tbuckley/cabot-search huggingface dataset:
Human Papillomavirus Genotypes Conferring Poor Prognosis in Head and Neck Squamous Cell Carcinoma—Reply
Authors: Scott V. Bratman, John N. Waldron, Fei-Fei Liu
Journal: JAMA Oncology (2016)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study
Authors: Andrew J Stewardson, Arthur Allignol, Jan Beyersmann, Nicholas Graves, Martin Schumacher, Rodolphe Meyer, Evelina Tacconelli, Giulia De Angelis, Claudio Farina, Fabio Pezzoli, Xavier Bertrand, Houssein Gbaguidi-Haore, Jonathan Edgeworth, Olga Tosas, Jose A Martinez, M Pilar Ayala-Blanco, Angelo Pan, Alessia Zoncada, Charis A Marwick, Dilip Nathwani, Harald Seifert, Nina Hos, Stefan Hagel, Mathias Pletz, Stephan Harbarth
Journal: Eurosurveillance (2016)

We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34–2.42, HR = 1.81; 95% CI: 1.49–2.20 and HR = 2.42; 95% CI: 1.66–3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2–9.4, 11.5 days; 95% CI: 11.5–11.6 and 13.3 days; 95% CI: 13.2–13.4, respectively). BSI with third-generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8–5.9) but not hazard of death (1.16; 95% CI: 0.98–1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13–2.35), excess LOS (4.9 days; 95% CI: 1.1–8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae.
Allogeneic Hematopoietic Stem Cell Transplantation (HCT) Compared to Chemotherapy Only in Acute Myeloid Leukemia (AML) Patients 60 Years and Older: A Center for International Blood and Marrow Transplantation Research (CIBMTR)/ Cancer and Leukemia Group B (CALGB) Study.
Authors: Sherif Farag, Kati Maharry, Waleska S. Perez, Mei-Jie Zhang, John F. DiPersio, Donald Bunjes, Guido Marcucci, Maria R. Baer, Richard A. Larson, Martin Tallman, Clara D. Bloomfield, Daniel J. Weisdorf
Journal: Blood (2009)
Adjuvant chemotherapy and overall survival in adult medulloblastoma
Authors: Benjamin H. Kann, Nataniel H. Lester-Coll, Henry S. Park, Debra N. Yeboa, Jacqueline R. Kelly, Joachim M. Baehring, Kevin P. Becker, James B. Yu, Ranjit S. Bindra, Kenneth B. Roberts
Journal: Neuro-Oncology (2016)

Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004–2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32–0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI.
123I-FP-CIT-SPECT in Encephalitis Involving Substantia Nigra
Authors: Hubert Tissot, Solene Frismand, Pierre-Yves Marie, Nicolaie Gospodaru, Antoine Verger
Journal: Clinical Nuclear Medicine (2016)

I-FP-CIT-SPECT is currently used to detect functional impairment of striatal structures. We report herein a case where I-FP-CIT abnormalities are seemingly related to an encephalitis involving substantia nigra. A few months after a documented encephalitis, a 19-year-old woman experienced a Parkinsonism with a right dominance. There was a reduction in the striatal binding of I-FP-CIT, especially on the left side, in accordance with the right dominance of the Parkinsonism.
Timeline cluster: a graphical tool to identify risk of bias in cluster randomised trials
Authors: Agnès Caille, Sally Kerry, Elsa Tavernier, Clémence Leyrat, Sandra Eldridge, Bruno Giraudeau
Journal: BMJ (2016)

 Cluster randomised trials can be at risk of bias when participants are identified and recruited after randomisation  Reports of cluster randomised trials often fail to adequately describe the recruitment process and whether participants and trial staff are blinded to allocation status at key stages of the trial  This article presents a graphical tool depicting the time sequence and blinding status of the different stages of a cluster randomised trial together with examples to help researchers describe the storyline of such trials  Our graphical tool should be used at both the protocol and report-writing stages to clarify the trial process and to help identify the risk of bias StandfirstRobust evidence of the effectiveness of interventions relating to policy, practice and organisation of healthcare often comes from well-conducted cluster randomised trials.However, such trials are prone to recruitment bias depending on whether participants are recruited before the randomisation of clusters and whether the recruiter is blinded to the allocation status.In most cases, participants and trial staff cannot be blinded to the intervention, which may lead to performance and detection bias.Unfortunately, cluster trial reports often do not provide a clear description of the timing of trial processes and blinding, and these aspects are not covered by current reporting tools.This article proposes a graphical tool depicting the time sequence of steps and blinding status in cluster randomised trials.The tool may be helpful at both the protocol and report-writing stages to clarify the process and to help identify potential bias in cluster randomised trials.
HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins
Authors: Damien Bertheloot, Eicke Latz
Journal: Cellular and Molecular Immunology (2016)

