tbuckley/cabot-search huggingface dataset:
Safety of Long-term Treatment With Certolizumab Pegol in Patients With Crohn's Disease, Based on a Pooled Analysis of Data From Clinical Trials
Authors: Edward V. Loftus, Jean-Frederic Colombel, Stefan Schreiber, Charles W. Randall, Miguel Regueiro, Tauseef Ali, Catherine Arendt, Jason Coarse, Marshall Spearman, Gordana Kosutic
Journal: Clinical Gastroenterology and Hepatology (2016)

Background & AimsTreatments for Crohn's disease (CD) have been linked to serious infections, malignancies, and dermatologic complications. We pooled and analyzed clinical trials of certolizumab pegol, a pegylated humanized Fab' fragment against tumor necrosis factor, to quantify safety events in patients with CD.MethodsWe collected data from 5 placebo-controlled trials, 9 open-label studies, and 1 dose-regimen study, conducted globally through April 2014. A total of 2570 patients with moderate to severe CD were treated with certolizumab pegol, with 4378.1 patient-years of exposure. Data were analyzed in 2 groups: patients from placebo-controlled (PC) trials treated with placebo (n = 875) or certolizumab pegol (n = 919) for 6 to 38 weeks (the PC group) or all patients exposed to certolizumab pegol (n = 2570), for durations of 6 to 362 weeks (the all-studies group). Incidence rates (IRs; incidence/100 patient-years) of adverse events (AEs) were calculated from first dose through 70 days (approximately 5 half-lives) after the last dose.ResultsIn the PC group, IRs for serious AEs were similar among patients given certolizumab pegol (31.35/100 patient-years) vs placebo (24.33/100 patient-years). IRs of serious infections or malignancies were low among patients receiving short-term treatment with certolizumab pegol (8.49/100 patient-years and 1.01/100 patient-years, respectively, in the PC group) and did not increase with long-term treatment (6.47/100 patient-years and 0.80/100 patient-years, respectively, in the all-studies group). IRs of psoriasis or psoriasiform dermatitis were low in the PC group (1.01/100 patient-years and 0/100 patient-years, respectively); in the placebo group, these IRs were 0.38 per 100 patient-years and 0 per 100 patient-years, respectively. IRs of psoriasis or psoriasiform dermatitis did not increase with long-term treatment (0.93/100 patient-years and 0.09/100 patient-years, respectively, in the all-studies group).ConclusionsBased on an analysis of data pooled from 15 trials of patients with CD, the safety profile for long-term therapy with certolizumab pegol therapy is similar to that reported from short-term studies. Overall rates of AEs, serious infections, malignancies, and psoriasis did not increase with long-term treatment, suggesting a favorable risk–benefit ratio with long-term certolizumab pegol therapy in CD. Clinicaltrials.gov identifiers: NCT00291668, NCT00152490, NCT00152425, NCT00308581, NCT00349752, NCT00552058, NCT00329550, NCT00329420, NCT00160524, NCT00160706, NCT00297648, NCT00333788, NCT00307931, NCT00356408, and NCT00552344 (https://www.clinicaltrials.gov/ct2/search).
Vemurafenib in patients with BRAFV600E-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial
Authors: Marcia S Brose, Maria E Cabanillas, Ezra E W Cohen, Lori J Wirth, Todd Riehl, Huibin Yue, Steven I Sherman, Eric J Sherman
Journal: The Lancet Oncology (2016)
Case 50-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, James C. Melby, Robert H. Young
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 73-year-old woman was admitted to the hospital because of dyspnea.She was apparently well until 10 or more years earlier, when arthralgia developed. Seven months before admission a corticosteroid was administered because of arthritis. Three months before entry the steroid medication was discontinued because of ecchymoses on the arms. For an uncertain interval the patient had experienced dyspnea and weakness on getting out of a chair and on standing.Five weeks before admission the patient came to the Emergency Ward of this hospital because of increasing dyspnea. Examination showed that she was afebrile, and the blood . . .
Familial AML With Germline CEBPA Mutations: Extended Clinical Outcomes and Analysis Of Secondary Mutations Using Whole Exome Sequencing
Authors: Kiran Tawana, Aline Renneville, Jun Wang, Panayiotis Georgiades, Xavier Thomas, Valerie Mialou, Aleksander Savic, Frederik W Van Delft, Jennifer G. Treleaven, Sameena Iqbal, Norio Asou, Naokuni Uike, Konstanze Döhner, Lars Bullinger, Matthias Stelljes, Csaba Bödör, James D. Cavenagh, Doris Steinemann, Tim Ripperger, Brigitte Schlegelberger, Peter Vandenberghe, Anne Uyttebroeck, Josep F. Nomdedeu, Henrik Hjorth-Hansen, Rosemary E Gale, Cynthia L. Toze, Michael J. Barnett, Marianna Zombori, Krisztian Kallay, Jiri Pavlu, Pim Mutsaers, Fred H Menko, Angela Thomas, Christine Wright, Jessica Okosun, Chey Loveday, Pierre Fenaux, Hamish Scott, Claude Preudhomme, Claude Chelala, Alison Male, Carolyn J. Owen, Matthew Smith, Jude Fitzgibbon
Journal: Blood (2013)
Disrupted sleep the night before breast cancer surgery is associated with increased post-surgical pain
Authors: C. E. Wright, G. H. Montgomery, A. Goldfarb, B. Pace, J. H. Silverstein, C. Weltz, D. H. Bovbjerg
Journal: Journal of Clinical Oncology (2007)

