tbuckley/cabot-search huggingface dataset:
A willingness-to-pay study of vascular endothelial growth factor inhibitors among patients with advanced non-small cell lung cancer
Authors: R. J. Goldberg, R. W. Jang, N. B. Leighl
Journal: Journal of Clinical Oncology (2009)

6581 Background: Bevacizumab, a recombinant antibody which neutralizes vascular endothelial growth factor (VEGF), has been approved for the treatment of advanced non-small cell lung cancer (NSCLC). Costs of novel anticancer medications such as bevacizumab can be prohibitive for many lung cancer patients. This study sought to determine patients’ willingness-to pay (WTP) for bevacizumab and identify Canadian patient attitudes towards unfunded chemotherapeutic drugs. Methods: Participants attending outpatient lung cancer clinics at a major Canadian cancer center were given information pertaining to the risks and benefits of treatment with bevacizumab and were then asked about their WTP for this agent. Demographic and socioeconomic data were collected. A semi-structured interview was utilized to define the factors that limit patient access to unfunded chemotherapeutic agents. Results: 35 advanced NSCLC patients with a median age of 64.5 years and a median income of $40,000-$60,000 CAD consented to participate. Overall, participants were willing to pay a median of $75 CAD ($19-$250 CAD) per month for VEGF inhibitors, much less than the market cost of $8,000 CAD per month. 25 of 35 (71.4%) participants felt that the government should cover 100% of the drug cost, while 0%, 2.9%, 5.7%, and 20% of participants felt that the government should cover 0%, 25%, 50%, and 75% of the cost, respectively. Qualitative themes that arose included: (1) financial barriers are the primary obstacle in gaining access; (2) patients understand that the government cannot fund all novel cancer therapies; (3) patients are not willing to take loans or seek treatment outside of Canada without the prospect of cure; and (4) patients believe their oncologist will discuss all potential therapies, irrespective of access issues. Conclusions: Novel chemotherapeutic agents are unaffordable for the majority of NSCLC patients. Most patients would like the government to cover the cost of treatment, but many agree that the modest benefits of novel therapies may not always justify the large associated cost for government and publicly funded healthcare systems. [Table: see text]
Abstract 12530: Cardiac Resynchronization Therapy Affects Sleep Apnea and Quality of Sleep in Patients With Chronic Heart Failure
Authors: Aleksander Kusiak, Jerzy Wilinski, Danuta Czarnecka, Katarzyna Styczkiewicz, Bogumila Bacior, Marek Jastrzebski, Tomasz Sondej, Malgorzata Kloch-Badelek
Journal: Circulation (2012)

Background: Patients with chronic heart failure(CHF)often have sleep-related breathing disorders that contribute to exacerbation of CHF. Biventricular stimulation (CRT) not only improves mechanical...
KSHV-encoded vIL-6 collaborates with deregulated c-Myc to drive plasmablastic neoplasms in mice
Authors: T R Rosean, C J Holman, V S Tompkins, X Jing, M D Krasowski, S Rose-John, S Janz
Journal: Blood Cancer Journal (2016)

KSHV-encoded vIL-6 collaborates with deregulated c-Myc to drive plasmablastic neoplasms in mice
Epidemiology of Mycoplasma pneumoniae infections in Poland : 28 years of surveillance in Warsaw 1970-1997
Authors: W Rastawicki, S Kaluzewski, M Jagielski, R Gierczyski
Journal: Eurosurveillance (1998)

Mycoplasma pneumoniae is a common cause of lower respiratory tract disease in humans, particularly among older children, adolescents, and young adults. Infections are endemic in cities and epidemic increases are observed at intervals of 4 to 7 years. M. p
Abstract P332: Thirty Day Readmissions After Myocardial Infarction in the Community
Authors: Shannon M Dunlay, Susan A Weston, Jill M Killian, Malcolm R Bell, Allan S Jaffe, Veronique L Roger
Journal: Circulation (2012)

