tbuckley/cabot-search huggingface dataset:
Diagnostic and treatment challenges of adolescent and young adult oncology patients.
Authors: Yanqing Xu, Mauro Cardoso, Michael Ostaric Palumbo, Olivia Ishibashi, Petr Kavan
Journal: Journal of Clinical Oncology (2012)

9557 Background: Adolescent and young adult (AYA) cancer patients are faced with obstacles and challenges related to their diagnosis and treatment compared to children and older adults. The aim of this study was to explore the patient and health care system-related delays in the interval from cancer symptom onset to diagnosis and treatment as well as to identify the possible contributing factors to these delays in the AYA group. Methods: This study was based on a questionnaire conducted in 2010-2011 completed by patients diagnosed with a malignancy between the ages of 16 and 39 in addition to older patients diagnosed with a pediatric type malignancy. Four categories of delays: patient delay (time from patient symptom onset until first health care contact date), health care system delay (time from first health care contact until diagnosis date), treatment delay (time from diagnosis date until first treatment) and oncologist delay (time from first health care contact until first medical oncologist meeting) were calculated. Median delay (in days) with interquartile interval (IQI) was the main outcome measure. Median time for each category of delay was further analysed to explore how they vary with different patient characteristics. Results: We identified a median patient delay of 30 days (IQI 1-131), a median health care system delay of 53 days (IQI 1-213), a median treatment delay of 36 days (IQI 5-92) and a median oncologist delay of 77 days (IQI 30-281). Patient delay was affected by patient gender, age at diagnosis and type of first health care contact. Health care system delay was associated with patient marital status, financial situation and attitude of first health care professional. Treatment delay was related to type of cancer. Conclusions: The health care system delay (including oncologist delay) accounts for much of the delay from symptom onset to first treatment. Professional characteristics of frontline medical personnel as well as socioeconomic and biological characteristics of the patients may contribute to delay. Healthcare professionals and the general community as a whole need to be aware of the factors contributing to delay in diagnosis and treatment in the underserved patient population.
MSF rejects EU funding in protest at refugee deal
Authors: Owen Dyer
Journal: BMJ (2016)

The aid charity Medecins Sans Frontieres has announced that it will reject all funding from European Union member states and institutions in protest at the EU’s deal with Turkey to stem the flow of refugees across Europe’s borders.

The decision takes effect immediately and will apply to MSF’s projects worldwide, the charity said in a statement. It was prompted by a new European Commission proposal to “replicate the EU-Turkey logic across more than 16 countries in Africa and the Middle East,” adjusting trade and aid deals according to countries’ willingness to stem outward migration or to accept forced returns of refugees. …
Computed Tomography Perfusion and Diffusion-Weighted Imaging in Patients With Acute Stroke—Reply
Authors: Salvatore Rudilosso, Xabier Urra, Ángel Chamorro
Journal: JAMA Neurology (2016)

In Reply We thank Luo and colleagues for their interest and comments regarding our article on patients presenting lacunar syndrome with altered brain computed tomography perfusion (CTP) and normal magnetic resonance imaging (MRI) findings.1
Neuroleptic augmentation with alprazolam: clinical effects and pharmacokinetic correlates
Authors: R Douyon, B Angrist, E Peselow, T Cooper, J Rotrosen
Journal: American Journal of Psychiatry (1989)

Alprazolam added to stable doses of neuroleptics in nine schizophrenic patients was associated with a 20%-30% mean reduction in positive and negative symptoms, although clinical response was variable and in some patients particularly brisk. The authors examined the possibilities of a pharmacokinetic effect of alprazolam on neuroleptic plasma levels and of a clinical effect of alprazolam. The modest increase in mean neuroleptic plasma levels did not correlate with clinical change, but those patients with the highest alprazolam plasma levels tended to show more robust clinical responses.
Soundings: We won’t forget you, Bill
Authors: Liam Farrell
Journal: BMJ (1998)

A month ago my car became unwell and I had to bring it to the mechanic. My opinion of the mechanic rested solely on his ability to fix my car; his personal life, and specifically whether or not he had committed adultery in the recent past, was of no concern to me. Neither was it any of my business. We are not made of rock, we are not gods; we are flesh and blood, we are all human, and we all share the vulnerability of our humanity.

