tbuckley/cabot-search huggingface dataset:
Abstract 13610: Native T1-based Cardiovascular Magnetic Resonance Imaging for Characterizing Chronic Myocardial Infarctions in Patients
Authors: Avinash Kali, Eui Y Choi, Behzad Sharif, Young J Kim, Xiaoming Bi, Bruce Spottiswoode, Ivan Cokic, Hsin J Yang, Mourad Tighiouart, Debiao Li, Daniel S Berman, Byoung W Choi, Hyuk J Chang, Rohan Dharmakumar
Journal: Circulation (2014)

Introduction: Late Gadolinium Enhancement (LGE) Cardiovascular Magnetic Resonance (CMR) is the gold standard for characterizing chronic myocardial infarctions (MIs), but it is contraindicated in patients with end-stage chronic kidney disease. Hypothesis: We investigated whether native T1 mapping at 3T can reliably characterize chronic MIs in two pilot patient populations with prior STEMI and NSTEMI. Methods: Patients with prior STEMI (n=15) and NSTEMI (n=17) underwent CMR at a median of 13.6 years after acute MI and native T1 maps and LGE images were acquired. Infarct location, size and transmurality were measured from LGE and T1 maps using standard threshold criterion and compared against one another. Visual conspicuity for detecting chronic MI territories on LGE images and T1 maps were assessed by independent reviewers. Results: LGE images and native T1 maps were not different for measuring infarct size (STEMI: p=0.87; NSTEMI: p=0.93) and transmurality (STEMI: p=0.19; NSTEMI: p=0.24). Statistical analyses showed good agreement between LGE images and T1 maps for measuring infarct size (STEMI: bias = -0.4±2.1%; R2=0.97; NSTEMI: bias = -1.1±3.9%; R2=0.87) and transmurality (STEMI: bias = 1.5±2.9%; R2=0.99; NSTEMI: bias = -2.2±7.4%; R2=0.71). Sensitivity and specificity of native T1 maps for detecting chronic MIs based on threshold criterion were 93% and 97% respectively (STEMI); and 93% and 92% respectively (NSTEMI). Mean visual conspicuity score for detecting chronic MI on LGE images was greater than that of native T1 maps (p&lt;0.001). Sensitivity and specificity of native T1 maps using visual detection were: 61% and 85% (STEMI); and 67% and 90% (NSTEMI). Conclusions: Chronic MIs in STEMI and NSTEMI patients can be reliably characterized using threshold-based detection with native T1 maps when the location of remote myocardium is known. The current visual detectability of remote myocardium on native T1 maps has a certainty of 85% in STEMI and 90% in NSTEMI patients.
Tumor suppressor IKZF1 mediates glucocorticoid resistance in B-cell precursor acute lymphoblastic leukemia
Authors: R Marke, J Havinga, J Cloos, M Demkes, G Poelmans, L Yuniati, D van Ingen Schenau, E Sonneveld, E Waanders, R Pieters, R P Kuiper, P M Hoogerbrugge, G J L Kaspers, F N van Leeuwen, B Scheijen
Journal: Leukemia (2015)
Perforin Expressing CD4+T Cells Respond to CMV Antigens in CMV Seropositive Patients with B Cell Chronic Lymphocytic Leukaemia (B-CLL).
Authors: James Walton, Keirissa Lawson, Maria S. Manoussaka, Amit Nathwani, Vincent Emory, Peter M. Lydyard, Nino Porakishvili
Journal: Blood (2004)
Optimisation of a treat-to-target approach in rheumatoid arthritis: strategies for the 3-month time point
Authors: Daniel Aletaha, Farideh Alasti, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Treat-to-target (T2T) is a widely accepted management strategy for rheumatoid arthritis (RA) with a key decision point at 3 months after treatment initiation. At this time point, it remains unclear which patients will benefit from treatment adaptation or from continuation of existing treatment. <h3>Methods</h3> We performed a pooled analysis of patient-level clinical trial data of patients with RA. We used a diagnostic testing methodology and a probabilistic approach employing logistic regression to investigate which levels of response at 3 months can inform treatment decisions in regard to achieving the target at 6 months. <h3>Results</h3> To be at least 80% sensitive for achieving the low disease activity (LDA) target at 6 months, a change at 3 months in Simplified Disease Activity Index/Clinical Disease Activity Index (SDAI or CDAI) of 58% needs to be observed at 3 months. Higher changes are needed to sensitively predict remission (REM). Not reaching the (minor) SDAI 50% response level is afflicted with very low negative likelihood ratios (LRs) (0.28 for LDA and 0.07 for REM at 6 months). Experiencing (major) SDAI 85% response has substantial positive LRs of 9.2 for reaching LDA and 6.2 for reaching REM at 6 months. In logistic regression, the change at 3 months is significantly associated with reaching of the target at 6 months. <h3>Conclusions</h3> The 3-month time point is a critical decision point. Not achieving minor responses at 3 months makes reaching of the treatment target at 6 months highly unlikely, while reaching major responses is highly predictive of reaching the treatment target.
Across-Species Transfer of Protection by Remote Ischemic Preconditioning With Species-Specific Myocardial Signal Transduction by Reperfusion Injury Salvage Kinase and Survival Activating Factor Enhancement Pathways
Authors: Andreas Skyschally, Sabine Gent, Georgios Amanakis, Christiane Schulte, Petra Kleinbongard, Gerd Heusch
Journal: Circulation Research (2015)

