tbuckley/cabot-search huggingface dataset:
SAT0161 Majority of Patients do not Store Their Biological Disease Modifying Antirheumatic Drugs Within Recommended Temperature Range
Authors: N.D. Vlieland, H. Gardarsdottir, M.L. Bouvy, A.C. Egberts, B.J. van den Bemt
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Proper storage and controlled distribution of biological disease modifying antirheumatic drugs (bDMARDs) is essential to ensure drug quality. Deviations from the manufacturers9 Summary of Product Characteristics (SmPC) recommended temperature range (2°C-8°C) at patients9 home may lead to protein aggregation which has been associated with an increased immunogenicity and formation of antibodies. This could result in decreased clinical efficacy and increased risk of adverse drug reactions. <h3>Objectives</h3> To evaluate whether patients9 home storage temperatures for bDMARDs comply with SmPC recommended storage temperature range. <h3>Methods</h3> This prospective observational follow-up study was conducted in eight Dutch outpatient pharmacies from December 2013 till January 2015. Consenting adult patients using bDMARDs (etanercept, adalimumab, golimumab, certolimumab pegol or abatacept) received their bDMARDs in the original package inserted in a sealbag containing a validated temperature logger. Patients were instructed to store their packages according to standard label instructions and to return the temperature logger(s) after use. Primary outcome was defined as the number of patients that stored their bDMARDs within the SmPC recommended temperature range without excursions longer than 48 hours below 2°C or above 8°C. Deviations from the SmPC recommended temperature range were further defined as 1) the frequency of episodes longer than 2 hours consecutive time below 0°C or above 25°C and 2) longest duration of a single episode below 0°C or above 25°C. <h3>Results</h3> 338 patients (mean age 52.4 (SD 13.5), 54.4% female) received 1309 temperature loggers in total. 278 (82.2%) patients (mean age 52.9 (SD 13.4), 52.0% female) returned in total 756 temperature loggers (57.8%). The majority (95.7%) of the patients were treated with etanercept or adalimumab. 79 patients (28.5%) stored their bDMARD within the SmPC recommended temperature range without excursions longer than 48 hours below 2°C or above 8°C (Figure 1). 23.4% of the patients stored one or more bDMARD packages for more than 2 hours consecutive time below 0°C (per package – frequency: 4 times [IQR 1–14], median longest duration: 7.2 hours [IQR 4.3–21.3], maximum duration: 46 days). 1.8% of patients stored bDMARDs above 25°C for episodes longer than 2 hours consecutive time (per package – median frequency: 1 time [IQR 1–2], median longest duration: 10.9 hours [IQR 6.1–33.9], maximum duration: 16 days). <h3>Conclusions</h3> The majority of patients do not store their bDMARDs within the SmPC recommended storage temperature range. To what extent moderate and extreme deviations in storage temperatures could affect product quality, influence efficacy and occurrence of side-effects of the bDMARDs needs further investigation. <h3>Disclosure of Interest</h3> None declared
The Action of Mustard Gas (ββ′Dichlorodiethylsulphide) on Living Cells in Vitro I. The Immediate Cytological Effects of Mustard Gas and of Its Hydrolysis Products II. The Effect on Cell Growth of Adding Small Concentrations of Mustard Gas to the Culture Medium
Authors: Honor B. Fell, C. B. Allsopp
Journal: Cancer Research (1948)
Use of BIBW 2992, a novel irreversible EGFR/HER2 TKI, to induce regression in patients with adenocarcinoma of the lung and activating EGFR mutations: Preliminary results of a single-arm phase II clinical trial
Authors: C. Yang, J. Shih, T. Chao, C. Tsai, C. Yu, P. Yang, M. Streit, M. Shahidi, V. A. Miller
Journal: Journal of Clinical Oncology (2008)

