tbuckley/cabot-search huggingface dataset:
Separately tackling the development of erosions with denosumab: ultimately closing a gap in the treatment of patients with rheumatoid arthritis or trying too hard too late?
Authors: P Verschueren, R Westhovens
Journal: Annals of the Rheumatic Diseases (2016)

Patients with rheumatoid arthritis (RA) have benefited from an unprecedented treatment improvement over the last two decades. Taking the disease seriously, with earlier and more intensive treat-to-target strategies and new treatment options with biologicals, has led to a better long-term disease control. Classical antirheumatic therapies, primarily directed against the inflammatory/immunological processes that determine RA disease activity, are successfully improving pain and the severe clinical and functional burden patients are confronted with. Moreover, one of the most important previous hallmarks of this disease, severe joint destruction with subsequent deformations, can now in most cases be prevented thanks to the development of new treatment strategies and the introduction of novel therapeutics. The Cobra trial1 demonstrated the existence of a window of opportunity for preventing joint damage in early RA and the Attract trial2 showed an arrest in further X-ray damage—at least at the group level—in severe methotrexate (MTX) refractory disease treated with infliximab, which was unprecedented at that time. Thanks to more effective treatments prevention of further damage was reported and even, in a (small) number of cases, what could be considered as healing of erosions.3 ,4 Other publications focused on a potential uncoupling between controlling inflammation and damage. Prevention of X-ray progression appeared possible independent from successfully reducing disease activity, at least with certain therapeutics.5 Despite the fact that today joint damage can be prevented in the large majority of cases, it is still an important determinant in the evaluation of RA treatment efficacy given the link between X-ray progression and future physical disability.6

Takeuchi et al 7 demonstrate an additional inhibitory effect on the progression of bone erosions (not joint space narrowing) of three different dosages of denosumab on top of the traditional RA treatment over a 12-month period in Japanese patients with RA, …
Hes1 Is Responsible For Notch Signaling-Mediated Suppression Of Acute Myeloid Leukemia Development Via Suppression Of FLT3 Expression
Authors: Takayasu Kato, Mamiko Sakata-Yanagimoto, Hidekazu Nishikii, Yasuyuki Miyake, Yasuhisa Yokoyama, Yukitugu Asabe, Naoshi Obara, Kazumi Suzukawa, Ryoichiro Kageyama, Shigeru Chiba
Journal: Blood (2013)
Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations
Authors: Viktor Ljungström, Diego Cortese, Emma Young, Tatjana Pandzic, Larry Mansouri, Karla Plevova, Stavroula Ntoufa, Panagiotis Baliakas, Ruth Clifford, Lesley-Ann Sutton, Stuart J. Blakemore, Niki Stavroyianni, Andreas Agathangelidis, Davide Rossi, Martin Höglund, Jana Kotaskova, Gunnar Juliusson, Chrysoula Belessi, Nicholas Chiorazzi, Panagiotis Panagiotidis, Anton W. Langerak, Karin E. Smedby, David Oscier, Gianluca Gaidano, Anna Schuh, Frederic Davi, Christiane Pott, Jonathan C. Strefford, Livio Trentin, Sarka Pospisilova, Paolo Ghia, Kostas Stamatopoulos, Tobias Sjöblom, Richard Rosenquist
Journal: Blood (2015)
Retrospective immunohistochemical study of VDR, RXR, Ki-67, and Bcl-2 expression in primary and metastatic osteosarcoma
Authors: O. Tawfik, R. Garimella, J. Tancabelic, J. Keighley, D. Pinson, Q. Khan, K. Templeton
Journal: Journal of Clinical Oncology (2009)

