tbuckley/cabot-search huggingface dataset:
A phase I study of BIBF 1120, an orally active triple angiokinase inhibitor (VEGFR, PDGFR, FGFR) given continuously to patients with advanced solid tumours, incorporating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)
Authors: C. P. Lee, N. J. Taylor, G. Attard, P. D. Nathan, J. S. De Bono, G. Temple, A. Tang, A. R. Padhani, I. R. Judson, G. J. Rustin
Journal: Journal of Clinical Oncology (2006)

3015 Background: BIBF 1120 is a potent inhibitor of VEGFR, PDGFR, FGFR kinases, and of members of the Src family of tyrosine kinases (Src, Lck, Lyn). Methods: Patients (Pts) with advanced solid tumours were enrolled. BIBF 1120 was administered orally once daily (q.d.) continuously, starting at 100 mg/day. Dosing was later amended to twice daily (b.i.d.) in view of transaminitis seen with q.d. dosing. DCE-MRI studies were performed at baseline, days 2 and 28. All pts underwent pharmacokinetic (PK) sampling. Results: 51 pts (26M/25F; median age 57 y, range 22–78 y; ECOG PS 0/1 = 22/27) were treated at: 100 mg q.d. (n = 6), 200 mg q.d. (n = 6), 300 mg q.d. (n = 7), 400 mg q.d. (n = 16), 450 mg q.d. (n = 5); 250 mg b.i.d. (n = 11). Median treatment duration was 57 days (range: 1 day– 22 m). The most common toxicities were nausea, vomiting, diarrhoea, abdominal pain and fatigue, all ≤ grade (G)2. Asymptomatic, reversible elevation of liver enzymes which was dose limiting in 2/5 pts at 450 mg q.d. defined the MTD at 400 mg q.d. At 250 mg b.i.d., 2/11 pts had DLT (G3 elevation in liver enzymes: n = 1; G3 abdominal pain: n = 1). 44 pts treated for ≥2 m were assessable for response: 13 pts had SD for ≥3 m (median 7m, range 3–22 m; renal, prostate, colorectal, chondrosarcoma, leiomyomatosis, fibromatosis). 3 pts with renal cancer had SD for 8, 14+ and 22 m respectively. PK evaluations generally showed increasing gMean C max and AUC values with increasing doses, with high inter-patient variability. T max was ∼2h post-dosing. gMean t 1/2 values ranged from 6.8–26.4h. DCE-MRI of target lesions in 35 pts showed significant antivascular/antiangiogenic effects in some patients and dose cohorts, particularly at 200 mg q.d. and ≥400 mg q.d. DCE-MRI effects were most pronounced at 28 days, especially in metastatic liver lesions. Conclusions: BIBF 1120 is well-tolerated in patients with advanced solid malignancies and induces in vivo antiangiogenic effects detectable by DCE-MRI. Some patients experienced clinically meaningful disease stabilisation. The recommended dose for future Phase II studies was determined to be 250 mg b.i.d. [Table: see text]
Effectiveness of insertion and maintenance bundles to prevent central-line-associated bloodstream infections in critically ill patients of all ages: a systematic review and meta-analysis
Authors: Erwin Ista, Ben van der Hoven, René F Kornelisse, Cynthia van der Starre, Margreet C Vos, Eric Boersma, Onno K Helder
Journal: The Lancet Infectious Diseases (2016)
Physiologic MRI for assessment of response to therapy and prognosis in glioblastoma
Authors: Mark S. Shiroishi, Jerrold L. Boxerman, Whitney B. Pope
Journal: Neuro-Oncology (2015)

Aside from bidimensional measurements from conventional contrast-enhanced MRI, there are no validated or FDA-qualified imaging biomarkers for high-grade gliomas. However, advanced functional MRI techniques, including perfusion- and diffusion-weighted MRI, have demonstrated much potential for determining prognosis, predicting therapeutic response, and assessing early treatment response. They may also prove useful for differentiating pseudoprogression from true progression after temozolomide chemoradiation and pseudoresponse from true response after anti-angiogenic therapy. This review will highlight recent developments using these techniques and emphasize the need for technical standardization and validation in prospective studies in order for these methods to become incorporated into standard-of-care imaging for brain tumor patients.
Chronic administration of an HDAC inhibitor treats both neurological and systemic Niemann-Pick type C disease in a mouse model
Authors: Md. Suhail Alam, Michelle Getz, Kasturi Haldar
Journal: Science Translational Medicine (2016)

