tbuckley/cabot-search huggingface dataset:
Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea
Authors: Johan van Griensven, Tansy Edwards, Xavier de Lamballerie, Malcolm G. Semple, Pierre Gallian, Sylvain Baize, Peter W. Horby, Hervé Raoul, N’Faly Magassouba, Annick Antierens, Carolyn Lomas, Ousmane Faye, Amadou A. Sall, Katrien Fransen, Jozefien Buyze, Raffaella Ravinetto, Pierre Tiberghien, Yves Claeys, Maaike De Crop, Lutgarde Lynen, Elhadj Ibrahima Bah, Peter G. Smith, Alexandre Delamou, Anja De Weggheleire, Nyankoye Haba
Journal: New England Journal of Medicine (2016)

In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea.
The PIG-A Mutation and Absence of Glycosylphosphatidylinositol-Linked Proteins Do Not Confer Resistance to Apoptosis in Paroxysmal Nocturnal Hemoglobinuria
Authors: Russell E. Ware, Jun-ichi Nishimura, M. Anthony Moody, Clay Smith, Wendell F. Rosse, Thad A. Howard
Journal: Blood (1998)
Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study
Authors: Walter Ageno, Lorenzo G Mantovani, Sylvia Haas, Reinhold Kreutz, Danja Monje, Jonas Schneider, Martin van Eickels, Martin Gebel, Elizabeth Zell, Alexander G G Turpie
Journal: The Lancet Haematology (2015)
Validation study of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).
Authors: A. C. Dueck, T. R. Mendoza, B. B. Reeve, J. A. Sloan, C. S. Cleeland, J. Hay, Y. Li, A. M. O'Mara, A. Denicoff, E. M. Basch
Journal: Journal of Clinical Oncology (2010)

TPS274 Background: Adverse symptoms in cancer clinical trials are reported by clinicians using the NCI's standard lexicon for adverse event reporting, the Common Terminology Criteria for Adverse Events (CTCAE). To directly include the patient perspective into this process, the NCI contracted to create patient-reported outcomes measures of CTCAE symptoms (N02-PC-85002-29; PI: Basch). Items representing 77 CTCAE symptoms were developed and refined via cognitive interviewing. In the current study, we will assess the validity, reliability, and sensitivity to change of these items; compare 1-, 2-, 3-, and 4-week recall periods versus daily reports; and compare patient- and clinician-reported symptom ratings. Methods: This NCI-sponsored multi-site validation study will accrue 700 patients receiving chemotherapy or radiotherapy representing the diversity of disease burden and symptoms at five cancer centers (Memorial Sloan-Kettering; Mayo; Duke; M.D. Anderson; Dana-Farber) and selected community sites in NCI's Community Cancer Center Program network. Patients must be able to complete PRO-CTCAE items in English using a clinic-based laptop and cannot be cognitively impaired. Patients will complete PRO-CTCAE items at 2 visits 1-6 weeks apart. Patients will also complete a quality of life (QOL) assessment (EORTC QLQ-C30) at these visits and items assessing global impressions of change at the 2nd visit. Clinical anchors will include clinician-reported ECOG performance status (PS), CTCAE grades, cancer treatment type, and supportive medications. The primary validation analysis will compare each PRO-CTCAE item at the 1st visit between patients with ECOG PS 0-1 vs. 2-4. Hochberg's step-up method will be used to adjust for multiple testing. Validity will be further established by assessing the association between each item and QOL domains, cancer type, and clinical anchors. A subset of patients will also complete PRO-CTCAE items on consecutive days for assessing test-retest reliability; and a subset of patients will report symptoms daily via an automated telephone system for 28 days and complete PRO-CTCAE items weekly with varying reference periods for investigating recall accuracy. No significant financial relationships to disclose.
Medullary Microvascular Thrombosis and Injury in Sickle Hemoglobin C Disease
Authors: Mei Lin Z. Bissonnette, Kammi J. Henriksen, Kristie Delaney, Nicole Stankus, Anthony Chang
Journal: Journal of the American Society of Nephrology (2015)

