tbuckley/cabot-search huggingface dataset:
Mutational activation of the N-ras oncogene assessed in primary clonogenic culture of acute myeloid leukemia (AML): implications for the role of N-ras mutation in AML pathogenesis
Authors: A Bashey, R Gill, S Levi, CJ Farr, R Clutterbuck, JL Millar, IB Pragnell, CJ Marshall
Journal: Blood (1992)
Conservation of Epithelial Cell Phenotypes During Hematogenous Metastasis From Mammary Carcinomas&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: D Glaves, D A Ketch, B B Asch
Journal: JNCI Journal of the National Cancer Institute (1986)

The phenotypic heterogeneity of epithelial cells during hematogenous metastasis from primary mammary carcinomas of BALB/cfC3H mice was examined. Antisera to keratins were used in immunofluorescence assays to identify epithelial and myoepithelial cells. Both cell types were located in frozen sections of not only the primary lesions but also pulmonary metastases. Tumor cells disseminating to the lungs were recovered from the bloodstream of tumor-bearing mice with the use of a quantitative density gradient centrifugation procedure. Carcinoma cells were detected in the circulation of 62% of mice at the time of assay, but all tumors examined had released cells into the circulation at some point in their history. Epithelial cells and myoepithelial cells were detected simultaneously in 21% of mice, whereas other mice had only epithelial cells (16%) or myoepithelial cells (25%) in their circulation at the time of assay. Single cells and multicellular emboli of each cell type were disseminated, together with similar numbers of heterogeneous emboli containing both epithelial and myoepithelial cells. The evidence shows that the presence of both mammary epithelial and myoepithelial cells in pulmonary metastases from mouse mammary carcinomas can be accounted for by their hematogenous delivery as differentiated cells.
Mediating pathways from central obesity to childhood asthma: a population-based longitudinal study
Authors: An-Hsuan Chih, Yang-Ching Chen, Yu-Kang Tu, Kuo-Chin Huang, Tai-Yuan Chiu, Yungling Leo Lee
Journal: European Respiratory Journal (2016)

The mediating pathways linking obesity and asthma are largely unknown. We aimed to investigate the mediating pathways and to search for the most prominent pathological mechanism between central obesity and childhood asthma. In the Taiwan Children Health Study, we collected data on an open cohort of children aged 9–13 years. Children's respiratory outcomes, atopic conditions, obesity measures and pulmonary function were surveyed annually between 2010 and 2012. Exhaled nitric oxide fraction concentrations were recorded in 2012. Generalised estimating equations and general linear models were used to examine the associations between central obesity, possible mediators and asthma. Structural equation models were applied to investigate the pathways that mediate the link between central obesity and asthma. Central obesity (waist-to-hip ratio) most accurately predicted childhood asthma. In the active asthma model, the percentage of mediation was 28.6% for pulmonary function, 18.1% for atopy and 5.7% for airway inflammation. The percentage of mediation for pulmonary function was 40.2% in the lifetime wheeze model. Pulmonary function was responsible for the greatest percentage of mediation among the three mediators in both models. Decline in pulmonary function is the most important pathway in central obesity related asthma. Pulmonary function screening should be applied to obese children for asthma risk prediction.
Abstract 13046: Treat and Repair Strategy in Patients With Atrial Septal Defect and Severe Pulmonary Arterial Hypertension
Authors: Teiji Akagi, Yasuhumi Kijima
Journal: Circulation (2015)