8026 Background: BIBW 2992 is a highly potent dual EGFR and HER2 inhibitor with preclinical activity in cell lines harboring EGFR activating mutations (H1650, IC50=0.7 nM) as well as those with T790M mutations (H1975, IC50=99 nM). A phase II study of BIBW 2992 in chemotherapy-treated EGFR tyrosine kinase domain mutation positive patients is being conducted. Methods: Two-stage study conducted in Taiwan and US with first analysis planned when 40 patients have completed one course of treatment(28 days); if 16 or more patients respond, accrual will expand to a total of 80 patients. Eligibility criteria include stage IIIB/IV lung adenocarcinoma, EGFR mutation present in exons 18–21 (tested by direct sequencing), measurable disease, ECOG performance status of 0–2, adequate end organ function and progressive disease following neoadjuvant/adjuvant chemotherapy or one chemotherapy regimen for metastatic disease. Patients receive 50 mg BIBW 2992 once daily until disease progression. Tumor assessments are performed every course for 3 courses and every 2 courses thereafter. The primary endpoint is objective response rate. Results: Samples from 48 consented patients from Taiwan were sequenced. Twenty-one (43.7%) had detectable EGFR mutations, including del19 (N=10), L858R (N=7) and other mutations (N=4). Ten patients started treatment. Preliminary analysis of the first 6 patients (3F/3M) who were treated for at least 28 days and had tumor response assessment is reported here. Five patients had PR (3 del19;1 L858R and 1 with G719S/S768I), and one had SD (L858R). Tumor regressions were readily observed on plain chest X-ray on day 8 of treatment in 5 patients. Most frequently occurring side effects included skin toxicity (Grade 3 in one patient) and diarrhea (Grade 3 in two patients). One patient had dose reduction to 30 mg per day due to Grade 3 hand-foot syndrome and paronychia; one to 40 mg per day due to Grade 3 diarrhea. Conclusions: BIBW 2992 50 mg per day induced rapid responses and seems promising in NSCLC patients harboring EGFR activating mutations. Manageable cutaneous toxicity and diarrhea are the main adverse events. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim
Marrow Transplantation in Preleukemia&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H J Deeg
Journal: JNCI Journal of the National Cancer Institute (1986)

Preleukemia has generally been treated by palliative measures. Several reports have indicated that cytarabine given as low-dose infusion results in responses, albeit short lived, in a fraction of patients. We have shown recently that marrow transplantation offers a useful alternative. Twelve patients have been treated and followed for a minimum of 1 year. Three were conditioned with cyclophosphamide (CY) only, and all died with recurrent or persistent disease. Nine were conditioned with CY and total-body irradiation; all but 1 had lasting engraftment, and 7 are surviving, free of disease, 16-36 (median 27) months after transplantation. These data show that marrow transplantation can provide successful therapy for preleukemia.
Chaperonin Containing TCP-1 Protein Level in Breast Cancer Cells Predicts Therapeutic Application of a Cytotoxic Peptide
Authors: Rania Bassiouni, Kathleen N. Nemec, Ashley Iketani, Orielyz Flores, Anne Showalter, Amr S. Khaled, Priya Vishnubhotla, Robert W. Sprung, Charalambos Kaittanis, Jesus M. Perez, Annette R. Khaled
Journal: Clinical Cancer Research (2016)

Metastatic disease is a leading cause of death for patients with breast cancer, driving the need for new therapies. CT20p is a peptide previously discovered by our group that displays cancer-specific cytotoxicity. To design the optimal therapeutic use of the peptide, we identified the intracellular target of CT20p in breast cancer cells, correlating expression patterns of the target with susceptibility to CT20p.Using polymeric nanoparticles to deliver CT20p, we assessed cytoskeletal changes, cell migration, adhesion, and viability in cells treated with the peptide. Protein pull-down experiments, coupled to mass spectrometry, enabled identification of the peptide's intracellular target. Biochemical and histologic techniques validated target identity in human cell lines and breast cancer tissue microarrays and revealed susceptibility patterns to CT20p.Chaperonin containing TCP-1 (CCT) was identified as the intracellular target of CT20p. Cancer cells susceptible to CT20p had increased CCT, and overexpression of CCTβ, a subunit of the CCT complex, enhanced susceptibility to CT20p. Susceptible cells displayed reduced tubulin, a substrate of CCT, and inhibition of migration upon CT20p treatment. CCTβ levels were higher in invasive ductal carcinomas than in cancer adjacent tissues and increased with breast cancer stage. Decreased breast cancer patient survival correlated with genomic alternations in CCTβ and higher levels of the chaperone.Increased CCT protein in breast cancer cells underlies the cytotoxicity of CT20p. CCT is thus a potential target for therapeutic intervention and serves as a companion diagnostic to personalize the therapeutic use of CT20p for breast cancer treatment. Clin Cancer Res; 22(17); 4366-79. ©2016 AACR.
CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability
Authors: Stoyan Ivanov, Joshua P. Scallan, Ki-Wook Kim, Kathrin Werth, Michael W. Johnson, Brian T. Saunders, Peter L. Wang, Emma L. Kuan, Adam C. Straub, Melissa Ouhachi, Erica G. Weinstein, Jesse W. Williams, Carlos Briseño, Marco Colonna, Brant E. Isakson, Emmanuel L. Gautier, Reinhold Förster, Michael J. Davis, Bernd H. Zinselmeyer, Gwendalyn J. Randolph
Journal: Journal of Clinical Investigation (2016)

Lymphatic collecting vessels direct lymph into and from lymph nodes (LNs) and can become hyperpermeable as the result of a previous infection. Enhanced permeability has been implicated in compromised immunity due to reduced flow of lymph and immune cells to LNs, which are the primary site of antigen presentation to T cells. Presently, very little is known about the molecular signals that affect lymphatic collecting vessel permeability. Here, we have shown that lymphatic collecting vessel permeability is controlled by CCR7 and that the chronic hyperpermeability of collecting vessels observed in Ccr7–/– mice is followed by vessel fibrosis. Reexpression of CCR7 in DCs, however, was sufficient to reverse the development of such fibrosis. IFN regulatory factor 4–positive (IRF4+) DCs constitutively interacted with collecting lymphatics, and selective ablation of this DC subset in Cd11c-Cre Irf4fl/fl mice also rendered lymphatic collecting vessels hyperpermeable and fibrotic. Together, our data reveal that CCR7 plays multifaceted roles in regulating collecting vessel permeability and fibrosis, with one of the key players being IRF4-dependent DCs.
AB0603 Periodontal Disease is Common in Patients with Systemic Lupus Erythemathosus
Authors: P. de Pablo, K. Dewan, T. Dietrich, I. Chapple, C. Gordon
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Periodontal disease is a common chronic inflammatory disease that has been associated with rheumatoid arthritis and a potential causal role has been suggested. However, data on the prevalence of periodontal disease in patients with systemic lupus erythematosus (SLE) are scarce. <h3>Objectives</h3> To investigate the prevalence of periodontal disease in patients with systemic lupus erythematosus and compare it to that of the general population. <h3>Methods</h3> We examined the periodontal status in dentate patients with SLE who met the ACR criteria for SLE. Mild periodontitis was defined as having at least one periodontal probing depth of 4+mm. Severe periodontitis was defined as having at least one periodontal probing depth of 6+mm. We compared the prevalence of periodontal disease in SLE patients with that of a geographically matched dentate sub-sample of the Adult Dental Health Survey (ADHS), West Midlands, a representative population survey in the UK (reference group). Age-standardized prevalence estimates were calculated and logistic regression was used to evaluate the association between SLE and periodontal disease adjusting for age and sex. <h3>Results</h3> We examined a total of 105 individuals with SLE, with a mean age of 45.6 years (IQR 36-56), of whom 98 (92%) were women. The reference group included 484 participants, with a mean age of 48.9 years (IQR 36-63), of whom 271 (56%) were women. The age-standardised prevalence of periodontitis was 85% (95% CI: 79% to 92%) in SLE patients, compared with 55% (95% CI: 51% to 60%) in the general West Midlands population. After adjustments for age and sex, patients with SLE were significantly more likely to have periodontitis than ADHS participants (OR 7.25, 95% CI 3.84 to 13.68). Results were similar when analyses were restricted to women only (OR 7.51, 95% CI: 3.85 to 14.64). The age-standardised prevalence of severe periodontitis was 11% (95% CI: 5% to 18%) in patients with SLE and 11% (95% CI: 8% to 14%) in the West Midlands population. No significant association of SLE with severe periodontitis was observed (OR 1.15, 95% CI: 0.56 to 2.36). <h3>Conclusions</h3> Our data suggests that periodontal disease is more common among individuals with SLE compared to a representative geographically matched sample. However, the prevalence of severe periodontal disease is similar between SLE and the general population. Further studies are necessary to confirm the possible association between periodontitis and SLE. <h3>Disclosure of Interest</h3> None declared