e21516 Background: Osteosarcoma (OS) is a highly malignant tumor with a peak incidence in adolescents and young adults. Patient's prognosis is limited to clinical parameters whereas molecular markers of tumor aggression are yet to be identified. Vitamin D (Vit D) has been postulated as a novel therapeutic option for a variety of malignancies such as breast and prostatic carcinomas. The biologic effect of vitamins is mainly mediated through receptors. Vit D receptors (VDRs) are members of the steroid hormone superfamily and are ubiquitous in a various tissues including bone. Upon activation by its ligand, VDR combines with retinoid receptor (RXR) forming a heterodimer initiating a cascade of cellular events. How Vit D induces its antineoplastic activity in OS remains to be elucidated. Methods: Immunohistochemical analysis for VDR, RXR, Ki-67, and bcl-2 was performed on 87 OS specimens to evaluate differentiation, proliferation and apoptosis. Clinical data including site of the primary tumor, presence or absence of metastasis, therapeutic regimens, and outcome were recorded. Results: The mean age of OS patients is 25.7 years (range 7–68). Fifty-four patients were &lt;30 years. Thirty-five OSs were conventional, 17 chondroblastic, 6 giant cell, 6 fibroblastic, 6 mixed, 3 telangiectatic, and 2 epithelioid variants. Twelve of the 87 samples were metastatic. All metastatic OSs were high grade, located in the lungs with a mean age of 25 years (range 7–52). The majority of the OSs expressed VDR (74/87, 85%) and RXR (72/78, 92%). Proliferative activity varied between tumors types with highest Ki-67 percentage noticed in conventional variant (29%), followed by chondroblastic variant (16%). Metastatic tumors consistently had the highest proliferative activity as compared to primary tumors (35%). None of the tumors studied was immunoreactive for bcl-2. Conclusions: Our results demonstrate that VDR and RXR are expressed on most OSs. A significant relationship exists between tumor histologic types and proliferative activity. Metastatic OSs appears to have a significantly higher level of proliferative activity as compared to primary tumors. These results would establish a foundation for elucidating mechanisms by which Vit D induces its antineoplastic activity in OS. No significant financial relationships to disclose.
Metabotropic NMDA receptor signaling couples Src family kinases to pannexin-1 during excitotoxicity
Authors: Nicholas L Weilinger, Alexander W Lohman, Brooke D Rakai, Evelyn M M Ma, Jennifer Bialecki, Valentyna Maslieieva, Travis Rilea, Mischa V Bandet, Nathan T Ikuta, Lucas Scott, Michael A Colicos, G Campbell Teskey, Ian R Winship, Roger J Thompson
Journal: Nature Neuroscience (2016)
Phase II trial of sorafenib (bay 43–9006) in patients with advanced anaplastic carcinoma of the thyroid (ATC)
Authors: G. Nagaiah, P. Fu, J. K. Wasman, M. M. Cooney, C. Mooney, D. Afshin, P. Lavertu, J. Bokar, P. Savvides, S. C. Remick
Journal: Journal of Clinical Oncology (2009)

6058 Background: Sorafenib (bay 43–9006) is an oral, small molecule tyrosine kinase inhibitor of the raf-1 protein kinase receptor, VEGFR2 and PDGFR-β with antiangiogenic properties. We are conducting an open label, phase II study of sorafenib in patients with biopsy-proven ATC to evaluate if its objective response rate is &gt;20% and to further characterize its safety profile. Methods: Patients with progressive ATC, after cytotoxic chemotherapy with or without radiation were given sorafenib, on a fixed dosing schedule of 400 mg PO bid on 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or patient refusal. Response was evaluated every 8 weeks with body scans using RECIST criteria. We employed a 2-stage study design: if none of the first 18 patients respond the study is terminated, otherwise accrual is continued to a total of 36 patients at which point if ≤3 of the patients respond, the treatment option is rejected. Results: To date 16 patients (10 male) have enrolled in the study. Median age is 55 years; with (range 28–79). Median time on study is 2 months. Median number of cycles given is 2 (range 1–27). Two of 15 evaluable patients (13%) have partial response (PR) and 4 patients (27%) have stable disease (SD). Median duration of PR/SD is 5.1 months (range 1–24.7months). Median time to progression is 1.5 months. Median duration of survival is 3.5 months (range 1–26 months). All patients at time of reporting are deceased. Most common toxicities are lymphopenia (81%) and fatigue (62%). Grade 3 toxicities include lymphopenia (25%), rash with desquamation, weight loss, and chest pain (all 12%). Grade 4 toxicities include dyspnea (6%) and lymphopenia (6%). There has been no significant cardiovascular toxicity. One patient died on study with rapidly progressive disease. Conclusions: Sorafenib demonstrates objective tumor response in the first 15 evaluable and pretreated patients with advanced ATC. This trial is ongoing and supported in part by NIH grant nos. CA62502. [Table: see text]
Effect of Nutrition on Survival Time of Thyroidectomized Rats Bearing a Transplantable Leukemia&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: David M. Morris, Albert Mokal
Journal: JNCI Journal of the National Cancer Institute (1963)

