tbuckley/cabot-search huggingface dataset:
NON-CONTRAST MAGNETIC RESONANCE ANGIOGRAPHY CAN ACCURATELY DEFINE ILEOFEMORAL ARTERIAL ACCESS SIZE IN PATIENTS REFERRED FOR TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Troy M. LaBounty, Nicole Bhave, Shivraman Giri, Jonathon Leipsic, Kevin Packard, James Balter, Stanley Chetcuti, G. Michael Deeb, Paul Grossman, Himanshu Patel, Smita Patel, Venkatesh Murthy
Journal: Journal of the American College of Cardiology (2015)
PWE-205 Propofol-balanced anaesthesia for single balloon enteroscopy: a comparison between antegrade and retrograde intubation
Authors: S Amornyotin, W Chalayonnawin, S Kongphlay
Journal: Gut (2012)

<h3>Introduction</h3> Single balloon enteroscopy (SBE) procedure is a procedure for diagnosis and treatment in patients with abnormality of gastrointestinal tract especially for small bowel. It commonly performed either anterograde or retrograde intubation. The aim of the study is to compare and evaluate the success rate of propofol-balanced anaesthesia (PBA) for the SBE procedure between antegrade and retrograde intubation. <h3>Methods</h3> We undertook a retrospective review of the sedation service records of patients who underwent SBE by using PBA technique. All procedures were classified into two groups according to route of the intubation: group A (antegrade) and group B (retrograde). The primary outcome variable of the study was the successful completion of the procedure. Failed procedure is defined as the procedure can not be completed by using PBS technique or sedation-related serious adverse events such as severe hypoxaemia (SpO<sub>2</sub> &lt;85% more than 3 min and can not relief by airway management), severe cardiorespiratory instability, are occurred. The secondary outcome variables were sedation-related complications, mortality rate and haemodynamic parameters. <h3>Results</h3> 108 patients underwent SBE procedure during the study period. After matching age, gender, weight, height, ASA physical status, duration of endoscopy and indications of procedures, there were 21 patients in group A and 19 patients in group B. There were no significant differences in age, gender, weight, height, ASA physical status, duration and indication of procedures, type of enteroscopy, anaesthetic personnel and haemodynamic parameters between the two groups. All procedures were successful completion of the endoscopies. Mean dose of propofol, fentanyl and midazolam in both groups was comparable. Overall and cardiorespiratory-related adverse events were not significantly different between the two groups. All adverse events were transient, mild degree and easier treatable. Serious adverse events were none. <h3>Conclusion</h3> PBA for SBE procedure in adult patients by experienced anaesthesiologist is relative safe and effective. The success rate of the endoscopy does not depend on the route of intubation. Serious adverse events were rare in our population. <h3>Competing interests</h3> None declared.
High Extracerebral Soft Tissue Activity on Tc-99m Ethyl Cysteinate Dimer Brain SPECT
Authors: W J Shih, B Bognar, J Coupal
Journal: Clinical Nuclear Medicine (2001)

From the Nuclear Medicine Service,* and Radiology Service, † Lexington VA Medical Center, and Nuclear Medicine Division, Department of Diagnostic Radiology, University of Kentucky Medical Center, Lexington, Kentucky Received for publication July 19, 2000. Revision accepted November 17, 2000. Reprint requests: Dr. Wei-Jen Shih, Nuclear Medicine Service, Lexington VA Medical Center, Lexington, Kentucky 40511. E-mail: [email protected]
18F-Fluoride PET/CT Aspect of an Unusual Case of Erdheim-Chester Disease With Histologic Features of Langerhans Cell Histiocytosis
Authors: Cécile Caoduro, Constantin Marius Ungureanu, Boris Rudenko, Orland Angoue, Oleg Blagosklonov, Frédéric Paycha, Hatem Boulahdour
Journal: Clinical Nuclear Medicine (2013)

We report the case of a 63-year-old woman with Erdheim-Chester disease (ECD) and histologic features of Langerhans cell histiocytosis, both extremely rare histiocytic proliferations responsible of skeletal and extraskeletal involvement. 18F-Fluoride PET/CT revealed multiple intense focal uptake scattered throughout the skeleton. We also performed an 18F-FDG PET/CT which point out visceral and vascular involvement. This case illustrates the interest of PET/CT in ECD, a rare polymorphus and systemic disease, and in our knowledge, this is the first reported illustration of 18F-fluoride PET/CT findings in this pathology.
Abstract 1065: Growth factor-mediated resistance to BRAF/MEK inhibitors in BRAF mutant melanoma
Authors: Bart Lutterbach, Chris Ware, Lenora Davis, Qing Zhang, Leigh Zawel, John Reilly, Bo-Sheng Pan
Journal: Cancer Research (2012)

