tbuckley/cabot-search huggingface dataset:
A prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy: Final results of the CONKO-004 trial.
Authors: H. Riess, U. Pelzer, B. Opitz, M. Stauch, P. Reitzig, S. Hahnfeld, L. Müller, J. Stieler, B. Dörken, H. Oettle
Journal: Journal of Clinical Oncology (2010)

4033 Background: Treatment of patients (pts) with advanced pancreatic cancer (APC) is often complicated by venous thromboembolic events (VTE). Anticoagulation therapy with low molecular weight heparin (LMWH) Enoxaparin (E) prevents VTE in APC and is under discussion to improve overall survival (OS) in cancer pts. Methods: Calculation was based on an expected reduction of the primary endpoint symptomatic VTE (sVTE) within the first 3 months (m) of treatment from 10% to 3%. Time to progression (TTP) and OS were among the secondary endpoints of the study. Chemotherapy naive pts with histologically or cytologically confirmed APC were randomized to receive (E) or not (O) to receive additional LMWH (E:1 mg/kg once daily for 3 m, followed by 40 mg/d) simultaneous to palliative systemic chemotherapy. Results: From Apr 2004 to Jan 2009 312 (O: 152/ E: 160) pts were recruited. ITT demonstrate significant decreases in sVTE after 3 m (O: 9.87%; E: 1.25%) and 12 m (O: 15.13%; E: 5.00%). Treatment was well tolerated and showed no significant differences in major bleeding. After a median follow up of 45.44 m TTP (O: 5.42 m; E: 5.03 m; p = 0.941) and OS (O: 7.98 m; E: 8.28 m; p = 0.501) are not different. Prespecified analysis excluding pts with sVTE showed no significance in OS (O: 8.15 m; E: 7.92 m; p = 0.054). Conclusions: Enoxaparin is effective and safe in the primary prevention of sVTE applied simultaneously with cytotoxic chemotherapy in pts with APC but does not prolong TTP or OS. No significant financial relationships to disclose.
The use of complementary and alternative medicine (CAM) in cancer patients participating in clinical trials
Authors: R. Epelbaum, B. Vizel
Journal: Journal of Clinical Oncology (2004)

6096 Background: The use of CAM has increased over the past decade. However, detailed research addressing the use of CAM in specific populations has yet to be undertaken. Patients giving informed consent in clinical trials might have a unique health-related behavior, characterized by more openness and a greater awareness of their ability to control the disease. In addition, they receive more conventional care. This study evaluates the extent and pattern of CAM use among patients participating in phase II and III trials. Methods: Forty patients with breast, colon and pancreatic cancer, participating in phase II and III trials, were included in the study. Interviews were conducted prior to the initiation of chemotherapy and before last cycle. Results: A total of 17 patients (42%) used CAM. Most of them started CAM before or during first cycle of chemotherapy. The most commonly used therapies were homeopathy (30%), food supplements (30%) and herbs (23%). Patients learned about CAM from a friend or family member (59%), self-reading (35%) and advertisement (18%). Lack of information about CAM (48% ), disbelief ( 43%) and the cost of therapy (35%) were the most commonly identified barriers to the use of CAM. Patients expected CAM to alleviate side effects of chemotherapy (64%), to improve physical and mental status (35%) and to better treat their tumors (18%). CAM users and nonusers did not differ with respect to age and gender. However, users tended to differ from nonusers with respect to education (more education, 88 vs 61%, respectively), place of birth ( native-born, 59 vs 30%), place of residence ( rural, 24 vs 5%) and relegious affiliation ( nonsecular, 30 vs 18%). All patients stated that they wanted information about CAM from their physicians, and most would prefer to receive CAM therapies within the hospital. Conclusions: CAM use is common among patients participating in clinical trials. Documentation of CAM use should become part of the assessment of these patients, as CAM therapies may be affecting evaluation of conventional therapies. No significant financial relationships to disclose.
Retrospective analysis of prognostic and predictive markers in patients with locally advanced unresectable and metastatic pancreatic adenocarcinoma treated with gemcitabine/nabpaclitaxel: Influence of the presence of stent.
Authors: Ana Fernandez Montes, Paula Gonzalez Villarroel, Manuel Valladares Ayerbes, Juan Cruz De la Cámara Gómez, Guillermo Quintero, Lidia Vazquez TuÃ±as, Mercedes Salgado Fernández, Mónica Jorge Fernández
Journal: Journal of Clinical Oncology (2015)