Sickle cell nephropathy is a common complication in patients with sickle cell hemoglobinopathies. In these disorders, polymerization of mutated hemoglobin S results in deformation of red blood cells, which can cause endothelial cell injury in the kidney that may lead to thrombus formation when severe or manifest by multilayering of the basement membranes (glomerular and/or peritubular capillaries) in milder forms of injury. As the injury progresses, the subsequent ischemia, tubular dysfunction, and glomerular scarring can result in CKD or ESRD. Sickle cell nephropathy can occur in patients with homozygous hemoglobin SS or heterozygous hemoglobin S (hemoglobin SC, hemoglobin S/ β 0 -thalassemia, and hemoglobin S/ β + -thalassemia). Clinical manifestations resulting from hemoglobin S polymerization are often milder in patients with heterozygous hemoglobin S. These patients may not present with clinically apparent acute sickle cell crises, but these milder forms can provide a unique view of the kidney injury in sickle cell disease. Here, we report a patient with hemoglobin SC disease who showed peritubular capillary and vasa recta thrombi and capillary basement membrane alterations primarily involving the renal medulla. This patient highlights the vascular occlusion and endothelial cell injury in the medulla that contribute to sickle cell nephropathy.
Cytochrome P450 2D6 status predicts breast cancer relapse in women receiving adjuvant tamoxifen (Tam)
Authors: S. K. Knox, J. N. Ingle, V. J. Suman, J. M. Rae, D. A. Flockhart, D. Zeruesenay, M. M. Ames, D. W. Visscher, E. A. Perez, M. P. Goetz
Journal: Journal of Clinical Oncology (2006)

504 Background: CYP2D6 genetic variants and concurrent administration of potent inhibitors (Inh) of the enzyme markedly reduce the plasma concentrations of endoxifen (Jin. JNCI 2005;97:30–9). We have shown that genetic variation in CYP2D6 is associated with a higher risk of relapse in Tam treated patients (pts) (Goetz. JCO 2005;23:9312–18), but the impact of CYP2D6 inhibition on Tam clinical outcome is unknown. Methods: Using the North Central Cancer Treatment Group 89–30–52 adjuvant Tam trial (1989–1994), we evaluated the effect of co-administration of CYP2D6 Inh and CYP2D6*4 genotype on relapse in pts receiving tam alone. Patient charts were reviewed at each randomizing site to record the following known CYP2D6 Inh: fluoxetine (F), paroxetine (P), sertraline (S), cimetidine (C), amiodarone (A), doxepin (D), ticlopidine (T) and haloperidol (H). Poor metabolizers (PM) were defined as pts who were CYP2D6 *4/*4 and/or known to receive a CYP2D6 Inh. Intermediate metabolizers (IM) were defined as WT/*4 without CYP2D6 Inh, and extensive metabolizers (EM) as WT/WT without CYP2D6 Inh. The association between CYP2D6 status and Tam clinical outcome was determined using the log-rank test. Multivariate Cox modeling was performed using traditional prognostic factors. Results: CYP2D6*4 genotype was obtained in 190 of 256 eligible pts, with a CYP2D6*4/*4 genotype frequency of 6.8% as described previously (Goetz JCO 2005). Medication history was available in 171/256 eligible pts and in 143/190 pts with CYP2D6 genotype. Eleven of 173 patients were concomitantly administered these CYP2D6 Inh: F(2), P(2), S(2), H(1), C(4), and D(1). The median duration of use was 2.5 yrs. Twenty-four pts met criteria for PM [13 by *4/*4 genotype and 11 by CYP2D6 Inh (7 WT/WT, 1 WT/*4, and 3 unknown genotype)], 21 for IM, and 102 for EM. Compared with either IM or EM, PMs had significantly worse time to recurrence and disease free survival in both the univariate (HR 2.5, p=0.02; and 2.2, p=0.01) and multivariate (HR 2.7, p=0.01; and HR 2.2 p=.02) analyses utilizing tumor size, nodal status, and tumor grade. Conclusion: Our data indicate that CYP2D6 status can be used to identify pts who should receive tam therapy and tam treated pts should not be co-administered potent CYP2D6 inhibitors. No significant financial relationships to disclose.
Abstract 11810: Coexistence of Three Vulnerable Plaque Characteristic Factors in Non Calcified Coronary Plaques was Greater Risk Predictor for Major Cardiac Events on CT Following a Median of 82 Months Using Kaplan-Meier Analysis
Authors: Hiroyuki Takaoka, Nobusada Funabashi, Masae Uehara, Koya Ozawa, Yoshio Kobayashi
Journal: Circulation (2012)
Vascular endothelial growth factor-induced angiogenesis: crouching tiger or hidden dragon?∗∗Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Douglas W Losordo, Jeffrey M Isner
Journal: Journal of the American College of Cardiology (2001)
Abstract #LB-167: Poorly differentiated TCCs show higher frequent aberrant DNA methylation than moderately differentiated TCCs by bladder cancer methylome
Authors: Woonbok Chung, Bogdan Czerniak, Jean-Pierre Issa
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Bladder cancer is the fourth most common solid malignancy in the United States. The molecular mechanisms of bladder transitional cell carcinoma (TCC) development and progression remain poorly understood. Genetic and epigenetic alterations contribute to TCC formation, as with most other cancers. DNA hypermethylation is a common epigenetic abnormality in cancer and may serve as a useful marker of cancer related genes as well as biomarkers of clinical disease activity for early detection and/or prognosis. To analyze CpG islands methylated in bladder TCC, we used methylated CpG island amplification coupled with microarray (MCAM), which contained 7,089 autosomal genes with CpG islands, on cancer cell lines and primary cancers of bladder. Based on validated experiments, we used a cut-off corresponding to a two-fold increase of the Cy5 signal from bladder TCC over the Cy3 signal from normal bladder mixture to call a cancer as methylation positive (above the cut-off) and it showed 90.5% accuracy. For further analyses, we select 867 genes with CpG island close to TSS. In bladder cancer cell line analysis, UC14 (the most aggressive TCC cell line, 447 genes (54.3 %) methylation of 823 autosomal genes) showed all most two times higher frequent methylation than UC16 (the least aggressive TCC cell line, 253 genes (30.7 %)) or SVHUC (immortalized bladder cell line, 206 genes (25.0%). In primary bladder TCCs (n=33), poorly differentiated TCCs (Grade 3, n = 17) showed higher frequent aberrant methylation than moderately differentiated TCCs (Grade 2, n = 16) (178 ± 65.8 genes vs. 151 ± 76.5 genes, 21.6 ± 8.0 % vs. 18.3 ± 9.3 %). Bladder cancer cell lines (n = 12) exhibited 2 times higher levels of CpG island hypermethylation than primary TCCs (326.4 ± 63.0 genes vs. 165.3 ± 71.4 genes, 37.7 ± 7.7 % vs. 19.1 ± 8.7 %). Our data suggest that DNA methylation is an important factor in bladder TCC progression and provide MCAM method that could be useful for genome-wide screening of changes in methylation profile in clinical samples.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-167.
The prognostic effects of performance status (PS) and quality of life (QoL) scores on progression-free survival (PFS) and overall survival (OS) in advanced ovarian cancer
Authors: M. S. Carey, M. Bacon, D. Tu, A. Bezjak, G. C. Stuart
Journal: Journal of Clinical Oncology (2006)

