tbuckley/cabot-search huggingface dataset:
Effect of Multiple Sclerosis Disease-Modifying Therapies on B Cells and Humoral Immunity
Authors: Erin E. Longbrake, Anne H. Cross
Journal: JAMA Neurology (2015)

The unequivocal success of B-cell-depleting agents in reducing magnetic resonance imaging and clinical activity in therapeutic trials indicates that B cells play a vital role in mediating the clinical course of relapsing multiple sclerosis (MS). Although no agent that specifically targets B cells has yet been approved for clinical use, all existing disease-modifying therapies (DMTs) for MS modulate B-cell immunity to some degree. This review examines the effects of MS DMTs on B-cell immunity. Most MS DMTs induced a relative decrease in circulating memory B cells with concomitant expansion of circulating B-cell precursors and/or naive B cells. B-cell function was also altered; most DMTs induced B-cell production of the anti-inflammatory cytokine interleukin 10 while inhibiting B-cell expression of proinflammatory cytokines. The commonalities in the effects of approved DMTs on B-cell phenotype and function among treated patients with MS are striking and suggest that effects on B cells underlie part of their efficacy. More complete understanding of how the existing DMTs modulate B-cell immunity may identify future targets for therapeutic intervention.
The World Health Organization Classification of Neoplastic Diseases of the Hematopoietic and Lymphoid Tissues
Authors: N.L. Harris, E.S. Jaffe, J. Diebold, G. Flandrin, H.K. Muller-Hermelink, J. Vardiman, T.A. Lister, C.D. Bloomfield
Journal: Annals of Oncology (1999)
Close genetic relationship between Salmonella enterica serovar Enteritidis isolated from patients with diarrhoea and poultry in the Republic of Korea
Authors: D.-H. Lee, J.-Y. Hyeon, J. Kim, J.S. Kim, S.J. Kim, S.-E. Jeon, S.-W. Choi, W.-T. Hong, C.-S. Song, S.-W. Lee
Journal: Clinical Microbiology and Infection (2015)
Response to Comment on Powers et al. Diabetes Self-management Education and Support in Type 2 Diabetes: A Joint Position Statement of the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics. Diabetes Care 2015;38:1372–1382
Authors: Margaret A. Powers, David G. Marrero
Journal: Diabetes Care (2015)

We agree with the letter from Bialo et al. (1) that the emotional health needs of people with diabetes need to be addressed. Indeed, increasing evidence shows that emotional health is a significant issue in people with diabetes. In this context, the American Diabetes Association (ADA) is committed to addressing all needs of people with diabetes and presents its recommendations in …
Abstract 1305: Erectile Dysfunction Predicts Cardiovascular Events in High Risk Patients Receiving Telmisartan, Ramipril or Both
Authors: Michael Bohm, Magnus Baumhakel, Koon Teo, Peter Sleight, Jeffrey Probstfield, Peggy Gao, Johannes H Mann, Rafael Diaz, Gilles R Dagenais, Garry L Jennings, Lisheng Liu, Petr Jansky, Salim Yusuf, Ontarget
Journal: Circulation (2009)

Background: Erectile Dysfunction (ED) is associated with cardiovascular risk factors and atherosclerosis. Inhibition of the renin-angiotensin system in high-risk patients reduces cardiovascular eve...
Cardiovascular-Specific Mortality and Kidney Disease in Patients Undergoing Vascular Surgery
Authors: Matthew Huber, Tezcan Ozrazgat-Baslanti, Paul Thottakkara, Salvatore Scali, Azra Bihorac, Charles Hobson
Journal: JAMA Surgery (2015)