483 Background: Placement of a biliary stent is a standard measure for patients (pts) with pancreatic cancer. We evaluated prognostic/predictive factors that could predict the benefit of gemcitabine/nabpaclitaxel in pts with locally advanced unresectable and metastatic pancreatic adenocarcinoma and whether the presence of a biliary stent reduced the treatment efficacy Methods: We retrospectively analyzed 39 pts with locally advanced and metastatic pancreatic cancer treated with gemcitabine/nabpaclitaxel. Data included lactate dehydrogenase (LDH) level, alkaline phosphatase, neutrophil/lymphocyte ratio (NLR), performance status (PS), weight loss, presence of stent, analgesics use and CA 19.9 level. The correlation with response rate, progression-free survival (PFS) and overall survival (OS) was analyzed. Objective toxicities were assessed. Results: 30 pts (77%) had metastatic disease and 9 (23%) locally advanced pancreatic cancer. 46% had liver metastases and 41% lung metastases. Mean age of pts: 62 years (62% male). 20% had PS:0, 67% PS:1 and 13% PS:2. Stents were placed in 30% of pts, 69% had weight loss and 64% used analgesics at diagnosis. At the time of analysis 14 pts had died (25 alive). 56% had progressed, 3% were lost to follow-up and 41% had not progressed. A total of 54% disease stabilizations, 21% partial responses and 18% progressions were achieved (deaths: 7%). 43% required dose reduction. The main toxicity was hematologic (grade 1 anemia). Median PFS: 6 months (95%CI 4.4-7.6). Median OS: 15 months (95%CI 10.4-19.6). There was a statistically significant relationship between LDH level, NLR and PS and OS: LDH level higher than 363 increased the risk of death, NLR above 3.1 increased 1.8 times the risk of death and mean OS of pts with ECOG:0,1 was greater than that of pts with ECOG:2. No relationship between the presence of stent and PFS or OS was found, as well as with any of the other variables. Conclusions: The presence of stent did not reduce the efficacy of gemcitabine/nabpaclitaxel. Univariate analysis showed PS as a prognostic factor while multivariate showed LDH and NLR.
The pharmacology of intraperitoneally administered bleomycin.
Authors: S B Howell, M Schiefer, P A Andrews, M Markman, I Abramson
Journal: Journal of Clinical Oncology (1987)

The clinical pharmacology of intraperitoneally administered bleomycin was examined in 11 patients with malignancies confined predominantly to the peritoneal cavity. Bleomycin (60 mg/m2) was mixed in 2 L of 0.9% NaCl, and administered rapidly into the peritoneal cavity via a Port-a-Cath (Pharmacia Nu Tech, Inc, Walpole, MA). The cavity was drained following either a four- or eight-hour dwell time. Bleomycin concentration in the peritoneal cavity and plasma was determined by radioimmunoassay. A total of 15 courses was studied. The peak peritoneal: plasma concentration ratio averaged 22, and total exposure for the peritoneal cavity averaged seven-fold greater than that for the plasma. The peritoneal and plasma half-lives for bleomycin were 3.2 and 6.0 hours, respectively. The peritoneal clearance of bleomycin averaged 11.3 mL/min/m2. Abdominal pain occurred on 47% of courses; other toxicities included fever, skin rash, and mucositis. We conclude that there is a substantial pharmacologic advantage to the peritoneal route for tumors confined to the peritoneum, but that the advantage is less, and the local toxicity greater, than that found with the intraperitoneal administration of many other anticancer drugs.
Abstract 284: Load-Distributing-Band CPR for Cardiac Arrest Patients Improves Regional Cerebral Oxygen Saturation
Authors: Yoshihito Ogawa
Journal: Circulation (2013)