Background: Hospital readmissions are considered to be a quality of care indicator, yet little is known about their occurrence and predictors after myocardial infarction (MI) in the community. Methods: We identified all Olmsted County residents with incident MI from 1987-2007 and evaluated 30-day rehospitalizations. The reason for readmission was categorized based on ICD-9 code. Safety endpoints of revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or fibrinolysis included stroke, acute kidney injury (rise in creatinine post-procedure of &gt;0.5 mg/dL), access site complication (PCI), and gastrointestinal or other bleeding. Cox proportional hazard regression models were used to examine the predictors of readmission. Results: A total of 2617 patients (mean age 67 years, 41% female) had incident MI (32% with ST-elevation) from 1987-2007 and survived their initial hospitalization. A total of 583 readmissions occurred within 30 days among 512 (19.6%) patients. Approximately half (n=286, 49.1%) of readmissions were due to cardiovascular causes, and of these, most were due to ischemic heart disease (n=175, 61.2%) or heart failure (n=56, 19.6%). The proportion of non-cardiovascular rehospitalizations increased over time, from 42.2% from 1993-97 to 59.4% from 2003-07 (p for trend=0.01). A minority of those readmitted for cardiovascular reasons required repeat angiogram (n=110, 38.5%) or revascularization (n=88, 50 PCI, 38 CABG). After adjustment for confounders, key factors were associated with increased rehospitalization risk ( Figure ). Following PCI (n=1230), a stroke or bleeding event (adjusted HR 1.69, 95% CI 1.09-2.61, p=0.02) and acute kidney injury (HR 2.50, 95% CI 1.61-3.87, p&lt;0.01) were associated with markedly increased readmission risk. Conclusions: Half of readmissions within 30 days of MI are for non-cardiovascular reasons, and this proportion has increased. Comorbidity and complications of revascularization are key predictors of readmission.
Molecular identification of carcinoma of unknown primary (CUP) with gene expression profiling
Authors: K. Z. Qu, H. Li, J. D. Whetstone, A. D. Sferruzza, R. A. Bender
Journal: Journal of Clinical Oncology (2007)

21024 Background: We previously reported a method for determining the site of tumor origin for CUP by comparing a 92- gene expression profile to that in a database created from 600 primary and metastatic tumor bank specimens of known origin. K-nearest neighbor analysis was used to determine the likelihood of an unknown patient specimen originating from a particular site with the likelihood assigned as a confidence level and reported as high, medium, low, or unclassified. Herein, we report the analysis of the gene expression profiling results from our initial series of clinical CUP specimens. Methods: We reviewed the results of 76 consecutive de-identified patient samples submitted to our laboratory for routine CUP testing. RNA was extracted from the formalin-fixed, paraffin-embedded (FFPE) tissue blocks and cDNA products used in a semi-quantitative real-time PCR to detect 87 tumor-associated genes and 5 reference genes. Gene expression data were then compared with our database and k-nearest neighbor analysis used to identify the 5 closest neighbors. If all 5 or 4/5 were the same, the result was classified as “high likelihood”, 3/5 = “moderate likelihood”, 2/5 = “low likelihood” and none matching was “unclassifiable”. Results: For the 76 clinical CUP samples tested, gene profiling analysis yielded high-likelihood predictions for 34 (45%), moderate for 12 (16%), low for 12 (16%), and unclassified for 14 (18%); amplification was inadequate for 4 (5%) samples. Overall, gene profiling analysis yielded classifiable predictions in 58 (76%) of clinical CUP samples. An occult carcinoid, metastatic melanoma and adenocarcinoma of the endocervix were identified and then found clinically using this assay. Conclusions: Our previous findings indicate that gene expression profiling can correctly identify the site of tumor origin in a high percentage of tumor bank samples. Data from the present study suggests that this approach can identify a primary site of tumor origin in 76% of actual clinical specimens from pathologist-submitted CUP cases. No significant financial relationships to disclose.
Improved survival in esophageal cancer in the period 1978 to 1983.
Authors: G Morstyn, R J Thomas, M Mullerworth, D J St John, P S Bhathal, M Abbott, R Van Cooten
Journal: Journal of Clinical Oncology (1986)

