tbuckley/cabot-search huggingface dataset:
Psychosocial distress screening in cancer care.
Authors: N Mullai
Journal: Journal of Clinical Oncology (2016)

187 Background: Distress is a multifactorial, emotional experience that may interfere with patients’ ability to cope with cancer and its treatment. Recognizing and managing distress may benefit patients. The Commission on Cancer requires implementation of Standard 3.2, Psychosocial Distress Screening in 2015 and integrating distress intervention in cancer care. This study evaluates patients’ perception on benefits in this regard. Methods: Patients were screened at least once at a pivotal medical visit using a questionnaire that included various aspects of stress. NCCN’s Psychosocial Distress Screening Tool was used to measure seriousness of distress. Patients marked their distress level on a scale of 1 to 10. A threshold of 5 was set as a trigger point to start addressing distress. Results: Answers from 311 cancer patients (male 61%; female 39%) were evaluated since January 2015. A majority of patients had breast cancer (29%), followed by lung (18%), GI (18%), and hematological (12%) malignancies. The mean distress score was 3.72 (male 3.14; female 3.97). 131 patients had a score above five. Age group, 40-49 years had a higher distress (4.79) compared to others. Esophageal cancer (1%) had the highest mean score 7.33 followed by head &amp; neck cancer (4%) with 5.67. In most patients, anxiety about cancer and its treatment was the cause of distress. However, they did not want any additional psychosocial intervention except for talking to their oncologist and primary physician. The distress of some patients was family related and they were unsure of the help needed. Two patients refused screening stating the questions were intrusive. Conclusions: Coordinated psychosocial care may benefit cancer patients with significant distress. NCCN tool helps to assess the severity of patients’ distress and to determine the need for intervention. The results (mean score of 3.72) suggest most cancer patients need no major intervention or special psychosocial counseling other than discussing with their physician and family, which is done routinely in most oncology practices. However, when stress is expressed, this tool does help the treating physicians to determine the specific area and degree of stress, to focus on the type of help needed for the patient, and to channel resources appropriately.
Nausea in early pregnancy is linked to low risk of loss
Authors: Jacqui Wise
Journal: BMJ (2016)

Women who experience nausea and vomiting in early pregnancy may have a reduced risk of pregnancy loss, a prospective study published in JAMA Internal Medicine has shown.1

Nausea, with or without vomiting, is reported by as many as 80% of women during pregnancy. Much of the published literature has reported on studies that enrolled women after a clinically recognised pregnancy, so they did not include women with early pregnancy losses, or they relied on retrospective collection of data on nausea and vomiting symptoms. …
Evaluation of the Benefit/Risk Profile of Ponatinib in CP-CML Patients over Time: 4-Year Follow-up of the Phase 2 PACE Study
Authors: Jorge E. Cortes, Dong-Wook Kim, Javier Pinilla-Ibarz, Philipp D. le Coutre, Ronald Paquette, Charles Chuah, Franck E. Nicolini, Jane F. Apperley, H Jean Khoury, Moshe Talpaz, Daniel J. DeAngelo, Elisabetta Abruzzese, Delphine Rea, Michele Baccarani, Martin C. Müller, Carlo Gambacorti-Passerini, Stephanie Lustgarten, Maureen Conlan, Francois Guilhot, Mochael W. Deininger, Andreas Hochhaus, Timothy P. Hughes, Hagop M. Kantarjian, Neil P. Shah
Journal: Blood (2015)
Managing and Mitigating the Health Risks of Climate Change: Calling for Evidence-Informed Policy and Action
Authors: Shilu Tong, Ulisses Confalonieri, Kristie Ebi, Jorn Olsen
Journal: Environmental Health Perspectives (2016)

Summary:Climate change affects many natural and social systems and processes that are essential for life. It disrupts the Earth's life-support systems that underpin the world's capacity to supply adequate food and fresh water, and it disturbs the eco-physical buffering against natural disasters. Epidemiologists need to develop and improve research and monitoring programs to better understand the scale and immediacy of the threat of climate change to human health and to act within a much larger and more comprehensive framework. To address one of the greatest environmental issues of our lifetime, the scientific and policy-making communities should work together to formulate evidence-informed public policy to mitigate greenhouse gas emissions and adapt to its inevitable impacts in this generation and, more importantly, in future generations to come.
Memory Impairment in Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Patients (pts) Treated with Dasatinib Tyrosine Kinase Inhibitor (TKI) Therapy,
Authors: Naveen Pemmaraju, Hagop M. Kantarjian, Maria F Tanaka, Susan O'Brien, Elias Jabbour, Alfonso Quintas-Cardama, Gautam Borthakur, Farhad Ravandi, Srdan Verstovsek, Elizabeth Burton, Brenda Walker, Jorge E. Cortes
Journal: Blood (2011)
Histopathology of a benign bile duct lesion in the liver: Morphologic mimicker or precursor of intrahepatic cholangiocarcinoma
Authors: Kyoung-Bun Lee
Journal: Clinical and Molecular Hepatology (2016)

