, Lauren P. Wallner, Sarah T. Hawley, Lawrence C. An, Kevin C. Ward, Ann S. Hamilton, Monica Morrow, Reshma Jagsi
Journal: JAMA Surgery (2017)

Guidelines assert that contralateral prophylactic mastectomy (CPM) should be discouraged in patients without an elevated risk for a second primary breast cancer. However, little is known about the impact of surgeons discouraging CPM on patient care satisfaction or decisions to seek treatment from another clinician.
The ADEBAR-trial: Effect of participation in a randomized phase III study (evaluating the role of adjuvant docetaxel in high-risk breast cancer patients) on treatment strategies and individual patient care in recruiting centers
Authors: H. Sommer, W. J. Janni, B. Rack, D. Steinfeld, W. Simon, D. Augustin, M. Heinrigs, F. V. Bismarck, N. Harbeck, M. Kiechle
Journal: Journal of Clinical Oncology (2004)

587 Background: ADEBAR is a multicenter phase III trial to evaluate whether breast cancer (BC) pts with > 3 axillary lymph metastases benefit from a sequential anthracycline-docetaxel regimen (E90C–D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21 days followed by 4 cycles docetaxel [D] 100mg/m2 q21 days) compared to dose-intensive anthracycline-containing polychemotherapy (FE120C: 6 cycles E 60 mg/m2 d 1+8, 5-FU 500mg/m2 d 1+8 and C 75 mg/m2 d 1–14, q4 weeks). ADEBAR is currently the best recruiting adjuvant chemotherapy trial in this specific risk group in Germany. Patients and Methods: As of 1.12.2003, 149 actively participating centers recruited 675 patients (25.0 patients/month, median) in the ADEBAR-study. A questionnaire was sent to all participating centers (comprising large hospital departments and community oncology practices) in order to evaluate, in which extend their participation in the ADEBAR-study had changed their treatment strategies and patient care. Results: 67.4% (n=93) of the questionnaires were returned. In the year preceding ADEBAR, 54.8% of study centers had not entered high-risk breast cancer patients into a clinical trial. Outside of the ADEBAR protocol, 51.7% of high-risk patients would have routinely received less effective chemotherapy, such as CMF or EC/CMF. 43% of centers reported that participating in the trial had increased their intensitiy of patient care and 53.7 % noted an improvement in their professional knowledge by being part of an investigators' network. More than one third of the centers (35.5%) reported substantial improvements in the overall quality of their patient care. Conclusion: Our results demonstrate that, by participation in clinical trials, there is an improvement of treatment strategies and individual patient care in recruiting centers. Moreover, our excellent recruitment rate demonstrates that modern trials, which are easy to carry out under routine care conditions, have the potential of acquiring additional centers to conduct clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis; Amgen; Pfizer; Novartis; AstraZeneca