tbuckley/cabot-search huggingface dataset:
Immunologic profiling of adenoid cystic carcinoma (acc)
Authors: Vishwajith Sridharan, Xiaoyun Liao, Nicole G Chau, Robert Haddad, Adel El-Naggar, Gordon J Freeman, F Stephen Hodi, Scott J Rodig, Glenn Dranoff, Jonathan D Schoenfeld
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adenoid cystic carcinoma (ACC) is among the most common malignant salivary gland tumors. Approximately 50% of patients develop distant metastases and up to one third die within 2 years. Chemotherapy provides limited benefit, and is not associated with a survival advantage.
Photodynamic Therapy for Head and Neck Lesions in the Subtropics
Authors: Francisco Civantos
Journal: Journal of the National Comprehensive Cancer Network (2012)

Surgery, radiotherapy, and chemotherapy remain standard treatment options for patients with head and neck carcinomas, but because they are often associated with complications, there is room for improvement. Although not widely practiced and still off-label, photodynamic therapy (PDT) is a promising alternative for superficial malignant or premalignant lesions of the upper aerodigestive tract. It also may be useful for those with recurrent surface disease after surgery or radiotherapy. After an historic look at the data on PDT for head and neck tumors, this article offers a current perspective from a fairly selective PDT program that has achieved dramatic lasting responses. Where PDT may fit in the treatment spectrum for head and neck cancers is one of the unanswered questions requiring further study.
Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis
Authors: Karen Cusack, Daniel E. Jonas, Catherine A. Forneris, Candi Wines, Jeffrey Sonis, Jennifer Cook Middleton, Cynthia Feltner, Kimberly A. Brownley, Kristine Rae Olmsted, Amy Greenblatt, Amy Weil, Bradley N. Gaynes
Journal: Clinical Psychology Review (2015)
Variations in the prevalence of respiratory symptoms, self-reported asthma attacks, and use of asthma medication in the European Community Respiratory Health Survey (ECRHS)
Authors: P Burney, S Chinn, D Jarvis, C Luczynska, E Lai
Journal: European Respiratory Journal (1996)

Asthma is a common chronic disorder which may be increasing in prevalence. However, little is known of its distribution and determinants. The European Community Respiratory Health Survey (ECRHS) is a multicentre survey of the prevalence, determinants and management of asthma. This paper presents a descriptive account of the variation in self-reported attacks of asthma and asthma symptoms across Europe, and in part fulfils the first aim of the study. A screening questionnaire, including seven questions relating to the 12 month prevalence of symptoms of asthma, was distributed to representative samples of 20-44 year old men and women in 48 centers, predominantly in Western Europe. The median response rate to the questionnaire was 75% but, after removing from the denominator those who were the wrong age, were known to have moved out of the area, or had died, it was 78% (range 54-100). The prevalence of all symptoms varied widely. Although these were generally lower in northern, central and southern Europe and higher in the British Isles, New Zealand, Australia and the United States, there were wide variations even within some countries. Centres with a high prevalence of self-reported attacks of asthma also reported high prevalences of nasal allergies and of waking at night with breathlessness. The use of asthma medication was more common where wheeze and asthma attacks were more frequent. In most centres in The Netherlands, Sweden, New Zealand and the United Kingdom over 80% of those with a diagnosis of asthma were currently using asthma medication. In Italy, France and Spain the rate was generally less than 70%. These data are the best evidence to date that geographical differences in asthma prevalence exist, are substantial and are not an artefact of the use of noncomparable methods.
Efficacy of anti-ICOS agonist monoclonal antibodies in preclinical tumor models provides a rationale for clinical development as cancer immunotherapeutics
Authors: Christopher Harvey, Kutlu Elpek, Ellen Duong, Tyler Simpson, ChengYi J Shu, Lindsey Shallberg, Matthew Wallace, Sriram Sathyanarayanan, Robert Mabry, Michael Briskin, Jennifer Michaelson, Thomas F Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts ICOS (inducible co-stimulator molecule) is a T cell encoded member of the extended B7/CD28 superfamily that is up-regulated upon early T cell activation. Previous studies have shown that higher ICOS expression on circulating T cells, post treatment with ipilimumab, is associated
BSA dosing and suboptimal 5-FU exposure among colorectal cancer patients of varying gender and age.
Authors: Abebe Haregewoin, Stephanie A. Hamilton, Charles E. Grier, Rajesh R. Kaldate
Journal: Journal of Clinical Oncology (2012)