Discriminant analysis of posttraumatic stress disorder among a group of Viet Nam veterans
Authors: J S Frye, R A Stockton
Journal: American Journal of Psychiatry (1982)

The authors designed a study to identify those independent variables which would statistically discriminate between a group of Viet Nam veterans who were experiencing posttraumatic stress disorder and those who were not. DSM-III criteria for diagnosis were used to measure and operationally define posttraumatic stress disorder. Five variables distinguished between groups: veterans with the disorder reported a negative perception of their family's helpfulness on return home, a higher level of combat, a more immediate discharge after the war, an external locus of control, and a more supportive attitude toward the war before they entered the service. The authors discuss the implications and limitations of these findings.
Sustained change in parents receiving preventive interventions for families with depression
Authors: W R Beardslee, P Salt, E M Versage, T R Gladstone, E J Wright, P C Rothberg
Journal: American Journal of Psychiatry (1997)

The purpose of this study was to compare the sustained effects of two cognitive, psychoeducational preventive interventions for families in which a parent had an affective disorder.Thirty-seven families, in which there was a child between the ages of 8 and 15 years (mean = 11.5 years) and at least one parent who had experienced a recent episode of affective disorder according to the Research Diagnostic Criteria, were studied 1.5 years after enrollment in the study. The families were randomly assigned to one of two interventions, clinician-facilitated or lecture. The two interventions were similar in content but differed in the degree of involvement of the children and the linking of information to the families' life experiences. Nineteen families participated in the clinician-facilitated intervention, which consisted of six to 10 sessions. Eighteen families were assigned to the lecture condition, which consisted of two lectures attended only by parents. Family members were interviewed both before and after the interventions with diagnostic interviews and semistructured measures designed to assess response to the interventions.Sustained effects of the interventions were reported 1.5 years after enrollment. The clinician-facilitated intervention was associated with more positive self-reported and assessor-rated changes than the lecture intervention.These short-term preventive interventions, particularly the clinician-facilitated one, have long-term benefits for families with parental affective disorder.
Modulation of N-Nitrosodimethylamine Kidney Tumorigenesis by Unilateral Hydronephrosis and Multiple Putrescine Administrations
Authors: T Ohmori, R Tabei
Journal: JNCI Journal of the National Cancer Institute (1983)

The effects of unilateral hydronephrosis by ligation of the right ureter and/or multiple injections of putrescine on kidney tumorigenesis by a single intrarenal injection of N-nitrosodimethylamine (DMN) were studied. Inbred female W rats in the unilateral hydronephrotic groups given or not given putrescine developed kidney tumors and/or neoplastic or preneoplastic lesions of the liver at an incidence of 55.6%. Almost all kidney tumors developed in the contralateral kidneys, which showed hypertrophy due to unilateral hydronephrosis. Rats having unilateral hydronephrosis and subjected to long-term putrescine administration after DMN injection frequently contracted large mesenchymal cell tumors (83%), whereas the group not given putrescine developed no mesenchymal cell tumors. Histologically, epithelial cell tumors showed a marked decrease in both gamma-glutamyltransferase activity and trypan blue uptake, but mesenchymal cell tumors did not.