Our immune system is based on the close collaboration of the innate and adaptive immune systems for the rapid detection of any threats to the host. Recognition of pathogen-derived molecules is entrusted to specific germline-encoded signaling receptors. The same receptors have now also emerged as efficient detectors of misplaced or altered self-molecules that signal tissue damage and cell death following, for example, disruption of the blood supply and subsequent hypoxia. Many types of endogenous molecules have been shown to provoke such sterile inflammatory states when released from dying cells. However, a group of proteins referred to as alarmins have both intracellular and extracellular functions which have been the subject of intense research. Indeed, alarmins can either exert beneficial cell housekeeping functions, leading to tissue repair, or provoke deleterious uncontrolled inflammation. This group of proteins includes the high-mobility group box 1 protein (HMGB1), interleukin (IL)-1α, IL-33 and the Ca2+-binding S100 proteins. These dual-function proteins share conserved regulatory mechanisms, such as secretory routes, post-translational modifications and enzymatic processing, that govern their extracellular functions in time and space. Release of alarmins from mesenchymal cells is a highly relevant mechanism by which immune cells can be alerted of tissue damage, and alarmins play a key role in the development of acute or chronic inflammatory diseases and in cancer development.
Overall survival in patients with glioblastoma before and after bevacizumab approval.
Authors: Derek Richard Johnson, Antonio Marcilio Padula Omuro, Arliene Ravelo, Nicolas Sommer, Annie Guerin, Raluca Ionescu-Ittu, Alexander R Macalalad, Sherry Shi, Joon H. Uhm
Journal: Journal of Clinical Oncology (2016)

2062 Background: Glioblastoma (GBM) is an aggressive disease with limited therapeutic options. While bevacizumab was approved in 2009 for the treatment of patients with recurrent GBM, its impact on overall survival (OS) remains unclear. This study utilizes population-based cancer registry data to compare OS of patients diagnosed with GBM before versus after bevacizumab approval. Methods: Adult patients diagnosed with GBM were identified in the SEER database and divided into 2 cohorts: patients diagnosed in 2006-2008 (Pre-Bevacizumab Cohort, n=6,120) and patients diagnosed in 2010-2012 (Post-Bevacizumab Cohort, n=6,753). All patients were included irrespective of the treatments received. OS was assessed from diagnosis (dx) date up to 3-years post-dx. Results: Among 12,873 patients with GBM, the median age was 62 years, 41% were females, 31% underwent gross total resection, and 75% received radiation therapy. OS rates at 1 and 2 years post-dx were significantly higher for the Post-Bevacizumab Cohort versus the Pre-Bevacizumab Cohort (44 vs 40% and 21 vs 19%, p <.01, Table). After adjusting for potential confounders, the hazard of death remained significantly lower in the Post-Bevacizumab Cohort (hazard ratio [HR] 0.91, p <.01, Table). Survival was stable within the 2006-2008 period (median survival = 9 months for all years), but increased after year 2009 (median survival = 10 and 11 months for years 2010-2011 and 2012, respectively). Conclusions: Based on this large population-based study, the survival following glioblastoma diagnosis improved in 2010-2012 compared to 2006-2008. While the cause of this improvement cannot be proven in a retrospective analysis, the timing of the survival increase may indicate a potential benefit of bevacizumab on recurrent GBM survival. Pre-Bevacizumab Cohort Post-Bevacizumab Cohort p-value OS rates (95% CI)* <.01 1-year post-dx 40% (38 – 41) 44% (43 – 45) 2-years post-dx 19% (17 – 20) 21% (19 – 22) Median survival* (months) 9 11 Adjusted HR Post vs Pre (95% CI)† 0.91 (0.87 – 0.96) * From Kaplan-Meier analyses. † HRs estimated from Cox regression models adjusted for age, gender, race, radiation therapy, and surgery type. A HR<1 indicates the Post-Bevacizumab Cohort had longer survival.
Abstract 18574: Examination of a Highly Penetrant Mouse Model of Bicuspid Aortic Valve Demonstrates that Endothelial Notch1 is Required for Proper Morphogenesis of the Aortic Valve
Authors: Kevin M Bosse, Sara N Koenig, Hannah Huang, Vidu Garg
Journal: Circulation (2013)

