tbuckley/cabot-search huggingface dataset:
What can physicians do to promote patient involvement in decision making (DM) in the oncology consultation?
Authors: P. M. Ellis, S. Dimitry, C. Charles, M. O’Brien, T. J. Whelan
Journal: Journal of Clinical Oncology (2007)

19553 Background: Facilitating patient involvement in TDM is a desirable feature of the oncology consultation. Greater patient involvement in TDM may lead to improved patient satisfaction, compliance and reduced psychological morbidity. However, there is little empiric evidence defining physician behaviors and attributes that facilitate patient involvement in TDM. This study used qualitative methods to identify such behaviors and attributes suggested by both practicing oncologists and patients. Methods: Semi-structured interviews were conducted with 11 medical, 10 radiation oncologists and 19 patients with breast, lung, GI, or GU cancer to determine physician behaviors and attributes that facilitate patient involvement in TDM. Interviews were audiotaped and transcribed verbatim, then analyzed independently by two researchers using inductively derived coding categories and predetermined coding rules. Behaviors and attributes were identified and coded into common themes. Six focus groups with an additional 37 patients were conducted to review these behaviors and attributes. Results: A total of 231 individual physician behaviors and attributes were identified by physicians (179) and patients (52) that facilitate patient involvement in DM. Common behaviors and attributes identified from the interviews include: assessing patient’s understanding and preferences, providing information, explaining the DM process, providing information on treatment options, allowing time to consider treatment options, checking patient understanding of options and inviting patient input into decisions. Other behaviors such as physicians’ communication skills were reported as facilitating TDM. Specific physician personality attributes, such as empathy, were identified as important facilitators. Conclusions: Physicians and patients identify a large number of physician behaviors and attributes that may facilitate patient involvement in TDM. These include both behaviors that are important in general physician-patient communication, as well as those that are specifically related to the decision making process. Further research is ongoing to determine the importance of these factors and approaches to encourage their use in the oncology consultation. No significant financial relationships to disclose.
In Vivo Bioluminescence Imaging of Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation with Ex Vivo Manipulated Murine T Cells.
Authors: Michael P. Rettig, Julie K. Ritchey, Julie L. Prior, David Piwnica-Worms, Mark L. Bonyhadi, John F. DiPersio
Journal: Blood (2004)
PI-103, a Dual Inhibitor of Class IA Phosphatidylinositol 3-Kinase and Mammalian Target of Rapamycin, Has Cytotoxic Activity in T-Cell Acute Lymphoblastic Leukemia Cells: A New Therapeutic Strategy in T-Cell Acute Lymphoblastic Leukemia.
Authors: Francesca Chiarini, Federica Fala, Francesca Ricci, PierLuigi Tazzari, Annalisa Astolfi, Andrea Pession, James McCubrey, Alberto M. Martelli
Journal: Blood (2008)
Tissue-dependent and tissue-independent gene expression changes in metastatic colon cancer
Authors: P. Shen, G. M. Hellmann, W. H. Gmeiner
Journal: Journal of Clinical Oncology (2006)

20014 Background: Changes in gene expression that occur during cellular transformation and establishment of metastases provide valuable information that may help determine prognosis and direct treatment. We have obtained gene expression profiles from primary colon tumors and metastases to the liver (V), lung (L), and peritoneum (P). Methods: Ten cases, with matched controls, were profiled for the expression of &gt;18,000 human transcripts using Affymetrix U133A chips. Data were filtered using GeneSifter analysis software to identify genes with 2-fold or greater differences in expression relative to the control group. Gene expression levels for primary colon samples were compared to normal colon while metastatic tissues were compared to primary colon samples. Differentially regulated genes were then associated with KEGG pathways for additional analysis. Results: Relative to normal colon samples, primary colon samples displayed high positive z-score values for genes involved in nitrogen and sulfur metabolism (7.30 and 8.10, respectively). Expression level changes for individual genes in each cluster were statistically significant (e.g. p = 0.014 for carbonic anhydrase I in the nitrogen metabolism cluster). Metastatic tissue from liver, lung and peritoneum all displayed substantially decreased expression for genes involved in butanoate and propanoate metabolism, valine, leucine and isoleucine degradation, and moderately decreased expression for genes involved in JAK-STAT signaling. For example, L-3-hydroxyacyl-Coenzyme A dehydrogenase (short chain), a gene involved in both butanoate metabolism and valine, leucine and isoleucine degradation, was down-regulated in tissue from all three metastatic sites relative to primary colon tumor tissue [p = 0.024 (V), p = 0.022 (L), p = 0.005 (P)]. In addition, genes involved in phosphatidylinositol signaling were down-regulated in liver metastases but not in lung or peritoneal metastatic tissue. Conclusions: These results demonstrate that changes in expression levels for genes involved in basic metabolism and cell signaling occur during the course of metastasis. The changes that occur during development of the metastatic phenotype can be independent of, or specific to, the site of metastasis. No significant financial relationships to disclose.
Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma
Authors: H. Ege, M. Gertz, S. N. Markovic, M. Q. Lacy, A. Dispenzieri, S. R. Hayman, S. K. Kumar, M. R. Litzow, D. A. Gastineau, L. F. Porrata
Journal: Journal of Clinical Oncology (2006)

7605 Background: In the setting of autologous stem cell transplantation (ASCT) in multiple myeloma (MM), it has been shown that peripheral blood absolute lymphocyte count (ALC) on day 15 is an independent prognostic factor for clinical outcomes. Recently the International Staging System (ISS) for MM has been developed as a simple staging system to assess survival in newly diagnosed MM patients. The role of ALC on survival in newly diagnosed MM patients is unknown. Methods: Between 1994 and 2002, 1,835 consecutive MM patients were evaluated at the Mayo Clinic, Rochester. Of these patients, we retrospectively analyzed 584 MM patients that were originally diagnosed and followed at the Mayo Clinic. The primary end point was to assess the role of ALC at the time of MM diagnosis on overall survival (OS). OS was measured from the date of diagnosis to time of death or last follow-up. ALC was analyzed as a continuous variable and dichotomized based on finding the optimal cut point based on the log-rank statistic. ALC was then compared to the ISS. Results: The median age of the cohort was 67 years (range: 29–94 years), including 234 females and 350 males. The median follow-up was 32 months (range: 1–136 months). The median ALC at diagnosis was 1.2 x 10 9 /L (range: 0.12–5.44 x 10 9 /L). ALC, as a continuos variables was identified as a prognostic factor for OS (HR= 0.466, 95%CI= 0.396–0.547, p &lt; 0.0001). MM patients with an ALC ≥ 1.3 x 10 9 /L experienced a superior OS compared with MM patients with an ALC &lt; 1.3 x 10 9 /L (55.5 months versus 22.6 months, p&lt; 0.0001). In the multivariate analysis, ALC was independent prognostic factor when compared to the ISS (HR = 0.580, 95%CI=0.518–0.647, p&lt; 0.0001). Conclusions: Our study shows that ALC at diagnosis for MM is an independent prognostic factor for OS, suggesting how the host immune status plays a critical role in the survival of patients with MM. No significant financial relationships to disclose.
Bariatric Surgery in Women of Childbearing Age, Timing Between an Operation and Birth, and Associated Perinatal Complications
Authors: Brodie Parent, Ira Martopullo, Noel S. Weiss, Saurabh Khandelwal, Emily E. Fay, Ali Rowhani-Rahbar
Journal: JAMA Surgery (2016)

Metabolic changes after maternal bariatric surgery may affect subsequent fetal development. Many relevant perinatal outcomes have not been studied in this postoperative population, and the risks associated with short operation-to-birth (OTB) intervals have not been well examined.To examine the risk for perinatal complications in women with a history of bariatric surgery (postoperative mothers [POMs]) by comparing them with mothers without operations (nonoperative mothers [NOMs]) and examining the association of the OTB interval with perinatal outcomes.This investigation was a population-based retrospective cohort study (January 1, 1980, to May 30, 2013) at hospitals in Washington State. Data were collected from birth certificates and maternally linked hospital discharge data. Participants were all POMs and their infants (n = 1859) and a population-based random sample of NOMs and their infants frequency matched by delivery year (n = 8437).Bariatric operation before birth or categories of OTB intervals.The primary outcomes were prematurity, neonatal intensive care unit (NICU) admission, congenital malformation, small for gestational age (SGA), birth injury, low Apgar score (≤8), and neonatal mortality. Poisson regression was used to compute relative risks (RRs) and 95% CIs, with adjustments for maternal body mass index, delivery year, socioeconomic status, age, parity, and comorbid conditions.A total of 10 296 individuals were included in the analyses for this study. In the overall cohort, the median age was 29 years (interquartile range, 24-33 years). Compared with infants from NOMS, infants from POMs had a higher risk for prematurity (14.0% vs 8.6%; RR, 1.57; 95% CI, 1.33-1.85), NICU admission (15.2% vs 11.3%; RR, 1.25; 95% CI, 1.08-1.44), SGA status (13.0% vs 8.9%; RR, 1.93; 95% CI, 1.65-2.26), and low Apgar score (17.5% vs 14.8%; RR, 1.21; 95% CI, 1.06-1.37). Compared with infants from mothers with greater than a 4-year OTB interval, infants from mothers with less than a 2-year interval had higher risks for prematurity (11.8% vs 17.2%; RR, 1.48; 95% CI, 1.00-2.19), NICU admission (12.1% vs 17.7%; RR, 1.54; 95% CI, 1.05-2.25), and SGA status (9.2% vs 12.7%; RR, 1.51; 95% CI, 0.94-2.42).Infants of mothers with a previous bariatric operation had a greater likelihood of perinatal complications compared with infants of NOMs. Operation-to-birth intervals of less than 2 years were associated with higher risks for prematurity, NICU admission, and SGA status compared with longer intervals. These findings are relevant to women with a history of bariatric surgery and could inform decisions regarding the optimal timing between an operation and conception.
