tbuckley/cabot-search huggingface dataset:
"WHAT'S WHAT."
Authors: R. P. Smith
Journal: BMJ (1902)

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Brisk and prolonged daily walking is needed to outpace the Grim Reaper
Authors: P. Abraham, G. A. Tew, P. S. Abraham, A. Le Faucheur
Journal: BMJ (2012)

Stanaway and colleagues reported that 1.36 m/s is the optimal walking speed to avoid the Grim Reaper.1 With the aim of transposing this to clinical practice, we wondered how far Death can walk each day. A minimum of 30 minutes’ daily walking is recommended to achieve health benefits, such as reduced …
PMO-055 Quality of life following laparoscopic banded (silastic ring) sleeve gastrectomy
Authors: L Pearless, M Clarke, M Booth
Journal: Gut (2012)

<h3>Introduction</h3> Placement of a silastic ring around a sleeve gastrectomy (SG) may minimise long-term dilatation and weight regain. This study assessed medium term quality of life outcomes. <h3>Methods</h3> A questionnaire was sent to 46 patients that underwent surgery between November 2006 and February 2010. During the procedure the stomach was divided 3 cm proximal to the pylorus. Orogastric bougie diameter was 36 French (November 2006–June 2008) or 32 Fr (thereafter). A 6.5–7 cm diameter silastic ring was placed around the mid-portion of the SG. <h3>Results</h3> Responses were received from 29 (63%) patients (25 female, 4 male) with a mean (range) age of 49 (33–65) years and mean pre-op BMI of 37.5 kg/m<sup>2</sup>. Mean (SD) weight loss and % excess weight loss at 3 years was 31.1 (10.8) kg and 90.6 (28.9)% respectively. 66% were satisfied with surgery (median Likert score=9) although 48% reported weight regain. Physical—97% reported food intolerances: meat (59%), solids (35%) and vegetables (17%). 21 (72%) patients reported vomiting: daily (14%), twice weekly (14%), weekly (29%) or less frequently (43%). 66% had reflux, with a median Visick of 2. Exercise capacity increased in 96% of patients. Emotional—28% described depression or anxiety affecting their work or other activities. Social—28% found physical health /emotional problems following surgery interfered with social activities. Compliance—59% had blood tests at least annually, 79% continued multivitamins and 41% required vitamin/mineral supplementation. <h3>Conclusion</h3> Placement of a silastic ring around SG as a primary procedure should be avoided due to a high incidence of post-operative reflux, vomiting and food intolerance. <h3>Competing interests</h3> None declared.
THU0097 Work Participation in A Large Cohort of Patients with Axial Spondyloarthritis and Non-Specific Chronic Low Back Pain: Table 1
Authors: L. Van Hoeven, A. Boonen, M. Hazes, A. Weel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The average age at onset of axial spondyloarthritis (axSpA) is between 20 and 40 years, an age group wherein work plays an important role in a person9s life. However very little is known about work participation in axSpA patients. Chronic low back pain (CLBP) is often the first symptom of axSpA, therefore it would be interesting to know whether axSpA patients, both Ankylosing Spondylitis and non-radiographic axSpA (nr-axSpA), differ from CLBP patients, without axSpA, in work participation. <h3>Objectives</h3> To assess the impact of axSpA patients (both AS and nr-axSpA) compared to CLBP patients on work participation, expressed in absenteeism and presenteeism. <h3>Methods</h3> For this study we used all patients of the cross-sectional CaFaSpA 2 study.(1) Primary care patients (18-45 years) having CLBP were invited to participate. Participants were examined on the presence of axSpA (AS and nr-axSpA) based on the ASAS criteria. Demographics, Roland Morris Disability Questionnaire (RMDQ), BASDAI and ASDAS were collected. The work participation during the past 7 days was measured by the Work Productivity and Activity Impairment (WPAI) questionnaire.(2) Four sub scores were derived; percentage of absenteeism (a patient is unable to attend their work), percentage of presenteeism (reduced productivity while at work), overall percentage of work impairment (combines absenteeism and presenteeism) and percentage of impairment in activities performed outside of work. <h3>Results</h3> In total 579 patients participated, (41% male, mean age 35.9 years (SD 7.0)). None of the patients had ever been referred to the rheumatologist or diagnosed with axSpA. Of all patients, 412 patients (71.2%) were employed. In the working population the mean absenteeism was 6.2%, mean presenteeism was 26.0%, mean work impairment was 29.7%. In Table 1 the results of AS, nr-axSpA and non-specific CLBP patients are shown. <h3>Conclusions</h3> To the best of our knowledge is this the first study that looked into the absenteeism and presenteeism in axSpA patients. AS patients have more absenteeism, presenteeism, work and activity impairment than nr-axSpA and CLBP patients. Non-specific CLBP patients have more worse work outcomes than nr-axSpA patients. <h3>References</h3> van Hoeven L., et al. EULAR 2013 poster. Reilly MC et al, PharmacoEconomics 1993; 4(5):353-65. <h3>Disclosure of Interest</h3> : L. Van Hoeven: None declared, A. Boonen: None declared, M. Hazes: None declared, A. Weel Grant/research support: Unrestricted grant from Abbvie <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5241
Functional Activities of Autoantibodies to Acetylcholine Receptors and the Clinical Severity of Myasthenia Gravis
Authors: Daniel B. Drachman, Robert N. Adams, Lorraine F. Josifek, Steven G. Self
Journal: New England Journal of Medicine (1982)