Abstract BRAF and MEK inhibitors induce striking tumor regressions in BRAF V600E melanoma patients. However, relapse occurs in the majority of patients within several months. Reported resistance mechanisms include acquisition of NRAS mutations, PDGFR or IGF1R activation, Cot amplification, or truncated BRAF upregulation. We report here that hepatocyte growth factor (HGF), neuregulin-1 (NRG1), and fibroblast growth factor-2 (FGF2) cause robust resistance in vitro to BRAF or MEK inhibitors in BRAF mutant melanoma cell lines. NRAS mutant lines were similarly resistant to MEK inhibition in the presence of these growth factors. By contrast other mitogenic factors such as PDGF, EGF, NGF, BDNF, MSP, MDK, GRO, and IGF1 did not maintain cell viability or growth. HGF, NRG1 and FGF2 prevented growth arrest and cell death and in some cell lines maintained cells in progressive growth. In addition, HGF and NRG1 could prevent growth arrest after dual treatment with BRAF and MEK inhibitors. Western analysis revealed that HGF and NRG1 reactivated Erk signaling and activated S6RP and AKT phosphorylation. Combined pharmacological inhibition mTor signaling and Akt signaling was required to fully block growth factor-mediated proliferation. In addition, small molecule Met inhibitors and an anti-HGF antibody blocked HGF-mediated resistance, while lapatinib and an anti-NRG1 antibody blocked NRG1-mediated resistance. While combined Akt and mTor inhibition potently inhibited cell line growth independent of BRAF or MEK inhibition, lapatinib and Met inhibitors had minimal effect on growth, suggesting potential for less adverse events with receptor inhibitors. In vitro co-culture experiments revealed that primary cells present in normal skin can cause resistance, and we have identified growth factors produced by these cells that contribute to resistance. We are analyzing receptor activation (Met and Erbb3) and FGF2 expression in wildtype, NRAS, and BRAF mutant primary melanoma samples. In future experiments we plan to test clinical samples from patients treated with BRAF/MEK inhibitors, and we hypothesize that HGF, NRG1, and FGF2 signaling is elevated in patients with poor initial responses or relapse to BRAF or MEK inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1065. doi:1538-7445.AM2012-1065
Closure of a rectal perforation by clipping the margins to presacral tissue
Authors: H. Sashiyama, K. Fu, Y. Hamahata, O. Tsutsumi, T. Hoshino, Y. Tsujinaka
Journal: Endoscopy (2011)