Introduction: An effective therapeutic strategy in patients with atrial septal defect (ASD) and significant pulmonary arterial hypertension (PAH) remains controversial. Hypothesis: PAH-specific medications contribute to improvement of PAH. Subsequent transcatheter ASD closure may lead to further reduction of PAP. Methods: Among 646 patients with ASD, 22 who were complicated by definite PAH had successful transcatheter ASD closure. Among them, eight patients received PAH-specific medications prior to the transcatheter procedure (PHM group) and 14 patients did not (non-PHM group). Results: The mean age at the procedure in the PHM group was 37±15 years. Initially, the PHM group had significantly higher mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) compared with the non-PHM group (62±21 vs. 35±8 mmHg, p&lt;0.01; 9.6±3.8 vs. 4.1±1.1 Wood units, p&lt;0.01). PAP and PVR in the PHM group significantly decreased to 41±10 mmHg (p&lt;0.01) and to 4.0±0.8 Wood units (p&lt;0.01), respectively, after treatment with PAH-specific medications. In the PHM group, after ASD closure, further reduction of estimated systolic PAP was observed (72±19 to 41±11 mmHg, p&lt;0.01). Conclusions:Treat and repair is a valid therapeutic strategy for patients with ASD and significant PAH.
PTU-075 Utility of measuring adalimumab drug levels and anti-drug antibodies in clinical practice: a large IBD referral centre experience
Authors: BD Warner, EL Johnston, JL Digby-Bell, N Unsworth, S Anderson, JD Sanderson, Z Arkir, PM Irving
Journal: Gut (2015)

<h3>Introduction</h3> The development of adalimumab (Ada) drug and antibody testing has allowed a personalised approach to complex inflammatory bowel disease (IBD) treatment. We present our 2-year experience at a tertiary IBD referral centre. <h3>Method</h3> All Ada drug and antibody levels carried out at Guy’s and St. Thomas’ Hospital were analysed. The indications for carrying out levels, the subsequent changes in management and the long-term patient outcomes were evaluated. <h3>Results</h3> 143 levels were carried out on 105 patients from October 2012 to October 2014. The median value was 5 µg/ml (range 0- &gt;8 µg/ml). 74 levels (52%) were done on patients who had symptoms indicative of loss of response (LOR). 13 patients, all with no detectable antibodies had their dose increased, 10 of these patients had low levels (&lt;5.0 µg/ml), 6 of whom responded. 1 patient had high levels of antibodies and therefore Ada was stopped. A further 8 patients had their Ada stopped and were referred for surgery or switched to infliximab. 5 levels (4%) were measured after induction (week 12–14) resulting in 1 patient with a low level (3.5 µg/ml) and clinically active disease escalating to 40 mg weekly with good response. 38 levels (27%) were done as part of annual reassessment resulting in only 2 changes in management: 1 patient had dose de-escalation from weekly to every other week due to levels &gt;8 µg/ml and the other had their dose increased to weekly due to low levels (1.4 µg/ml). The remaining levels were done to aid decisions regarding discontinuation of concomitant immunosuppressant (1%), dose de-escalation (11%) and discontinuation of Ada (2%), or to assess response to dose escalation (3%). 39 (27%) of the levels were sub therapeutic in 32 patients. In the 30 patients that did not have antibodies to Ada, 13 patients underwent dose escalation. Ada antibodies were detected in only 2 patients (1%). 1 patient, who had previously had a reaction to infliximab continued on Ada with minimal improvement in her symptoms. The other patient was lost to follow-up shortly after the levels were tested. <h3>Conclusion</h3> Measuring Ada levels in our cohort resulted in a change of management for 25% of patients, a percentage similar to that seen for infliximab. The majority of patients with LOR who had sub therapeutic levels responded well to Ada dose escalation. Antidrug antibody development is infrequent in our cohort of patients. <h3>Disclosure of interest</h3> B. Warner: None Declared, E. Johnston: None Declared, J. Digby-Bell: None Declared, N. Unsworth: None Declared, S. Anderson: None Declared, J. Sanderson: None Declared, Z. Arkir: None Declared, P. Irving Speaker Bureau of: MSD, Abbvie and Takeda.
Use of high-sensitivity cardiac troponin T to predict changes in left ventricular function in cancer patients treated with doxorubicin.
Authors: A. Rehman, A. H. Blaes, X. Luo, M. R. Menge, D. Yee, E. Missov
Journal: Journal of Clinical Oncology (2010)