A bile duct lesion originating from intrahepatic bile ducts is generally regarded as an incidental pathologic finding in liver specimens. However, a recent study on the molecular classification of intrahepatic cholangiocarcinoma has focused on the heterogeneity of this carcinoma and has suggested that the cells of different origins present in the biliary tree may have a major role in the mechanism of oncogenesis. In this review, benign intrahepatic bile duct lesions—regarded in the past as reactive changes or remnant developmental anomalies and now noted to have potential for developing precursor lesions of intrahepatic cholangiocarcinoma—are discussed by focusing on the histopathologic features and its implications in clinical practice. Keywords: Intrahepatic cholangiocarcinoma; Ductal plate malformation; Bile duct adenoma; Peribiliary cyst
Association of response and survival in Allovectin melanoma trials.
Authors: D. D. Kharkevitch, A. Chu, L. G. Strause, L. R. Muenz, R. T. Kenney, A. Rolland
Journal: Journal of Clinical Oncology (2011)

8572 Background: Allovectin is a plasmid-based immunotherapy expressing HLA-B7 and β2 microglobulin genes designed to stimulate both local and systemic anti-tumor responses. In a phase II single-arm study, VCL-1005-208 (2 mg, intralesional injection in 127 subjects), overall response rate (ORR) was 11.8% and median overall survival (OS) was 18.8 months. Median duration of response was 13.8 months and all responses were durable (> 6 months). A subsequent phase III trial (LX01-315) recently completed enrollment of 390 pts in more than 90 sites in 15 countries. Subjects in phase II with characteristics corresponding to those in this phase III study (chemonaïve with a single lesion injected) had an ORR that was 17% and median OS was 22.5 months. Methods: A time-dependent covariate (TDC) analysis with the Cox proportional hazards model (SAS/STAT PROC PHREG) was used to evaluate the relationship between a time-varying covariate (responder status) to survival in the phase II study. The Cox model analysis combines these results across times (one time point per death) to yield a single p-value for the prognostic significance of responder status. Results: In our analysis of the VCL-1005-208 data, each patient had a single covariate, responder status that permanently switched from 1 to 0 when a non-responder became a responder. The single covariate approach tested the hypothesis that responder status predicted survival. The resulting hazard ratio for the TDC was 4.13 (95% CI: 1.67-10.25, score test p-value=0.002), which is relatively large and highly significant. A simpler analysis, using responder status as if it were a baseline covariate, gave a hazard ratio of 4.82 (95% CI 1.95-11.89, p-value<0.001). The TDC analysis indicates that in a small, open-label phase II trial, responder status strongly predicted survival. Analysis of two other trials (using 10 mcg DNA), VCL-1005-205 (phase II) and VCL-1005-301 (phase III), showed similar results. Conclusions: In three Allovectin melanoma trials, response was a strongly significant predictor of survival and may serve as a marker of clinical benefit for this novel class of cancer immunotherapeutic agents.
Gastro-intestinal effects of different doses of arabinoxylanoligosaccharides in healthy volunteers: gastric emptying, oro-caecal transit time, total transit and H2-excretion
Authors: Lieselotte Cloetens, Vicky De Preter, Katrien Swennen, Christophe Courtin, Jan Delcour, Paul Rutgeerts, Kristin Verbeke
Journal: Gut (2006)
MDM2 Inhibitor Nutlin-3a Triggers Autophagic Cell Death In Addition to Apoptosis In Leukemia Cell Lines with Wild-Type p53
Authors: Seshagiri Duvvuri, Vivian Ruvolo, Duncan H. Mak, Kensuke Kojima, Marina Konopleva, Michael Andreeff, Gautam Borthakur
Journal: Blood (2010)
Hepatocytic differentiation in cholangiocellular carcinoma suggesting hepatic progenitor cell origin
Authors: Mina Komuta, Sara Vander Borght, Bart Spee, Rita De Vos, Chris Verslype, Raymond Aerts, Baki Topal, Frederik Nevens, Valeer J Desmet, Tania A Roskams
Journal: Hepatology (2008)
Predictive impact of IDH1 or IDH2 mutations on outcome and response to temozolomide in low-grade gliomas.
Authors: C. Houillier, X. Wang, G. Kaloshi, K. Mokhtari, J. Laffaire, B. Boisselier, A. Idbaih, K. Hoang-Xuan, M. Sanson, J. Delattre
Journal: Journal of Clinical Oncology (2010)