Acute kidney injury (AKI) affects as many as 40% of patients undergoing surgery and is associated with increased all-cause mortality. Chronic kidney disease (CKD) is a well-known risk factor for cardiovascular mortality.To determine the association between kidney disease and long-term cardiovascular-specific mortality after vascular surgery.A single-center cohort of 3646 patients underwent inpatient vascular surgery from January 1, 2000, to November 30, 2010, at a tertiary care teaching hospital. To determine cause-specific mortality for patients undergoing vascular surgery, a proportional subdistribution hazards regression analysis was used to model long-term cardiovascular-specific mortality while treating any other cause of death as a competing risk. Kidney disease constituted the main covariate after adjusting for baseline patient characteristics, surgery type, and admission hemoglobin level. Final follow-up was completed July 2014 to assess survival through January 31, 2014, and data were analyzed from June 1, 2014, to September 7, 2015.Perioperative AKI, presence of CKD, and overall and cause-specific mortality.Among the 3646 patients undergoing vascular surgery, perioperative AKI occurred in 1801 (49.4%) and CKD was present in 496 (13.6%). The top 2 causes among the 1577 deaths in our cohort were cardiovascular disease (845 of 1577 [53.6%]) and cancer (173 of 1577 [11.0%]). Adjusted cardiovascular mortality estimates at 10 years were 17%, 31%, 30%, and 41%, respectively, for patients with no kidney disease, AKI without CKD, CKD without AKI, and AKI with CKD. Adjusted hazard ratios (95% CIs) for cardiovascular mortality were significantly elevated among patients with AKI without CKD (2.07 [1.74-2.45]), CKD without AKI (2.01 [1.46-2.78]), and AKI with CKD (2.99 [2.37-3.78]) and were higher than those for other risk factors, including increasing age (1.03 per 1-year increase; 1.02-1.04), emergent surgery (1.47; 1.27-1.71), and admission hemoglobin levels lower than 10 g/dL (1.39; 1.14-1.69) compared with a hemoglobin level of 12 g/dL or higher.Perioperative AKI is common in patients undergoing vascular surgery and is associated with a high risk for cardiovascular-specific mortality comparable to that seen with CKD. These findings reinforce the importance of preoperative and postoperative risk stratification for kidney disease and the implementation of strategies now available to help prevent perioperative AKI.
Lack of Adherence With the Analgesic Regimen: The Cancer Patients’ Perspective on a Two-Sided Problem
Authors: Marco Musi, Christine Miaskowski
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.12.2907 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12065570 Lack of Adherence With the Analgesic Regimen: The Cancer Patients’ Perspective on a Two-Sided Problem Marco MusixMarco MusiSearch for articles by this author Christine MiaskowskixChristine MiaskowskiSearch for articles by this author Show More Regional Hospital, Aosta, ItalyUniversity of California, San Francisco, San Francisco, CA https://doi.org/10.1200/JCO.2002.20.12.2907 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15062002In Reply:We appreciate the comments of Dr Musci and agree with his major points. It was not our intent to suggest any failure on the part of the patient. Our intent was to emphasize that clinicians need to include an evaluation of the patient’s level of adherence with the analgesic regimen as part of the ongoing evaluation of the effectiveness of a pain management plan.1 Equally important, as Dr Musci points out, is the need to determine why patients are not taking their analgesic medications as prescribed and what their specific goals are. Pain management is much more than decreasing pain intensity scores and increasing analgesic intake. Effective pain management includes caring for the whole person and assisting patients in achieving optimal pain control with minimal side effects.REFERENCE1. Miaskowski C, Dodd MJ, West C, et al: Lack of adherence with the analgesic regimen: A significant barrier to effective cancer pain management. J Clin Oncol 19:: 4275,2001-4279, Link, Google Scholar
Lung cancer survival in Norway, 1997–2011: from nihilism to optimism
Authors: Yngvar Nilssen, Trond Eirik Strand, Lars Fjellbirkeland, Kristian Bartnes, Bjørn Møller
Journal: European Respiratory Journal (2015)