e19504 Background: The use of doxorubicin to treat solid and hematological malignancies is limited by a dose-dependent cardiotoxicity. Predicting individual patient susceptibility to doxorubicin remains difficult. The objective of this study is to determine if a new generation high-sensitivity cardiac troponin T assay (hscTnT) can predict changes in left ventricular ejection fraction (LVEF) secondary to treatment with doxorubicin. Methods: Eighteen patients with breast carcinoma or non-Hodgkin lymphoma were enrolled. Blood samples for hscTnT (detection limit <1 pg/mL) and traditional cardiac troponin T (cTnT, detection limit <0.01 ng/mL) were drawn at baseline and after the last doxorubicin treatment. LVEF was measured by multi gated acquisition scan at the same points in time. Results: Levels of hscTnT but not cTnT increased in all patients and were significantly higher after the last treatment compared to baseline (22.18 ± 4.71 pg/mL vs 2.33 ± 0.66 pg/mL, P=0.0006). Sixty seven percent of the patients had a mean LVEF decline of 6% (95% CI 3 to 9, P<0.01) after receiving a cumulative doxorubicin dose of 240 mg/m2. Baseline hscTnT but not cTnT correlated with the change in LVEF (Spearman correlation -0.54, 95% CI -0.80 to -0.08, P=0.02). Conclusions: High-sensitivity cTnT predicts changes in LVEF in patients treated with an intermediate cumulative dose of doxorubicin. The use of a more sensitive assay provides clinically relevant information. No significant financial relationships to disclose.
NHS reports record waiting times in busiest year ever
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Emergency departments in England faced their busiest year and recorded their worst waiting times ever in 2015-16, new official data have shown.

The figures from NHS England, published on 12 May, showed that in March the NHS had the worst performance against the four hour target for patients to be seen in emergency departments and against the target for planned treatment waiting times since targets were introduced in 2004 and 2012, respectively.1 …
Clincial and Genetic Landscapes Differ Between IGH-CRLF2 and P2RY8-CRLF2 Acute Lymphoblastic Leukaemia
Authors: Lisa Jane Russell, Lisa Jones, Amir Enshaei, Jamie Rutherford, Stefano Tonin, Sarra Ryan, Jeyanthy Eswaran, Elli Papaemmanuil, Jose Tubio, Peter J Campbell, Anthony V Moorman, Christine Harrison
Journal: Blood (2015)
One-Year Outcomes in Caregivers of Critically Ill Patients
Authors: Jill I. Cameron, Leslie M. Chu, Andrea Matte, George Tomlinson, Linda Chan, Claire Thomas, Jan O. Friedrich, Sangeeta Mehta, Francois Lamontagne, Melanie Levasseur, Niall D. Ferguson, Neill K.J. Adhikari, Jill C. Rudkowski, Hilary Meggison, Yoanna Skrobik, John Flannery, Mark Bayley, Jane Batt, Claudia dos Santos, Susan E. Abbey, Adrienne Tan, Vincent Lo, Sunita Mathur, Matteo Parotto, Denise Morris, Linda Flockhart, Eddy Fan, Christie M. Lee, M. Elizabeth Wilcox, Najib Ayas, Karen Choong, Robert Fowler, Damon C. Scales, Tasnim Sinuff, Brian H. Cuthbertson, Louise Rose, Priscila Robles, Stacey Burns, Marcelo Cypel, Lianne Singer, Cecilia Chaparro, Chung-Wai Chow, Shaf Keshavjee, Laurent Brochard, Paul Hébert, Arthur S. Slutsky, John C. Marshall, Deborah Cook, Margaret S. Herridge
Journal: New England Journal of Medicine (2016)

Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU).We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge.The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time.In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).
99mTc-MAA Pulmonary Scintigraphy in Hereditary Hemorrhagic Telangiectasia
Authors: Fang Yang, Leilei Yuan, Daqing Ma, Jigang Yang
Journal: Clinical Nuclear Medicine (2016)