The pathogenesis of myasthenia gravis involves a humorally mediated autoimmune attack directed against acetylcholine receptors of skeletal muscles. Antibodies against acetylcholine receptors are detected in the serum of more than 80 per cent of patients, but the antibody titers correspond poorly with the severity of disease. To distinguish between antibody titers and antibody activity, we measured the ability of serum immunoglobulin from 49 patients to induce accelerated degradation or blockade of the binding sites of acetylcholine receptors, using a mammalian skeletal-muscle tissue-culture system. Immunoglobulin from 41 of 45 patients tested (91 per cent) increased the rate of degradation of acetylcholine receptors, and the relative increase in the degradation rate corresponded closely (P<0.001) with clinical status. Immunoglobulin from 42 of 48 patients tested (88 per cent) produced blockade of receptors, and the extent of the blockade also corresponded with clinical status (P<0.001). An index of the combined activities of the immunoglobulin in accelerating degradation and producing blockade of acetylcholine receptors was elevated in 43 of 44 patients (98 per cent) whose immunoglobulins were tested for both activities; this index predicted the patients' clinical status significantly better (P<0.001) than either measure alone. This finding suggests that the functional ability of antibodies to decrease the number of available acetylcholine receptors by these two mechanisms is clinically relevant in the pathogenesis of myasthenia gravis. (N Engl J Med. 1982; 307:769–75.)
THU0390 Prolonged disease-free interval in familial mediterranean fever: A distinct subset with unique clinical, demographic and molecular characteristics
Authors: I. Ben-Zvi, T. Krichely-Vachdi, O. Feld, M. Lidar, S. Kivity, A. Livneh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Familial Mediterranean fever (FMF) is a genetic, autoinflammatory disease, characterized by episodes of fever and serosal or cutaneous inflammation. Between the attacks, patients are usually asymptomatic, but subclinical inflammation may persist. A rare and under-recognized phenomenon in FMF is prolonged disease-free intervals (of 3 years or more), even without colchicine treatment. <h3>Objectives</h3> We aimed to clinically, genetically and demographically characterize FMF patients with prolonged disease-free intervals during the course of the disease. <h3>Methods</h3> Over a 5 year period, 1000 FMF patients, coming to their regular follow up visit, were screened for prolonged disease-free interval (≥3 years) occurring sometime along the course of their disease. Clinical, demographic and genetic parameters of the patients identified were compared to those of randomized selected control subjects, derived from the same patient population. The severity of the disease was determined using the Mor severity score <h3>Results</h3> Thirty three patients with prolonged disease-free interval (remission) were identified (3.3% of the screened population). Compared to the 33 control subjects, in patients with long term remission the disease was of milderseverity (23 vs 11 patients with mild disease in the remission and control groups, respectively, p=0.003) and with longer diagnosis delay (21 vs 13.4 years, p=0.04). Patients with long term remission presented mostly with abdominal attacks, low rate of attacks in other sites and low rate of chronic and non-attack manifestations. The disease in patients with long term remission responded well to colchicine, despite using a lower dose (p&lt;0.001). None of the patients in the remission group were homozygous for the M694V mutation compared to 10 in the control group (p=0.0008) <h3>Conclusions</h3> Long-term remission defines a rare and milder form of FMF with unique clinical, demographic, and molecular characteristics. <h3>Disclosure of Interest</h3> None Declared
PTU-137 Does a prompt from the histology report to perform serology to exclude coeliac disease mean this is done?
Authors: E Byrne, K Lloyd, S Nayagam, H Williams, M Walker
Journal: Gut (2012)