Integrated, long-term HDAC inhibitor therapy treats neurodegeneration and systemic disease in a mouse model of Niemann-Pick type C.
A phase II trial of lapatinib (GW572016) in patients with recurrent prostate cancer as evident by a rising PSA
Authors: Y. Chen, G. Wilding, J. Gee, R. P. DiPaola, M. Pins, M. A. Carducci, M. N. Stein, G. Bubley, G. Liu
Journal: Journal of Clinical Oncology (2008)

5170 Background: Patients (pts) with rising PSA after primary radical prostatectomy/radiation therapy have recurrent prostate cancer (PC). Given the negative effects of castration therapy, most men would prefer to avoid androgen deprivation therapy (ADT) for PSA relapsed disease alone. Activation of epidermal growth factor is important in cancer development and the transcription of androgen receptor regulated genes. Lapatinib is a selective dual tyrosine kinase inhibitor of epidermal growth factor receptor and ErbB2. It is hypothesized that lapatinib will have activity in androgen-dependent PC as evident by changes in PSA kinetics. Methods: Pts with rising PSA after primary therapy for PC were enrolled. A PSA doubling time (PSADT) of < 12 months was required (calculated from a minimum of 3 PSA obtained at least 6 weeks apart, within 6 months of enrollment). No radiographic evidence of metastasis was allowed. Prior (neo)adjuvant ADT was not allowed within 1 year of enrollment. All pts had serum testosterone > 150 ng/dL at baseline. Lapatinib was administered at 1,500 mg orally daily. Endpoints included PSA response (consensus criteria), change in PSA slope/PSADT, and assessment of safety and tolerability in this population. Results: 49 pts were enrolled (10 ineligible), resulting in 39 pts included in the main analysis. No PSA response was observed; however, 31 (79.5%) maintained stable disease for 12 weeks. Pretreatment PSA slope was 0.18 log PSA/mo (median PSADT 4.6 mo), in contrast to the on treatment slope of 0.12 log PSA/mo (median PSADT 7.3 mo); p=0.01. Median duration on study among pts who completed treatment was 5.5 mo (range 0.3 - 13.2 mo). Lapatinib was fairly well tolerated. The most common AEs were grade 1/2 rash (69%) and diarrhea (67%). One grade 3 fatigue was observed and no other grade > 3 AE was reported. Conclusions: Although no PSA responses were observed, lapatinib may have biologic activity in men with androgen-dependent PC as evidenced by a significant decrease in PSA slope in this non-randomized study. Analysis of Her2, EGFR, AKT, and ERK expression by IHC and Her2 amplification by FISH were performed on the primary tumors and will be correlated with individual clinical results. A combination of lapatinib with ADT would be of interest in this patient population. No significant financial relationships to disclose.
Basaloid Adenomas of the Mammary Gland in Beagle Dogs Administered Investigational Contraceptive Steroids23
Authors: R. P. Kwapien, R. C. Giles, R. G. Geil, H. W. Casey
Journal: JNCI Journal of the National Cancer Institute (1977)

A series of 82 basaloid adenomas (BA) occurred in the mammary glands of 29/171 female beagle dogs administered oral contraceptive steroids for 5–7 years. These BA, comprising approximately 10% of the mammary nodules that developed during the study, were observed in 29 of 85 dogs (34%) that developed mammary nodules. The BA generally were less than 1 cm in diameter and usually remained static after an Initial short period of growth. Evidence of metastasis or invasion was not seen. The tumors were well delineated, having expansive, noninfiltrating borders, and were composed of uniform cords and clusters of monomorphic epithelial cells. By light and electron microscopy, the peripheral cells were palisaded and oriented against a thin basal lamina. The centrally located cells were randomly arranged and occasionally showed squamous and glandular differentiation. These tumors resembled the basal cell adenoma described in the human salivary gland as well as the cutaneous basal cell tumor and certain adnexal tumors of man and dog. The BA were seen only in bitches treated with investigational progestins, given either alone or in combination with estrogens. BA were not observed in 18 control beagles or in 30 dogs administered mestranol alone. The Incidence of BA was highest in female dogs administered WY-4355 plus mestranol or anagestone acetate plus mestranol and lower in dogs administered ethynerone plus mestranol or ethynerone alone. To our knowledge, this canine mammary tumor has not been reported previously. The mammary lesions represented a distinct morphologic entity in this series of female beagle dogs and were associated with prolonged administration of certain progestin contraceptives.
Docetaxel - efficacy of this drug in the second line treatment of non-small-cell lung cancer in a regional oncology unit
Authors: A. C. Duarte, P. Costa, S. Barroso
Journal: Journal of Clinical Oncology (2004)