Iatrogenic colorectal perforation during therapeutic colonoscopy is a rare but serious complication [1]. It is usually managed with immediate open surgery. However, conservative therapy has recently been advocated [2], provided that adequate precolonoscopic bowel preparation has been carried out and that no peritoneal signs are present [3]. Asymptomatic perforations after colonoscopic polypectomy have been conservatively managed using close observation, even in the presence of intra-abdominal free air [4]. Recently, endoclip closure was used to treat iatrogenic colonic perforation conservatively [5]; however, endoclipping cannot be used to repair perforations that are larger than the endoclip (diameter 11 mm) [5].
SAT0444 Administration of Routine Preventative Vaccinations in Children with Juvenile Idiopathic Arthritis Receiving Adalimumab
Authors: N. Mozaffarian, M. Karunaratne, V. Arora
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adalimumab, a fully human monoclonal antibody to tumor necrosis factor-alpha (TNF) has been shown to be safe and effective in juvenile idiopathic arthritis (JIA), and is approved for this use in several countries.<sup>1</sup> <h3>Objectives</h3> Patients with JIA are candidates for routine childhood vaccinations. This post hoc report describes the observed use of vaccines in JIA patients receiving adalimumab for up to 4 years in a clinical trial setting. <h3>Methods</h3> Patients with active JIA were enrolled in one of the following trials: M10-444 (ages 2-4 or ≥ age 4 weighing &lt;15 kg in US, EU), M10-240 (ages 4-17 in Japan), or DE038 (ages 4-17 in US, EU). Patients received treatment with ADA (weight-based dosing) every other week, either with or without methotrexate use. Any vaccinations administered were based on the judgment of the study investigators. Descriptive statistics were used to summarize all vaccinations, including influenza vaccine. Adverse events (AEs) related to active influenza virus infection were collected by a predefined MedDRA Query, and events occurring within 270 days of influenza vaccination were identified. <h3>Results</h3> A summary of all vaccinations is presented in the Table. Among the different types of vaccines, the most frequently administered were: influenza virus vaccine polyvalent in DE038 and M10-240 (n=59 and 63 vaccinations, respectively), and pneumococcal in M10-444 (n=28 vaccinations). In DE038 and M10-240, 2 patients each received &gt;5 vaccinations and in M10-444, 10 patients received &gt;5 vaccinations. The majority of vaccinated patients in each study received &gt;1 type of vaccination. However, influenza vaccine was administered to only 34/171 (20%), 20/25 (80%), and 4/32 (13%) of children during the course of the study in DE038, M10-240, and M10-444, respectively, and the mean (SD) time to 1st influenza vaccination was high: DE038, 675 (618) days; M10-444, 189 (80) days, and M10-444, 83 (76) days. <h3>Conclusions</h3> These data support the idea that JIA patients treated with adalimumab can be safely immunized with routine, inactive, preventative vaccines, including influenza vaccine. However, based on the CDC recommended schedule, not all of the eligible children were vaccinated, suggesting that physicians may be reluctant to use vaccines in children receiving antirheumatic therapies. Further investigation regarding rheumatologists' vaccination practices for patients with JIA is warranted. <h3>References</h3> Lovell DJ, et al. <i>NEJM</i> 2008;359:810-820. <h3>Acknowledgements</h3> Douglas E. Dylla, Ph.D., AbbVie Inc., for abstract preparation. <h3>Disclosure of Interest</h3> N. Mozaffarian Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., M. Karunaratne Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., V. Arora Shareholder of: AbbVie Inc., Employee of: AbbVie Inc.
SP0044 Joint development and disease: The chicken limb model and the importance of GDF5
Authors: P. Seemann
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Abstract</h3> The chicken embryo is a widely used model for studying vertebrate limb development because of its ease of access and genetic and pharmacologic manipulation. During the formation of limbs the Growth Differentiation Factor 5 (GDF5) plays an essential role; it is expressed in the mesenchymal condensations that determine the cartilaginous anlagen, and later its expression shifts towards future joint zones and is therefore widely used as a genetic marker of joint development. Homozygous loss-of-function of GDF5 in humans is linked to acromesomelic chondrodysplasias, characterized by severe shortening of the limbs and absence of digits. Recently, a SNP in the promoter region of GDF5 reducing its transcription rate could be linked to osteoarthritis susceptibility. Heterozygous point mutations of GDF5 cause a spectrum of hand malformations like shortening of phalanges (brachydactyly) or joint fusions (proximal symphalangism or multiple synostosis syndrome). By functional analysis using the chicken as model organism, we have demonstrated that distinct interruptions of protein-protein interactions between GDF5 and its receptors or its antagonists are the cause for the distinct phenotypes: brachydactyly mainly caused by reduced receptor activation, whereas joint fusions resulting from insensitivity towards the antagonist NOGGIN. <h3>Disclosure of Interest</h3> None Declared
The Cytologic Method in the Diagnosis of Cancer
Authors: Maurice Fremont-Smith, Ruth M. Graham, Joe V. Meigs
Journal: New England Journal of Medicine (1948)

TO MAKE a balanced judgment is always difficult. It is a human failing to see things either black or white and, often with insufficient evidence, to render an immediate and final decision either for or against. We shall describe a new test for cancer and present evidence of its value. It is not our contention that this new test should compete with biopsy or replace that method in the diagnosis of cancer. The electrocardiograph did not supersede the older methods of diagnosis in the detection of diseases of the heart. The eyes, the ears and the hand still remain the . . .
P58 Indices of TB risk can help stratify recent immigrants registering with a GP for targeted screening
Authors: R. K. Panchal, P. Haldar, G. Woltmann
Journal: Thorax (2011)