2033 Background: Recent studies have shown that IDH1 and IDH2 mutations occur frequently in gliomas, including low-grade gliomas (LGG). However, their impact on the prognosis and chemosensitivity of LGG remains unclear. Methods: Search for IDH1 and IDH2 mutations, loss of heterozygosity on chromosomes 1p and 19q, MGMT promoter methylation and p53 expression was performed in a series of 271 LGG and correlated with overall survival (OS). A sub-group of 84 patients treated up-front with temozolomide (TMZ) was individualized. Response to TMZ was evaluated by progression-free survival (PFS), as well as by tumor size on successive MRI scans, and then correlated with molecular alterations. Results: IDH (IDH1 or IDH2) mutations were found in 132/189 patients (70%). IDH mutation and 1p-19q co-deletion were associated with prolonged OS in univariate (p = 0.002 and p = 0.0001 respectively) and multivariate analysis (p = 0.003 and p = 0.004 respectively). 1p-19q co-deletion, MGMT promoter methylation and IDH mutation (p = 0.01) were significantly correlated with a higher rate of response to TMZ. Thus we identified 3 LGG sub-groups with decreasing OS and chemosensitivity: (i) a group with both 1p-19q co-deletion and IDH mutation, (ii) a group with only IDH mutation and (iii) a group with none of the alterations. Further analysis of the course of the disease prior to any treatment except for surgery (“untreated subgroup”) showed that 1p-19q co-deletion was associated with prolonged PFS, whereas IDH mutation was not. Conclusions: IDH mutation appears, therefore, to be a significant marker of positive prognosis and chemosensitivity in LGG, independently of 1p-19q co-deletion, whereas its impact on the course of untreated tumors seems to be limited. No significant financial relationships to disclose.
Bone turnover marker (BTM) levels and clinical outcomes in advanced cancer patients (pts) treated with antiresorptive bone therapies.
Authors: Allan Lipton, Matthew R. Smith, Karim Fizazi, Alison Stopeck, David H. Henry, Neal Shore, Fred Saad, Andrew Spencer, Li Zhu, Douglas J Warner
Journal: Journal of Clinical Oncology (2015)

e22236 Background: Advanced cancer pts with metastatic bone disease typically have elevated BTM levels. Antiresorptive agents such as denosumab (DMAB) and zoledronic acid (ZA) can significantly reduce BTM levels. We evaluated BTM levels after treatment with these agents in advanced cancer pts with bone metastases. Methods: This post hoc analysis represents patient-level data from 3 identically designed, blinded, phase 3 trials with pts randomized to receive DMAB (120 mg SC) or ZA (4 mg IV, adjusted for creatinine clearance). The BTMs urinary N-telopeptide (uNTx) and bone-specific alkaline phosphatase (BSAP) were measured at study entry and 3 months. Disease progression (DP), overall survival (OS), and DP in the bone (DPB) were compared in pts with BTMs above and below median levels at month 3 by covariate analyses stratified by treatment and stratification factors based on month 3 assessments. Results: Pts with uNTx levels ≥ the median level of 10.04 nmol/mmol at month 3 had a significantly greater risk of DP (31%) and reduced OS (85%) than pts with uNTx levels < median (Table). Pts with BSAP levels ≥ the median level of 12.56 ng/mL at month 3 had an increased risk for DP (71%) and reduced OS (144%) compared with those who had BSAP levels < median. Pts with uNTx or BSAP levels ≥ the median at month 3 had an increased risk of DPB (11% for uNTX and 27% for BSAP). Conclusions: Pts with BTM levels ≥ median at month 3 of therapy had significantly worse clinical outcomes than pts whose BTM levels were < median. Assessment of BTM levels after antiresorptive therapy may add to identification of pts most at risk for DP and decreased OS. Clinical trial information: NCT00321464, NCT00321620, NCT00330759.Month 3* covariate analysis results: risk of decreased OS or increased DP or DPB. Hazard Ratio (95% Confidence Interval) P-value Decrease in OS uNTXa 1.845 (1.672, 2.036) <0.0001 BSAPb 2.443 (2.200, 2.712) <0.0001 Increase in DP uNTXa 1.307 (1.209, 1.412) <0.0001 BSAPb 1.706 (1.574, 1.848) <0.0001 Increase of DPB uNTXa 1.114 (1.005, 1.235) 0.0407 BSAPb 1.270 (1.142, 1.413) <0.0001 *Comparing ≥ median to < median. aMedian uNTx levels = 10.04 nmol/mmol. uNTx ≥ median, n=2150; uNTx < median, n=2149. bMedian BSAP level = 12.56 ng/mL. BSAP ≥ median, n=2157; BSAP < median, n=2159.
Realizing the Full Potential of Precision Medicine in Health and Health Care
Authors: Victor J. Dzau, Geoffrey S. Ginsburg
Journal: JAMA (2016)