579 Background: 5-Fluorouracil (5-FU) remains the cornerstone of colorectal cancer (CRC) therapy and its dosing is based on body surface area (BSA). Although convenient, BSA dosing disregards factors that impact 5-FU PK such as genotype, age, gender, etc. Thus, patients receiving the same BSA based dose show a wide range of 5-FU plasma levels (measured as AUC in mg·h/L), resulting in ineffective or toxic doses affecting therapy outcome. An optimal therapeutic AUC target range of 20-30 mg·h/L has been proposed. Methods: Plasma samples from the initial treatment cycle of 927 CRC patients who received 2400 mg/m 2 continuous infusion of 5-FU over 44-48 hours, with or without bevacizumab, were tested for 5-FU exposure using an immune-based assay (OnDose). AUC results were analyzed to evaluate gender and age effects. Results: There are 391 (42.2%) female and 536 (57.8%) male patients with age ranging from 17-93 years (mean/SD: 58.5/11.8). These analyses indicate that in comparison to the proposed optimal AUC target range of 20-30 mg·h/L, females receive supra-optimal doses compared to males (p=0.0083). Age also affects the 5-FU AUC (p=0.0002), with younger patients more likely to receive sub-optimal doses than older patients. Conclusions: BSA dosing is an unreliable indicator of exposure and may lead to under dosing in males and younger patients, and overdosing in females and older patients, potentially resulting in corresponding diminished efficacy or increased toxicity. Data suggest that therapy could be optimized by 5-FU dose adjustment in subsequent cycles based on PK monitoring so that AUC values will converge towards the target range irrespective of gender or age. A large clinical trial is in progress to validate these findings.
Genetic testing in a cohort of young patients with HER2-amplified breast cancer
Authors: D.M. Eccles, N. Li, R. Handwerker, T. Maishman, E.R. Copson, L.T. Durcan, S.M. Gerty, L. Jones, D.G. Evans, L. Haywood, I. Campbell
Journal: Annals of Oncology (2015)
BMA Annual Representative Meeting: BMA's annual meeting rejects governance review of association
Authors: Linda Beecham
Journal: BMJ (2003)

Representatives at the BMA's annual meeting have dismissed the findings of an internal review of the association's representative and decision making machinery.​machinery.




Figure 1





Representatives get to grips with the new voting technology

Credit: BRUNO VINCENT




They rejected the second consultation document from the committee that was set up to recommend changes and called for the committee to be replaced by a more representative body.

The meeting said that the review was not credible, because it lacked openness, transparency, and accountability. It also criticised the current committee for being hand picked.

A project team was set up a year ago and has consulted widely. More than 20 000 members responded to a questionnaire, and there have been regular reports to the council of the BMA and to the various craft committees.

No one doubted that there should be a review of governance, but in a heated debate speakers complained that they had been presented with a fait accompli without the opportunity to discuss the different solutions.

Despite the amount of feedback, they were concerned that this had not been translated into the latest document. They believed that too much power would be in the hands of the centre and too little with the grassroots of the association.

Dr Stephen Austin from the council and the Junior Doctors Committee said that the list of possible options took up half a page, whereas the preferred option of the committee took up 10 pages. “Where is the detailed analysis of the options?” he asked. “We deserve better than this.”

Mrs Anna Athow, from Enfield and Haringey, wanted the document to be completely rewritten. She did not like the proposals to delegate the executive function to an executive board or to substitute regions for divisions.