The president of the United States is a uniquely powerful and influential figure. Since the Troubles began in Ulster in 1968 no president has taken any great interest in us. This is quite understandable. The US has its own problems, and on a global scale we are too small and unlovely to worry about.

And then Bill Clinton became president and leant his ear and the authority of his office to the solving of our problems; the pressures and influences he was able to bring to bear have been a vital part of the peace process, lending it an unstoppable momentum. I accept that his behaviour with Monica Lewinsky was cheap and tawdry, and his attempts to cover up also hard to defend. “O what a tangled web we weave....” The reputation of his presidency will forever be tarnished by his mistakes; the office demands a degree of dignity the squalid publicity surrounding the affair has denied him.

But we shouldn’t lose sight of the great good he has done for Ireland; set against his achievements his mistakes become very trivial indeed. In his two visits here he displayed charisma and knowledge and enthusiasm enough to battle and charm even the most hardened cynics. Well, perhaps not all of them; “Lock up your women” was Ian Paisley’s response to the president’s last visit.

Just this month we have seen traditional antagonists, previously defined almost purely by their mutual enmity, sitting down together in a democratically elected body, something unthinkable and beyond all hope a short time ago. Our children now have a future where the big issues will be the real ones, the environment and the economy, rather than which flag flies over us or which football team we support.

So thanks Bill; you will always have our gratitude and always be welcome in Ireland.
Relative Stability Of Plasma Cells Immunophenotype In Multiple Myeloma Over Time
Authors: Benoit Tessoulin, Steven Legouill, Marion Eveillard, Nelly Robillard, Soraya Wuilleme, Thomas Gastinne, Cyrille Touzeau, Catherine Pellat-Deceunynck, Marie C Bene, Philippe Moreau
Journal: Blood (2013)
Technology Assessment
Authors: Seymour Perry
Journal: New England Journal of Medicine (1986)

It is now a decade since Congress asked the Office of Technology Assessment (OTA) to examine "federal policies and existing medical practices to determine whether a reasonable amount of justification should be provided before costly new medical technologies and procedures are put into general use." The report by the OTA, issued in 1976,1 made a strong case for establishing formal mechanisms for assessing medical technologies. The document also played a part in the creation of the consensus-development program of the National Institutes of Health in 19772 and helped to persuade Congress to pass legislation the following year establishing the National . . .
Protein C zymogen in severe sepsis: a double-blinded, placebo-controlled, randomized study
Authors: Federico Pappalardo, Martina Crivellari, Ambra L. Di Prima, Nataliya Agracheva, Malgorzata Celinska-Spodar, Rosalba Lembo, Daiana Taddeo, Giovanni Landoni, Alberto Zangrillo
Journal: Intensive Care Medicine (2016)
Role of Myeloma-Derived MIF in Myeloma Cell Adhesion to Bone Marrow and Chemotherapy Response
Authors: Yuhuan Zheng, Qiang Wang, Tianshu Li, Jianfei Qian, Yong Lu, Yi Li, Enguang Bi, Frederic Reu, Yu Qin, Judy Drazba, Eric Hsi, Jing Yang, Zhen Cai, Qing Yi
Journal: JNCI Journal of the National Cancer Institute (2016)