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Phase I trial of bortezomib in combination with topotecan in advanced solid tumor malignancies
Authors: R. Morgan, F. Valdes-Albini, T. Synold, G. Somlo, S. Shibata, W. A. Chow, D. Lim, S. Koehler, P. Frankel, J. Doroshow
Journal: Journal of Clinical Oncology (2006)

12004 Background: Bortezomib (B) and topotecan (T) have been shown in pre-clinical testing to be synergistic. Based on this data we have performed a phase I study to determine the maximally tolerated dose and toxicities (tox) of B and T delivered sequentially. Methods: 24 pts (KPS&lt;ECOG 3) with advanced malignancies were treated with T (2.0, 2.5, 3.0 or 3.5 mg/m 2 in sequential cohorts) IV on days 1 and 8 of each three week cycle. B 1.3 mg/m 2 iv was administered six hours following T on days 1 and 8, and alone on days 4 and 12. Pts were treated in cohorts of 3, the MTD dose was expanded to include 10 additional pts for PK analysis. There was no limit on prior therapies. DLT was defined as any gr 3 or 4 non-hematologic toxicity not reversible in 48h or any gr 3 thrombocytopenia lasting &gt;7 days or associated with bleeding or any gr 4. Results: Tumor types included: breast (4), ovary (5), lung (3), others (12). 24 pts were entered (11M 13F). The median age was 55 (range: 34–83). DLT was thrombocytopenia, observed in two pts at 3.5 mg/m 2 and one pt at 3.0 mg/m 2 (MTD). Other grade 3 or 4 tox included fatigue, lymphopenia, hypomagnesemia, and hypertriglyceridemia. Of the 24 enrolled pts, stable disease was observed in 4 (4 or 5 cycles), 9 progressed, 5 were inevaluable and 6 are too early. PK analysis is pending. Conclusions: T and B delivered sequentially are well tolerated on a weekly schedule. DLT is thrombocytopenia. PK will be presented.(Supported by NCI Grant CA33572). [Table: see text]
The TET RNA-binding proteins, EWSR1 and TAF15, are involved in acute lymphoblastic leukemia, through fusion with a new transcription factor, CIZ/NMP4
Authors: A Martini, H Janssen, C Bilhou-Nabera, R La Starza, Anniek Corveleyn, Christina Mecucci, Anne Hagemeijer-Hausman, Peter Marynen
Journal: Blood (2002)
Time Dependent Platelet Attrition Identifies Biological Subgroup In Intermediate But Not Low-Risk Myelodysplastic Syndrome (MDS) Revised-IPSS (R-IPSS) Exhibiting Distinct Overall Survival
Authors: Gustavo A. Rivero, Maria Otazo, Sarvari Venkata Yellapragada, Ang Li, Matthew Zheng, Ruben Hernandez Perez, Martha Mims
Journal: Blood (2013)
Emerging treatments for severe obesity in children and adolescents
Authors: Nicole Coles, Catherine Birken, Jill Hamilton
Journal: BMJ (2016)