We examine changes in survival and patient-, tumour- and treatment-related factors among resected and nonresected lung cancer patients, and identify subgroups with the largest and smallest survival improvements.National population-based data from the Cancer Registry of Norway, Statistics Norway and the Norwegian Patient Register were linked for lung cancer patients diagnosed during 1997-2011. The 1- and 5-year relative survival were estimated, and Cox proportional hazard regression, adjusted for selected patient characteristics, was used to assess prognostic factors for survival in lung cancer patients overall and stratified by resection status.We identified 34 157 patients with lung cancer. The proportion of histological diagnoses accompanied by molecular genetics testing increased from 0% to 26%, while those accompanied by immunohistochemistry increased from 8% to 26%. The 1-year relative survival among nonresected and resected patients increased from 21.7% to 34.2% and 75.4% to 91.5%, respectively. The improved survival remained significant after adjustment for age, sex, stage and histology. The largest improvements in survival occurred among resected and adenocarcinoma patients, while patients ≥80 years experienced the smallest increase.Lung cancer survival has increased considerably in Norway. The explanation is probably multifactorial, including improved attitude towards diagnostic work-up and treatment, and more accurate diagnostic testing that allows for improved selection for resection and improved treatment options.
Scalp-cooling by DIGNICAP system for the prevention of chemotherapy-induced hair loss in breast cancer patients.
Authors: M. Kato
Journal: Journal of Clinical Oncology (2010)

e11034 Background: The DigniCap system (Dignitana AB, Sweden) is an established, highly effective and safe device to prevent hair loss by cooling the scalp. This study evaluates the DigniCap system and presents the results of scalp hypothermia on breast cancer patients undergoing chemotherapy. Methods: DigniCap is using a digitized system for controlled scalp-cooling with a refrigerator integrated into a control unit with the soft and tight-fitting silicon cap. Scalp temperature was maintained at +5 centigrades throughout drug administration and for at least 30 min after discontinuing the infusion. Photographs of each patient's scalp were taken before starting chemotherapy. The evaluation was made using a visual analogue scale. All patients answered a questionnaire with 15 questions regarding physical and psychological issues. Results: From August 2007 to October 2009, 255 patients, aged 25-77 yrs (mean 47.4), with breast cancer were examined completely. The patients were treated with either paclitaxel (60 mg/m2 weekly) plus cyclophosphamide (500 mg/m2) (176 patients) or paclitaxel plus Herceptin combination (29 patients) or epirubicine (40 mg/m2 biweekly) plus cyclophosphamide (28 patients). Remaining 22 patients were treated either combination by 5FU, CPT-11, vinorelbine or CBDCA. The results were as follows: 141 patients (55.3%) were classed as grade 0, 68 patients (26.7%) as grade 1, 40 patients (15.7%) as grade 2 and 6 patients (2.4%) as grade 3. Conclusions: DigniCap system using scalp-cooling is effective method to prevent chemotherapy-induced hair loss in patients with cancer of the breast. No significant financial relationships to disclose.
Updated report of a phase III study of induction therapy with gemcitabine + carboplatin (GC) followed by either delayed vs. immediate second-line therapy with docetaxel (D) in advanced non-small cell lung cancer (NSCLC)
Authors: P. Fidias, S. R. Dakhil, A. P. Lyss, D. M. Loesch, D. Waterhouse, J. Cunneen, Z. Ye, F. Tai, C. K. Obasaju, J. H. Schiller
Journal: Journal of Clinical Oncology (2006)

7032 Background: GC is an active regimen in patients with advanced NSCLC. For non-progressors after induction treatment, optimal timing of sequential therapy is unclear. Is it best to sequence immediately to an active non-cross resistant agent or delay the introduction of this agent until time of disease progression (PD)? This trial was designed to answer this question. Methods: Pts with Stage IIIB or IV NSCLC were enrolled. G 1000mg/m 2 was administered on day 1,8 followed by C at AUC 5.0 on day 1. After 4 cycles, non-progressers were then randomized to immediate D (75mg/m 2 administered on day 1 every 3 wks) or delayed D (pts were observed until first evidence of PD). Conclusions: This study confirms that it is possible to deliver docetaxel immediately following four cycles of GC without significantly increasing toxicity. The response rate of 42.1% and clinical benefit rate (CR+PR+SD) of 88.2% observed in the immediate D arm compares favorably with the rates of 6.1% and 60.6% of the delayed D arm. Additional toxicity and response information will be available at the time of the meeting. [Table: see text] [Table: see text]
Clinical pharmacist integration into the oncology medical home.
Authors: Mandy Y. Chan, Andrew Kenneth Yu, Rebecca W. Lau, Eva Linh, Eric Y. Chen, Karen Birmingham
Journal: Journal of Clinical Oncology (2015)