Public Health Science Conference: a call for abstracts
Authors: May C I van Schalkwyk, Robert W Aldridge, Robert W Aldridge, Simon Capewell, Llion Davies, Felix Greaves, Richard Horton, Ruth Hunter, Anne M Johnson, Frank Kee, Ronan A Lyons, Serena Luchenski, Martin McKee, Klim McPherson, G J Melendez-Torres, Ivan J Perry, Harry Rutter, Emily Tweed, May C I van Schalkwyk, Charlotte Vrinten, Helen Walters, Claire Wilson, Jane V Woodside, Wahyu Wulaningsih
Journal: The Lancet (2018)
Five endometrial cancer risk loci identified through genome-wide association analysis
Authors: Timothy H T Cheng, Deborah J Thompson, Tracy A O'Mara, Jodie N Painter, Dylan M Glubb, Susanne Flach, Annabelle Lewis, Juliet D French, Luke Freeman-Mills, David Church, Maggie Gorman, Lynn Martin, Shirley Hodgson, Penelope M Webb, John Attia, Elizabeth G Holliday, Mark McEvoy, Rodney J Scott, Anjali K Henders, Nicholas G Martin, Grant W Montgomery, Dale R Nyholt, Shahana Ahmed, Catherine S Healey, Mitul Shah, Joe Dennis, Peter A Fasching, Matthias W Beckmann, Alexander Hein, Arif B Ekici, Per Hall, Kamila Czene, Hatef Darabi, Jingmei Li, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo Runnebaum, Frederic Amant, Stefanie Schrauwen, Hui Zhao, Diether Lambrechts, Jeroen Depreeuw, Sean C Dowdy, Ellen L Goode, Brooke L Fridley, Stacey J Winham, Tormund S Njølstad, Helga B Salvesen, Jone Trovik, Henrica M J Werner, Katie Ashton, Geoffrey Otton, Tony Proietto, Tao Liu, Miriam Mints, Emma Tham, Mulin Jun Li, Shun H Yip, Junwen Wang, Manjeet K Bolla, Kyriaki Michailidou, Qin Wang, Jonathan P Tyrer, Malcolm Dunlop, Richard Houlston, Claire Palles, John L Hopper, Julian Peto, Anthony J Swerdlow, Barbara Burwinkel, Hermann Brenner, Alfons Meindl, Hiltrud Brauch, Annika Lindblom, Jenny Chang-Claude, Fergus J Couch, Graham G Giles, Vessela N Kristensen, Angela Cox, Julie M Cunningham, Paul D P Pharoah, Alison M Dunning, Stacey L Edwards, Douglas F Easton, Ian Tomlinson, Amanda B Spurdle
Journal: Nature Genetics (2016)
Response Monitoring, Tolerability, and Effectiveness of Imatinib Treatment for Chronic Myeloid Leukemia in a Retrospective Research Database
Authors: David D. Stenehjem, Frederick Albright, Kuan-Ling Kuo, Karina Raimundo, Hillevi Bauer, Paul J. Shami, Michael W. Deininger, Lei Chen, Diana I. Brixner
Journal: Journal of the National Comprehensive Cancer Network (2014)

Retrospective review of imatinib monitoring through electronic health records (EHR) can provide valuable insight into the current management of chronic myelogenous leukemia (CML). This study retrospectively reviewed EHRs from 2001 to 2010 of patients with chronic phase CML (CP-CML) treated with first-line imatinib. Chart evaluations included a review of cytogenetic and molecular testing, overall survival, adverse drug events (ADEs), and therapy modifications. A total of 54 patients with CP-CML were treated with first-line imatinib and had either cytogenetic or molecular testing within 18 months of imatinib initiation. Within the first 18 months of treatment, 33 of 45 patients (73%) undergoing cytogenetic testing experienced a complete cytogenetic response (median, 241 days; range, 110-542 days) and 24 of 48 patients (50%) receiving molecular testing achieved at least a major molecular response (median, 253 days; range, 99-546 days). The average number of