5066 Background: Performance status is an important prognostic factor in advanced ovarian cancer. We sought to evaluate the relationship between PS and EORTC QLQ-C30 QoL scores and the PFS and OS in advanced ovarian cancer. Methods: Canadian data was analyzed as part of an intergroup randomized trial in ovarian cancer (NCIC-OV10). Patients were randomized to receive either standard chemotherapy using cisplatin/cyclophosphamide or cisplatin/paclitaxel chemotherapy. The EORTC QoL questionnaire QLQ-C30 was administered just prior to starting chemotherapy, at each cycle, and every 3 months thereafter for two years or until disease progression. We determined PS and QoL scores in the following domains: physical, role, emotion, cognitive, social function and global QoL at baseline and 6 months after completing chemotherapy. Effects of multiple variables including treatment, PS, QoL scores, age, stage, grade, residual disease and histology were analyzed by Cox stepwise regression using PFS and OS as the outcome variables. Results: At baseline and at 6 months after chemotherapy, there were 151 and 80 patients respectively who completed QoL assessments. The Cox model revealed that baseline PS, global QoL and treatment were independent predictors for both PFS and OS, and grade and cognitive functioning were additional independent predictors for OS. Physical function at six months after completion of chemotherapy was the only significant independent predictor of both PFS and OS, with age and grade as two additional independent predictors for subsequent OS. Conclusions: Performance status and global quality of life scores at baseline are prognostic factors in advanced ovarian cancer for both PFS and OS. Higher baseline cognitive functioning scores were also associated with improved survival. Higher physical function scores at six months after completing chemotherapy predicted longer PFS and OS. (This research was supported by the NCIC through funds received by the Canadian Cancer Society). No significant financial relationships to disclose.
Observational Demetra study: Survival of metastatic breast carcinoma patients after treatment with trastuzumab
Authors: S. Ménard
Journal: Journal of Clinical Oncology (2008)