Thyroidectomized Fischer rats bearing a transplantable leukemia had a significantly longer survival time than sham-operated rats similarly treated. Since the former animals fed ad libitum ate significantly less food than the controls, the effect of thyroidectomy on survival time in rats maintained at various nutritional levels was tested. The data show the increased survival time of the tumor-bearing thyroidectomized rat is attributable to some factor other than the reduced dietary intake induced by this operation. However, an influence of reduced food consumption is shown by the fact that the effect of thyroidectomy is less marked in animals maintained at low food-intake levels than in those fed ad libitum.
Authors’ reply to Sasich and Linden
Authors: Joanna Le Noury, John M Nardo, David Healy, Jon Jureidini, Melissa Raven, Catalin Tufanaru, Elia Abi-Jaoude
Journal: BMJ (2015)

Restoring Study 329 was important for several reasons. Firstly, in October 2002 the Food and Drug Administration issued an approvable letter to GlaxoSmithKline’s application to license paroxetine for paediatric major depressive disorder (MDD) and obsessive-compulsive disorder despite noting “we agree that the results from . . . [Study] 329 . . . …
Respiratory muscle strength and physical performance in elderly hospitalized patients
Authors: Anna Zito, Claudio Pedone, Renato Giua, Simona Santangelo, Elena Frezzotti, Domenica Chiurco, Simone Scarlata, Raffaele Antonelli Incalzi
Journal: European Respiratory Journal (2012)

Age-related changes in pulmonary function increase respiratory muscle work.In front of this increased demand,sarcopenia frequently associated with age and multimorbidity,can reduce endurance and strength of respiratory muscles.Furthermore,sarcopenia may per se contribute to reduction of physical performance.   Aim of the study :to evaluate the correlation between the respiratory muscle strength and physical performance in elderly.   Population: 75 patients(30 men and 40 women) aged over 65 years(mean 78 yrs, SD: 6.6) admitted to the acute care geriatric ward of the Hospital University Campus Bio-Medico.Exclusion criteria:active malignancies,thyroid disease,renal failure(GFR   Results : The mean age of our sample was 77,8 ± 6,6, 31 patients had COPD (GOLD I: 36%, GOLD II: 48%, GOLD III: 16%).There was a statistically significant correlation between MIP and dynamometry (r 2 =0.23 p=0.07) and between MIP/MEP and 6MWT (MIP: r 2 =0. 38, p=0.001; MEP: r 2 =0.398, p
Use of hospital-based cancer registries to evaluate the quality of cancer care: A survey to the international community of oncologists.
Authors: S. C. Howard, A. Bustos, A. Carrato
Journal: Journal of Clinical Oncology (2010)