Reduction of myocardial infarct size by remote ischemic preconditioning (RIPC), that is, cycles of ischemia/reperfusion in an organ remote from the heart before sustained myocardial ischemia/reperfusion, was confirmed in all species so far, including humans.To identify myocardial signal transduction of cardioprotection by RIPC.Anesthetized pigs were subjected to RIPC (4×5/5 minutes hindlimb ischemia/reperfusion) or placebo (PLA) before 60/180 minutes coronary occlusion/reperfusion. Phosphorylation of protein kinase B, extracellular signal-regulated kinase 1/2 (reperfusion injury salvage kinase [RISK] pathway), and signal transducer and activator of transcription 3 (survival activating factor enhancement [SAFE] pathway) in the area at risk was determined by Western blot. Wortmannin/U0126 or AG490 was used for pharmacological RISK or SAFE blockade, respectively. Plasma sampled after RIPC or PLA, respectively, was transferred to isolated bioassay rat hearts subjected to 30/120 minutes global ischemia/reperfusion. RIPC reduced infarct size in pigs to 16±11% versus 43±11% in PLA (% area at risk; mean±SD; P<0.05). RIPC increased the phosphorylation of signal transducer and activator of transcription 3 at early reperfusion, and AG490 abolished the protection, whereas RISK blockade did not. Signal transducer and activator of transcription 5 phosphorylation was decreased at early reperfusion in both RIPC and PLA. In isolated rat hearts, pig plasma taken after RIPC reduced infarct size (25±5% of ventricular mass versus 38±5% in PLA; P<0.05) and activated both RISK and SAFE. RISK or SAFE blockade abrogated this protection.Cardioprotection by RIPC in pigs causally involves activation of signal transducer and activator of transcription 3 but not of RISK. Protection can be transferred with plasma from pigs to isolated rat hearts where activation of both RISK and SAFE is causally involved. The myocardial signal transduction of RIPC is the same as that of ischemic postconditioning.
A Case of Alpha-Fetoprotein(Afp)- Producing Pancreatic Ductal Carcinoma Responding to Gemcitabine and Erlotinib Therapy
Authors: Osamu Inatomi, Rie Osaki, Ayano Sonoda, Shigeki Bamba, Hiromitsu Ban, Makoto Shioya, Takashi Nishimura, Eiji Mekata, Yataro Daigo, Akira Andoh
Journal: Annals of Oncology (2014)
Peter Brontë Gatenby
Authors: David Coakley
Journal: BMJ (2015)

Peter Bronte Gatenby was the son of James Bronte Gatenby, a pioneering cytologist and professor of zoology at Trinity College, Dublin. Gatenby studied medicine at Trinity and had a brilliant undergraduate career. In 1953 he joined the staff of Dr Steevens’ Hospital as consultant physician and subsequently he was also appointed consultant physician to the Meath Hospital and visiting physician to the Rotunda Hospital.