<h3>Introduction</h3> Lymphocytic duodenosis (LD) is a histological diagnosis comprising normal duodenal architecture, but an intraepithelial lymphocyte (IELs) count &gt;25/100 enterocytes. A diagnosis of coeliac disease (CD) can be made in up to 16% of cases where LD is seen.<sup>1</sup> CD serology (antibodies to tissue transglutaminase) should be performed in all cases of LD. The aim of this study was to identify the rate of CD serological investigations following a diagnosis of LD. <h3>Methods</h3> All duodenal biopsies taken at St Marys Hospital, London between March and August 2011 were evaluated. The histological reports for all duodenal biopsies coded as abnormal were reviewed. Serology results were checked in all cases where LD was diagnosed. <h3>Results</h3> 280 duodenal biopsies were performed of which 24 met the criteria for a diagnosis of LD (8.6%). The indication for biopsy was anaemia in 12/24 (50%), dyspepsia in 4/24 (16.7%), abdominal pain in 3/24 (12.5%), dysphagia in 1/24 (4.2%) and an indication was not indicated in 1/24 (4.2%). The numbers of lymphocytes per 100 enterocytes varied from 26 to 62. Serological testing for CD was carried out prior to or following the diagnosis of LD in 12/24 (50%). In all cases where serology was performed the result was negative. <h3>Conclusion</h3> Opportunities to diagnose CD are being missed in 50% of cases. These figures are similar to an audit carried out in the same department in 2009 which showed that serological testing for CD was being carried out in 56% of cases where LD was diagnosed. Diagnosis and treatment of CD has been shown to reduce morbidity and mortality<sup>2</sup><sup>3</sup> and reduce the cost of medical care.<sup>4</sup> Therefore it is important that opportunities to diagnose CD are taken and follow-up on the diagnosis of LD with serological testing by clinicians is imperative. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Aziz I</b>, Evans KE, Hopper AD, <i>et al.</i> A prospective study into the aetiology of lymphocytic duodenosis. <i>Aliment Pharmacol Ther</i> 2010;<b>32</b>:1392–7. 2. <b>Rubio-Tapia A</b>, Kyle RA, Kaplan EL, <i>et al.</i> Increased prevalence and mortality in undiagnosed coeliac disease. <i>Gastroenterology</i> 2009;<b>137</b>:88–93. 3. <b>Godfrey JD</b>, Brantner TL, Brinjikji W, <i>et al.</i> Morbidity and mortality among older individuals with undiagnosed coeliac disease. <i>Gastroenterology</i> 2010;<b>139</b>:763–9. 4. <b>Long KH</b>, Rubio-Tapia A, Wagie AE, <i>et al.</i> The economics of celiac disease: a population-based study. <i>Aliment Pharmacol Ther</i> 2010;<b>32</b>:261–9.
Abstract P4-01-05: Utility of Preoperative Routine MRI and PET/CT in Breast Cancer Staging vs. Surgical Staging
Authors: K Higaki, M Kochi, M Ito, S Otani
Journal: Cancer Research (2012)