e20703 Background: Over the last decade, the use of oral oncolytics has increased dramatically. In 2011, Group Health Oncology recognized the need for management of complex high-risk and high-cost medication therapies in patients who often have comorbidities. In response to the demand, Group Health pharmacy designed a clinical oral chemotherapy management program aligned with our existing primary care medical home model. The program's goal is to integrate oncology trained clinical pharmacists (OTP) into the medical oncology care team to provide comprehensive medication management for cancer patients. This abstract describes our training, design, and implementation of our oral chemotherapy program. Methods: Three clinical pharmacists with 30 years of combined primary care experience received ten intensive weeks of oncology training outlined below. Results: After completing training, pharmacists received referrals from oncologists and managed patients on oral oncolytics. A comprehensive evaluation of disease states, labs, and drug interactions was conducted before the onboarding office visit. During this face to face visit, OTP provided education about cancer therapy, supportive care, and side effect management. OTP also managed drug therapy for other chronic diseases. In addition, OTP helped expedite the start of therapy by removing barriers, such as insurance authorization, financial burden, and procurement of drug therapy. Follow up appointments were scheduled throughout the course of therapy to ensure safety, tolerability, adherence, and efficacy. Conclusions: Group Health has integrated clinical pharmacists successfully into our oncology medical home model. It is possible to develop a training program for general practice clinical pharmacists to become proficient in comprehensive cancer care management. Based on three months of data, over 40 significant and cost saving interventions were made by our three OTP. Our future direction is to expand pharmaceutical care to all oncology patients beyond oral oncolytics management. Didactic Training Focus Areas Common oncology disease states, drug therapy, supportive care Experiential Training Work shadow with oncology team members: providers, nurses, social workers, pharmacists
Non steroidal anti-inflammatory drugs and breast cancer: Study of gene-environment interaction among african-american women
Authors: John S. Sesay, Veronica C. Nwosu, Robert C. Millikan, Patricia G. Moorman
Journal: Cancer Research (2005)

2549  Background: Breast cancer is the most common cancer among U.S. women, with approximately 200,000 women diagnosed each year. Given the magnitude of the problem, identification of prevention strategies is a high priority in cancer research. Recent findings suggest use of non-steroidal anti-inflammatory drugs (NSAIDs) and a polymorphism in the COX-2 gene may be associated with a lower risk of certain types of cancer, particularly colon cancer. Breast cancers overexpress COX-2, however there are no published data on whether the COX-2 polymorphism affects breast cancer risk. Methods: We used data and blood samples from a population-based, case-control study in North Carolina to evaluate the relationship between NSAID’s use, a COX-2 polymorphism (valine to alanine at residue 511), and breast cancer. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to determine if carriers of the COX-2 polymorphism were at lower risk for breast cancer and if there was an interaction between this polymorphism and NSAID use. Results: NSAID users were at reduced risk for breast cancer (OR= 0.4, 95% CI 0.3 - 0.6). However, we found no evidence that the COX-2 polymorphism reduced breast cancer risk; carriers of the ala allele had an OR of 1.1 (95% CI 0.7 - 1.6). There was no significant interaction between NSAID exposure and genotype (Tables I, II, and III). Conclusions: The COX-2 pathway represents a possible target for breast cancer prevention. Our data suggest NSAIDs reduce breast cancer risk, but additional work is needed to determine the genetic pathways through which they affect carcinogenesis. This work was supported by CA091410 - Comprehensive Minority Biomedical Branch, Minority Institution Cancer Center Partnership of the National Cancer Institute, NIH, and P20CA091433.
Development of TRX518, an aglycosyl humanized monoclonal antibody (Mab) agonist of huGITR.
Authors: M. Rosenzweig, J. Ponte, I. Apostolou, D. Doty, J. Guild, M. Slavonic, P. Ponath, L. Vaickus
Journal: Journal of Clinical Oncology (2010)