7352 Background: Evaluate the efficacy of docetaxel in previously carboplatin treated patients with advanced nom-small-cell-lung cancer (NSCLC). Methods: 34 patients (pts), 30 male and 4 female, mean ages 63,3 years with advanced lung cancer (locoregional and metastatic) that relapsed or progress after first line treatment with carboplatin regimens (associated with vinorelbin or gemcitabin) were studied. Docetaxel (75 mg/m2) was given every 3 weeks (1 h infusion). All pts received premedication with clemastin and corticosteroids. Results: Complete Response (CR) –2 (5,9%), Partial Response (PR) –15 (44,1%), Stable Disease (SD) –9 (26,5%) and Progression Disease (PD) –8 (23,5%). The mean duration of response was 32 weeks while the median time to progression after docetaxel is 26 weeks. The mean overall survival was 36 weeks and 1-year survival –11 (32%). A total of 159 cycles was administrated with a median of 4,6 cycles/pts. The major complication was neutropenia grade 3 in 14 pts (41,1%), neutropenic fever in 2 pts (5,8%), grade 2 peripheral neuropathy in 7 pts (20,5%) and alopecia in all patients. Conclusions: Docetaxel is a good single agent for second line treatment of relapsed or progressed NSCLC after the first line chemotherapy. No significant financial relationships to disclose.
Antibacterial Surfaces: A Smart Antibacterial Surface for the On‐Demand Killing and Releasing of Bacteria (Adv. Healthcare Mater. 4/2016)
Authors: Ting Wei, Qian Yu, Wenjun Zhan, Hong Chen
Journal: Advanced Healthcare Materials (2016)

On page 449, Q. Yu, H. Chen, and co-workers show how they developed a smart antibacterial surface with on-demand switchable functionalities by exploring the synergistic effects of combining stimuli-responsive polymers and nanomaterials with unique topographies. This platform serves as both a dynamic reservoir for the loading and release of antimicrobials and a self-cleaning platform for the release of dead bacteria and the re-loading of new antimicrobials for repeatable applications.
Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY‐3+)
Authors: Vincent Leroy, Peter Angus, Jean‐Pierre Bronowicki, Gregory J. Dore, Christophe Hezode, Stephen Pianko, Stanislas Pol, Katherine Stuart, Edmund Tse, Fiona McPhee, Rafia Bhore, Maria Jesus Jimenez‐Exposito, Alexander J. Thompson
Journal: Hepatology (2016)

Patients with hepatitis C virus (HCV) genotype 3 infection, especially those with advanced liver disease, are a challenging population in urgent need of optimally effective therapies. The combination of daclatasvir (DCV; pangenotypic nonstructural protein 5A inhibitor) and sofosbuvir (SOF; nucleotide nonstructural protein 5B inhibitor) for 12 weeks previously showed high efficacy (96%) in noncirrhotic genotype 3 infection. The phase III ALLY-3+ study (N = 50) evaluated DCV-SOF with ribavirin (RBV) in treatment-naïve (n = 13) or treatment-experienced (n = 37) genotype 3-infected patients with advanced fibrosis (n = 14) or compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive open-label DCV-SOF (60 + 400 mg daily) with weight-based RBV for 12 or 16 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). SVR12 (intention-to-treat) was 90% overall (45 of 50): 88% (21 of 24) in the 12-week (91% observed) and 92% (24 of 26) in the 16-week group. All patients with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% overall (31 of 36): 83% (15 of 18) in the 12-week (88% observed) and 89% (16 of 18) in the 16-week group; for treatment-experienced patients with cirrhosis, these values were 87% (26 of 30), 88% (14 of 16; 93% observed), and 86% (12 of 14), respectively. One patient (12-week group) did not enter post-treatment follow-up (death unrelated to treatment). There were 4 relapses (2 per group) and no virological breakthroughs. The most common adverse events (AEs) were insomnia, fatigue, and headache. There were no discontinuations for AEs and no treatment-related serious AEs.The all-oral regimen of DCV-SOF-RBV was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of treatment among genotype 3-infected patients with advanced liver disease, irrespective of past HCV treatment experience.
Reply to T.J. Kruser et al
Authors: Olivier L. Chinot, Martin J.B. Taphoorn, Carlos Bais, Richard Bourgon, Heidi S. Phillips, Lauren E. Abrey, Wolfgang Wick, Warren Mason, Roger Henriksson, Frank Saran, Ryo Nishikawa, Timothy Cloughesy
Journal: Journal of Clinical Oncology (2016)