The outcome of therapy of adenocarcinomas and squamous-cell carcinomas of the esophagus is so poor that the results of new approaches to therapy, such as the addition of radiotherapy or chemotherapy, are often compared with those achieved in historical controls. To determine the validity of this approach in cancers with a poor outcome, the results of therapy were analyzed at our institution from Jan 11, 1978 to Aug 9, 1981 (77 patients) and compared with the results achieved in the period from Aug 14, 1981 to Feb 19, 1984 (77 patients). The patients were evenly matched for prognostic factors. It was found that the median survival of the first group of patients (4 months) was significantly less (P less than .01) than that of the recently treated group (10 months). This was due to the better median survival of patients treated surgically from 4 months in the early group to 29 months at present (P less than .01). There was no change in the survival of the other patients. The major improvement in the outcome of surgery was due to the reduction of the perioperative mortality rate to less than 5%. There was no detectable change in patient selection for surgery. The results indicate that even in tumors with a very poor outcome, such as esophageal cancer, large changes in results can occur without a specific change in therapy, and that historical controls may be misleading.
Relationship of<i> CRLF2</i> expression and outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): A report from the Children’s Oncology Group.
Authors: I. Chen, R. Harvey, C. G. Mullighan, M. L. Loh, M. Devidas, M. J. Borowitz, S. K. Tasian, D. Payne-turner, W. Wharton, J. Pullen, A. J. Carroll, W. L. Carroll, B. M. Camitta, S. Hunger, N. J. Winick, C. L. Willman
Journal: Journal of Clinical Oncology (2011)

9505 Background: We previously reported a highly significant association between over-expression of CRLF2 (cytokine receptor-like factor 2) and poor clinical outcomes in 207 uniformly-treated children with high-risk B-ALL (Blood 115:5312, 2010). To validate and extend these studies to standard risk cases we studied 896 B-ALL patients from COG P9905. Eligible patients included 344 with NCI high-risk (HR) features and 552 with standard-risk (SR) features. Methods: Quantitative RT-PCR assays were used to determine CRLF2 expression in the diagnostic leukemic cells. Averages of duplicate assays were used to establish ΔCt values relative to a control gene (EEF2). Using the ΔCt threshold determined from our prior studies, 117/896 B-ALL samples had elevated CRLF2 expression. These 117 samples and other 35 samples below the threshold were tested for genomic rearrangements of CRLF2 to detect the P2RY8-CRLF2 fusion or CRLF2 F232C mutations. Studies to detect the IGH@-CRLF2 translocation, IKZF1 (IKAROS) deletions, and JAK mutations are ongoing. Outcomes were evaluated using relapse-free survival (RFS) and other known risk factors. Results: CRLF2 overexpression was associated with a poorer outcome in HR, but not in SR, B-ALL. Among the 246 HR cases lacking detectable end-induction minimal residual disease, CRLF2 expression levels could further distinguish those B-ALL patients who had a very good (>80%) vs. poor (<40%) RFS (Hazard Ratio = 2.59; P=0.002). While P2RY8/CRLF2 fusions were seen only in high CRLF2-expressors, 6/17 CRLF2 F232C mutations were among low CRLF2 expressors. Down syndrome ALL cases had a relatively good outcome regardless of CRLF2 expression levels or NIH risk status. Conclusions: Elevated CRLF2 expression predicts a significantly poorer outcome in HR, but not SR, B-ALL and can be used with other prognostic factors to improve ALL risk classification. Standard-risk RFS High-risk RFS N Hazard ratio P N Hazard ratio P All cases (n=896) 552 – – 344 – – High CRLF2 81 1.20 .510 36 1.84 .019 Down syndrome (DS) 35 1.25 .571 5 0.94 .952 Genomic abnormalities 99 53 P2RY8 fusion 37 1.00 .988 14 1.64 .034 F232C mutation 15 – – 2 – –
Overall Prognosis of Advanced Breast Cancer (Abc) According to Chemotherapy (Ct) Treatment Lines: Correlation Analysis Between Progression-Free-, Post-Progression- and Overall- Survival (Pfs, Pps and Os)
Authors: R. Forcignanò, E. Bria, A. Fabi, L. Petrucelli, J. Furlanetto, L. Carbognin, A. Gambino, C. Vicentini, V. Saracino, L. Lupo, V.E. Chiuri, G. Cairo, G. Tortora, E. De Matteis, G. Ronzino, A. Tornesello, I. Sperduti, D. Giannarelli, M. Ciccarese
Journal: Annals of Oncology (2014)
Vitamin A-Induced Density-Dependent Inhibition of L-Cell Proliferation2
Authors: L. D. Dion, J. E. Blalock, G. E. Gifford
Journal: JNCI Journal of the National Cancer Institute (1977)

