tbuckley/cabot-search huggingface dataset:
Implementation of the Ottawa Knee Rule for the use of radiography in acute knee injuries
Authors: I. G. Stiell
Journal: JAMA (1997)

Context.\p=m-\TheOttawa Knee Rule is a previously validated clinical decision rule that was developed to allow physicians to be more selective and efficient in their use of plain radiography for patients with acute knee injuries. Objective.\p=m-\Toassess the impact on clinical practice of implementing the Ottawa Knee Rule. Design.\p=m-\Controlled clinical trial with before-after and concurrent controls. Setting.\p=m-\Emergencydepartments of 2 teaching and 2 community hospitals. Patients.\p=m-\All3907 consecutive eligible adults seen with acute knee injuries during two 12-month periods before and after the intervention. Intervention.\p=m-\Duringthe after period in the 2 intervention hospitals, the Ottawa Knee Rule was taught to all house staff and attending physicians who were encouraged to order knee radiography according to the rule. Main Outcome Measures.\p=m-\Referralfor knee radiography, accuracy and reliability of the rule, mean time in emergency department, and mean charges. Results.\p=m-\Therewas a relative reduction of 26.4% in the proportion of patients referred for knee radiography in the intervention group (77.6% vs 57.1%; P<.001), but a relative reduction of only 1.3% in the control group (76.9% vs 75.9%; P=.60). These changes over time were significant when the intervention and control groups were compared (P<.001). The rule was found to have a sensitivity of 1.0 (95% confidence interval [Cl], 0.94-1.0) for detecting 58 knee fractures. The \g=k\coefficient for interpretation of the rule was 0.91 (95% Cl, 0.82-1.0). Compared with nonfracture patients who underwent radiography during the after-intervention period, those discharged without radiography spent less time in the emergency department (85.7 minutes vs 118.8 minutes) and incurred lower estimated total medical charges for physician visits and radiography (US $80 vs US $183). Conclusions.\p=m-\Implementationof the Ottawa Knee Rule led to a decrease in use of knee radiography without patient dissatisfaction or missed fractures and was associated with reduced waiting times and costs. Widespread use of the rule could lead to important health care savings without jeopardizing patient care. JAMA. 1997;278:2075-2079
A Novel Multi-Gene Array Allows Relapse Risk Stratification in Acute Myeloid Leukemia Patients Undergoing Stem Cell Transplantation
Authors: Meghali Goswami, Katherine S. McGowan, Kit Lu, Natasha A Jain, Julián Candia, Nancy F. Hensel, Jingrong Tang, Katherine R. Calvo, Minoo Battiwalla, Austin John Barrett, Christopher S. Hourigan
Journal: Blood (2014)
AGMT MALT-2: A Phase II Study of Rituximab Plus Lenalidomide in Patients with Extranodal Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT lymphoma)
Authors: Barbara Kiesewetter, Richard Greil, Wolfgang Willenbacher, Peter Neumeister, Michael A. Fridrik, Raderer Markus
Journal: Blood (2015)
Recommendations for Conduct, Methodological Practices, and Reporting of Cost-effectiveness Analyses
Authors: Gillian D. Sanders, Peter J. Neumann, Anirban Basu, Dan W. Brock, David Feeny, Murray Krahn, Karen M. Kuntz, David O. Meltzer, Douglas K. Owens, Lisa A. Prosser, Joshua A. Salomon, Mark J. Sculpher, Thomas A. Trikalinos, Louise B. Russell, Joanna E. Siegel, Theodore G. Ganiats
Journal: JAMA (2016)