1062 Background: Demetra, a multicentric observational retrospective study, was performed with the aim to investigate therapy with trastuzumab for HER2 metastatic breast carcinomas in conventional clinical setting. Methods: Clinical data of 440 consecutive patients treated with trastuzumab in the years 2000–2001 were collected among 22 oncologic Italian centers. Results: The overall response rate (CR+PR) was 55% with 54% as CR. In 70% of patients, trastuzumab was given as first-line treatment in combination with chemotherapy. Out of the 440, 272 patients developed progression of the disease and/or new metastases during treatment. 154 of these patients (57%) continued the treatment with the antibody, while 118 (43%) suspended trastuzumab at progression. The overall survival of these two patient subgroups was highly significantly different (p <10-4): 36.6% (C.I. 25–48) vs 14.8% (C.I. 4–31) at 35 months (median exposition time). The following variables were found to discriminate the 2 patient groups: some explaining the improved prognosis in the continuation group: less visceral metastasis, more use of taxanes, more responses to treatment and others, opposite associated with a poorer prognosis: younger patients, shorter time interval from diagnosis. Also Center strongly discriminated the two groups: some centers tended to suspend whereas others tended to continue independently of the disease. In the multivariate analysis (Cox stratified by center, using a stepdown selection of variables), 4 covariates: response, metastatic site, continuation of trastuzumab at progression and time interval from diagnosis were found independently associated to survival. When responders and nonresponders after treatment were considered, according suspension or continuation of trastuzumab at progression, both experienced a strong significant advantage from continuation. Conclusions: These data suggest that response and improvement of survival may be not associated and that resistance to trastuzumab (absence of response in terms of tumor volume reduction or progression of the disease under therapy) might be an inappropriate concept as biological drugs are considered. No significant financial relationships to disclose.
Inactivation of autophagy ameliorates glucocorticoid-induced and ovariectomy-induced bone loss
Authors: Neng-Yu Lin, Chih-Wei Chen, Rosebeth Kagwiria, Ruifang Liang, Christian Beyer, Alfiya Distler, Julia Luther, Klaus Engelke, Georg Schett, Jörg HW Distler
Journal: Annals of the Rheumatic Diseases (2015)

Objectives Autophagy has recently been shown to regulate osteoclast activity and osteoclast differentiation. Here, we aim to investigate the impact of autophagy inhibition as a potential therapeutic approach for the treatment of osteoporosis in preclinical models. Methods Systemic bone loss was induced in mice by glucocorticoids and by ovariectomy (OVX). Autophagy was targeted by conditional inactivation of autophagy-related gene 7 (Atg7) and by treatment with chloroquine (CQ). Bone density was evaluated by microCT. The role of autophagy on osteoclastogenesis was analysed by osteoclastogenesis and bone resorption assays. The quantification of receptor activator of nuclear factor κ B ligand and osteoprotegerin proteins in cocultures was performed using ELISA whereas that of osteoclast and osteoblast differentiation markers was by qPCR. Results Selective deletion of Atg7 in monocytes from Atg7 fl/fl _x_LysM-Cre mice mitigated glucocorticoid-induced and OVX-induced osteoclast differentiation and bone loss compared with Atg7 fl/fl littermates. Pharmacological inhibition of autophagy by treatment with CQ suppressed glucocorticoid-induced osteoclastogenesis and protected mice from bone loss. Similarly, inactivation of autophagy shielded mice from OVX-induced bone loss. Inhibition of autophagy led to decreased osteoclast differentiation with lower expression of osteoclast markers such as NFATc1, tartrate-resistant acid phosphatase, OSCAR and cathepsin K and attenuated bone resorption in vitro. In contrast, osteoblast differentiation was not affected by inhibition of autophagy. Conclusions Pharmacological or genetic inactivation of autophagy ameliorated glucocorticoid-induced and OVX-induced bone loss by inhibiting osteoclastogenesis. These findings may have direct translational implications for the treatment of osteoporosis, since inhibitors of autophagy such as CQ are already in clinical use.
Access to care for stage 2 transitional cell carcinoma of the bladder
Authors: J. Gore, J. Lai, M. S. Litwin, C. S. Saigal
Journal: Journal of Clinical Oncology (2008)