Multiple myeloma (MM) remains an incurable cancer characterized by accumulation of malignant plasma cells in the bone marrow (BM). The mechanism underlying MM homing to BM is poorly elucidated.The clinical significance of migration inhibitory factor (MIF) expression was examined by analyzing six independent gene expression profile databases of primary MM cells using the Student's t test and Kaplan-Meier test. Enzyme-linked immunosorbent assay was used to examine MIF expression. In vivo bioluminescent imaging was used to determine MM cell localization and treatment efficacy in human MM xenograft mouse models, with three to four mice per group. MM cell attachment to BM stromal cells (BMSCs) was monitored by cell adhesion assay. MIF regulation of the expression of adhesion molecules was determined by chromatin immunoprecipitation (ChIP) assay. Statistical tests were two-sided.High levels of MIF were detected in MM BM (MIF level in BM plasma: healthy = 10.72 ± 5.788 ng/mL, n = 5; MM = 1811 ± 248.7 ng/mL, n = 10; P < .001) and associated with poor survival of patients (Kaplan-Meier test for MM OS: 87 MIF(high) patients, 86 MIF(low) patients, P = .02). Knocking down MIF impaired MM cell adhesion to BMSCs in vitro and led to formation of extramedullary tumors in SCID mice. MIF acted through surface receptor CXCR4 and adaptor COPS5 to regulate the expression of adhesion molecules ALCAM, ITGAV, and ITGB5 on MM cells. More importantly, MIF-deficient MM cells were sensitive to chemotherapy in vitro when cocultured with BMSCs and in vivo. MIF inhibitor 4-IPP sensitized MM cells to chemotherapy.MIF is an important player and a novel therapeutic target in MM. Inhibiting MIF activity will sensitize MM cells to chemotherapy.
Surveillance du syndrome hémolytique et urémique chez les enfants de moins de 15 ans en France en 1998
Authors: S Haeghebaert, V Vaillant, B Decludt, P. A.D. Grimont
Journal: Eurosurveillance (2000)

En France, l’incidence du syndrome hemolytique et uremique (SHU) en 1998 chez les enfants de moins de 15 ans, observee via le reseau national de services de nephrologie pediatrique, etait de 0,7 cas pour 100 000. Les cas surviennent sous forme sporadique. Six des 85 cas notifies en 1998 etaient des cas importes, ce qui souligne la necessite de renforcer les systemes d'alerte nationaux et internationaux pour ces infections. La proportion de cas avec une reponse serologique positive diminue depuis la mise en place de ce systeme de surveillance en 1996. Cela suggere l’hypothese de l’emergence de nouveaux serogroupes d’Escherichia coli non inclus dans le serodiagnostic actuel.
Measuring and understanding quality of survival in oncology.
Authors: Stacie Hudgens, Anna Forsythe, Andrew Lloyd, Pablo Lapuerta
Journal: Journal of Clinical Oncology (2016)

e291 Background: Health status, burden of illness, and quality of life (QOL) are considered crucial for clinical decision making in cancer. More specifically, quality of survival (QOS) in patients with cancer must be paramount in treatment considerations from early stage disease to palliative care. Measuring QOL provides information beyond biomedical outcomes, offers a unique understanding from the patient's perspective, and has demonstrated influence over study conclusions where differences in QOL are more often detected in studies comparing intervention to no intervention rather than comparative studies with systemic therapies. Methods: This panel presentation is focused on the crossfunctional perspectives of critical research areas for understanding QOS in oncology. As such, this presentation seeks to address the need for patient-focused research in oncology including: 1) the importance of the patient's voice in early and metastatic disease, 2) what endpoints should we consider in oncology trials for understanding the impact on patients, 3) modeling time to patient reported decline as a critical endpoint in understanding survival, 4) quality of life as a story rather than a statistic, 5) understanding health states for response and progression. Results: The authors of this panel seek to present real world examples for each of the above topics as well as introduce methodologies for improving QOS value messaging in oncology. Conclusions: In cancer studies, the primary response is measured as survival benefit with the ability to measure biomarkers such as tumor response, blood levels, etc. However, measureable endpoints in oncology from patient report contribute to the understanding of symptom improvement or decline (change over the course of treatment), change in function (e.g., physical functioning), side effects (treatment toxicity; e.g., patient reported potential with the PRO common terminology criteria for adverse events), economic aspects, interaction between biomarkers of progression or response and patient-reported symptoms, function, and QOL should be carefully estimated to fully understand treatment efficacy and safety, and inform patients of duration and cycle of toxicity onset; disease symptoms and changes.
Upregulation Of IL1RAP On Human Progenitor/Stem Cells Induces Features Of a Myeloproliferative Disorder In Mice
Authors: Nils Hansen, Kristian Reckzeh, Helena Agerstam, Maria Askmyr, Sandra Gordon, Marianne Rissler, Carl Högberg, Johan Richter, Marcus Järås, Thoas Fioretos
Journal: Blood (2013)
Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer
Authors: Zoe Hall, Zsuzsanna Ament, Catherine H. Wilson, Deborah L. Burkhart, Tom Ashmore, Albert Koulman, Trevor Littlewood, Gerard I. Evan, Julian L. Griffin
Journal: Cancer Research (2016)