e16531 Background: Hospital-Based Cancer Registries (HBCRs) are key tools to plan and monitor the quality of care and outcome of cancer patients. However, data regarding the utility of HBCR in cancer services is limited. This study describes the rate of use of HBCR data and evaluates the relationship of HBCR data use to geographic and logistical factors. Methods: Between May 2008 and April 2009, we conducted an unpaid online survey of oncology professionals, who previously reported to have a HBCR at their centers to determine the ways in which registry data was used. Potential predictors of HBCR uses were continent, type and size of institution, personnel involved in data entry, specialization of registry system, completeness of data, case ascertainment and data standardization. Chi-squared tests and multivariate logistic regressions were used for the analysis. Results: A total of 490 of 1,402 (35%) oncologists having a HBCR at their center completed the questionnaire. The reported HBCR uses were transmission of data to population registries (66%), service as a data-source for hospital administration and resource allocation tasks (55%), evaluation of delivered treatments (54%), evaluation of patient outcomes (47%) and assessment of diagnostic procedures (35%) at cancer departments. In multivariate analysis, independent predictors of HBCR use to evaluate patient outcomes were the continent (North America 58%, Europe 37%, Asia 26%, South America 28%, p = 0.02), specialization of registry software (78% vs. 33%, p = 0.003), completeness of data fields (p = 0.001) and the entry of data by trained registrants (60% vs. 17%, p = 0.003). Conclusions: The use of HBCR data to evaluate the quality of cancer care and patient outcomes at cancer services is not optimal. Increasing the availability of trained registrants, specialized cancer registry software and maximizing completeness of data, could potentially increase their usefulness as tools to improve cancer care. Additional research is needed to determine reasons for non-use of HBCR data. No significant financial relationships to disclose.
Abstract P310: The Distribution of Total- and HDL Cholesterol and Triglycerides is Significantly Different across Quartiles of Vitamin D in Chest-Pain Patients with a Suspected Acute Coronary Syndrome
Authors: Patrycja A Naesgaard, Ricardo A Leon de la Fuente, Stein Tore Nilsen, Torbjoern Aarsland, Leik Woie, Heidi Grundt, Cato Brede, Harry Staines, Patricio Gallo, Silvia Dib Ashur, Augusto Torino, Dennis W Nilsen
Journal: Circulation (2012)

Background: The purpose of this study was to assess the distribution of serum lipids including total cholesterol, HDL cholesterol and triglycerides across quartiles of vitamin D in blood samples collected from 982 chest-pain patients with a suspected acute coronary syndrome (ACS) from Salta, Northern-Argentina. Methods: Vitamin D status was obtained by determination of 25-hydroxy-vitamin D (25(OH)D) in serum. Blood samples for measurement of 25(OH)D and circulating lipid fractions in serum were obtained immediately following admission. Results: In the total population the concentration of total cholesterol, HDL cholesterol and triglycerides was found to differ significantly across quartiles of 25(OH)D, p = 0.016, p = 0.01 and p = 0.000, respectively. See Figure 1, 2 and 3, respectively. In the Troponin T (TnT) positive population (TnT &gt; 0.01 ng/mL), only total cholesterol and triglycerides differed significantly across the 25(OH)D quartiles, p = 0.000 and p = 0.003, respectively, whereas HDL cholesterol alone differed in the TnT negative group, p = 0.025. Conclusion: Concentrations of the main lipid fractions are related to the vitamin D status in patients admitted with chest pain and suspected ACS.
Comparative Study of the Morphologic, Histochemical, and Proliferative Changes Induced in the Large Intestine of ICR/Ha and C57BL/Ha Mice by 1,2-Dimethylhydrazine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J T James, A M Shamsuddin, B F Trump
Journal: JNCI Journal of the National Cancer Institute (1983)

The mouse model of 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis was studied to determine the susceptibility of different anatomic segments of the large intestine in ICR/Ha (susceptible) and C57BL/Ha (resistant) mice. In ICR/Ha mice numerous exophytic macroscopic neoplasms were found in the distal colon and rectum after 15 weekly injections of DMH (20 mg/kg). The proximal colon was free of any microscopic or macroscopic neoplasms. In contrast, C57BL/Ha mice given the same treatment showed no macroscopic neoplasms. However, foci of dysplastic crypts were observed throughout the large intestine of C57BL/Ha mice with highest incidence in the distal colon and rectum. In some areas dysplastic crypts were clearly invading the muscularis mucosae and were, therefore, microscopic carcinomas (microcarcinomas). Thus C57BL/Ha mice were not totally resistant to the neoplastic stimulus of DMH, and the susceptibility of the large intestine is site-specific in both mouse strains.
WHO analgesic ladder and chronic pain: the need to search for treatable causes
Authors: Roberto J Guiloff, Heather Angus-Leppan
Journal: BMJ (2016)