Abstract Background: Staging of breast cancer is one of the most important factors in determining treatment options. The aim of this study is to assess the utility of routine magnetic resonance imaging (MRI) and positron emission tomography and computed tomography (PET/CT) in preoperative breast cancer staging. Patients and methods: We examined 616 consecutive patients, who were newly-diagnosed with operable primary breast cancer less than 3 cm, at our institution between 2009 and 2011. They all underwent MRI and PET/CT to assign the clinical stage by TNM classification. Tumor size was measured by contrast MRI examinations and node status and metastases were evaluated on PET/CT. We examined their clinical and pathological T and N status retrospectively to assess the utility and concordance rate of preoperative imaging studies. Patients with tumors more than 3 cm were excluded from this study, since preoperative systemic therapy is the standard therapeutic strategy for those patients. Results: The concordance rate of T status was 79.9% in clinical T1 patients (366/458) and 55.6% in clinical T2 patients (88/158). The concordance rate of N status was 83.8% in clinical N0 patients (495/591) and 60.0% in clinical N1 patients (15/25). As a result, the concordance rate of clinical stage was 66.5% in clinical stage I patients (296/445) and 55.0% in clinical stage II patients (94/171). In addition, 43 patients were diagnosed as contrary breast cancer by MRI (7.5%) and 31 contrary breast cancer (5.4%) and 12 other malignant disease (1.9%) were found by PET/CT. Conclusions: MRI and PET/CT are valuable tools to provide information on tumor size, lymph node involvement, distant metastases and other occult primary disease. Preoperative routine MRI and PET/CT studies have a substantial impact on patients with operable primary breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-05.
2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease
Authors: Glenn N. Levine, Eric R. Bates, John A. Bittl, Ralph G. Brindis, Stephan D. Fihn, Lee A. Fleisher, Christopher B. Granger, Richard A. Lange, Michael J. Mack, Laura Mauri, Roxana Mehran, Debabrata Mukherjee, L. Kristin Newby, Patrick T. O’Gara, Marc S. Sabatine, Peter K. Smith, Sidney C. Smith
Journal: Journal of the American College of Cardiology (2016)
Detecting BRCA2 protein truncation in breast tissue biopsies to identify hereditary cancer.
Authors: R Lieberman, C Snyder, V Clark, H Lynch, J Holt
Journal: Cancer Research (2009)

Abstract Abstract #501 Background: Mutations in the BRCA2 gene are dominantly inherited but cause cancers when the wildtype allele has LOH (loss of heterozygosity) within the cancer. It is important to identify breast cancer patients with BRCA mutations so they can be appropriately treated and affected family members can implement cancer prevention strategies. Because most disease-associated BRCA2 mutations are truncating mutations, a test for truncated BRCA2 proteins should identify most BRCA2 hereditary cancers. Methods: We have developed a tissue truncation test to identify truncated BRCA2 proteins in breast cancer tissue biopsies by direct immunohistochemistry, without amplification or genetic manipulations. N-terminal and C-terminal antibodies are used to visualize protein truncation by demonstrating that the beginning of the protein is present but the end (terminus) is absent. Results: A quantitative C-terminal immunostaining score or a C/N terminal truncation ratio correctly classified 20/21 breast cancers from BRCA2 mutation carriers and 57/58 sporadic breast cancers. This represents a sensitivity of 95% and specificity of 98%. Figure 1 shows a loss of C-terminal staining (except for a lymphocyte) in the upper panel but strong N-terminal staining in the lower panel sections of the same hereditary breast cancer.&amp;#x2028; &amp;#x2028; Due to the presence of C-terminal BRCA2 protein and atypical clinical features of the misclassifed cancer in a BRCA2 mutation carrier,we performed PCR and sequence analyses on this cancer. The results showed continued presence of the BRCA2 wildtype allele in the cancer, indicating that this represents a sporadic cancer which occurred in a mutation carrier. Conclusions: This immunohistochemistry based test (which takes only 4 hours) appears to identify BRCA2 hereditary cancer with high accuracy. The test also appears to diagnose the biochemical loss of BRCA2 protein in cancers (BRCA2 mutant genotype) which will usually but not always agree with the presence of a germline BRCA2 mutation found by susceptibility testing by DNA sequencing of blood samples. This rapid but accurate tissue test can diagnose hereditary BRCA2 breast cancer at time of biopsy, allowing medical oncologists to implement targeted therapies and surgeons to perform timely prophylactic surgery without the usual 4 week wait for DNA sequencing results. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 501.
Abstract LB-335: DHODH regulates transcriptional elongation during melanoma evolution: insights from zebrafish screening
Authors: Richard M. White, Leonard I. Zon
Journal: Cancer Research (2011)