Defending the document, the chairman of the governance committee, Dr Russell Walshaw, maintained that the process had been more open than any previous exercise. The committee had been asked to come up with realistic and achievable solutions.
Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2–Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC—A Randomized Phase III Trial
Authors: J. Randolph Hecht, Yung-Jue Bang, Shukui K. Qin, Hyun C. Chung, Jianming M. Xu, Joon O. Park, Krzysztof Jeziorski, Yaroslav Shparyk, Paulo M. Hoff, Alberto Sobrero, Pamela Salman, Jin Li, Svetlana A. Protsenko, Zev A. Wainberg, Marc Buyse, Karen Afenjar, Vincent Houé, Agathe Garcia, Tomomi Kaneko, Yingjie Huang, Saba Khan-Wasti, Sergio Santillana, Michael F. Press, Dennis Slamon
Journal: Journal of Clinical Oncology (2015)

To evaluate the efficacy of adding lapatinib to capecitabine and oxaliplatin (CapeOx) in patients with previously untreated human epidermal growth factor receptor 2 (HER2) -amplified advanced gastroesophageal adenocarcinoma.Patients with HER2-positive advanced gastroesophageal adenocarcinoma were randomly assigned at a one-to-one ratio to CapeOx plus lapatinib 1,250 mg or placebo daily. Primary end point was overall survival (OS) in patients with centrally confirmed HER2 amplification in the primary efficacy population.A total of 545 patients were randomly assigned, and 487 patients comprised the primary efficacy population. Median OS in the lapatinib and placebo arms was 12.2 (95% CI, 10.6 to 14.2) and 10.5 months (95% CI, 9.0 to 11.3), respectively, which was not significantly different (hazard ratio, 0.91; 95% CI, 0.73 to 1.12). Median progression-free survival in the lapatinib and placebo arms was 6.0 (95% CI, 5.6 to 7.0) and 5.4 months (95% CI, 4.4 to 5.7), respectively (hazard ratio, 0.82; 95% CI, 0.68 to 1.00; P = .0381). Response rate was significantly higher in the lapatinib arm: 53% (95% CI, 46.4 to 58.8) compared with 39% (95% CI, 32.9 to 45.3) in the placebo arm (P = .0031). Preplanned exploratory subgroup analyses showed OS in the lapatinib arm was prolonged in Asian and younger patients. No correlation was observed between HER2 immunohistochemistry status and survival. There were increased toxicities in the lapatinib arm, particularly diarrhea.Addition of lapatinib to CapeOx did not increase OS in patients with HER2-amplified gastroesophageal adenocarcinoma. There were clear differences in the effect of lapatinib depending on region and age. Future studies could examine this correlation.
Approaches to Prevention of Cardiovascular Disease
Authors: Valery L. Feigin, Bo Norrving, David O. Wiebers
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Guidelines for the Management of Breakthrough Pain in Patients With Cancer
Authors: Augusto Caraceni, Andrew Davies, Philippe Poulain, Hernán Cortés-Funes, Sunil J Panchal, Guido Fanelli
Journal: Journal of the National Comprehensive Cancer Network (2013)

The moral imperative to adequately manage pain is being increasingly recognized worldwide. A comprehensive pain management approach that addresses the various presentations of pain in patients with cancer is required, including appropriate management of breakthrough pain. Breakthrough pain commonly occurs in patients with advanced cancer and is disabling to the individual and burdensome to society, yet it is often inadequately managed. Because pain is heterogeneous, the best management of an individual's pain, including breakthrough pain in cancer, requires a thorough assessment to tailor the treatment strategies. Recently developed guidelines support this approach and recommend treating breakthrough pain using rapid- or short-acting opioids with pharmacodynamics that mirror the rapid onset and short duration of the presenting pain. This approach should be part of a comprehensive strategy to treat pain within the context of the primary disease trajectory, offering continuity of care and access to specialized palliative care when appropriate.
Using Cellular Mechanisms to Develop Effective Combinations of Photodynamic Therapy and Targeted Therapies
Authors: Tayyaba Hasan
Journal: Journal of the National Comprehensive Cancer Network (2012)

The bond between the research laboratory and the clinic is especially strong in the field of photomedicine. Much is learned in preclinical animal models, which is translated to the clinic for investigation, and then refinements in theory and technique are explored back in the laboratory. With many cancers becoming resistant to treatment, photodynamic therapy (PDT) offers a mechanistically distinct alternative. Studies have shown that PDT not only mitigates chemoresistance but also synergizes with chemotherapy and molecularly targeted therapies. From the world of biochemistry comes this unique look at 2 approaches to maximize the photodynamic effect through PDT combinations with targeted therapies: 1) using the molecular response after PDT to guide the selection of targeted agents and 2) preconditioning cancer cells to modulate nuclear molecular targets before PDT.
Athletic groin pain (part 1): a prospective anatomical diagnosis of 382 patients—clinical findings, MRI findings and patient-reported outcome measures at baseline
Authors: É C Falvey, E King, S Kinsella, A Franklyn-Miller
Journal: British Journal of Sports Medicine (2015)