Retinoic acid, the acid form of vitamin A, was found to have an inhibitory effect on the proliferation of L-929 mouse cells. Cultures treated with retinoic acid (5.0 µg/ml) were shown to cease proliferation at cell densities corresponding to confluent monolayers (10.0±1.0×104 cells/cm2). Control cultures, however, continued to proliferate and consistently reach densities two to four times higher than those of treated cultures. Viability was determined by trypan blue exclusion, and the results (80–90% viable) excluded cytotoxicity as an explanation of decreased proliferation. Replenishing the medium on confluent retinoic acid-treated cultures failed to stimulate further proliferation, while control cells continued to grow exponentially with each medium change. Therefore, the cessation of cell proliferation at confluence did not result from medium depletion. Studies of cell growth after seeding at relatively low cell densities have indicated that retinoic acid-treated cultures had greater nutritional requirements than did control cultures. Cell-cloning experiments have shown that DNA synthesis was not blocked, since clones formed by cells seeded with retinoic acid contained an average of 27 cells after 9 days of incubation (indicating between four and five cell divisions). However, clones developing from treated cells had fewer cells per clone (27 vs. 54) and were less dense than control clones. These data suggested the restoration of contact inhibition (topoinhibition) to L-929 cells treated with retinoic acid.
Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients
Authors: Kim Timmermans, Matthijs Kox, Michiel Vaneker, Maarten van den Berg, Aaron John, Arjan van Laarhoven, Hans van der Hoeven, Gert Jan Scheffer, Peter Pickkers
Journal: Intensive Care Medicine (2016)

Danger-associated molecular patterns (DAMPs) released of trauma could contribute to an immune suppressed state that renders patients vulnerable towards nosocomial infections. We investigated DAMP release in trauma patients, starting in the prehospital phase, and assessed its relationship with immune suppression and nosocomial infections. Blood was obtained from 166 adult trauma patients at the trauma scene, emergency room (ER), and serially afterwards. Circulating levels of DAMPs and cytokines were determined. Immune suppression was investigated by determination of HLA-DRA gene expression and ex vivo lipopolysaccharide-stimulated cytokine production. Compared with healthy controls, plasma levels of nuclear DNA (nDNA) and heat shock protein-70 (HSP70) but not mitochondrial DNA were profoundly increased immediately following trauma and remained elevated for 10 days. Plasma cytokines were increased at the ER, and levels of anti-inflammatory IL-10 but not of pro-inflammatory cytokines peaked at this early time-point. HLA-DRA expression was attenuated directly after trauma and did not recover during the follow-up period. Plasma nDNA (r = −0.24, p = 0.006) and HSP70 (r = −0.38, p < 0.0001) levels correlated negatively with HLA-DRA expression. Ex vivo cytokine production revealed an anti-inflammatory phenotype already at the trauma scene which persisted in the following days, characterized by attenuated TNF-α and IL-6, and increased IL-10 production. Finally, higher concentrations of nDNA and a further decrease of HLA-DRA expression were associated with infections. Plasma levels of DAMPs are associated with immune suppression, which is apparent within minutes/hours following trauma. Furthermore, aggravated immune suppression during the initial phase following trauma is associated with increased susceptibility towards infections.
Differentiation Between Early and Late Membrane Antigen on Human Lymphoblastoid Cell Lines Infected With Epstein-Barr Virus. II. Immunoelectron Microscopy 2
Authors: D. Silvestre, I. Ernberg, C. Neauport-Sautes, F.M. Kourilsky, G. Klein
Journal: JNCI Journal of the National Cancer Institute (1974)