Background: Despite advances in therapeutic strategies and improved guidelines, morbidity and mortality rates for out-of-hospital cardiac arrest (OHCA) remain high. Especially, neurological prognosis is one of the most important problems although brain protection therapy for patients with OHCA has greatly improved in recent years due to the development of emergency post-cardiac arrest interventions, for example, mild therapeutic hypothermia, early percutaneous coronary intervention and extracorporeal cardiopulmonary resuscitation (CPR). Recently, Regional cerebral Oxygen Saturation (rSO2) have received attention as a valuation method of cerebral oxygenation. We have reported that conventional chest compression could not improve rSO2 of cardiac arrest patients if they did not get return of spontaneous circulation. It is, however, not determined whether the mechanical CPR device is helpful for improvement of rSO2. Objective: The purpose of this study is to evaluate the effects of Load-Distributing-Band CPR (LDB-CPR) on rSO2. Methods: Prospectively, LDB-CPR was performed for OHCA with AutoPulse from arrival to hospital. During mechanical CPR, rSO2 were recorded continuously from the forehead of the patients. CPR for patients with OHCA was performed according to the JRC-guidelines 2010 except for using AutoPulse instead of manual chest compression. Results: From December 2012 to May 2013, 18 patients with OHCA were included in this study. The mean age was 74.5±13.8 years old. Duration of time from recognition of cardiac collapse to arrival to hospital was 28.7±5.3 min. Before starting of LDB-CPR, rSO2 was 42.6±8.4% (baseline). rSO2 was significantly increased from baseline to 4, 8 and 12-minute after initiating LDB-CPR (46.9±7.3%, 46.2±6.8%, 47.3±6.8%, respectively p&lt;0.05). Conclusion: LDB-CPR increased rSO2 of cardiac arrest patients.
Serum Human Epidermal Growth Factor 2 Extracellular Domain as a Predictive Biomarker for Lapatinib Treatment Efficacy in Patients With Advanced Breast Cancer
Authors: Chee Khoon Lee, Lucy Davies, Val J. Gebski, Sarah J. Lord, Angelo Di Leo, Stephen Johnston, Charles Geyer, David Cameron, Michael F. Press, Catherine Ellis, Sherene Loi, Ian Marschner, John Simes, Paul de Souza
Journal: Journal of Clinical Oncology (2016)

We examined the prognostic and predictive value of serum human epidermal growth factor 2 (HER2) extracellular domain (sHER2) in patients with advanced breast cancer treated with lapatinib using data from three randomized trials.We analyzed sHER2 and tissue HER2 (tHER2) data from 1,902 patients (84%) who were randomly assigned to receive lapatinib or control in the trials EGF30001, EGF30008, and EGF100151. Cox regression analyses were performed to correlate both biomarkers with progression-free survival (PFS) and overall survival (OS).Median sHER2 levels were 25.1 and 10.1 ng/mL in tHER2-amplified (tHER-positive) and nonamplified (tHER-negative) populations, respectively (r = 0.42 for sHER2-tHER2 correlation). Lapatinib had significant PFS benefit over control (hazard ratio [HR], 0.855; P = .004), but not OS (HR, 0.941; P = .33). Lapatinib PFS benefit is independently predicted by higher sHER2 values (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.009 v nonlapatinib-containing therapies, 1.044; P(interaction) < .001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; P(interaction) = .001). Within the tHER2-positive subpopulation (n = 515), higher sHER2 values still independently predicted lapatinib PFS benefit (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.017 v nonlapatinib-containing therapies, 1.041; P(interaction) = .008). In control arms (n = 936), higher sHER2 was associated with worse prognosis in multivariable analyses (PFS HR per 10 ng/mL: PFS, 1.024; P < .001; and OS, 1.018; P < .001).Higher sHER2 predicts greater PFS benefit with lapatinib independent of tHER2 status. High sHER2 is also independently prognostic for worse survival in patients who received nonlapatinib-containing therapies. The predictive role of sHER2 for other anti-HER2 agents requires further research.
Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR
Authors: Derek J C Tai, Ashok Ragavendran, Poornima Manavalan, Alexei Stortchevoi, Catarina M Seabra, Serkan Erdin, Ryan L Collins, Ian Blumenthal, Xiaoli Chen, Yiping Shen, Mustafa Sahin, Chengsheng Zhang, Charles Lee, James F Gusella, Michael E Talkowski
Journal: Nature Neuroscience (2016)
Delayed Onset of Hemolytic Anemia in CBA-Pk-1slc/Pk-1slc Mice With a Point Mutation of the Gene Encoding Red Blood Cell Type Pyruvate Kinase
Authors: Kumiko Tsujino, Hitoshi Kanno, Koji Hashimoto, Hisaichi Fujii, Tomoko Jippo, Eiichi Morii, Young-Mi Lee, Hidekazu Asai, Shiro Miwa, Yukihiko Kitamura
Journal: Blood (1998)
Training for the 21st Century?
Authors: Michael D. Stillman
Journal: Annals of Internal Medicine (2014)