Background Athletic groin pain remains a common field-based team sports time-loss injury. There are few reports of non-surgically managed cohorts with athletic groin pain. Aim To describe clinical presentation/examination, MRI findings and patient-reported outcome (PRO) scores for an athletic groin pain cohort. Methods All patients had a history including demographics, injury duration, sport played and standardised clinical examination. All patients underwent MRI and PRO score to assess recovery. A clinical diagnosis of the injured anatomical structure was made based on these findings. Statistical assessment of the reliability of accepted standard investigations undertaken in making an anatomical diagnosis was performed. Result 382 consecutive athletic groin pain patients, all male, enrolled. Median time in pain at presentation was (IQR) 36 (16–75) weeks. Most (91%) played field-based ball-sports. Injury to the pubic aponeurosis (PA) 240 (62.8%) was the most common diagnosis. This was followed by injuries to the hip in 81 (21.2%) and adductors in 56 (14.7%) cases. The adductor squeeze test (90° hip flexion) was sensitive (85.4%) but not specific for the pubic aponeurosis and adductor pathology (negative likelihood ratio 1.95). Analysed in series, positive MRI findings and tenderness of the pubic aponeurosis had a 92.8% post-test probability. Conclusions In this largest cohort of patients with athletic groin pain combining clinical and MRI diagnostics there was a 63% prevalence of PA injury. The adductor squeeze test was sensitive for athletic groin pain, but not specific individual pathologies. MRI improved diagnostic post-test probability. No hernia or incipient hernia was diagnosed. Clinical trial registration number NCT02437942.
Leukemia/lymphoma development in IL-15-deficient TCR-transgenic mice
Authors: Sigrid Dubois, Juergen Mueller, Lionel Feigenbaum, Thomas A Waldmann
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Sporadic mouse tumor models are valuable tools to understand disease development and treatment efficacies. Here we show that a transgenic T cell receptor expression predisposes mice to leukemia/lymphoma development. Leukemia/lymphoma precursors expressed low amounts of MHC class I
The “Three-Parent Baby”: A Case Study of How Language Frames the Ethical Debate Regarding an Emerging Technology
Authors: Vardit Ravitsky, Stanislav Birko, Raphaelle Dupras-Leduc
Journal: The American Journal of Bioethics (2015)

Language, terminology, and metaphors play a role in framing public debate, policy, and research directions. O'Keefe and colleagues (2015) explore the impact of language in the case of gene editing ...
Impaired aldehyde dehydrogenase 1 subfamily member 2A-dependent retinoic acid signaling is related with a mesenchymal-like phenotype and an unfavorable prognosis of head and neck squamous cell carcinoma
Authors: Katharina Seidensaal, Andre Nollert, Agnes Hiou Feige, Marie Muller, Thomas Fleming, Nikolas Gunkel, Karim Zaoui, Niels Grabe, Wilko Weichert, Klaus-Josef Weber, Peter Plinkert, Christian Simon, Jochen Hess
Journal: Molecular Cancer (2015)