The specificity of Epstein-Barr virus (EBY)associated membrane antigen (MA) on the membrane of cells replicating virus and on extracellular virus particles in EBY-producing human Iymphoblastoid cell lines was studied by immunoelectron microscopy. The results corroborate immunofluorescence findings and support the assumption that cells replicating EBY express on their membrane a late MA (LMA) distinct from the early MA (EMA) detected on cells devoid of viral capsid antigen and early antigens. Anti-MA sera repeatedly absorbed with EBY-infected, cytosine arabinoside-treated Raji cells retained a residual activity for the membrane of viruscontaining cells in the culture, as demonstrated by indirect immunoferritin labeling or direct immunoferritin methods with absorbed anti-MA ferritin conjugates. The specificity of the anti-LMA immunoferritin reaction was ensured by blocking experiments. The LMA and EMA were thus detected on the envelope of extracellular EB virions. Blocking of anti-MA ferritin conjugates with absorbed and unabsorbed anti-MA reagents indicated expression of both EMA and LMA on the membrane of cells replicating virus. By contrast, host-cell HL-A antigens, absent or barely detectable on the viral envelope, were readily detected on cells replicating EBY.
LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia
Authors: Hetty H. Helsmoortel, Silvia Bresolin, Tim Lammens, Hélène Cavé, Peter Noellke, Aurélie Caye, Farzaneh Ghazavi, Andrica de Vries, Henrik Hasle, Veerle Labarque, Riccardo Masetti, Jan Stary, Marry M. van den Heuvel-Eibrink, Jan Philippé, Nadine Van Roy, Yves Benoit, Frank Speleman, Charlotte Niemeyer, Christian Flotho, Giuseppe Basso, Geertruy te Kronnie, Pieter Van Vlierberghe, Barbara De Moerloose
Journal: Blood (2015)
Anorexia Nervosa Presenting as Reversible Hypoglycaemic Coma
Authors: A M Zalin, A F Lant
Journal: Journal of the Royal Society of Medicine (1984)

Hypoglycaemic coma was the presenting feature in two patients with anorexia nervosa, both of whom rapidly regained consciousness following intravenous administration of glucose. This uncommon complication of malnutrition does not appear to have been reported previously in anorexia nervosa.
Safety and effectiveness of malignant pleural mesothelioma patients treated with pemetrexed: A postmarketing drug registered study under performance linked access system
Authors: M. Watanabe, T. Yamamoto, K. Arakawa, J. Imai, R. Sekiguchi, S. Enatsu, Y. Nambu
Journal: Journal of Clinical Oncology (2009)