In 1957 Gatenby joined a group of influential and like-minded consultants to discuss the amalgamation of the small voluntary hospitals associated with Trinity College. Long and tedious negotiations led at first to the federation of these hospitals and eventually to their amalgamation in the two new major Dublin teaching hospitals, St James’s Hospital and Tallaght Hospital.

In 1960 he was appointed to the first full time chair of medicine at Trinity College. The resources given to him were meagre, and one of his successors in the chair of medicine reflected: “It …
Cancer Neoantigens and Applications for Immunotherapy
Authors: Alexis Desrichard, Alexandra Snyder, Timothy A. Chan
Journal: Clinical Cancer Research (2015)

Recent advances in immune checkpoint blockade therapy have revolutionized the treatment of cancer. Tumor-specific antigens that are generated by somatic mutation, neoantigens, can influence patient response to immunotherapy and contribute to tumor shrinkage. Recent evidence demonstrating the success of checkpoint blockade immunotherapy in boosting T-cell reactivity against patient-specific neoantigens constitutes a strong rationale for the development of personalized vaccines against these nonself peptides. With the decreasing cost of next-generation sequencing, peptide manufacturing, and improvement of in silico prediction of peptide immunogenicity, it is increasingly important to evaluate the potential use of neoantigens in both diagnosis and treatment. Specifically, these neoantigens could be useful both as predictors of immune checkpoint blockade therapy response and/or incorporated in therapeutic vaccination strategies.
TOMOX compared to FOLFOX4 as first-line treatment in patients (pts) with advanced colorectal cancer (ACRC): Results of a multicenter randomized phase II trial
Authors: C. Grávalos, C. García-Girón, A. Salut, A. León, R. García-Carbonero, J. Maurel, I. Sevilla, B. Esteban, E. M. Ciruelos, H. Cortes-Funes
Journal: Journal of Clinical Oncology (2005)

3563
Continuous fat-free mass decline in COPD: fact or fiction?
Authors: Erica P.A. Rutten, Martijn A. Spruit, Merry-Lynn N. McDonald, Stephen Rennard, Alvar Agusti, Bartolome Celli, Bruce E. Miller, Courtney Crim, Peter M.A. Calverley, Corrine Hanson, William MacNee, Frits M.E. Franssen, Lowie Vanfleteren, Emiel F.M. Wouters
Journal: European Respiratory Journal (2015)

Patients with chronic obstructive pulmonary disease (COPD) generally have lower fat-free mass (a surrogate marker of skeletal muscle mass) compared with their healthy peers [1, 2], and this is associated with decreased functional capacity [3], the presence of other comorbidities ( e.g. osteoporosis and renal impairment) [4] and increased mortality risk [5]. To date, longitudinal observational studies have shown no difference in the mean decline in fat-free mass over time between COPD patients and non-COPD control subjects [6, 7]. However, it remains unknown whether and to what extent a subgroup of COPD patients suffer continuous loss of fat-free mass. We hypothesised that COPD patients have 1) a higher prevalence of continuous fat-free mass decline, and 2) that this subgroup has a steeper decline of fat-free mass compared with a non-COPD control group with a continuous fat-free mass decline. We tested this hypothesis in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study, which had a 3 year follow-up period. Only a small proportion of COPD patients suffer continuous decline of fat-free mass <http://ow.ly/R6ioA>
Fasting Blood Ammonia Predicts Risk and Frequency of Hepatic Encephalopathy Episodes in Patients With Cirrhosis
Authors: John M. Vierling, Masoud Mokhtarani, Robert S. Brown, Parvez Mantry, Don C. Rockey, Marwan Ghabril, Richard Rowell, Marzena Jurek, Dion F. Coakley, Bruce F. Scharschmidt
Journal: Clinical Gastroenterology and Hepatology (2015)