MYC-mediated pathogenesis in lung cancer continues to attract interest for new therapeutic strategies. In this study, we describe a transgenic mouse model of KRAS-driven lung adenocarcinoma that affords reversible activation of MYC, used here as a tool for lipidomic profiling of MYC-dependent lung tumors formed in this model. Advanced mass spectrometric imaging and surface analysis techniques were used to characterize the spatial and temporal changes in lipid composition in lung tissue. We found that normal lung tissue was characterized predominantly by saturated phosphatidylcholines and phosphatidylglycerols, which are major lipid components of pulmonary surfactant. In contrast, tumor tissues displayed an increase in phosphatidylinositols and arachidonate-containing phospholipids that can serve as signaling precursors. Deactivating MYC resulted in a rapid and dramatic decrease in arachidonic acid and its eicosanoid metabolites. In tumors with high levels of MYC, we found an increase in cytosolic phospholipase A2 (cPLA2) activity with a preferential release of membrane-bound arachidonic acid, stimulating the lipoxygenase (LOX) and COX pathways also amplified by MYC at the level of gene expression. Deactivating MYC lowered cPLA2 activity along with COX2 and 5-LOX mRNA levels. Notably, inhibiting the COX/5-LOX pathways in vivo reduced tumor burden in a manner associated with reduced cell proliferation. Taken together, our results show how MYC drives the production of specific eicosanoids critical for lung cancer cell survival and proliferation, with possible implications for the use of COX and LOX pathway inhibitors for lung cancer therapy. Cancer Res; 76(16); 4608-18. ©2016 AACR.
Case 43-1979
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Barry W. Levine, David L. Gang
Journal: New England Journal of Medicine (1979)

Presentation of CaseA nine-year-old black girl was admitted to the hospital because of dyspnea.She was well until nine months earlier, when she began to have episodes of unconsciousness without seizure activity. During one attack she struck her occiput and was brought to the hospital, where she was observed for 24 hours. An electroencephalogram revealed generalized spike activity that increased with sleep. Phenobarbital was administered. Seven months before admission she suddenly became pale, slumped over in bed and appeared dyspneic and sweaty, without loss of consciousness. She was brought to the hospital.The temperature was 37.2°C, the pulse 132, . . .
Immunostimulatory CpG-Oligonucleotide Activated Metaphase Cytogenetics Is Feasible in Routine Diagnostics of Chronic Lymphocytic Leukaemia and Reveals More Abnormalities Than Interphase FISH.
Authors: Claudia Schoch, Susanne Schnittger, Wolfgang Kern, Torsten Haferlach, Frank Dicker
Journal: Blood (2005)
Phase 3 study of first-line crizotinib vs pemetrexed−cisplatin/carboplatin (PCC) in East Asian patients (pts) with ALK+ advanced non-squamous non-small cell lung cancer (NSCLC).
Authors: Shun Lu, Tony Mok, You Lu, Jianying Zhou, Yuankai Shi, Virote Sriuranpong, James C. M. Ho, Choo Khoon Ong, Chun-Ming Tsai, Chin-Hee Chung, Keith D. Wilner, Yiyun Tang, Elizabeth Masters, Paulina Selaru, Yi-Long Wu
Journal: Journal of Clinical Oncology (2016)