A 5-year-old boy was admitted due to shortness of breath. Blood gas analysis showed hypoxemia. However, thoracic and abdominal CT, brain MRI, and MR angiography were all normal. A 99mTc-MAA pulmonary scintigraphy revealed right-to-left shunting of the blood. Further genetic analysis showed the mutations in the activin receptor-like kinase 1 gene, and a diagnosis of hereditary hemorrhagic telangiectasia was made.
Coexistence of Egfr Mutations with Alk, Ros1 or Ret Rearrangements in Lung Adenocarcinoma: a Clinicopathological Analysis from 646 Chinese Patients with Lung Adenocarcinoma
Authors: W. Cai, C. Zhou, S. Ren, X. Chen, G. Gao, X. Li, W. Li, C. Zhao
Journal: Annals of Oncology (2014)
Abstract 13460: Echocardiographic Atrioventricular Delay Optimization during Exercise Improves Cardiac Function in Cardiac Resynchronization Therapy Patients
Authors: Jing Ping Sun, Ming-Jui Hung, David DeLurgio, Xing Sheng Yang, Angel Leon, John D Merlino
Journal: Circulation (2010)

Background: Atrioventricular (AV) intervals for cardiac resynchronization therapy (CRT) patients are typically optimized at rest. There is limited data on the impact of heart rate change (HR) on AV...
Use of parenteral antibiotics in neutropenic patients.
Authors: F A Manian, D A Janssen
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.1994.12.11.2517 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7964971 Use of parenteral antibiotics in neutropenic patients. F A ManianxF A ManianSearch for articles by this author , D A JanssenxD A JanssenSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.11.2517 First Page PDF © 1994 by American Society of Clinical Oncology
Prostate Cancer Epidemiology: Widowerhood and Cancer in Spouses<xref ref-type="fn" rid="FN1">2</xref>
Authors: P Greenwald, V Kirmss, W S Burnett
Journal: JNCI Journal of the National Cancer Institute (1979)

Higher prostate cancer mortality rates among widowered than married men of the same age groups plus the rarity of prostate cancer in men below age 40 years suggested a need for focusing epidemiologic studies on the late middle-age period. Duration of widowerhood and cancer deaths in spouses were studied in 169 widowers dying with prostate cancer, 451 matched control widowers dying of any causes except prostate cancer, and 150 matched control widowers dying of other types of cancer. The average duration of widowerhood and frequency of multiple wives were the same for patients with prostate cancer and controls. Predeceased wives (i.e., wives dying before their husbands) of the prostate cancer patients had breast cancer 9.9% of the time, as compared to predeceased wives of the controls, who had breast cancer 5.8% of the time. The respective endometrial cancer rates for wives of patients and controls were 2.0 and 0.2%. Neither these results nor results from a confirmatory study of cancer among wives of married prostate cancer patients were statistically significant. Overstatement of widowerhood status on 6.1% of death certificates, lack of case-control differences in durations of widowerhood, and decreasing widower-married mortality ratios as age-specific groupings were made smaller indicated that the high rates of prostate cancer among widowers may be due to artifacts of classifying and tabulating vital records.
Dysregulation of type 2 innate lymphoid cells and T H 2 cells impairs pollutant-induced allergic airway responses
Authors: Katrien C. De Grove, Sharen Provoost, Rudi W. Hendriks, Andrew N.J. McKenzie, Leen J.M. Seys, Smitha Kumar, Tania Maes, Guy G. Brusselle, Guy F. Joos
Journal: Journal of Allergy and Clinical Immunology (2016)

BackgroundAlthough the prominent role of TH2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can also contribute to orchestration of allergic responses. Several experimental and epidemiologic studies have provided evidence that allergen-induced airway responses can be further enhanced on exposure to environmental pollutants, such as diesel exhaust particles (DEPs). However, the components and pathways responsible remain incompletely known.ObjectiveWe sought to investigate the relative contribution of ILC2 and adaptive TH2 cell responses in a murine model of DEP-enhanced allergic airway inflammation.MethodsWild-type, Gata-3+/nlslacZ (Gata-3–haploinsufficient), RAR-related orphan receptor α (RORα)fl/flIL7RCre (ILC2-deficient), and recombination-activating gene (Rag) 2−/− mice were challenged with saline, DEPs, or house dust mite (HDM) or DEP+HDM. Airway hyperresponsiveness, as well as inflammation, and intracellular cytokine expression in ILC2s and TH2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed.ResultsConcomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and TH2 cells, type 2 cytokine production, and airway hyperresponsiveness compared with sole DEPs or HDM. Reduced Gata-3 expression decreased the number of functional ILC2s and TH2 cells in DEP+HDM-exposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. Interestingly, although the DEP-enhanced allergic inflammation was marginally reduced in ILC2-deficient mice that received combined DEP+HDM, it was abolished in DEP+HDM-exposed Rag2−/− mice.ConclusionThese data indicate that dysregulation of ILC2s and TH2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown on concomitant DEP+HDM exposure.Graphical abstract
Case 3-1972
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Joseph T. Ferrucci, Austin L. Vickery
Journal: New England Journal of Medicine (1972)