Identification of Patients Who Benefit From Bevacizumab in High-Grade Glioma-An Easy Question Turned Difficult : Treat the Scan or the Patient? Reply
Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain
Authors: Xiaowei Li, Stephany Y. Tzeng, Xiaoyan Liu, Markus Tammia, Yu-Hao Cheng, Andrew Rolfe, Dong Sun, Ning Zhang, Jordan J. Green, Xuejun Wen, Hai-Quan Mao
Journal: Biomaterials (2016)
Neurally Adjusted Ventilatory Assist (NAVA) improves the matching of diaphragmatic electrical activity and tidal volume in comparison to pressure support (PS)
Authors: L Piquilloud, YS Chiew, E Bialais, Bernard Lambermont, J Roeseler, JG Chase, Thomas Desaive, T Sottiaux, D Tassaux, P Jolliet, JP Revelly
Journal: Intensive Care Medicine (2011)
Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component
Authors: Duncan B. Richards, Louise M. Cookson, Alienor C. Berges, Sharon V. Barton, Thirusha Lane, James M. Ritter, Marianna Fontana, James C. Moon, Massimo Pinzani, Julian D. Gillmore, Philip N. Hawkins, Mark B. Pepys
Journal: New England Journal of Medicine (2015)

The amyloid fibril deposits that cause systemic amyloidosis always contain the nonfibrillar normal plasma protein, serum amyloid P component (SAP). The drug (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC) efficiently depletes SAP from the plasma but leaves some SAP in amyloid deposits that can be specifically targeted by therapeutic IgG anti-SAP antibodies. In murine amyloid A type amyloidosis, the binding of these antibodies to the residual SAP in amyloid deposits activates complement and triggers the rapid clearance of amyloid by macrophage-derived multinucleated giant cells.We conducted an open-label, single-dose-escalation, phase 1 trial involving 15 patients with systemic amyloidosis. After first using CPHPC to deplete circulating SAP, we infused a fully humanized monoclonal IgG1 anti-SAP antibody. Patients with clinical evidence of cardiac involvement were not included for safety reasons. Organ function, inflammatory markers, and amyloid load were monitored.There were no serious adverse events. Infusion reactions occurred in some of the initial recipients of larger doses of antibody; reactions were reduced by slowing the infusion rate for later patients. At 6 weeks, patients who had received a sufficient dose of antibody in relation to their amyloid load had decreased liver stiffness, as measured with the use of transient elastography. These patients also had improvements in liver function in association with a substantial reduction in hepatic amyloid load, as shown by means of SAP scintigraphy and measurement of extracellular volume by magnetic resonance imaging. A reduction in kidney amyloid load and shrinkage of an amyloid-laden lymph node were also observed.Treatment with CPHPC followed by an anti-SAP antibody safely triggered clearance of amyloid deposits from the liver and some other tissues. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT01777243.).
Trends in hospital admission rates for anorexia nervosa in Oxford (1968–2011) and England (1990–2011): database studies
Authors: Josephine Holland, Nick Hall, David GR Yeates, Michael Goldacre
Journal: Journal of the Royal Society of Medicine (2015)