The geography of imported malaria to non-endemic countries: a meta-analysis of nationally reported statistics
Authors: Andrew J Tatem, Peng Jia, Dariya Ordanovich, Michael Falkner, Zhuojie Huang, Rosalind Howes, Simon I Hay, Peter W Gething, David L Smith
Journal: The Lancet Infectious Diseases (2016)

BackgroundMalaria remains a problem for many countries classified as malaria free through cases imported from endemic regions. Imported cases to non-endemic countries often result in delays in diagnosis, are expensive to treat, and can sometimes cause secondary local transmission. The movement of malaria in endemic countries has also contributed to the spread of drug resistance and threatens long-term eradication goals. Here we focused on quantifying the international movements of malaria to improve our understanding of these phenomena and facilitate the design of mitigation strategies.MethodsIn this meta-analysis, we studied the database of publicly available nationally reported statistics on imported malaria in the past 10 years, covering more than 50 000 individual cases. We obtained data from 40 non-endemic countries and recorded the geographical variations.FindingsInfection movements were strongly skewed towards a small number of high-traffic routes between 2005 and 2015, with the west Africa region accounting for 56% (13 947/24 941) of all imported cases to non-endemic countries with a reported travel destination, and France and the UK receiving the highest number of cases, with more than 4000 reported cases per year on average. Countries strongly linked by movements of imported cases are grouped by historical, language, and travel ties. There is strong spatial clustering of plasmodium species types.InterpretationThe architecture of the air network, historical ties, demographics of travellers, and malaria endemicity contribute to highly heterogeneous patterns of numbers, routes, and species compositions of parasites transported. With global malaria eradication on the international agenda, malaria control altering local transmission, and the threat of drug resistance, understanding these patterns and their drivers is increasing in importance.FundingBill & Melinda Gates Foundation, National Institutes of Health, UK Medical Research Council, UK Department for International Development, Wellcome Trust.
Five-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting
Authors: André Lamy, P.J. Devereaux, Dorairaj Prabhakaran, David P. Taggart, Shengshou Hu, Zbynek Straka, Leopoldo S. Piegas, Alvaro Avezum, Ahmet R. Akar, Fernando Lanas Zanetti, Anil R. Jain, Nicolas Noiseux, Chandrasekar Padmanabhan, Juan-Carlos Bahamondes, Richard J. Novick, Liang Tao, Pablo A. Olavegogeascoechea, Balram Airan, Toomas-Andres Sulling, Richard P. Whitlock, Yongning Ou, Peggy Gao, Shirley Pettit, Salim Yusuf
Journal: New England Journal of Medicine (2016)

We previously reported that there was no significant difference at 30 days or at 1 year in the rate of the composite outcome of death, stroke, myocardial infarction, or renal failure between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report the results at 5 years (the end of the trial).A total of 4752 patients (from 19 countries) who had coronary artery disease were randomly assigned to undergo off-pump or on-pump CABG. For this report, we analyzed a composite outcome of death, stroke, myocardial infarction, renal failure, or repeat coronary revascularization (either CABG or percutaneous coronary intervention). The mean follow-up period was 4.8 years.There were no significant differences between the off-pump group and the on-pump group in the rate of the composite outcome (23.1% and 23.6%, respectively; hazard ratio with off-pump CABG, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72) or in the rates of the components of the outcome, including repeat coronary revascularization, which was performed in 2.8% of the patients in the off-pump group and in 2.3% of the patients in the on-pump group (hazard ratio, 1.21; 95% CI, 0.85 to 1.73; P=0.29). The secondary outcome for the overall period of the trial - the mean cost in U.S. dollars per patient - also did not differ significantly between the off-pump group and the on-pump group ($15,107 and $14,992, respectively; between-group difference, $115; 95% CI, -$697 to $927). There were no significant between-group differences in quality-of-life measures.In our trial, the rate of the composite outcome of death, stroke, myocardial infarction, renal failure, or repeat revascularization at 5 years of follow-up was similar among patients who underwent off-pump CABG and those who underwent on-pump CABG. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294 .).