An inverse correlation between expression of the aldehyde dehydrogenase 1 subfamily A2 (ALDH1A2) and gene promoter methylation has been identified as a common feature of oropharyngeal squamous cell carcinoma (OPSCC). Moreover, low ALDH1A2 expression was associated with an unfavorable prognosis of OPSCC patients, however the causal link between reduced ALDH1A2 function and treatment failure has not been addressed so far.Serial sections from tissue microarrays of patients with primary OPSCC (n = 101) were stained by immunohistochemistry for key regulators of retinoic acid (RA) signaling, including ALDH1A2. Survival with respect to these regulators was investigated by univariate Kaplan-Meier analysis and multivariate Cox regression proportional hazard models. The impact of ALDH1A2-RAR signaling on tumor-relevant processes was addressed in established tumor cell lines and in an orthotopic mouse xenograft model.Immunohistochemical analysis showed an improved prognosis of ALDH1A2(high) OPSCC only in the presence of CRABP2, an intracellular RA transporter. Moreover, an ALDH1A2(high)CRABP2(high) staining pattern served as an independent predictor for progression-free (HR: 0.395, p = 0.007) and overall survival (HR: 0.303, p = 0.002), suggesting a critical impact of RA metabolism and signaling on clinical outcome. Functionally, ALDH1A2 expression and activity in tumor cell lines were related to RA levels. While administration of retinoids inhibited clonogenic growth and proliferation, the pharmacological inhibition of ALDH1A2-RAR signaling resulted in loss of cell-cell adhesion and a mesenchymal-like phenotype. Xenograft tumors derived from FaDu cells with stable silencing of ALDH1A2 and primary tumors from OPSCC patients with low ALDH1A2 expression exhibited a mesenchymal-like phenotype characterized by vimentin expression.This study has unraveled a critical role of ALDH1A2-RAR signaling in the pathogenesis of head and neck cancer and our data implicate that patients with ALDH1A2(low) tumors might benefit from adjuvant treatment with retinoids.
Respiratory health at the extremes of the ageing population: Initial results of the UK Newcastle 85+ study
Authors: Therese Small, Joanna Collerton, Karen Davies, Mohammed Yadegarfar, Thomas Kirkwood, Paul Corris, Andrew Fisher
Journal: European Respiratory Journal (2012)

People aged 85+ years are demographically the fasting growing age group worldwide increasing the burden on healthcare resources. In the Newcastle 85+ study subjects born in 1921, recruited from the Newcastle area, underwent domiciliary health assessment, including respiratory history, symptoms, spirometry and review of general practitioner (GP) records for pre-existing disease. 845 participants (319 Male: 526 Female) took part, regardless of current health status.

Significant occupational exposure to heavy industry was reported by 42% men and 17 % women. 71% men and 52% women were current or ex- regular smokers. Review of GP records showed 18% men and 16% women had a diagnosis of Chronic Obstructive Pulmonary Disease (COPD); 7% men and 13% women a diagnosis of Asthma; and 10% men and 7% women had other primary respiratory diagnoses.

92% performed reproducible spirometry. 28% males had normal spirometry, 13% restrictive and 59% obstructive spirometry (Mild 36%; Moderate 46%; Severe 15% and very severe 3%). In the females, 33% had normal spirometry, 16% restrictive and 51% obstructive spirometry (Mild 44%; Moderate 43%; Severe 11% and very severe 2%). The MRC Dyspnoea score was ≥2 in 38% men and 40% women.

This study presents data on a large population of very elderly people. It shows a high prevalence of diagnosed airways diseases with 25% men and 29% women having asthma or COPD. Obstructive spirometry was reported in 59% men and 50% women with significant disability shown by MRC-dyspnoea score. These initial results suggest a significant burden of respiratory compromise with potential for significant impact on health care services in the coming years.
Survival of Patients with Stage I Lung Cancer Detected on CT Screening
Authors: Claudia I Henschke, David F Yankelevitz, Daniel M Libby, Mark W Pasmantier, James P Smith, Olli S Miettinen
Journal: New England Journal of Medicine (2006)

The outcome among patients with clinical stage I cancer that is detected on annual screening using spiral computed tomography (CT) is unknown.In a large collaborative study, we screened 31,567 asymptomatic persons at risk for lung cancer using low-dose CT from 1993 through 2005, and from 1994 through 2005, 27,456 repeated screenings were performed 7 to 18 months after the previous screening. We estimated the 10-year lung-cancer-specific survival rate among participants with clinical stage I lung cancer that was detected on CT screening and diagnosed by biopsy, regardless of the type of treatment received, and among those who underwent surgical resection of clinical stage I cancer within 1 month. A pathology panel reviewed the surgical specimens obtained from participants who underwent resection.Screening resulted in a diagnosis of lung cancer in 484 participants. Of these participants, 412 (85%) had clinical stage I lung cancer, and the estimated 10-year survival rate was 88% in this subgroup (95% confidence interval [CI], 84 to 91). Among the 302 participants with clinical stage I cancer who underwent surgical resection within 1 month after diagnosis, the survival rate was 92% (95% CI, 88 to 95). The 8 participants with clinical stage I cancer who did not receive treatment died within 5 years after diagnosis.Annual spiral CT screening can detect lung cancer that is curable.