There is controversy over the use of measuring blood levels of ammonia (NH3) in the management of patients with overt hepatic encephalopathy (HE).We performed a retrospective analysis of data from a randomized, double-blind study of 178 patients with cirrhosis given glycerol phenylbutyrate (an NH3-lowering agent) or placebo for 16 weeks. Blood samples were collected at baseline and on study days 7 and 14 and NH3 levels were measured. The probabilities of having an HE episode, based on ammonia values, were modeled using binary logistic regression. A Cox proportional model was used to determine the risk of HE episodes in patients with baseline fasting NH3 levels ≤1.5-fold the upper limit of normal (ULN) versus patients with fasting NH3 levels >1.5-fold the ULN.The risk and frequency of HE episodes and HE-related hospitalizations correlated with baseline (mean, 51 ± 6 μmol/L; ULN, 35 μmol/L) and on-study fasting levels of NH3, and increased sharply at levels >1.5-fold the ULN. Regardless of baseline level, NH3 exposure and the relative risk of HE episodes were decreased by glycerol phenylbutyrate.In analysis of data from a phase 2 study of the effects of glycerol phenylbutyrate in patients with cirrhosis, we found that fasting levels of NH3 in blood can identify patients at risk for HE-related morbidity. Patients with HE might benefit from NH3-lowering therapy. ClinicalTrials.gov no: NCT 00999167.
NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component
Authors: Hexin Shi, Ying Wang, Xiaohong Li, Xiaoming Zhan, Miao Tang, Maggy Fina, Lijing Su, David Pratt, Chun Hui Bu, Sara Hildebrand, Stephen Lyon, Lindsay Scott, Jiexia Quan, Qihua Sun, Jamie Russell, Stephanie Arnett, Peter Jurek, Ding Chen, Vladimir V Kravchenko, John C Mathison, Eva Marie Y Moresco, Nancy L Monson, Richard J Ulevitch, Bruce Beutler
Journal: Nature Immunology (2015)
Health impacts of anthropogenic biomass burning in the developed world
Authors: Torben Sigsgaard, Bertil Forsberg, Isabella Annesi-Maesano, Anders Blomberg, Anette Bølling, Christoffer Boman, Jakob Bønløkke, Michael Brauer, Nigel Bruce, Marie-Eve Héroux, Maija-Riitta Hirvonen, Frank Kelly, Nino Künzli, Bo Lundbäck, Hanns Moshammer, Curtis Noonan, Joachim Pagels, Gerd Sallsten, Jean-Paul Sculier, Bert Brunekreef
Journal: European Respiratory Journal (2015)

Climate change policies have stimulated a shift towards renewable energy sources such as biomass. The economic crisis of 2008 has also increased the practice of household biomass burning as it is often cheaper than using oil, gas or electricity for heating. As a result, household biomass combustion is becoming an important source of air pollutants in the European Union. This position paper discusses the contribution of biomass combustion to pollution levels in Europe, and the emerging evidence on the adverse health effects of biomass combustion products. Epidemiological studies in the developed world have documented associations between indoor and outdoor exposure to biomass combustion products and a range of adverse health effects. A conservative estimate of the current contribution of biomass smoke to premature mortality in Europe amounts to at least 40 000 deaths per year. We conclude that emissions from current biomass combustion products negatively affect respiratory and, possibly, cardiovascular health in Europe. Biomass combustion emissions, in contrast to emissions from most other sources of air pollution, are increasing. More needs to be done to further document the health effects of biomass combustion in Europe, and to reduce emissions of harmful biomass combustion products to protect public health.
Adjuvant doxorubicin-based chemotherapy for the treatment of malignant peripheral nerve sheath tumors
Authors: C. M. Ogilvie, E. A. Crawford, L. Hartner, R. D. Lackman, A. P. Staddon
Journal: Journal of Clinical Oncology (2008)