cytogenetic and molecular tests conducted within the first 18 months was 2.5 and 3.8, respectively. Nineteen of 54 (35%) had a dose increase of imatinib (>400 mg; median, 329 days; range, 21-1968 days). The 5-year estimated overall survival rate was 88.5%. Between 2006 and 2010 (n=30; 56%), 7 patients (23%) transitioned to dasatinib or nilotinib (median, 399 days from diagnosis; range, 180-1046 days) because of suboptimal response or treatment failure (n=5) and imatinib ADEs (n=2). Forty-six imatinib-associated ADEs occurred in 31 patients (57%), of which 10 (32%) received dose reductions (median, 52 days) and 6 (19%) had discontinuations (median, 139 days). Closely monitored patients with CML treated with imatinib at an NCCN Member Institution experienced outcomes comparable to those reported in key clinical trials.
Abstract 10336: Left Ventricular Deformation at 2-year Follow-up in Treatment-naive Rheumatoid Arthritis Patients is Associated With High Inflammation Parameters: A Open Cohort Study
Authors: Brian B Løgstrup, Dzenan Masic, Trine B Laurbjerg, Lone K Deibjerg, Grazina Urbonavience, Agnete Hedemann-Nielsen, Torkell Ellingsen
Journal: Circulation (2015)

Introduction: Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). The role of autoimmunity and especially citrullination in the pathogenesis of the increased risk of CVD and the time-course of left ventricular (LV) dysfunction are unknown. Hypothesis: To assess LV function by speckle-tracking echocardiography and the amount of coronary calcium by coronary computer tomography (CCT) in relation to anti-cyclic citrullinated peptide antibody (anti-CCP) status during a 2-year follow-up period in a open cohort of treatment-naive RA patients. Methods: Thirty-nine treatment-naive early RA patients (21 women) were included at time of diagnosis and followed for 2 years. Disease activity, IgM rheumatoid factor (IgM-RF) and anti-CCP was assessed at time of diagnosis and at 2-year follow-up. We assessed both the LV deformation by speckle-tracking echocardiography whereby we measured global longitudinal systolic strain (GLS) and coronary calcium score (Agatston′s score) by coronary computer tomography (CCT) at time of diagnosis and at 2-year follow-up. Results: We found GLS similar at baseline and after 2-year follow-up (GLSBASELINE: -16.56±3.1% vs. GLS2-YEAR: -16.27±2.8%; p=0.66). However, in patients with anti-CCP ≥340 at baseline and patients who persistently had an anti-CCP ≥340 at 2-year follow-up (n=10), we observed a significant decrease in deformation compared to patients who did not (n=29); (2.9±3.2% vs. -0.6±2.7%; p=0.002). Furthermore, we observed a significant association between the changes in GLS over 2 years (GLSDELTA: 0.27±3.21%) and anti-CCP (r=0.63; p&lt;0.0001), which remained significantly associated (p&lt;0.0001) after correction for relevant confounders. No significant progression in coronary calcium score was observed in the observation period. Conclusions: LV deformation is reduced in treatment-naive RA patients with persistently elevated anti-CCP and deformation abnormalities is associated with the degree of anti-CCP positivity in a 2-year follow-up period. Our observations make deformation analysis by speckle-tracking echocardiography a strong tool to detect early development of myocardial dysfunction in treatment naive RA.