<h3>Importance</h3> Since publication of the report by the Panel on Cost-Effectiveness in Health and Medicine in 1996, researchers have advanced the methods of cost-effectiveness analysis, and policy makers have experimented with its application. The need to deliver health care efficiently and the importance of using analytic techniques to understand the clinical and economic consequences of strategies to improve health have increased in recent years. <h3>Objective</h3> To review the state of the field and provide recommendations to improve the quality of cost-effectiveness analyses. The intended audiences include researchers, government policy makers, public health officials, health care administrators, payers, businesses, clinicians, patients, and consumers. <h3>Design</h3> In 2012, the Second Panel on Cost-Effectiveness in Health and Medicine was formed and included 2 co-chairs, 13 members, and 3 additional members of a leadership group. These members were selected on the basis of their experience in the field to provide broad expertise in the design, conduct, and use of cost-effectiveness analyses. Over the next 3.5 years, the panel developed recommendations by consensus. These recommendations were then reviewed by invited external reviewers and through a public posting process. <h3>Findings</h3> The concept of a "reference case" and a set of standard methodological practices that all cost-effectiveness analyses should follow to improve quality and comparability are recommended. All cost-effectiveness analyses should report 2 reference case analyses: one based on a health care sector perspective and another based on a societal perspective. The use of an "impact inventory," which is a structured table that contains consequences (both inside and outside the formal health care sector), intended to clarify the scope and boundaries of the 2 reference case analyses is also recommended. This special communication reviews these recommendations and others concerning the estimation of the consequences of interventions, the valuation of health outcomes, and the reporting of cost-effectiveness analyses. <h3>Conclusions and Relevance</h3> The Second Panel reviewed the current status of the field of cost-effectiveness analysis and developed a new set of recommendations. Major changes include the recommendation to perform analyses from 2 reference case perspectives and to provide an impact inventory to clarify included consequences.
Abstract 690: Characterization of serine/threonine phosphatase LAPP1 as a diagnostic and therapeutic target for lung cancer
Authors: Yataro Daigo, Atsushi Takano, Yusuke Nakamura
Journal: Cancer Research (2015)

Abstract Lung cancer is the leading cause of cancer deaths worldwide. Since the number of patients responding well to current standard therapies is still small, further development of new anti-cancer drugs with minimum risk of adverse event is urgently awaited. To screen oncoantigens which could be used for the development of new diagnostic biomarkers and molecular targeted drugs, we have established a screening system as follows; i) To identify overexpressed genes in 120 lung cancers by genome-wide screening using the microarray representing 27,648 genes and pure populations of tumor cells taken from cancer tissues by laser microdissection, ii) To verify the candidate genes for their very low or absent expression in normal tissues by northern-blotting, iii) To validate the clinicopathological significance of their expression with tissue microarray covering hundreds of archived lung cancers, iv) To verify whether the target genes are essential for the growth or survival of cancer cells by RNAi and cell growth assays. During this process, we selected dozens of druggable oncoproteins with various enzymatic activities, and identified overexpression of Serine/Threonine phosphatase LAPP1 (lung cancer-associated protein phosphatase 1) in the majority of lung cancers and its scarce expression in normal tissues except testis. Strong LAPP1 expression was an independent prognostic factor for lung cancer patients who underwent curative surgery (P&amp;lt;0.0001). We identified EF-1δ (a cadmium-responsive proto-oncogene) as a LAPP1-interacting protein that was also over-expressed in cancer cells. Knock-down of LAPP1 or EF-1δ expression by siRNAs inhibited cell growth, whereas exogenous expression of LAPP1 in EF-1δ(+) cells enhanced the dephosphorylation of EF-1δ(+), and subsequent increase in the levels of active phospho-AKT. Inhibition of interaction between LAPP1 and EF-1δ by a cell-permeable peptide corresponding to a leucine zipper motif in EF-1δ, resulted in the destabilization of EF-1δ and inhibited cancer cell growth and invasion. LAPP1 is likely to be a prognostic biomarker and a potential therapeutic target for lung cancer. Citation Format: Yataro Daigo, Atsushi Takano, Yusuke Nakamura. Characterization of serine/threonine phosphatase LAPP1 as a diagnostic and therapeutic target for lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 690. doi:10.1158/1538-7445.AM2015-690
P1-095: Evaluation of FDG-PET/CT for lung cancer and lymph nodes metastasis
Authors: Hiroaki Toba, Kazuya Kondo, Taeko Nagao, Mituteru Yoshida, Kouichiro Kenzaki, Takanori Miyoshi, Shouji Sakiyama, Akira Tangoku
Journal: Journal of Thoracic Oncology (2007)
Blockade of β-catenin signaling attenuates toluene diisocyanate-induced experimental asthma
Authors: L. Yao, H. Zhao, H. Tang, J. Xiong, W. Zhao, L. Liu, H. Dong, F. Zou, S. Cai
Journal: Allergy (2016)