Letters18 November 2014Training for the 21st Century?Michael D. Stillman, MDMichael D. Stillman, MDFrom University of Louisville School of Medicine, Louisville, Kentucky.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L14-5023-3 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Kothari delineates a devaluation of the “core science of internal medicine” and an overemphasis on nonclinical aspects of practice. A corollary to his argument, I believe, is that physicians must scrupulously ensure that those guidelines and mandates that we adopt actually benefit our patients. Dr. Kothari chillingly observes that, while chronic disease is laying waste to our population, medical educators are stressing systems-based practice. This disconnect from clinical care seems difficult to justify.Dr. Scheuer argues that recent educational requirements have dodged evidence-based scrutiny and wonders whether they have been objectively evaluated. I myself have questioned this. ...Reference1. Accreditation Council for Graduate Medical Education; American Board of Internal Medicine. The Internal Medicine Milestone Project. Chicago: Accreditation Council for Graduate Medical Education; 2012. Accessed at www.acgme.org/acgmeweb/Portals/0/PDFs/Milestones/InternalMedicineMilestones.pdf on 28 September 2014. Google Scholar Author, Article, and Disclosure InformationAuthors: Michael D. Stillman, MDAffiliations: From University of Louisville School of Medicine, Louisville, Kentucky.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2358. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTraining for the 21st Century? Michael D. Stillman Metrics 18 November 2014Volume 161, Issue 10Page: 761KeywordsBehaviorConflicts of interestDisclosureHealth care ePublished: 18 November 2014 Issue Published: 18 November 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Paclitaxel-induced "recall" soft tissue injury occurring at the site of previous extravasation with subsequent intravenous treatment in a different limb.
Authors: J Shapiro, G E Richardson
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.10.2237 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7931497 Paclitaxel-induced "recall" soft tissue injury occurring at the site of previous extravasation with subsequent intravenous treatment in a different limb. J ShapiroxJ ShapiroSearch for articles by this author , G E RichardsonxG E RichardsonSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.10.2237 PDF "Paclitaxel-induced "recall" soft tissue injury occurring at the site of previous extravasation with subsequent intravenous treatment in a different limb.." Journal of Clinical Oncology, 12(10), pp. 2237–2238© 1994 by American Society of Clinical Oncology
In Vivo Host Response and Degradation of Copolymer Scaffolds Functionalized with Nanodiamonds and Bone Morphogenetic Protein 2
Authors: Salwa Suliman, Yang Sun, Torbjorn O. Pedersen, Ying Xue, Joachim Nickel, Thilo Waag, Anna Finne‐Wistrand, Doris Steinmüller‐Nethl, Anke Krueger, Daniela E. Costea, Kamal Mustafa
Journal: Advanced Healthcare Materials (2016)

The aim is to evaluate the effect of modifying poly[( l ‐lactide)‐co‐(ε‐caprolactone)] scaffolds (PLCL) with nanodiamonds (nDP) or with nDP+physisorbed BMP‐2 (nDP+BMP‐2) on in vivo host tissue response and degradation. The scaffolds are implanted subcutaneously in Balb/c mice and retrieved after 1, 8, and 27 weeks. Molecular weight analysis shows that modified scaffolds degrade faster than the unmodified. Gene analysis at week 1 shows highest expression of proinflammatory markers around nDP scaffolds; although the presence of inflammatory cells and foreign body giant cells is more prominent around the PLCL. Tissue regeneration markers are highly expressed in the nDP+BMP‐2 scaffolds at week 8. A fibrous capsule is detectable by week 8, thinnest around nDP scaffolds and at week 27 thickest around PLCL scaffolds. mRNA levels of ALP, COL1α2, and ANGPT1 are significantly upregulating in the nDP+BMP‐2 scaffolds at week 1 with ectopic bone seen at week 8. Even when almost 90% of the scaffold is degraded at week 27, nDP are observable at implantation areas without adverse effects. In conclusion, modifying PLCL scaffolds with nDP does not aggravate the host response and physisorbed BMP‐2 delivery attenuates inflammation while lowering the dose of BMP‐2 to a relatively safe and economical level.
Results of a completed phase I clinical trial of CYT-6091: A pegylated colloidal gold-TNF nanomedicine
Authors: S. K. Libutti, G. F. Paciotti, L. Myer, R. Haynes, W. Gannon, M. Walker, G. Seidel, A. Byrnes, N. Yuldasheva, L. Tamarkin
Journal: Journal of Clinical Oncology (2009)