Presentation of CaseA 21-year-old man was admitted to the hospital because of an abdominal mass.Four and a half years previously ulcerative colitis developed, with bloody diarrhea, fever and abdominal cramps. A barium-enema examination (Fig. 1) revealed involvement of the entire colon, with mucosal ulceration, pseudopolyps and shortening of the colon with loss of the normal haustral pattern; in the terminal portion of the ileum "backwash ileitis" was demonstrated; the distal region of the sigmoid and the rectum were less severely involved. An upper gastrointestinal series and small-bowel follow-through study revealed that the small bowel was normal except that . . .
Changing The Treatment Paradigm For Previously Treated Chronic Lymphocytic Leukemia Patients With Del(17p) Karyotype
Authors: Deborah M Stephens, Amy Stark, Jeffrey A. Jones, Jennifer A. Woyach, Kami Maddocks, Samantha M. Jaglowski, Leslie A. Andritsos, Joseph M. M. Flynn, Michael R. Grever, Gerard Lozanski, Amy J. Johnson, Natarajan Muthusamy, Nyla A. Heerema, John C. Byrd
Journal: Blood (2013)
The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma
Authors: F. Bernard-Arnoux, M. Lamure, F. Ducray, G. Aulagner, J. Honnorat, X. Armoiry
Journal: Neuro-Oncology (2016)

There is strong concern about the costs associated with adding tumor-treating fields (TTF) therapy to standard first-line treatment for glioblastoma (GBM). Hence, we aimed to determine the cost-effectiveness of TTF therapy for the treatment of newly diagnosed patients with GBM.We developed a 3-health-state Markov model. The perspective was that of the French Health Insurance, and the horizon was lifetime. We calculated the transition probabilities from the survival parameters reported in the EF-14 trial. The main outcome measure was incremental effectiveness expressed as life-years gained (LYG). Input costs were derived from the literature. We calculated the incremental cost-effectiveness ratio (ICER) expressed as cost/LYG. We used 1-way deterministic and probabilistic sensitivity analysis to evaluate the model uncertainty.In the base-case analysis, adding TTF therapy to standard of care resulted in increases of life expectancy of 4.08 months (0.34 LYG) and €185 476 per patient. The ICER was €549 909/LYG. The discounted ICER was €596 411/LYG. Parameters with the most influence on ICER were the cost of TTF therapy, followed equally by overall survival and progression-free survival in both arms. The probabilistic sensitivity analysis showed a 95% confidence interval of the ICER of €447 017/LYG to €745 805/LYG with 0% chance to be cost-effective at a threshold of €100 000/LYG.The ICER of TTF therapy at first-line treatment is far beyond conventional thresholds due to the prohibitive announced cost of the device. Strong price regulation by health authorities could make this technology more affordable and consequently accessible to patients.
Plasmin is a natural trigger for bradykinin production in patients with hereditary angioedema with factor XII mutations
Authors: Steven de Maat, Jenny Björkqvist, Chiara Suffritti, Chantal P. Wiesenekker, Willem Nagtegaal, Arnold Koekman, Sanne van Dooremalen, Gerard Pasterkamp, Philip G. de Groot, Marco Cicardi, Thomas Renné, Coen Maas
Journal: Journal of Allergy and Clinical Immunology (2016)