<h3>Introduction</h3> The burden of tuberculosis (TB) in the UK may only be lowered significantly by identification and treatment of latent infection with <i>M tuberculosis</i> (LTBI) in recent immigrants from moderate (150–499/100 000) and high prevalence (500+/100 000) regions of disease. An approach that focuses immigrant capture to a limited number of GP practices is feasible in our region as the distribution of registrations and TB cases by GP practice is heavily skewed. However, strategies for identifying the most appropriate practices and immigrant subgroups for targeted screening are not known. <h3>Aims</h3> To evaluate indices of TB risk that may inform targeted screening strategies for newly registering immigrants to Leicestershire (Exeter/Flag-4). <h3>Methods</h3> A retrospective analysis was performed of all Flag 4 immigrant registrations between 2000 and 2010 and collated with data for all TB notifications over the same period. The top 10 practices defined by number of registrations (10R), number of TB cases (10TB) and a weighted index [WI=(TB cases/immigrant registrations) × TB cases] were identified and compared. Logistic regression was performed to model independent predictors of TB events. TB risk for specified immigrant subgroups was estimated using Kaplan–Meier analysis and pair-wise comparisons of risk computed as the rate ratio (95% CI). <h3>Results</h3> 564 TB cases were recorded in 34 764 registered immigrants at 148 practices. Independent predictors of TB risk were immigrant age at registration and gender and deprivation index of the GP practice locality. Compared with registration at a non-top 10 practice, the corresponding rate ratios for TB after 5 years at a top 10 practice were 1.32 (95% CI 1.1 to 1.57) for 10R; 1.72 (95% CI 1.44 to 2.1) for 10TB and 1.79 (95% CI 1.5 to 2.14) for 10WI. Compared with the unselected registering immigrant population, the 5 and 10 year TB rates in 10WI practices were significantly higher for immigrants aged 16–35 years but not older adults &gt;35 years (Abstract P58 table 1). <h3>Conclusion</h3> TB risk among immigrants newly registering with a GP is heterogeneous. Indices for risk stratification are identifiable that may improve cost-effectiveness of targeted screening.
Case 19-2012
Authors: Elizabeth A. Catlin, H. Shaw Warren, Randheer Shailam, Manuella Lahoud-Rahme, Madelyn Lew
Journal: New England Journal of Medicine (2012)

A premature newborn boy was admitted to the hospital because of respiratory distress. On his sixth day of life, sudden clinical deterioration and multiorgan system failure developed, and he died on his seventh day. An autopsy was performed.
Combination Chemotherapy With Doxorubicin, Dacarbazine, and Ifosfamide in Advanced Adult Soft Tissue Sarcoma
Authors: V. Bramwell, I. Quirt, D. Warr, S. Verma, V. Young, M. Knowling, E. Eisenhauer
Journal: JNCI Journal of the National Cancer Institute (1989)

Forty-three adult patients with locally advanced or metastatic soft tissue sarcoma entered a pilot study of combination chemotherapy comprising 50 mg of doxorubicin/m2 by intravenous bolus, 850 mg of dacarbazine/m2 by 1-hour infusion, and 5 g of ifosfamide/m2 by 24-hour infusion with mesna uro-protection. The overall response rate in 40 assessable patients was 25% with two complete remissions. Twenty-four episodes of infection occurred in 148 courses (16%). These infections were usually associated with neutropenia (granulocyte count <0.5 × 109/L), which occurred in 70% of the courses. These results do not differ from those elicited by each agent alone, and may reflect inadequacies of dose intensity or scheduling, or evaluation in a study population with adverse prognostic factors. [J Natl Cancer Inst 81:1496–1499, 1989]
Abstract 4860: Pan-HDAC inhibitor treatment sensitizes breast cancer cells to autophagy inhibitor 2-phenylethynesulfonamide: Molecular mechanism
Authors: Rekha Rao, Srilatha Nalluri, Warren Fiskus, Uma Mudunuru, Kapil N. Bhalla
Journal: Cancer Research (2010)