3586 Background: CYT-6091 is the first tumor-targeted nanomedicine formulation designed to safely deliver an API that itself is not approved for systemic administration due to unacceptable toxicity. CYT-6091, consisting of tumor necrosis factor-α (TNF) covalently linked to pegylated colloidal gold nanoparticles, has been safely administered in preclinical models, demonstrating an increased T1/2 compared to native TNF, a documented trafficking of nanoparticles to tumor, and no hypotension, the known DLT for TNF. Methods: CYT-6091 was tested in a phase I open label trial in solid tumor, advanced stage patients. Patients (n = 3/dose), admitted to the NIH Clinical Center ICU, received two IV injections of CYT-6091 on day 0 and 14. Dosing started at 50 μg/m2 of TNF, up to 600 μg/m2. Vital signs were monitored and blood samples were drawn over 48 h. The primary endpoint of the study was to determine the MTD for CYT-6091. Secondary endpoints included PK, disease response (staged 45 days post treatment by RECIST), and the detection of gold nanoparticles in tumors and in adjacent healthy tissue. Results: Twenty-nine patients were treated. Even at the lowest dose (50 μg/m2), patients exhibited a febrile response, which was mitigated by acetaminophen and indomethacin pretreatment. None of the 29 patients treated with doses of 50–600 μg/m2 showed a DLT hypotensive response, and in fact, no DLT was seen. T1/2 estimates for TNF, administered as CYT-6091, are 120, 131, 127, 146, 112, 113, 266, 371, and 160 minutes for 50, 100, 150, 200, 250, 300, 400, 500, 600 μg/m2, respectively (published T1/2 for native TNF is ∼27 minutes). In the 28 patients eligible for response assessment, there was 1 PR (100 μg/m2 dose, 7 months duration) and 3 SD (2, 2, and 3 months duration). Electron micrographs show gold nanoparticles in tumor biopsies. Conclusions: CYT-6091 is well tolerated at doses up to 600 μg/m2 of TNF, levels 3-times greater than the published MTD for native TNF. CYT-6091 targets tumors in humans. Efficacy studies in combination with chemotherapy are planned. [Table: see text]
Fluorodeoxyglucose (FDG) PET as an outcome measure for metastatic prostate cancer.
Authors: M. J. Morris, J. J. Fox, E. R. Dennis, K. Tse, E. Flatts, G. Heller, X. Jia, H. Schöder, S. M. Larson, H. I. Scher
Journal: Journal of Clinical Oncology (2010)

4638 Background: There are no reliable means of directly imaging metastatic prostate cancer, as it primarily localizes to bone. We are exploring new imaging modalities prospectively and systematically in order to establish a new biomarker for this disease. Methods: Under the auspices of an imaging trial, we prospectively scanned at baseline and post-treatment 3-13 wks patients (pts) with metastatic prostate cancer using FDG PET, controlling for pt disease progression, scanning algorithm, and interpretation. The SUV max average (SUVMAXAVG) was calculated by averaging the maximum SUV seen for each of 5 lesions. Lesion site and hottest lesion (SUVMAX) were also assessed. Univariate analysis and a multivariate model of all variables was built using stepwise variable selection procedure with cutoff p value <0.1. Results: 96 pts were scanned, 69 of whom have died. Median survival was 20 months (95% CI 17-25). 86 pts had evaluable follow up scans in the 3-13 week window. In the univariate analysis, baseline SUVMAX, SUVMAXAVG, lactate dehydrogenase (LDH), hemoglobin (Hgb) and alkaline phosphatase (ALK) were associated with OS, as was post treatment change in LDH (D LDH). In the multivariate analysis, baseline SUVMAXAVG, baseline LDH, and D LDH were significant for predicting OS. Conclusions: In this study exploring FDG PET as an outcome measure, baseline SUVMAXAVG, baseline LDH, and D LDH appear to be associated with OS. Post-treatment SUVMAXAVG changes were not significant, which may result from a low number of events in the dataset, the need to use more than 5 lesions to represent the degree of disease involvement, or the need to better account for new lesions in our methodology. We continue to build the dataset and refine the method of lesional quantification and analysis for future validation in phase III studies. Univariate analysis and multivariate analysis for baseline variables and post-treatment changes Univariate HR P Baseline SUVMAX 1.39 0.05 SUVMAXAVG 1.68 0.05 PSA 1.02 0.75 LDH 14.01 <0.0001 HGB 0.17 0.007 ALK 1.39 0.002 Post-Tx Δ SUVMAX 0.99 0.96 Δ SUVMAXAVG 0.98 0.92 Δ PSA 1.05 0.45 Δ LDH 2.39 0.02 Δ HGB 0.60 0.30 Δ ALK 1.48 0.11 Multivariate HR P Baseline SUVMAXAVG 2.04 0.04 LDH 11.44 <0.0001 Post-Tx Δ SUVMAXAVG 0.95 0.86 Δ LDH 2.66 0.02 No significant financial relationships to disclose.