9058 Background: The phase 3 study PROFILE 1014 showed a superior outcome of crizotinib over PCC in ALK+ NSCLC. A phase 3 study of similar design (ongoing; NCT01639001) was conducted in an East Asian population in China, Hong Kong, Malaysia, Taiwan, and Thailand. Methods: The study was designed to detect an improvement in median PFS from 6.4 to 10 mo with 80% power and 1-sided type I error of 0.025. Between Sep 2012 and Jul 2014, 207 pts with previously untreated ALK+ advanced NSCLC were randomized 1:1 (stratification: ECOG PS 0/1 vs 2) to receive crizotinib 250 mg PO BID (n = 104) or pemetrexed 500 mg/m2 with either cisplatin 75 mg/m2 or carboplatin AUC 5–6, IV q3w for ≤ 6 cycles (n = 103). Continuation of/crossover to crizotinib after PD (per independent radiological review) was allowed. The primary endpoint was PFS; key secondary endpoints were ORR, OS, safety, and PROs. Results: In the crizotinib and PCC arms, respectively, 91% and 93% were Han Chinese, 95% and 95% had ECOG PS 0/1, and 20% and 31% had brain metastases. The study met its primary objective: crizotinib significantly prolonged PFS vs PCC (HR: 0.40; 95% CI: 0.29–0.57; 1-sided P < 0.0001; median 11.1 and 6.8 mo). The ORR was significantly higher with crizotinib (87.5% vs 45.6%; 2-sided P < 0.0001). At data cutoff, 82 pts (80%) on PCC had crossed over to crizotinib and 59% of pts (122/207) remained in follow-up. With only 35% of OS events, there was a numerical (not statistically significant) improvement in OS with crizotinib (HR: 0.90; 95% CI: 0.56–1.45; 1-sided P = 0.33). Crizotinib and PCC safety profiles were consistent with those previously published. The most common all-causality AEs with crizotinib were elevated transaminases (69%), diarrhea (59%), and vision disorder (56%); the most common grade 3/4 AEs were neutropenia (16%) and elevated transaminases (12%). Two grade 5 AEs (death of unknown cause, interstitial lung disease) were considered crizotinib-related. Conclusions: These results confirm the findings from PROFILE 1014 and demonstrate that first-line crizotinib significantly improves PFS and ORR vs PCC in an East Asian population with ALK+ advanced NSCLC with an acceptable safety profile. Clinical trial information: NCT01639001.
Effect of Mesenchymal Stem Cells on the Viability, Proliferation and Differentiation of B Lymphocytes.
Authors: Soraya Tabera, Jose A. Perez-Simon, Maria Diez-Campelo, Luis I. Sanchez-Abarca, Belen Blanco, Ana Benito, Enrique Ocio, Fermin M. Sanchez-Guijo, Consuelo Canizo, J.F. San Miguel
Journal: Blood (2007)
Intratumoral gene expression profile of genes involved in 5-FU metabolism and angiogenesis, comparison with tumor invasion depth in patients with advanced gastric cancer.
Authors: Mizutomo Azuma, Akira Naruke, Myungchul Kim, Kenji Ishido, Chikatoshi Katada, Katsuhiko Higuchi, Tohru Sasaki, Satoshi Tanabe, Wasaburo Koizumi
Journal: Journal of Clinical Oncology (2013)

56 Background: The biopsy specimen by endoscopy can only show the surface of its gene profiles. We hypothesis whether the biopsy specimen can reflect all part of gene profile or not. We tested how 5-FU related genes and angiogenesis gene expressed in the invasion depth in the primary tumor of the Stage II or III advanced gastric cancer. Methods: Twenty-five patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed.Formalin-fixed, paraffin-embedded tumor tissues were dissected from the surface section (mainly mucosa), the middle section (mainly submucossa) and the deep section (the part invaded most deeply) of the primary tumor and the normal gastric mucosa tissue by the laser-captured microdissection technique and were analyzed for target gene expressions using a quantitative real-time polymerase chain reaction.We analyzed for target genes as TS, TP, DPD, ERCC1, EGFR, VEGF and HIF1α. Results: In the primary tumor, TP and HIF1α gene expression in the surface section was significantly higher than in the deep section (p=0.021, p=0.012). These gene expression and the depth of the primary tumor had a correlation coefficient (TP; r=0.29, HIF1α; r=0.33). There was no significantly difference between surface and deep section in the primary tumor in TS, DPD, ERCC1, VEGF, EGFR except TP and HIF1α. There was no significantly difference between surface and middle section in the primary tumor in all gene expression. There was no significantly difference between middle and deep section in the primary tumor in all gene expression. Conclusions: Only TP and HIF1α had tendency that these gene expression became higher as invaded from the surface section to the deep section of primary tumor. These data suggested that biopsy specimens could be predicted gene expression profile from the surface of gastric cancer. But as you know, gastric cancer has a heterogeneity gene profile. We need at least few samples to say whole gene expression of its tumors. This is preliminary data, it will need further study to proof these result.