Ballantyne and colleagues’ important message on the overuse of opioids in treating chronic pain is long overdue.1 As they point out, opioids are usually ineffective and they have major potential complications. The end result may be to blur the …
Plasma pharmacokinetics and cerebrospinal fluid concentrations of erlotinib in high-grade gliomas: A novel, phase I, dose escalation study
Authors: L. W. Buie, C. Lindley, T. Shih, M. Ewend, J. K. Smith, M. Skelton, L. Kwock, D. Morris, C. Tucker, F. Collichio
Journal: Journal of Clinical Oncology (2007)

2054 Background: Erlotinib (ERL) is an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. EGFR is overexpressed in glioblastoma multiforme (GBM). The primary objectives of this study were to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and to evaluate plasma and cerebrospinal fluid (CSF) ERL concentrations using a novel every 72 hour ERL dosing schedule. Methods: Patients = 18 years of age with GBM or high grade glioma with evidence of disease progression following first line therapy (surgery/XRT/chemotherapy) and Karnofsky performance status = 60 % were included. Patients were stratified based on use of enzyme-inducing antiepileptic drugs (EIAED). Patients not on EIAED were initiated on ERL 450 mg PO every 72h, while those on EIAED were initiated on 900 mg PO every 72 h. Results: Six patients have been enrolled and assessed for safety, 5 for plasma PK and 3 for CSF concentrations. For ERL, the area under the plasma concentration versus time curve (AUC) was greater and the half-life longer in patients not receiving EIAED. However, the AUC of OSI-420, the major metabolite of ERL, was lower in patients not receiving EIAED. The OSI-420 AUC: ERL AUC ratio was increased 3 fold among patients receiving EIAED, indicative of increased hepatic metabolism and increased clearance. CSF concentrations were detectable and ranged from 1 to 3% of peak plasma concentrations. Neither group has experienced a DLT or reached the MTD. The most common side effects (grade 1/2) have been diarrhea (83%), rash (100%) and fatigue (33%). To date, there has been 1 partial response, 1 patient with stable disease and 4 patients with disease progression. The partial response and stable disease have occurred in patients with GBM. Conclusions: ERL is a well tolerated therapy. Patient enrollment and subsequent dose escalation is ongoing and updated results will be presented at the ASCO 2007 meeting. [Table: see text] No significant financial relationships to disclose.
To Risk Adjust or Not to Risk Adjust
Authors: Jay G. Berry, Alyna T. Chien
Journal: JAMA Pediatrics (2016)

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Impact of checklist proforma on discharge and follow up care of patients admitted with COPD exacerbations
Authors: Mithun Murthy, Rahuldeb Sarkar, Holly Metcalfe, Sophie Taylor, Gwenno Jones, Jacqueline Bayliss, Robert Stead, Marta Babores
Journal: European Respiratory Journal (2011)

COPD management involves a multidisciplinary approach with input from specialist nurses, physiotherapists and dieticians. In 2009, we audited 14 criteria (NICE guidance) and showed scope for improvement. A discharge checklist was introduced.

Aim: To assess impact of discharge proforma on care of patients admitted with COPD exacerbations.

Method: We audited COPD patients admitted over Mar-Aug '09 and Aug-Dec '10, pre and post introduction of discharge checklist. Data collected: physician and nurse follow up, oxygen assessment, smoking cessation, pulmonary rehabilitation, COPD alert cards, dietetic follow up, domiciliary physiotherapy, community matron follow up, discussion regarding future ventilation, information leaflets, vaccination advice and psychological support.

Results: Table shows comparative results.

View this table:

Comparison of positive utilisation of resource





Conclusions: Introduction of a discharge checklist led to significant improvements in referrals to respiratory nurse, oxygen assessment, COPD alert cards, leaflets and vaccination advice. We have continued to use this intervention in our hospital.