9078 Background: Despite the best clinical care, pain following breast cancer surgery is a virtually universal patient experience that can have pervasive negative consequences. Given the sometimes prolonged impact of such pain, and the large variability across patients, additional research on modifiable presurgery risk factors is needed. Recent experimental studies have found that disruption of even a single night's sleep is sufficient to increase pain sensitivity the next day in healthy volunteers. The possible negative effects of poor sleep prior to cancer surgery have not been investigated despite the likelihood that sleep may be particularly disrupted at that time. We hypothesized that sleep disruption the night before outpatient breast cancer surgery would predict increased postsurgery pain. Methods: Pain was measured in 24 female lumpectomy patients using the Brief Pain Inventory 7 days postsurgery. Sleep disruption (% of time awake in the sleep period) was measured using an actigraph device for 10 nights, commencing 3 days before surgery. Statistical analyses included correlation and multiple regression. Results: Sleep disruption was significantly greater the night before surgery than 3 nights before surgery (p=.047). Heightened sleep disruption the night before surgery predicted increased pain intensity and pain interference with daily life (r=-.44, p=.034; r=-.49, p=.015), This relationship remained significant for pain interference even after controlling for age, race, surgery duration, presurgery mood, postoperative sleep disturbance and pain medication (B=-.12, C.I. -.23 to -.02, p=.027). Conclusions: This study is the first to document adverse effects of prior sleep disruption on pain sensitivity in a clinical oncology context. Future research should explore mechanisms responsible for these effects and examine the impact of interventions to improve sleep prior to surgery. No significant financial relationships to disclose.
New-onset atrial fibrillation and its influence on all-cause mortality and shock delivery in patients with ischemic and non-ischemic cardlomyopathy and an implantable cardioverter defibrillator
Authors: M Rienstra, PF Van Dessel, AC Wiesfeld, ES Tan, W Nieuwland, van Dirk Veldhuisen, van Isabelle Gelder
Journal: Circulation (2005)
PWE-035 Early experience of pancreatoscopy-directed electrohydraulic lithotripsy for pancreatic ductal stones in painful chronic pancreatitis: Abstract PWE-035 Table 1
Authors: N Bekkali, S Murray, G Johnson, M Chapman, S Pereira, G Webster
Journal: Gut (2015)