Severe obesity in childhood is increasing in prevalence and is associated with considerable morbidity. Studies into pediatric obesity have focused largely on interventions that do not necessarily target the unique biologic or psychological underpinnings for the weight gain in the individual child or adolescent. Outcomes show modest improvement and are of questionable benefit for patients with severe obesity. Although weight is a commonly used outcome, other psychological and metabolic parameters including normalization of physical activity and eating behaviors should be primary outcome goals. The durability of weight loss is often limited by physiologic systems that are evolutionarily designed to promote weight gain. Drug therapies for children are limited, as is their effect on weight and metabolism. Existing drugs that are incidentally found to cause weight loss through off-target effects are being actively investigated for obesity indications. Bariatric surgery results in the most significant weight reduction, but it is associated with potential morbidity and long term data are not available for adolescents undergoing this procedure. As understanding of the biologic and psychosocial contributors to eating behaviors and body weight regulation increases, multifaceted and targeted behavioral, pharmacological, and surgical treatment algorithms should be developed and applied to target the underlying pathways involved for the individual child or adolescent with severe obesity.
Development and optimization of a protocol for automated, low-throughput RNA purification from whole blood using the PAXgene blood RNA system
Authors: Kalle Guenther, Heike Balven-Ross, Ralf Wyrich
Journal: Clinical Cancer Research (2007)

A44    Introduction:    Gene expression analysis in peripheral blood is an important tool in molecular diagnostics, monitoring diseases at the molecular level, clinical research, and clinical trials of new drugs. Since the introduction of the PAXgene Blood RNA System, researchers have expressed a need for a low-throughput, automated (LTA) solution for RNA preparation from blood collected in PAXgene Blood RNA Tubes, with purification based on the proven silica-membrane spin-column technology in the PAXgene Blood RNA Kit. The aim of this research study was to develop and optimize a protocol for LTA RNA purification using PAXgene Blood RNA Tubes and the (manual) PAXgene Blood RNA Kit on a robotic platform.  (Note: The combination of the PAXgene Blood RNA Kit on the robotic platform is for research use only and not for use in diagnostic procedures. It has not received clearance or approval for clinical use in the US, Canada or Europe.)   Methods:    Replicate blood samples were collected in PAXgene Blood RNA Tubes, and starting from the resuspended nucleic acid pellet, RNA was purified using either the manual procedure according to the PAXgene Blood RNA Kit handbook (reference protocol) or the new automated purification procedure (test protocol). To enable comparison of the test and reference protocol performance, purified RNA from both protocols was analyzed spectrophotometrically, by capillary gel electrophoresis, in real-time quantitative RT-PCR (RQ-RT-PCR), and in PCR assays to measure RNA yield, purity, integrity, RQ-RT-PCR inhibition, and traces of genomic DNA (gDNA).   Results:    The new automated PAXgene Blood RNA protocol was highly reliable in that there were no failures in sample processing. Furthermore, the quantity and quality of purified RNA was comparable between both protocols: Greater than 95% of samples processed on the instrument yielded RNA of >3micrograms per tube, all samples contained  Conclusion:    This research study demonstrates that the new automated protocol using proven silica-membrane spin-column technology and existing chemistry with the new robotic platform provides an efficient and reliable alternative LTA solution to the manual protocol. Automated processing reduces user interaction and hands-on time, resulting in a more convenient workflow compared to the manual PAXgene Blood RNA procedure.
Evaluation of Minimal Residual Disease (MRD) By Next Generation Sequencing (NGS) Is Highly Predictive of Progression Free Survival in the IFM/DFCI 2009 Trial
Authors: Herve Avet-Loiseau, Jill Corre, Valerie Lauwers-Cances, Marie-Lorraine Chretien, Nelly Robillard, Xavier Leleu, Cyrille Hulin, Catherine Gentil, Bertrand Arnulf, Karim Belhadj, Sabine Brechignac, Laurent Garderet, Lionel Karlin, Gerald Marit, Lotfi Benboubker, Frederique Orsini-Piocelle, Bruno Royer, Bernard Drenou, Mourad Tiab, Thierry Lamy, Margaret MACRO, Paul G. Richardson, Kenneth C Anderson, Malek Faham, Thierry Facon, Philippe Moreau, Michel Attal, Nikhil C. Munshi
Journal: Blood (2015)
The Impact of Winter Months on Patients with Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE), a Retrospective Analysis of Hospital Outcomes in the United States (US) from 1998-2011
Authors: Danielle Krol, Parshva Patel, Konstantine Halkidis, Gaurav Varma, Ravindra Sangitha, Ananya Yalamanchi, Christina Trotta, Michael Styler, Kristine Ward, Maneesh Jain
Journal: Blood (2015)