Aberrant activation of β-catenin signaling by both WNT-dependent and WNT-independent pathways has been demonstrated in asthmatic airways, which is thought to contribute critically in remodeling of the airways. Yet, the exact role of β-catenin in asthma is very poorly defined. As we have previously reported abnormal expression of β-catenin in a toluene diisocyanate (TDI)-induced asthma model, in this study, we evaluated the therapeutic efficacy of two small molecules XAV-939 and ICG-001 in TDI-asthmatic male BALB/c mice, which selectively block β-catenin-mediated transcription.Male BALB/c mice were sensitized and challenged with TDI to generate a chemically induced asthma model. Inhibitors of β-catenin, XAV-939, and ICG-001 were respectively given to the mice through intraperitoneally injection.TDI exposure led to a significantly increased activity of β-catenin, which was then confirmed by a luciferase assay in 16HBE transfected with the TOPFlash reporter plasmid. Treatment with either XAV-939 or ICG-001 effectively inhibited activation of β-catenin and downregulated mRNA expression of β-catenin-targeted genes in TDI-asthmatic mice, paralleled by dramatically attenuated TDI-induced hyperresponsiveness and inflammation of the airway, alleviated airway goblet cell metaplasia and collagen deposition, decreased Th2 inflammation, as well as lower levels of TGFβ1, VEGF, HMGB1, and IL-1β.The results showed that β-catenin is a principal mediator of TDI-induced asthma, proposing β-catenin as a promising therapeutic target in asthma.
Regorafenib in previously treated metastatic colorectal cancer (mCRC): Analysis of age subgroups in the open-label phase IIIb CONSIGN trial.
Authors: Eric Van Cutsem, Fortunato Ciardiello, Marc Ychou, Jean Francois Seitz, Ralf Hofheinz, Yull Edwin Arriaga, Udit Verma, Rocio Garcia-Carbonero, Axel Grothey, Ashok Miriyala, Joachim Kalmus, Christian Kappeler, Alfredo Falcone, Alberto Zaniboni
Journal: Journal of Clinical Oncology (2016)

3524 Background: In the phase 3 CORRECT trial, regorafenib improved survival vs placebo in treatment-refractory mCRC. The large, single-arm, phase 3b CONSIGN trial (NCT01538680) was designed to provide continued access to regorafenib for patients with mCRC and to further characterize regorafenib safety. In CONSIGN, adverse events (AEs) and progression-free survival (PFS) were consistent with results reported in phase 3 trials. We performed a subgroup analysis of CONSIGN to assess outcomes by age. Methods: Patients with mCRC who progressed after standard therapies and had ECOG PS 0-1 received regorafenib 160 mg daily for the first 3 weeks of each 4-week cycle until disease progression, death, or unacceptable toxicity. The primary endpoint was safety. PFS, assessed per investigator, was the only efficacy measure collected. Results: A total of 2872 patients were assigned to treatment (<65: n=1720; ≥65: n=1152); n=1713 and n=1151, respectively, were evaluable for safety. ECOG PS 0/1 were 49%/51% (<65) and 44%/55% (≥65). The median (range) treatment duration was 2.5 months (0.03–30.4) and 2.3 months (0.03–28.5) in patients <65 and ≥65, respectively; mean (SD) percent of planned dose was 76% (20) and 74% (20), respectively. Most patients experienced a regorafenib-related AE (<65: 91%; ≥65: 92%; Table). AEs led to treatment discontinuation in 25% (<65) and 26% (≥65) of patients. Treatment-emergent NCI-CTCAE v4.0 hepatic grade ≥3 laboratory toxicities (<65; ≥65) included increased bilirubin (14%; 12%), increased AST (8%; 5%), and increased ALT (7%; 4%). Estimated median PFS (95% CI) in the <65 group was 2.7 months (2.6, 2.8) and in the ≥65 group was 2.6 months (2.5, 2.7). Conclusions: The safety profile of regorafenib was generally comparable in patients <65 and ≥65 years of age. PFS was similar across age subgroups. Clinical trial information: NCT01538680.Drug-related AEs, n (%) <65 years (n=1713) ≥65 years (n=1151) Grade ≥3* 939 (55) 690 (60) Hypertension 232 (14) 203 (18) HFSR 274 (16) 122 (11) Fatigue 180 (11) 196 (17) Diarrhea 78 (5) 57 (5) Hypophosphatemia 89 (5) 60 (5) Grade 5 8 (0.5) 5 (0.4) Serious 151 (9) 100 (9) *Occurring in ≥5% of patients overall; graded by NCI-CTCAE v4.0.
Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice
Authors: Qian Ba, Mian Li, Peizhan Chen, Chao Huang, Xiaohua Duan, Lijun Lu, Jingquan Li, Ruiai Chu, Dong Xie, Haiyun Song, Yongning Wu, Hao Ying, Xudong Jia, Hui Wang
Journal: Environmental Health Perspectives (2016)

Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear.
Striking dyserythropoiesis in a myelodysplastic syndrome
Authors: Wenchee Siow, Philippa C. May, Ruby Haji, Ian Gabriel, Barbara J. Bain
Journal: American Journal of Hematology (2016)

A bone marrow aspirate was hypercellular. Erythropoiesis was markedly increased at 79% and myelopoiesis was markedly reduced. Myeloblasts were not significantly increased at 3%. There was gross dyserythropoiesis with multinucleated and giant erythroblasts being prominent (Images); there were up to five nuclei per erythroblast and nuclei of a single cell sometimes differed in size and chromatin structure. Other erythroid abnormalities included nuclear fragmentation, internuclear bridges, prominent nucleoli (center Image), cytoplasmic vacuolation (center Image), and basophilic stippling. Most erythroblasts were normoblastic with a minority being megaloblastic. Some of the erythroblasts were reminiscent of those in congenital dyserythropoietic anemia but the presence of neutrophil dysplasia pointed to a diagnosis of myelodysplastic syndrome. The suspicion of a hematological neoplasm was confirmed by cytogenetic analysis. This revealed a complex male karyotype in seven of the ten metaphases analyzed. A single near diploid cell showed monosomy 5 and 12, additional material replacing the short arm of chromosome 21 and a marker chromosome of unknown origin. The remaining six abnormal cells showed a hypotetraploid karyotype. The abnormalities appeared to have arisen from a genome doubling event affecting an abnormal clone represented by the single near-diploid cell, with subsequent loss of chromosome 8, 9, 11, 14, 15, and 18. The abnormalities were variable between cells. The composite karyotype was 45,XY,−5,−12,add(21)(p10),+mar[1]/69∼73<4n>,X,−X,Y,−Y,−3,−3,−5,−5,−7,−7,−8,−9,−11,−12,−12,−15,−16,−16,−17,−17,−18,add(21)(p10),+add(21)(p10),+1∼2mar[cp6]/46XY[3]. The final diagnosis was refractory anemia with multilineage dysplasia (myelodysplastic syndrome with multilineage dysplasia in the 2016 revision of the WHO classification).
Feedback Activation of Leukemia Inhibitory Factor Receptor Limits Response to Histone Deacetylase Inhibitors in Breast Cancer
Authors: Hanlin Zeng, Jia Qu, Nan Jin, Jun Xu, Chenchu Lin, Yi Chen, Xinying Yang, Xiang He, Shuai Tang, Xiaojing Lan, Xiaotong Yang, Ziqi Chen, Min Huang, Jian Ding, Meiyu Geng
Journal: Cancer Cell (2016)
P1-243: Effectiveness of epoetin beta 30,000 IU once Weekly (QW) for treatment of chemotherapy-induced anemia in lung cancer (LC)
Authors: Kader Chouahnia, Dominique Spaeth, Elisabeth Quoix, Jean-Pierre Kleisbauer, François-Xavier Lebas, Pierre-Jean Souquet, Gaêl Deplanque, Arash Jenabian, Gaetan Des Guetz, Jean-François Morère
Journal: Journal of Thoracic Oncology (2007)
Fifteen‐year trends in the management of cardiogenic shock and associated 1‐year mortality in elderly patients with acute myocardial infarction: the FAST‐MI programme
Authors: Nadia Aissaoui, Etienne Puymirat, Yves Juilliere, Patrick Jourdain, Didier Blanchard, François Schiele, Pascal Guéret, Batric Popovic, Jean Ferrieres, Tabassome Simon, Nicolas Danchin
Journal: European Journal of Heart Failure (2016)
Encephalomyelitis Associated With Dengue Fever
Authors: Yara Dadalti Fragoso, Joseph Bruno Bidin Brooks
Journal: JAMA Neurology (2016)