21508 Background: Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas with a high tendency for local recurrence and metastasis. The use of adjuvant chemotherapy is controversial, but success with doxorubicin has been described. The goal of this study was to analyze the effect of doxorubicin-based chemotherapy on survival for MPNSTs. Methods: Pathology records were searched for patients with a diagnosis of MPNST treated in our clinic with doxorubicin-based chemotherapy. Overall survival (OS) was calculated from the date of diagnosis. Disease-free survival (DFS) was calculated from the date of surgery. Results: 21 patients with MPNST were identified. 5 were excluded because they did not receive chemotherapy (4 tumors were low grade, 1 patient had adjuvant radiation therapy only), 2 were treated elsewhere, and 4 had insufficient follow-up. This left 10 patients in the study group, 4 of whom had neurofibromatosis-1. Mean age was 43 (range 20–70). Mean follow-up was 22 months (6–68). Tumors were located in the lower extremity (5), upper extremity (3), chest wall (1), and jaw (1). 9 tumors were high grade and 1 was intermediate grade. 3 patients had metastases on presentation. Chemotherapy involved doxorubicin and ifosfamide in 9 patients and doxorubicin alone in 1. All patients had surgical excision of the tumor, and 7 had radiation therapy. 3 patients had positive margins. 1 patient developed local recurrence 10 months post-operatively; he received doxorubicin/ifosfamide for the recurrence but developed metastases 5 months later. 1 patient developed metastases 4 months postoperatively. Mean DFS was 8.3 months (0–31). Mean OS was 21.6 months (6–68). 4 patients had died at last follow-up. 1- and 2-year OS rates were 90% and 72%, respectively. 1- and 2-year DFS rates were both 45%. Wanebo et al. (1993) performed a study of 28 patients with MPNST of whom 96% had surgery, 25% had radiation therapy, and 18% had chemotherapy. The 3-year OS and DFS in this group were 62% and 46%, respectively. Conclusions: Treatment of MPNSTs with surgical excision and adjuvant doxorubicin-based chemotherapy had 2-year OS and DFS rates of 72% and 45%. Compared to existing literature, chemotherapy does not appear to provide a significant survival benefit, but longer follow-up is needed. No significant financial relationships to disclose.
Hands up for free wi-fi across the NHS
Authors: Fiona Godlee
Journal: BMJ (2015)

Financial pressure on the NHS in England continues to grow, with two thirds of trusts predicting a deficit at the end of 2015-16, up from 25% last year (doi:10.1136/bmj.h3670), and a predicted overall deficit of nearly £30bn by 2020. All of which translates into the steady erosion of patient care and staff morale.

New thinking is needed, although not of the sort that led the health secretary to propose printing the indicative cost of drugs on packs worth more than £20, alongside the phrase “funded by the UK tax payer” (doi:10.1136/bmj.h3637). The BMJ ’s sister journal the Drug and Therapeutics Bulletin rightly called this a headline …
Adjuvant chemotherapy in elderly patients: An analysis of National Cancer Institute of Canada Clinical Trials Group and Intergroup BR.10
Authors: C. Pepe, B. Hasan, T. Winton, L. Seymour, J. Pater, R. Livingston, D. Johnson, J. Rigas, K. Ding, F. Shepherd
Journal: Journal of Clinical Oncology (2006)