17568 Background: Receipt of aggressive therapy for invasive bladder cancer is influenced by clinical factors and patient sociodemographic characteristics. We assessed correlates of access to care for stage 2 transitional cell carcinoma (TCC) of the bladder where care algorithms are less equivocal and radical cystectomy (RC) remains the standard of care. We further stratified survival outcomes by treatment modality. Methods: SEER-Medicare subjects diagnosed with stage 2 TCC of the bladder from 1992–2000 were divided into 3 cohorts: those who underwent RC within 1 year, those who received chemotherapy or radiation therapy (Ch-XRT), and those who received no care (NC). We incorporated patient and provider characteristics into multivariate models comparing Ch-XRT and NC to RC. Multivariate Cox models compared survival stratified by treatment group adjusting for clinical determinants. Results: 21% of subjects with stage 2 TCC underwent RC; they were younger and had fewer comorbid conditions than Ch-XRT and NC subjects (p<0.001). Covariates associated with poor access to RC included age (OR 0.91, p<0.001), greater comorbidity (OR 0.32, p<0.001 for Charlson index ≥ 3 vs. Charlson 0), and cancer grade (OR 4.4, p<0.001 for grade 4 vs. grade 1). Use of RC did not vary by race, income, provider, or region. Subsetting a healthy cohort (age < 80 years, Charlson 0), death was associated with age (HR 1.03, p<0.001), being married (HR 0.68, p=0.007), cancer grade (HR 0.68, p=0.010 for grade 2 vs. 4), and treatment modality (HR 1.6, p<0.001 for Ch-XRT; HR 1.3, p=0.005 for NC vs. RC). Results were similar for the entire cohort (see Table). Conclusions: Few subjects with stage 2 TCC of the bladder undergo standard treatment. Although extirpative therapy appears to be determined by clinical parameters, we identified a large cohort of patients who would’ve benefited from more aggressive intervention. More detailed access models with incorporation of contextual variables may explain the differential care in these subjects. Cox model of mortality for SEER-Medicare subjects with stage 2 TCC of the bladder HR p-value Age (yrs) 1.05 <0.001 Female sex 1.40 <0.001 Ethnicity (vs. white) Black 1.17 0.30 Hispanic 1.00 0.99 Other 0.88 0.63 Married 0.82 0.14 Cancer grade (vs. 4) 2 9.68 0.005 3 1.08 0.43 Unknown 0.86 0.56 Region (vs. West) Northeast 1.03 0.80 Midwest 1.08 0.38 South 1.09 0.61 Treatment (vs. Ch-XRT) RC 1.17 0.45 NC 1.36 0.030 Interaction terms RC*Charlson 0 0.65 0.073 NC*Charlson 0 0.65 0.017 No significant financial relationships to disclose.
Allogeneic hematopoetic stem cell transplantation after reduced intensity conditioning for patients with indolent or mantle cell lymphoma
Authors: H. Schieder, N. Kröger, T. Zabelina, F. Ayuk, A. Kratochwille, B. Fehse, N. Fehse, N. Stute, H. Renges, A. R. Zander
Journal: Journal of Clinical Oncology (2004)

6628 Background: Allogeneic transplantation for Non-Hodkin Lymphoma ( NHL) is often associated with a high transplant related mortality. The aim of this retrospective single centre study was to analyse feasibility and efficacy of reduced intensity conditioning ( RIC) in patients with refractory or recurrent indolent and mantle cell NHL. Methods: From 11/99 to 5/2003 16 patients with refractory or relapsed NHL ( indolent n=8, mantle cell n=8) were transplanted after dose reduced conditioning ( Flu/Mel n=8, Flu/BEAM n=5, BEAM n=1, others n=2) with bone marrow ( n=3) or peripheral stem cells ( n=16) from a related ( n=9) or unrelated ( n=7) donor. Medium age was 46y ( 30–60y). GVHD prophylaxis consisted of cyclosporin A/ methotrexat ( n=15), cyclosporin A/MMF ( n=1) and anti thymocyte globulin ( ATG Freseniusn=16). 7 patients already relapsed prior to autologous transplantation. Results: 13 of 14 evaluable patients ( 93%) achieved a clinical complete remission ( CCR). With a medium follow up of 22 month ( 6–43 month) 10 patients ( 63%) are alive, seven of them ( 44%) still in CCR. 6 patients (37%)relapsed/ progressed within a median of 9 month ( 1–28 month) after transplantation. 3 patients developed grade II-IV GVHD. Severe grade III/IV GVHD was seen in 1 patient. 13 patients were evaluable for chronic GVHD. Two experienced limited GVHD. Extensive GVHD was seen in one patient.Transplant related mortality at one year was 19%. Conclusions: RIC is asociated with a low TRM, a high potency of remission induction and may lead to long lasting tumor control in patients with heavily pretreated indolent or mantle cell lymphoma. No significant financial relationships to disclose.
Ectopic Expression of HDAC9 in Murine Lymphoid System Leads to Altered Lymphocyte Numbers and Proliferation as Well as Predisposition to Tumorigenesis.
Authors: Veronica S. Gil, Louise M.C. Howell, Jenny Yeung, Kevin R. Petrie, Adrian Smith, Neil Sebire, Estela Matutes, Andy Wotherspoon, Tariq Enver, Eric So, Arthur Zelent
Journal: Blood (2007)