<h3>Introduction</h3> Painful chronic pancreatitis is often associated with main duct obstruction due to stones. Approaches to management are challenging, including surgery, extracorporeal shock wave lithotripsy (ESWL), or endoscopic approaches. All have their limitations. Electrohydraulic lithotripsy (EHL) using Spyglass<b>™ </b>directed visualisation is highly effective for treating difficult bile duct stones, and is increasingly used in the UK. Here we report our early experience of Spyglass ™ pancreatoscopy and EHL for pancreatic duct stones. <h3>Method</h3> We retrospectively audited our unit’s use of Spyglass<b>™</b>EHL in the period February 2013–February 2015, with a focus on those patients undergoing pancreatic EHL. Indication, procedural details, and clinical outcome were assessed. <h3>Results</h3> Eighty-five procedures for Spyglass<b>™</b>and EHL for stones were performed, of which 5 (6%) were carried out for pancreatic stones in 4 patients (3 female, mean age 46 years ±16 years). All patients had painful chronic pancreatitis, with radiological evidence of a dilated pancreatic duct, and main duct stone disease within 2 cm of the ampulla. Surgical options had been considered in all cases. Prior to EHL all patients had undergone pancreatic sphincterotomy and pancreatic duct stenting. Stone fragmentation and duct decompression was achieved in 75% (3/4) of cases. One patient required two EHL procedures to achieve clearance. In the patient with failed clearance, pancreatoscopy revealed that the stone was not in the main duct, but in the adjacent parenchyme. There were no procedure related complications. All patients with successful EHL had pain relief/marked improvement at clinical review (mean follow up - 6.8 ± 5 months). <h3>Conclusion</h3> Pancreatoscopy with EHL may have a valuable role in treating obstructing pancreatic duct stones, possibly avoiding the need for surgery in some patients. However, careful patient selection is mandatory, and more studies are needed to better define treatment approaches. <h3>Disclosure of interest</h3> None Declared.
Intended and unintended consequences: Ethics, communication, and prognostic disclosure in pediatric oncology.
Authors: Jonathan Michael Marron, Tammy I Kang, Angel Cronin, Jennifer W. Mack
Journal: Journal of Clinical Oncology (2015)

10 Background: Most patients wish for all available information about their prognosis, but physicians can be hesitant to discuss prognostic information with patients, particularly those with poor prognoses. For some, concerns that this will cause anxiety, depression, or decreased hope outweigh the ethical obligation to provide such information. Methods: We surveyed 353 parents of children with newly diagnosed cancer at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and the Children’s Hospital of Philadelphia. We used multivariable logistic regression to assess associations between parental report of elements of discussions of prognosis with the child’s oncologist (quality of information, quality of communication, prognostic disclosure) and the intended/unintended outcomes of these discussions (trust, hope, peace of mind, depression, anxiety). Analyses were stratified by the child’s prognosis: favorable ( ≥ 75% likelihood of cure) or less favorable ( &lt; 75% likelihood) as reported by the oncologist. Results: Among parents of children with less favorable prognoses (n = 140), those who reported receiving high quality information from the oncologist expressed greater peace of mind (odds ratio [OR] 4.44, 95% confidence interval [1.53, 12.90], p &lt; 0.01), and those who reported their oncologist to have provided high quality communication endorsed greater trust in the oncologist (OR 3.25 [1.22, 8.70], p = 0.02) and feelings of hope (OR 2.96 [1.24, 7.03], p = 0.01). Parents who received more information about prognosis were not significantly more anxious (p = 0.82), depressed (p = 0.55) or less hopeful (p = 0.86) than those who received less prognostic information. Similar findings were seen in the more favorable prognosis subset and the overall cohort. Conclusions: We find no evidence that greater prognostic disclosure leads to the unintended consequences of increased anxiety, depression, or decreased hope, even in parents of children with less favorable prognoses. Rather, communication processes may increase the intended consequences of peace of mind, trust, and hope, supporting the discussion of prognosis with all parents, even those of children with a lower likelihood of cure.
Fumbled Handoffs
Authors: Darius A. Rastegar
Journal: Annals of Internal Medicine (2005)

Letters4 October 2005Fumbled HandoffsDarius A. Rastegar, MDDarius A. Rastegar, MDFrom Johns Hopkins Bayview Medical Center, Baltimore, MD 21224.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-7-200510040-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Dr. Gandhi (1) documents an example of what appears to be a growing problem: “fumbled handoffs” as patients navigate our increasingly fragmented health care system. The author rightfully notes that “diffused responsibility” is partly to blame and offers some suggestions for remedying this. However, I would submit that there is a simpler, more straightforward solution: to have one person who coordinates care over time and follows the patient in the varied settings where care is provided. This person could see the “big picture” and would be ultimately responsible for ensuring that the patient receives adequate care. Of ...Reference1. Gandhi TK. Fumbled handoffs: one dropped ball after another. Ann Intern Med. 2005;142:352-8. [PMID: 15738454] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Darius A. Rastegar, MDAffiliations: From Johns Hopkins Bayview Medical Center, Baltimore, MD 21224.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoFumbled Handoffs: One Dropped Ball after Another Tejal K. Gandhi Fumbled Handoffs Kenneth M. Kessler Fumbled Handoffs Tejal K. Gandhi Metrics 4 October 2005Volume 143, Issue 7Page: 542KeywordsConflicts of interestHealth carePatientsPrimary care physicians ePublished: 4 October 2005 Issue Published: 4 October 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 3724: Combination of TRAIL and Chal-24 synergistically kills lung cancer cells through autophagy-mediated degradation of IAPs and c-FLIPL
Authors: Jennings Xu, Xiuling Xu, Shaoqing Shi, Qiong Wang, Bryanna Saxton, Chengguo Xing, Yong Lin
Journal: Cancer Research (2016)