7009 Background: Recent trials have shown significant survival benefit from adjuvant chemotherapy after resection of NSCLC. Whether elderly patients tolerate platinum-based adjuvant chemotherapy and derive the same survival advantage is unknown. This retrospective study evaluated the influence of age on survival, chemotherapy delivery and toxicity in NCIC CTG BR.10. Methods: Pretreatment characteristics and survival benefit from treatment were compared for patients ≤65 &amp; &gt;65. Chemotherapy delivery and toxicity were compared for 213 treated patients. Results: There were 327 young and 155 elderly patients. Baseline prognostic factors by age were similar with the exception of histology (adeno 58% young, 43% elderly; squamous 32% young, 49% elderly; p=0.001) and PS (PS 0 53% young, 41% elderly; p=0.01). Overall survival by age showed a trend favoring the young in univariate (HR 0.77, CI 0.58–1.04, p=0.084) and multivariate analyses (HR 0.75, CI 0.56–1.01, p=0.059). Patients &gt;75 years had significantly shorter survival than those aged 66–74 (HR 1.95, CI 1.11–3.41, p=0.02). Overall survival for patients &gt;65 was significantly better with chemotherapy v observation (HR 0.61, CI 0.38–0.98, p=0.04). Chemotherapy administration and toxicity were evaluated in 63 elderly and 150 young patients. Mean dose intensities of vinorelbine (V) and cisplatin (C) were 13.2 and 18.0 in the young and 9.9 and 14.1 in the elderly (V p=0.0004; C p=0.001). The elderly received significantly fewer doses of V (p=0.014) and C (p=0.006). Fewer elderly patients completed treatment and more refused treatment compared to the young (p=0.03). There were no significant differences in toxicities, G-CSF use or hospitalization by age group, except for myalgias and mood alteration (more frequent among the young). Six of 126 deaths (4.8%) in the young were from non-malignant causes v 12 of 71 (16.9%) in the elderly (p=0.008). Conclusions: In spite of receiving less chemotherapy than young patients, adjuvant chemotherapy improves overall survival in patients aged &gt;65 with acceptable toxicity. Adjuvant chemotherapy should not be withheld from elderly patients, although patients &gt;75 years of age require further study. No significant financial relationships to disclose.
Phase I study of the combination of everolimus (RAD001) with 5FU/LV in patients with refractory solid malignancies.
Authors: J. M. Davies, A. J. McRee, H. K. Sanoff, T. Triglianos, K. Keller, A. Ivanova, S. A. Bernard, R. M. Goldberg, E. C. Dees, B. H. O'Neil
Journal: Journal of Clinical Oncology (2011)

512 Background: mTOR is a controller of cellular growth and other processes that is activated by several oncogenic pathways in cancer. Everolimus is an oral inhibitor of mTOR activation. The mTOR inhibitor, temsirolimus, when combined with high dose 5FU, was limited by significant mucosal toxicity. Purpose: Phase I study to determine the maximum tolerated doses (MTD) and the safety of everolimus combined with 5FU/LV in patients with refractory solid tumors. Methods: Using a standard 3+3 design, starting doses were everolimus 15mg weekly, and q2 weekly 5FU 400mg/m 2 bolus and 1800mg/m 2 infusion (over 46 hours) and LV 400mg/m 2 . Daily dosing of everolimus was instituted during level 3 as data emerged about improved target inhibition and adverse event profile with daily dosing. Dose escalation to the maximum planned levels was achieved: everolimus 10mg daily, 5FU 400mg/m 2 bolus and 2400mg/m 2 infusion, and LV 400mg/m 2 . Dose limiting toxicities (DLT) were assessed in cycle 1 (4 weeks), defined as any grade 3/4 non-hematologic toxicity (except grade 3 skin rash, nausea and diarrhea), or complicated grade 3-4 heme toxicity. Tumors were measured every 8 weeks. Results: From 03/2008 and 11/2009, 21 patients were treated. Median age 58 (range 35-77), male/female 13/8, PS 0/1 10/11. One DLT was seen at dose level 1 (grade 3 hypersensitivity/angioedema); two at dose level 6 (grade 3 diarrhea, grade 3 hypophosphatemia). As such, dose level 5 is the MTD. Dose reductions were required in 4 patients for mouth sores (2), nasal sores (1), and grade 3 transaminitis (1). Responses are as follows: 11 stable disease and 8 progressive disease; 2 patients were not evaluable. Conclusions: MTD is everolimus 5mg daily, with q2 weekly 5FU 400mg/m 2 bolus and 2400mg/m 2 infusion and LV 400mg/m 2 . We are currently expanding the study to evaluate the addition of oxaliplatin and panitumumab to the 5-FU/LV and everolimus base. [Table: see text] [Table: see text]