C3-Mediated Extravascular Hemolysis In Paroxysmal Nocturnal Hemoglobinuria: An In Vitro Model to Dissect Complement C3 Activation Comparing the Effects of Complement Inhibitors Eculizumab, 3E7 and TT30 on C3 Fragment Processing and Hemolysis of PNH Erythrocytes
Authors: Antonio M. Risitano, Caterina Pascariello, Luigi Del Vecchio, Christopher J Horvath, Masha Fridkis-Hareli, V. Michael Holers, Margaret A Lindorfer, Ronald P Taylor
Journal: Blood (2010)
Chronic Fatigue Syndrome: An Update
Authors: A. L. Komaroff, D. S. Buchwald, MD
Journal: Annual Review of Medicine (1998)

Among the many patients who seek medical care for the complaint of fatigue, a small number suffer from chronic fatigue syndrome (CFS). CFS is a poorly understood condition characterized by debilitating fatigue and associated symptoms lasting at least six months. Studies indicate that the illness is not simply a manifestation of an underlying psychiatric disorder, but rather is an illness characterized by activation of the immune system, various abnormalities of several hypothalamic-pituitary axes, and reactivation of certain infectious agents.
The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models
Authors: Sen Zhang, Rana Anjum, Rachel Squillace, Sara Nadworny, Tianjun Zhou, Jeff Keats, Yaoyu Ning, Scott D. Wardwell, David Miller, Youngchul Song, Lindsey Eichinger, Lauren Moran, Wei-Sheng Huang, Shuangying Liu, Dong Zou, Yihan Wang, Qurish Mohemmad, Hyun Gyung Jang, Emily Ye, Narayana Narasimhan, Frank Wang, Juan Miret, Xiaotian Zhu, Tim Clackson, David Dalgarno, William C. Shakespeare, Victor M. Rivera
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Non–small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK+) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain. Mutations that confer resistance to second-generation ALK TKIs ceritinib and alectinib have also been identified. Here, we report the structure and first comprehensive preclinical evaluation of the next-generation ALK TKI brigatinib. Experimental Design: A kinase screen was performed to evaluate the selectivity profile of brigatinib. The cellular and in vivo activities of ALK TKIs were compared using engineered and cancer-derived cell lines. The brigatinib–ALK co-structure was determined. Results: Brigatinib potently inhibits ALK and ROS1, with a high degree of selectivity over more than 250 kinases. Across a panel of ALK+ cell lines, brigatinib inhibited native ALK (IC50, 10 nmol/L) with 12-fold greater potency than crizotinib. Superior efficacy of brigatinib was also observed in mice with ALK+ tumors implanted subcutaneously or intracranially. Brigatinib maintained substantial activity against all 17 secondary ALK mutants tested in cellular assays and exhibited a superior inhibitory profile compared with crizotinib, ceritinib, and alectinib at clinically achievable concentrations. Brigatinib was the only TKI to maintain substantial activity against the most recalcitrant ALK resistance mutation, G1202R. The unique, potent, and pan-ALK mutant activity of brigatinib could be rationalized by structural analyses. Conclusions: Brigatinib is a highly potent and selective ALK inhibitor. These findings provide the molecular basis for the promising activity being observed in ALK+, crizotinib-resistant patients with NSCLC being treated with brigatinib in clinical trials. Clin Cancer Res; 22(22); 5527–38. ©2016 AACR.
Dexamethasone combined with other antiemetics versus single antiemetics for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy: An updated systematic review and meta-analysis
Authors: Kamal Awad, Hussien Ahmed, Abdelrahman Ibrahim Abushouk, Safwat Al Nahrawi, Mohammed Yasser Elsherbeny, Salma Muhammad Mustafa, Attia Attia
Journal: International Journal of Surgery (2016)
Comparison of Different TBI Based Conditioning Regimen in Pediatric Haematological Malignancies: A Retrospective Study of 702 Patients from French Registry.