e19084 Background: Approximately 1000 patients are newly diagnosed as malignant pleural mesothelioma (MPM) each year in Japan, however MPM patient profile and their outcome are not well understood. Pemetrexed is the only approved chemotherapeutic agent for MPM. Limited safety information was available at launch of pemetrexed in Japan where drug induced interstitial pneumonitis are reported at higher rate than the rest of the world. Therefore postmarketing drug registered study (PDRS) for pemetrexed was conducted in Japan to investigate patient characteristics, adverse events and survival of MPM patients based on a regulatory requirement for approval. Methods: From February 2007 to May 2008, all of histologically proven MPM patients to be treated with pemetrexed were required to register the PDRS in Japan. The observation period was six-months. Supply of pemetrexed was restricted to institutes with experienced medical oncologists based on pre-determined criteria. Results: During the 15-months enrollment period, 948 MPM patients were registered. Until August 3 th 2008, data for 437 patients were collected. Among these, 389 were male, 48 female, median of age 65 (35–86). 72.3% patients had a known history of being exposed to asbestos. The treatment regimen mainly consists of 500 mg/m 2 of pemetrexed and 75 mg/m 2 of cisplatin every 21 days. Median treatment cycle was 3.0. Hematological NCI-CTC Grade ¾ adverse events in laboratory data were hemoglobin decrease 19.9 %, neutropenia 20.1%, thrombocytopenia 7.6%. Serious non-hematological adverse events were nausea 3%, vomiting 3.2%, fatigue 0.2%, constipation 0.2%, diarrhea 0.9%. Pneumotoxicity was found in 1.4%. 152 deaths (34.8%) were observed and six-month survival rate estimated by Kaplan-Meier method was 70.9%. Conclusions: This large size PDRS shows that safety profile of pemetrexed appeared similar to the previous clinical trial without additional safety signal. The study has minimum selection bias and provides useful information to health care professionals on safety and effectiveness of pemetrexed in real clinical setting in Japan. [Table: see text]
Abstract 13934: Scaffold Free “Cell Sheets” Composed of Mesenchymal Stromal Cells for the Treatment of Chronic Heart Failure; In Vivo Proof-of-Concept Study
Authors: Nobuko Tano, Masahiro Kaneko, Chiho Ikebe, Steven R Coppen, Manabu Shiraishi, Yasunori Shintani, Ken Suzuki
Journal: Circulation (2013)

Transplantation of bone marrow mesenchymal stromal cells (MSCs) is a promising treatment for heart failure mainly due to their secretion of beneficial factors to repair the damaged myocardium. We h...
Lung and circulating immune cell repertoires in PAH
Authors: Frederic Perros, David Montani, Barbara Girerd, Andrei Sefarian, Peter Dorfmuller, Klingel-Schmitt Isabelle, Anais Courtier, Orchidée Filipe-Santos, Gilles Parmentier, Solene Perez, Gerald Simonneau, Marc Humbert, Sylvia Cohen-Kaminsky
Journal: European Respiratory Journal (2013)

Background: In PAH, tertiary lymphoid tissues (tLTs) connected to remodeled vessels, Ig deposits in the lung, and circulating autoantibodies directed to vascular wall components, argue for a role of adaptive immune response and autoimmunity, beyond inflammation.

Aims and objectives: The presence of tLTs in the target organ is a hallmark of autoimmunity and suggests that lymphoid neogenesis could represent a critical step in maintaining humoral autoimmunity against persisting antigens, particularly autoantigens. Thus we searched for an immune signature in the lung and peripheral blood of PAH patients.

Methods: 27 patients with PAH among which 9 were transplanted and 24 controls were included. T and B cell repertoires were analyzed after laser-microdissection of perivascular tLTs and in peripheral purified CD4+ T and CD19+ B cells. A strategy based on genomic detection of TCR (ImmunTraCkeR®) and BCR (Immun’Ig®) rearrangements by multiplex PCR on the whole TCR and BCR loci (http://www.immunid.com) was used to perform an exhaustive quantitative analysis of the combinatorial diversity of immune repertoires.

Results: The repertoires in tLTs and in the periphery were compared assuming that stigmata of immune signatures in vascular lesions might be found in the periphery. Preliminary data revealed characteristic features in the immune repertoires in PAH patients. Changes in expression of specific rearrangements in CD4+ cells in the context of HLA type and presence of autoantibodies, together with restricted repertoires in tLTs, may suggest a local immune response.

Conclusions: Immune signature may represent a non-invasive early diagnostic and/or prognostic marker of PAH condition, which could then be translated in daily clinical practice.