Objectives To report on long-term trends in hospital admission rates for anorexia nervosa using two English datasets. Design We used data on hospital day-case and inpatient care across five decades in the Oxford Record Linkage Study (ORLS), and similar data for all England from 1990. We analysed rates of admission for anorexia nervosa in people aged 10–44 years, using hospital episodes (counting every admission) and first-recorded admissions (counting only the first record for each person). Setting Former Oxford NHS Region; and England. Participants None; anonymous statistical records were used. Results In the longstanding ORLS, the age-standardised first-recorded admission rate for women was 2.7 (95% confidence interval 1.6–3.8) per 100,000 female population aged 10–44 years in 1968–1971; 2.7 (2.1–3.3) in 1992–1996; and 6.3 (5.5–7.2) in 2007–2011. Male rates were zero in the 1960s; 0.07 (0.0–0.1) per 100,000 men in 1992–1996; and 0.4 (0.2–0.6) in 2007–2011. In England, female rates increased from 4.2 (4.0–4.4) in 1998–2001 to 6.9 (6.7–7.1) in 2007–2011; and the corresponding male rates were 0.2 (0.1–0.3) and 0.5 (0.4–0.6). Episode-based admission rates rose more than person-based rates. The highest rates by far were in girls and women aged 15–19 years. Conclusions In recent years, anorexia nervosa has become a greater burden on secondary care: not only have admission rates increased but so too have multiple admissions per person with anorexia nervosa. The increase in admission rates might reflect an increase in prevalence rates of anorexia nervosa in the general population, but other explanations, including lower clinical thresholds for admission, are possible and are discussed.
The relationship between service quality measures and patient willingness to recommend at a national oncology provider network: The Cancer Treatment Centers of America experience.
Authors: D. Gupta, M. Rodeghier, J. F. Grutsch, A. Roberts, C. G. Lis
Journal: Journal of Clinical Oncology (2010)

6097 Background: While “willingness to recommend” questions are being increasingly used to measure and manage patient loyalty, there is little data in the literature correlating factors to the top box scores. We evaluated the relationship between commonly used service quality measures and subsequent single top box “willingness to recommend” among oncology patients. Methods: 2,018 returning cancer patients treated at Cancer Treatment Centers of America responded to an internally developed service quality questionnaire, covering the following dimensions: operations and services, physicians and staff, and patient endorsements. Items were measured on a 7-point Likert scale ranging from “completely dissatisfied” to “completely satisfied.” Patient willingness to recommend, “will you recommend this facility to friends and associates?” was measured on an 11-point scale ranging from “not at all likely” to “extremely likely” and was dichotomized into 2 categories: top box response (10) versus all others (0-9). The relationship between service quality and “willingness to recommend” was assessed via Spearman's rho correlation. Results: 959 patients were newly diagnosed while 1059 were previously treated. 902 were males and 1116 females. Mean age was 54.7 years and the most frequent diagnoses were breast (412), lung (294), prostate (260), colorectal (179) and pancreas (169). Items showing the strongest relationship with “willingness to recommend” related to the physicians and staff dimension, including hospital providing you with a sense of well-being (rho = 0.45, p < 0.001), team explaining your treatment options (rho = 0.42, p = < 0.001), team helping you understanding your medical condition (rho = 0.42, p = < 0.001), amount of time team spent with you (rho = 0.40, p = < 0.001), and team involving you in decision making (rho = 0.40, p = < 0.001). There was no loss of statistical strength after controlling for age, gender and treatment history. Conclusions: In this multicenter study, we identified the key service quality drivers of patient loyalty as defined by the “willingness to recommend” question described herein. No significant financial relationships to disclose.
Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis after hematopoietic stem-cell transplantation.
Authors: B Gordon, A Spadinger, E Hodges, E Ruby, R Stanley, P Coccia
Journal: Journal of Clinical Oncology (1994)

Oral mucositis following high-dose chemotherapy may result in systemic infection and airway compromise, and the severity of oral mucositis may be dose-limiting. Here we investigate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), which significantly shortens duration of neutropenia after hematopoietic stem-cell transplantation (HSCT) on oral mucositis.Thirteen children undergoing HSCT were prepared with etoposide (VP-16), thiotepa (TT), and total-body irradiation (TBI), and 13 with VP-16, TT, and cyclophosphamide (CPM). Following transplantation, 14 patients received GM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion (six prepared with VP-16, TT, and TBI, and eight prepared with VP-16, TT, and CPM), and 12 patients received no growth factor.Mucositis was more severe and persisted longer in patients prepared with the TBI-containing regimen. For this regimen, the duration of severe oral mucositis was shortened by the administration of GM-CSF, although the severity of mucositis was unaffected. No statistically significant effect of GM-CSF could be shown in patients who received VP-16, TT, and CPM. The incidence of positive fungal oral or blood cultures did not appear different whether patients received GM-CSF or not.For patients undergoing stomatotoxic HSCT regimens, GM-CSF may reduce the duration of oral mucositis, but is unlikely to effect the severity of oral mucositis or risk of airway compromise, and the severity of mucositis is likely to remain dose-limiting.