Authors: C. Maurin, P. Bordigoni, G. Michel, K. Yakouben, E. Gluckman, J.P. Jouet, C. Galambrun, F. Mechinaud, J.Y. Cahn, G. Souillet, E. Vilmer, J.H. Dalle
Journal: Blood (2005)
Abstract B30: Discovery and functional characterization of novel anti-PD-1 antibodies using ex vivo cell-based assays, single-cell immunoprofiling, and in vivo studies in humanized mice
Authors: Felix Scheuplein, Sheila Ranganath, Thomas McQuade, Lei Wang, Vikki Spaulding, Sri Vadde, Jennifer Watkins-Yoon, Bin Feng, Shanu Mehta, Maria Isabel Chiu, Cokey Nguyen
Journal: Cancer Research (2016)

Abstract Given recent approvals of anti-PD-1 inhibitors Keytruda (pembrolizumab) and Opdivo (nivolumab) for treatment of metastatic melanoma and non-small cell lung cancer NSCLC, we asked whether additional anti-PD-1 inhibitors with different epitopes or potentially differentiated mechanisms of action can provide clinical benefit beyond the two marketed therapies. Using Enumeral's proprietary single cell technology, we generated more than 300 anti-PD-1 monoclonal antibodies from primary B cells. Bioinformatics analysis of sequences show these antibodies comprise 26 distinct clades, or families, that bind to PD-1. Results from binding studies further indicate we have discovered a family of novel antibodies that do not appear to compete with currently marketed antibodies for binding to PD-1, nor do they appear to compete with PD-L1, suggesting a differentiated mechanism of action. We have humanized two lead antibodies for preclinical testing and in preparation for clinical studies. Here we describe functional characterization of the two lead antibodies using cell-based ex vivo assays, patient-derived tumor profiling assays using our single-cell platform, and in vivo studies in humanized NSG mice. Results show that the two lead anti-PD-1 antibodies exhibit a higher level of T cell activation in mixed lymphocyte reaction (MLR) assays using primary human immune cells. Second, these antibodies also demonstrated dose-dependent increases in T cell CD25 expression. Next, to test the effect of the two lead anti-PD-1 antibodies on tumor growth, we are conducting a study using a patient-derived tumor (PDX) model on humanized NSG mice. NSG mice reconstitute a full human immune system including a functional T, B cell repertoire, enabling the direct, in vivo evaluation of our human anti-PD-1 antibodies. Effects of drug treatment on tumor growth, transcriptome (RNA seq) and protein expression (IHC) will be described. Finally, results from ex vivo tumor profiling comparing the immmunomodulatory effects of our anti-PD-1 antibodies on tumor-infiltrating lymphocyte function will also be presented. Citation Format: Felix Scheuplein, Sheila Ranganath, Thomas McQuade, Lei Wang, Vikki Spaulding, Sri Vadde, Jennifer Watkins-Yoon, Bin Feng, Shanu Mehta, Maria Isabel Chiu, Cokey Nguyen. Discovery and functional characterization of novel anti-PD-1 antibodies using ex vivo cell-based assays, single-cell immunoprofiling, and in vivo studies in humanized mice. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B30.
Once Weekly Bortezomib (Velcade) Preserves Bone Health by a Direct Effect on Osteoclast Function Independent of Its Effect on the Malignant Plasma Cells.
Authors: Shachar Peles, Nicholas M. Fisher, Feng Gao, Steven M. Devine, Michael H. Tomasson, John F. DiPersio, Ravi Vij
Journal: Blood (2005)
Incidence and Patient Survival of Myeloproliferative Neoplasms (MPNs) and Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPNs) in the United States: A Population-Based View of the Modern Diagnostic Era
Authors: Samer A Srour, Susan S Devesa, Lindsay M Morton, David P Check, Rochelle E Curtis, Martha S Linet, Graca M Dores
Journal: Blood (2015)
GW26-e2189 MiR-21 Ameliorates Cerebral Ischemia/Reperfusion Injury via PI3K/Akt/GSK-3β Pathway
Authors: Qian Wang, Jianbing Zhu, Lei Zhang, Huiying Xie, Chuanyong Wu, Xiaohui Liang, Shujun Xu, Jiatao Lou
Journal: Journal of the American College of Cardiology (2015)