Abstract Combination chemotherapy is an effective strategy for increasing anticancer efficacy, reducing side effects and alleviating drug resistance. Here we report that combination of the recently identified novel chalcone derivative, chalcone-24 (Chal-24), and TNF-related apoptosis-inducing ligand (TRAIL) significantly increases cytotoxicity in lung cancer cells. Chal-24 treatment significantly enhanced TRAIL-induced activation of caspase-8 and caspase-3, and the cytotoxicity induced by combination of these agents was effectively suppressed by the pan-caspase inhibitor z-VAD-fmk. Chal-24 and TRAIL combination suppressed expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein large (c-FLIPL) and cellular inhibitor of apoptosis proteins (c-IAPs), and ectopic expression of c-FLIPL and c-IAPs inhibited the potentiated cytotoxicity. In addition, TRAIL and Chal-24 cooperatively activated autophagy. Suppression of autophagy effectively attenuated cytotoxicity induced by the Chal-24 and TRAIL combination, which was associated with attenuation of c-FLIPL and c-IAPs degradation. Altogether, these results suggest that Chal-24 potentiates the anticancer activity of TRAIL through autophagy-mediated degradation of c-FLIPL and c-IAPs, and that combination of Chal-24 and TRAIL could be an effective approach in improving chemotherapy efficacy. Citation Format: Jennings Xu, Xiuling Xu, Shaoqing Shi, Qiong Wang, Bryanna Saxton, Chengguo Xing, Yong Lin. Combination of TRAIL and Chal-24 synergistically kills lung cancer cells through autophagy-mediated degradation of IAPs and c-FLIPL. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3724.
Erlotinib added to bevacizumab as maintenance therapy and health-related quality of life in patients with metastatic colorectal cancer: Results of the GERCOR DREAM phase III trial.
Authors: Amelie Anota, Dewi Vernerey, Christophe Tournigand, Benoist Chibaudel, Benoit Samson, Werner Scheithauer, David Brusquant, Thierry Andre, Aimery De Gramont, Franck Bonnetain
Journal: Journal of Clinical Oncology (2016)

3553 Background: The DREAM phase III clinical trial aimed to assess the efficacy and tolerability of maintenance bevacizumab (B) plus erlotinib (E) after a bevacizumab-based induction therapy in patients with unresectable metastatic colorectal cancer (Tournigand C. et al. Lancet Oncol. 2015). The addition of E to B improved maintenance progression-free survival (PFS) (median B: 4.9months; median B+E: 5.4 months; Hazard Ratio (HR) = 0.78 [0.68-0.96], P = 0.036) and overall survival (OS). This study presents the results of health-related quality of life (HRQoL) data (secondary endpoint). Methods: HRQoL was assed using EuroQoL EQ-5D generic questionnaire before maintenance randomization (T0), at 2 (T1) and 4 months (T2). Analysis of baseline missing data profile was done comparing responders to non responders according to baseline patients’ characteristics and OS. The longitudinal analysis of the visual analogue scale (VAS) of the EQ-5D was done with a linear mixed model (LMM) by including the arm, the time and their interaction. Time to HRQoL deterioration (TTD) was defined as the time from randomization to the first deterioration of 5-point at least of the VAS score as compared to T0. Univariate cox regression analyses were performed to estimate HR of the treatment effect with its 95% confidence interval. Results: Between 2007 and 2011, 700 patients were included. After induction therapy, 452 patients without disease progression were randomized in B arm (N = 228) or B+E arm (N = 224). Among them, 111 patients (24.5%) completed the EQ-5D at T0, 78 (17.3%) at T1 and 54 (11.9%) at T2. Effects introduced in the LMM were not significant: arm effect (coeff = 0.93 (ref = Arm A), P = 0.83), time effect (coeff = 0.25, P = 0.88) and treatment by time interaction (coeff = 1.80, P = 0.42) reflecting a similar HRQoL among arms throughout its measurement. Median of TTD was 4.5 months (2.7-NA) for B vs. 4.1 months (2.3-NA) for B+E (HR = 1.46 [0.67-3.19], P = 0.34). Conclusions: These HRQoL results suggest that the added value of erlotinib to bevacizumab is not associated with a HRQoL deterioration, while it allows to improve maintenance PFS and OS. Clinical trial information: NCT00265824.
Abstract 4373: Structural basis of recognition of farnesylated and methylated KRAS4b by PDEδ
Authors: Sathiya Dharmaiah, Lakshman Bindu, Peter Frank, William Gillette, Dominic Esposito, Dwight Nissley, Frank McCormick, Andrew Stephen, Dhirendra Simanshu
Journal: Cancer Research (2016)