Abstract The stress phenotype of transformed cells is associated with increased levels of heat shock proteins (hsp) and autophagy to avoid cell death. Autophagy is a conserved catabolic pathway in which cytoplasmic macromolecules and organelles are sequestered in autophagosomes, which fuse with lysosomes for protein degradation and amino acid recycling. The molecular cascade initiating autophagosome formation is triggered by a lipid kinase (PI3KC3) signaling complex (Vps34, Vps15, ATG6 and ATG14) that mediates phagophore nucleation. We have previously reported that treatment with panobinostat (PS), a pan-histone deacetylase (HDAC) inhibitor induced hyperacetylation of hsp70 and hsp90. In the present study we demonstrate that treatment of MB231 cells with PS increased the association of hyperacetylated hsp70 with the PI3KC3 VPS34, ATG6 (Beclin-1) and KAP1 (an E3 ligase for sumoylation). PS treatment also induced the levels of ATG7, ATG5 and LC3-II (a phosphatidylethanolamine conjugated ATG8) in MB-231 cells. Treatment with 2-phenylethynesulfonamide (PES), a small molecule inhibitor of hsp70 function resulted in the abrogation of PS-induced interaction of hsp70 with hsp40, VPS34 and (the lysosome-associated membrane protein A (LAMP-2A), a protein involved in chaperone mediated autophagy. Consequently, as compared to treatment with each agent alone, co-treatment with PS and PES resulted in significantly more cell death in MB-231 and SUM159PT cells (p &amp;lt; 0.05). Co-treatment with PS also significantly enhanced lethality of breast cancer MB-231 and MCF-7 cells due to autophagy inhibitor 3-methyl-adenosine (3-MA, inhibitor of Vps34), or hydroxychloroquine (inhibitor of lysosome acidification). In orthotopically implanted MB-231 xenografts in the mammary fat pads of NOD/SCID mice, tumor size increase to 100, 200, 500, 1000 and 2000 cu mm demonstrated tumor size-dependent increase in the intracellular levels of hsp90 and hsp70, hyperacetylated hsp70, ATG7, ATG5, Beclin1 as well as LC3-II. These in vivo findings suggest that as breast tumors grow they exhibit the stress-phenotype involving proteotoxic stress and autophagy. Our findings demonstrate the combination therapy with PS and autophagy inhibitor, which eliminates breast cancer cells with stress phenotype including autophagy, may be especially effective against established and enlarging breast cancers. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4860.
AB1057 Contextualisation of Safety Endpoints in the Tofacitinib Rheumatoid Arthritis (RA) Development Programme: Collaboration with the Consortium of Rheumatology Researchers of North America (CORRONA) Registry
Authors: J. Geier, K. Saunders, G. Reed
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Epidemiological data are needed throughout the product9s life cycle to contextualise safety findings particularly when interpretation of adverse events (AEs) is not feasible within clinical trial data (i.e., insufficient statistical power, lack of active comparator, paucity of quality published data). <h3>Objectives</h3> To develop a cohort of patients with RA with similar characteristics (i.e., demographics and disease severity) to patients within the tofacitinib global Phase 2, Phase 3 and long-term extension RA studies to: 1) estimate the baseline comorbidities within 3 cohorts of patients with RA; 2) quantify the background incidence of known and potential tofacitinib safety concerns in an RA population; and 3) quantify the background incidence of new potential safety concerns as they arise in an RA population. <h3>Methods</h3> Pfizer Inc collaborated with the CORRONA registry to establish 3 unique cohorts of patients to query for safety contextualisation: 1) all patients with RA; 2) patients with moderate to severe RA (operationalised as ≥4 Joint Count and American College of Rheumatology functional class of I, II or II); and 3) patients with moderate to severe RA with at least one cardiovascular risk factor. The primary outcomes of interest included serious infections, malignancies and cardiovascular endpoints as reported by physicians. To calculate the rate of each safety event, the number of incident events was divided by the total person-years of observation within the eligible RA cohort. <h3>Results</h3> Over 22,000 adult patients with RA with at least one follow-up visit were identified within the registry. Overall, the rate of AEs was higher among the cohort of patients with moderate to severe disease relative to the total RA population and among patients who were ≥65 years of age relative to those &lt;65 (Figure). <h3>Conclusions</h3> Expected rates of many identified and potential risks were estimated in various RA cohorts, allowing comparison with rates from the tofacitinib clinical trial programme. The results of this collaboration allowed for feasibility assessments for post-marketing studies, rapid analyses of safety events, and rate stratification by background comorbidities. Given the coverage of the CORRONA registry, these data are generalisable to the general US RA population. <h3>Acknowledgements</h3> This study is sponsored by CORRONA. In the past 2 years, AbbVie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Eli Lilly, Novartis, Pfizer, Vertex and UCB have supported CORRONA through contracted subscriptions. Medical writing support was provided by CMC, funded by Pfizer Inc. <h3>Disclosure of Interest</h3> J. Geier Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Saunders Employee of: CORRONA Inc., G. Reed Employee of: CORRONA Inc. <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2474