e13028 Background: Glucocorticoid-induced tumor necrosis factor receptor (GITR) is expressed on several cell types, including regulatory and effector T cells, B cells, NK cells, and antigen-presenting cells. In murine models, our agonistic anti-mouse (m) GITR antibody was a robust vaccine adjuvant and, in combination with chemotherapy, significantly reduced tumor burden and prolonged survival compared with antibody or chemotherapy alone. The anti-mGITR Mab enhanced effector T cell responses and ablation of T regulatory cell-mediated suppression. A similar effect was observed when a chimeric anti-human (hu) GITR Mab (Ch-6C8-Agly) was used in nonhuman primates (NHP). NHP treated with anti-huGITR had augmented humoral and cellular immune responses compared with controls. Mab treatment was well tolerated with no observed adverse events. Methods: TRX518, a fully humanized IgG1 anti-huGITR Mab, was constructed. In addition to humanization, heavy chain asparagine 297 was substituted with alanine to eliminate N-linked glycosylation. This mutation abrogates Fc region functionality, including antibody-dependent cellular cytotoxicity and complement-mediated lysis. Further in vitro and in vivo characterization of TRX518 was conducted. Results: TRX518 bound to GITR on CD4+ and CD8+ naïve and memory T cells, B cells, NK cells, NKT cells, monocytes, and macrophages, yet was nondepleting. Though TRX518 costimulated suboptimally activated peripheral blood lymphocytes it was not a superagonist, as it did not induce proliferation by itself. Plate-bound TRX518 did not induce appreciable cytokine release (IL-2, IL-6, IL-10, TNFa, IFNg). TRX518 blocked the interaction of GITR with its ligand and enhanced the cytotoxicity of NK cells. However, it did not block an allogeneic mixed lymphocyte reaction (MLR) or enhance an autologous MLR. Cynomolgous macaque and human tissue cross studies and an IND-enabling GMP toxicology study are complete. Conclusions: TRX518 is a promising candidate for evaluation in human cancer indications. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tolerx Tolerx
Hormonal Evaluation of Hyperandrogenism in Women
Authors: Susan Sam, David A. Ehrmann
Journal: JAMA (2015)

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Screening Process Failures for Hepatocellular Carcinoma
Authors: Amit G Singal, Jorge A Marrero, Adam Yopp
Journal: Journal of the National Comprehensive Cancer Network (2014)

More than 60% of patients with hepatocellular carcinoma (HCC) are diagnosed at a late stage, suggesting potential breakdowns in the HCC screening process. Understanding which steps in the screening process are not being performed is essential for designing effective interventions. To characterize HCC screening process failures, a retrospective cohort study of patients with cirrhosis diagnosed with HCC at a large urban safety-net hospital was conducted between 2005 and 2012. Screening process failures during the year before HCC diagnosis were characterized into 3 categories: absence of surveillance, failure of detection, and delayed follow-up. Univariate and multivariate analyses were performed to identify predictors of screening process failures. A total of 185 patients with cirrhosis and HCC were identified, of whom 91 (49%) were diagnosed at an early stage (Barcelona Clinic Liver Cancer system stage A). Only 16 (8.6%) patients successfully completed the screening process. Absence of surveillance was the most common screening process failure, found in 75.7% of all patients, and was associated with trends toward lower rates of early tumor detection (odds ratio, 0.51; 95% CI, 0.23-1.09) and worse overall survival (hazard ratio, 0.79; 95% CI, 0.49-1.25). Failure of detection and delayed follow-up were found in 11.4% and 2.7% of patients, respectively.