Abstract KRAS is the most frequently mutated member of RAS superfamily in all human cancers. Post-translational farnesylation and methylation of KRAS at its C-terminal end plays an important role in its trafficking to proper subcellular compartments for cell signaling events. PDEδ acts as a chaperone for farnesylated members of the RAS superfamily and plays a key role in their trafficking from the place of biosynthesis or post-translational modification to a transport vesicle or plasma membrane. We solved the structures of wild-type full-length KRAS4b (farnesylated and methylated) in complex with PDEδ in two different crystal forms at 2 Ang resolution. Our structure showed that only the last six amino acids of hypervariable region (and not the G-domain) of KRAS4b interact with PDEδ. Farnesyl and methyl groups present on Cys185 bind tightly in the central hydrophobic pocket present in PDEδ. In crystal form II, we could see all amino acids present in the hypervariable region of KRAS4b, thus providing atomic details of hypervariable region of KRAS4b for the first time. Comparison of the two crystal forms suggests how PDEδ could bind to both farnesylated as well as geranylgeranylated KRAS4b. The structure provides the rationale for nucleotide-independent binding of KRAS4b to PDEδ and its interaction with other farnesylated but not palmitoylated members of RAS superfamily. Citation Format: Sathiya Dharmaiah, Lakshman Bindu, Peter Frank, William Gillette, Dominic Esposito, Dwight Nissley, Frank McCormick, Andrew Stephen, Dhirendra Simanshu. Structural basis of recognition of farnesylated and methylated KRAS4b by PDEδ. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4373.
Abstract 3897: A novel c-Met targeting antibody drug conjugate for NSCLC
Authors: Lingna Li, Cathrine Fells, Julia Guo, Pia Muyot, Edwige Gros, Yanliang Zhang, Yingqing Sun, Hong Zhang, Yanwen Fu, Tong Zhu, Jian Cao, Gunnar Kaufmann, Gang Chen, Zhenwei Miao
Journal: Cancer Research (2016)

Abstract c-Met, the proto-oncogene transmembrane receptor tyrosine kinase, is involved in cell proliferation, survival, motility, and invasion in normal and tumor cells. It is widely expressed and associated with poor prognosis in breast, lung, liver, kidney and brain cancers. Hepatocyte growth factor (HGF) is the only known ligand of c-Met, also found in many tumors and cancers where activity is driven by the c-Met receptor. c-Met is accepted as an attractive anti-cancer target, but the development of cancer therapy targeting c-Met receptor or kinase remain very challenging. Clinical development of c-Met/HGF targeting antibodies has shown initial evidence of clinical efficacy but failed in phase III. Small molecule inhibitors often suffer from selectivity issues. Antibody drug conjugates (ADCs) which combine an antibody with highly potent cytotoxic agents, becomes an attractive approach against c-Met overexpressing cancers such NSCLC. We have identified an anti-c-Met antibody STI-0602 and generated ADCs from a panel of cytotoxic agents such as microtubulin inhibitor and DNA damaging agents. ADCs retained the binding to c-Met receptor and showed potent cell killing in a variety of c-Met-positive cell lines. ADCs also showed in vivo efficacy in a panel of c-Met-positive human NSCLC xenograft models like A549, H292, EBC-1, HCC827 and H1993, which suggest a potential therapy for c-Met overexpressing lung cancer and other cancers. Citation Format: Lingna Li, Cathrine Fells, Julia Guo, Pia Muyot, Edwige Gros, Yanliang Zhang, Yingqing Sun, Hong Zhang, Yanwen Fu, Tong Zhu, Jian Cao, Gunnar Kaufmann, Gang Chen, Zhenwei Miao. A novel c-Met targeting antibody drug conjugate for NSCLC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3897.