Bicuspid aortic valve (BAV) is the most common type of cardiac malformation with an estimated prevalence of 1-2% in the population. BAV results in significant morbidity as it is one of the leading causes of valve stenosis and regurgitation in adults. We previously reported that mutations in the signaling and transcriptional regulator, NOTCH1 , were a cause of BAV in non-syndromic autosomal-dominant human pedigrees. The Notch signaling pathway is critical for multiple cell differentiation processes, and Notch1 is expressed in the developing and adult aortic valve. Recently, we have generated a new highly penetrant mouse model of aortic valve malformations using Notch1 haploinsufficient mice that are backcrossed in a Nos3-null background. Notch1 and Nos3 compound mutant adult mice ( Notch1 +/- ;Nos3 -/- ) display a nearly 100% incidence of BAV. The aortic valves of adult mutant mice are thickened and have associated stenosis and regurgitation. We have also found that by postnatal day 10, compound mutant mice suffer ~50% lethality compared to NOS3 -/- littermates. Here, we have examined Notch1 +/- ;Nos3 -/- embryos at serial timepoints to elucidate the mechanisms underlying BAV. Examination at embryonic day 18.5 (E18.5) demonstrated normal Mendelian ratios and histologic examination revealed thickened, malformed valve leaflets accompanied by other outflow tract abnormalities in NOS3 -/- ;Notch1 -/+ mice, likely contributing to the neonatal lethality. Further investigation at E13.5 and E15.5 indicated that the NOS3 -/- ;Notch1 -/+ aortic valve leaflets were significantly thicker than controls, suggesting that outflow tract cushion formation and early remodeling may be affected. In addition, we have generated mice are null for Nos3 and haploinsufficient for Notch1 in endothelial-derived cells using mice harboring a Notch1 -floxed allele and Tie2-Cre mice. Our preliminary results indicate that NOS3 -/- ; Notch1 fl/+ ;Tie2Cre + mice recapitulate the NOS3 -/- ;Notch1 -/+ cardiac phenotype and suggest that endothelial Notch1 is required for proper development of the aortic valve. Overall our data indicate that loss of endothelial Notch1 results in abnormal remodeling of the outflow tract cushions and contributes to BAV.
NHS announces online symptom checker
Authors: Matt Limb
Journal: BMJ (2016)

The BMA has warned that planned new digital NHS services, including an online “symptom checker,” should not replace patients’ direct access to GPs.

Brian Balmer, who chairs the BMA’s General Practitioners Committee, said that any new technology that improved patient care and access was to be welcomed, especially if it made appointment booking easier. But he said, “The proposed symptom checker is not the same as a consultation with a GP and should not be considered as such.”

Plans for patients to be able to book appointments, access medical records, and order prescriptions via a new NHS.uk website, are part of a £4.2bn (€5bn; $5.6bn) …
Accuracy of oncologists’ life-expectancy estimates provided to their advanced cancer patients: Correlates and outcomes.
Authors: Jason P Lambden, Baohui Zhang, Holly Gwen Prigerson
Journal: Journal of Clinical Oncology (2016)

10032 Background: Oncologists are often reluctant to discuss life-expectancy estimates with their patients because of concerns about the inaccuracy of the estimates and limited evidence regarding benefits. This study explores oncologists’ accuracy in predicting their advanced cancer patients’ life-expectancy and correlates of prognostic accuracy. Methods: Data were derived from a multicenter, prospective, longitudinal study of 85 patients with metastatic solid malignancies with progressive disease after at least one chemotherapy regimen, assessed at baseline and followed to death. Patients were asked whether their oncologist had provided them with a life-expectancy estimate, and baseline socio-demographic and clinical characteristics were examined to determine associations with the accuracy of oncologists’ life-expectancy estimates. Oncologists’ accuracy of predicting life-expectancy was also examined for associations with chemotherapy use, trial participation, and completion of a do not resuscitate [DNR] order at the baseline assessment. Results: 74.1% (63/85) of oncologists’ life-expectancy estimates were accurate to within a year. The percentage of oncologists who accurately estimated life-expectancy to within 12 months increased with the patient’s proximity to death (Fisher’s exact p-value = 0.018). Factors positively associated (P < 0.05) with oncologists’ accuracy to within a year included patient age, poor performance status and quality of life, acknowledgment of being terminally ill, and a preference for avoiding chemotherapy at baseline. Oncologists’ prognoses that were accurate to within a year were also associated with patients’ greater likelihood of DNR order completion (OR = 2.94; 95% CI = 1.03-8.41), engaging in an EOL discussion (OR = 4.22, 95% CI = 1.45-12.29), avoiding use of palliative chemotherapy (OR = 0.30, 95% CI = 0.11-0.85), and lower likelihood of clinical trial enrollment (OR = 0.09, 95% CI = 0.02-0.50). Conclusions: Oncologists are able to estimate patient life-expectancy to within a year. Communicating estimates accurate to within a year is associated with more engagement in advance care planning and avoidance of palliative chemotherapy.
ODM-201, a new generation androgen receptor inhibitor for castration-resistant prostate cancer: Preclinical and phase I data.
Authors: Karim Fizazi, Christophe Massard, Nicholas David James, Stephane Culine, Robert Hugh Jones, Riikka Oksala, Anu Moilanen, Eija Aho, Laura Ravanti, Pekka Kallio
Journal: Journal of Clinical Oncology (2013)