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Bilateral Oophorectomy and Breast Cancer Risk in<i>BRCA1</i>and<i>BRCA2</i>Mutation Carriers
Authors: Joanne Kotsopoulos, Tomasz Huzarski, Jacek Gronwald, Christian F Singer, Pal Moller, Henry T Lynch, Susan Armel, Beth Karlan, William D Foulkes, Susan L Neuhausen, Leigha Senter, Nadine Tung, Jeffrey N Weitzel, Andrea Eisen, Kelly Metcalfe, Charis Eng, Tuya Pal, Gareth Evans, Ping Sun, Jan Lubinski, Steven A Narod
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers. Methods: Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided. Results: Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = .76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = .14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = .007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = .51). Conclusions: Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.
Commentary on “Recombinant Humanized Anti-HER2 Antibody (Herceptin) Enhances the Antitumor Activity of Paclitaxel and Doxorubicin against HER2/<i>neu</i> Overexpressing Human Breast Cancer Xenografts” (A Follow Up)
Authors: John Mendelsohn
Journal: Cancer Research (2016)

Visit the Cancer Research 75th Anniversary [timeline][1].

See related article by Baselga et al., [Cancer Res 1998;58:2825–31][2] .

It is an honor to have our publication reporting on combined therapy with a targeted antibody plus chemotherapy selected as a classic article from Cancer Research .
Preliminary activity and safety results from a phase I clinical trial of PF-00299804, an irreversible pan-HER inhibitor, in patients (pts) with NSCLC
Authors: P. A. Janne, J. H. Schellens, J. A. Engelman, S. G. Eckhardt, R. Millham, L. J. Denis, C. D. Britten, S. G. Wong, D. S. Boss, D. R. Camidge
Journal: Journal of Clinical Oncology (2008)

8027 Background: PF-00299804 (PF) is an orally bioavailable, potent, irreversible small molecule inhibitor of HER1, HER2, and HER4. HER1 overexpression/aberrant function is widely observed in NSCLC and HER1 mutations are implicated in mechanisms of tumorigenesis and are associated with sensitivity to EGFR inhibitors gefitinib (G) and erlotinib (E). Results in pts with refractory NSCLC enriched for HER gene amplification, HER1/HER2 mutation, or wild type (WT) KRAS, within the phase I study are reported. Methods: NSCLC pts (n=42) received PF 16 mg (n=1), 30 mg (n=2), 45 mg, the MTD (n=33) or 60 mg (n=6) QD either continuously or for 2 weeks of a 3- week cycle. NSCLC pts were included in both the dose-escalation phase and at MTD, when additional NSCLC pts with HER1 mutant or KRAS WT tumors were recruited. Results: 44 pts with NSCLC have been enrolled to date (29 evaluable for response). Baseline characteristics were: median age 57 yrs (range 26–77), prior EGFR inhibitors 94% (E n=21, G n=6, E + G n=3; cetuximab n=1), prior chemotherapy 79% (median no. of regimens 2; range 0–6), never smokers (48%), ex-smokers (45%) and current smokers (6%). Mutational status was known in part for 30 pts: HER1 mutant/WT: 23/7; KRAS WT/unknown: 17/13. The median duration of therapy was 2 mths (range 1- 6).23 pts received PF 45 mg QD for which the safety profile is as follows: G3: fatigue, DVT, nausea, acne, hypokalemia, diarrhea, hypoxia, and decreased appetite; G4: dyspnea, pulmonary embolism, and pain. The most frequently reported AEs (any grade) were diarrhea (78%) and rash (65%). Among 29 pts evaluable for tumor response, 2 PRs (RECIST) were noted and an additional 8 pts reported SD (clinical benefit rate 34%). Of the 2 PRs, one pt received PF 16 mg QD escalated to 30 mg QD and had previously received 6 lines of chemotherapy and G (6 months); the second received PF 45 mg QD, had previously received 3 lines of chemotherapy and E (4 months), and had a EGFR exon 20 insertion (D770delinsGI) mutation. Both PRs were durable (>200 days). Conclusions: PF-00299804 45 mg QD is well tolerated. Encouraging activity was seen in heavily pre-treated NSCLC pts, including 2 PRs after failure of prior treatment with reversible EGFR inhibitors. Phase II studies in refractory NSCLC pts are underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer AstraZeneca, Boehringer Ingelheim, Pfizer, Roche Pfizer GlaxoSmithKline Pfizer Genzyme
Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B
Authors: Ching-Lung Lai, Danny Wong, Philip Ip, Malgorzata Kopaniszen, Wai-Kay Seto, James Fung, Fung-Yu Huang, Brian Lee, Giuseppe Cullaro, Chun Kong Chong, Ringo Wu, Charles Cheng, John Yuen, Vincent Ngai, Man-Fung Yuen
Journal: Journal of Hepatology (2016)