65^ Background: Castration resistant prostate cancer (CRPC) is characterized by persistent, high level androgen receptor (AR) expression and resistance to conventional AR inhibitors. ODM-201 is a novel AR inhibitor with unique pharmacologic properties that has shown promising results in preclinical and clinical studies. Methods: AR binding affinity of ODM-201 to wild type AR was determined in cytosolic lysates obtained from ventral prostates of castrated rats using a competition binding assay. Additionally, effects of ODM-201 on the growth of castration resistant VCaP tumors was evaluated. Tumors were established by subcutaneous injection of VCaP prostate cancer cells into male nude mice. After initial tumor growth, mice were castrated. ODM-201 (50 mg/kg QD or BID orally) was initiated upon tumor regrowth. Since the risk of seizures has been reported for some second generation AR inhibitors, ODM-201 concentrations in mouse brain homogenates were studied after repeated oral administration to assess the risk. The clinical effects of ODM-201 (100, 200, 300, 500, 700, 900 mg BID) was examined in a Phase I/II dose-escalation trial in patients (N=24) with progressive metastatic CRPC. Results: ODM-201 binds to wild type AR with superior affinity compared to enzalutamide (Ki of 9 and 39 nM, respectively). In the VCaP CRPC model, ODM-201 significantly (p&lt;0.001 compared to castrated control), and more efficiently than enzalutamide, inhibited tumor growth. After oral administration, tissue/plasma ratio of ODM-201 in mouse brain homogenates was negligible in all studied doses. In the Phase I/II clinical study, ODM-201 (100 to 700 mg results available) was well tolerated, and most commonly reported adverse events were asthenia, diarrhea and nausea. A PSA response (defined as ≥ 50% decrease) was obtained in 13/15 patients evaluable at 12 weeks with all patients achieving partial response or stable disease by RECIST/PCWG2 criteria. Conclusions: ODM-201 is a new generation AR inhibitor with superior preclinical efficacy compared to enzalutamide and bicalutamide, it does not enter the brain in preclinical studies, and it shows very promising activity and no significant toxicity in patients with CRPC. Clinical trial information: NCT01317641.
Paul Haydon Rogers
Authors: D D R Williams
Journal: BMJ (2016)

Paul Haydon Rogers was a respected psychiatrist, who had a leading role in the development of modern psychiatric services in Northampton and Northamptonshire.

He was a son of the manse, who was born in Cardiff and brought up in the west country. After Caterham School he studied at Cambridge and went on to the London Hospital to study medicine. After qualifying he joined the Royal Army Medical Corps as a captain. He was soon posted abroad, initially to Normandy and later to Egypt and Palestine. On demobilisation in 1947 he returned to the academic unit at the London Hospital, but when he realised how tight the bottleneck for advancement in medicine was he switched to psychiatry and undertook further training at the Maudsley Hospital, London.

In 1955 he was appointed consultant psychiatrist and …
A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts
Authors: Rintaro Noro, Teruhide Ishigame, Naomi Walsh, Kouya Shiraishi, Ana I. Robles, Bríd M. Ryan, Aaron J. Schetter, Elise D. Bowman, Judith A. Welsh, Masahiro Seike, Akihiko Gemma, Vidar Skaug, Steen Mollerup, Aage Haugen, Jun Yokota, Takashi Kohno, Curtis C. Harris
Journal: Journal of Thoracic Oncology (2016)