Abstract Melanoma cells are derived from the neural crest, a transient, multipotent tissue present only during embryogenesis. Using zebrafish models, we aimed to determine whether these embryonic neural crest gene programs would make therapeutic targets in melanoma. Transgenic zebrafish expressing BRAFV600E under the mitf promoter develop melanoma when crossed with p53 mutants. From the earliest stages of transformation, and throughout overt tumorigenesis, these tumors express multiple embryonic neural crest progenitor markers such as SOX10, EDNRB and MITF. Human melanomas were similar: 50–75% expressed progenitor markers, but only 15% expressed the differentiation marker DCT. We performed a chemical genetic screen in zebrafish embryos to identify suppressors of the neural crest gene program to determine their therapeutic utility. Of 2000 small molecules, we found one class, inhibitors of the enzyme DHODH, that led to a complete abrogation of neural crest development during embryogenesis. Treated animals were essentially albino, devoid of all derivative melanocytes that eventually give rise to melanoma. Developmentally, DHODH suppression exerts this effect by blocking transcriptional elongation of genes such as MITF, in a manner dependent upon the elongation factor SUPT5H. In melanoma cells, we measured transcriptional elongation after DHODH inhibition via RNA pol II chromatin immunprecipitation coupled with massively parallel sequencing (ChIP-Seq). Similar to embryonic development, inhibiting DHODH leads to a defect in transcriptional elongation at select loci. We then tested whether leflunomide, a DHODH inhibitor approved for rheumatoid arthritis, could block melanoma growth. Either alone, or in combination with the BRAFV600E inhibitor PLX4032, leflunomide led to a dramatic decrease in melanoma growth in vitro and in vivo. These studies suggest that modulating the neural crest identity of melanoma cells is a distinct therapeutic avenue that is likely to cooperate with inhibiting oncogenic mutations such as BRAFV600E. We plan to extend this work into the clinical trial setting, highlighting the rapidity with which discoveries in zebrafish can be translated into the clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-335. doi:10.1158/1538-7445.AM2011-LB-335
Abstract 2602: FoxM1 is an attractive therapeutic target in a subset of papillary thyroid cancers
Authors: Maqbool Ahmed, Prashant Bavi, Azhar R. Hussain, Zeenath Jehan, Aishah S. Olyan, Tiezheng R. Bu, Abdulrehman Al-Nuaim, Saif Al-Sobhi, Tarek Amin, Shahab Uddin, Khawla S. Al-Kuraya
Journal: Cancer Research (2011)

Abstract The FoxM1 transcription factor promotes the pathogenesis of several malignancies. However, little is known about its expression and function in papillary thyroid cancers (PTC). In the present study we investigated the role of FoxM1 in the pathogenesis of PTC in a large series of PTC in a tissue micro array (TMA) format followed by studies using PTC cell lines and nude mice. Our data showed that expression of FoxM1 was over expressed in 28.4 % (141/496) of PTC and significantly associated with activated AKT (p&amp;lt;0.0001) and matrix metalloproteinase-9 (MMP-9) expression (p=0.0004). FoxM1 over expression was also strongly associated with antiapoptotic markers, XIAP (p=0.0024), and Bcl-Xl (p=0.0014). In vitro data using PTC cell lines showed that inhibition of FoxM1 by thiostrepton resulted in inhibition of proliferation and induction of apoptosis in a dose dependent manner. In addition, thiostrepton treatment caused downregulation of SKP2, and consequent increase expression of p21 in PTC cell lines. We also found that down-regulation of FoxM1 reduced the expression of MMP-2, MMP-9 and vascular endothelial growth factor, resulting in the inhibition of migration, invasion, and angiogenesis in PTC cells. Furthermore, pharmacological inhibition of FoxM1 or siRNA targeted against FoxM1 triggered caspase dependent apoptosis in PTC cells. Finally, treatment of PTC cell line xenografts with thiostrepton resulted in growth inhibition of tumors in nude mice via downregulation of FoxM1 and MMP9. Altogether, our results suggest that FoxM1 and its associated signaling pathway may be a potential target for therapeutic intervention for treatment of PTC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2602. doi:10.1158/1538-7445.AM2011-2602
Endovascular Treatment for Acute Ischemic Stroke — Still Unproven
Authors: Marc I. Chimowitz
Journal: New England Journal of Medicine (2013)

Most ischemic strokes are caused by an embolic or thrombotic occlusion of an intracranial artery. The immediate aims of acute stroke treatment are recanalization of the occluded artery and reperfusion of the ischemic brain region. Currently, intravenous thrombolysis that is administered within 4.5 hours after the onset of a stroke is the only proven treatment.1,2 However, recanalization rates within 24 hours after the administration of intravenous tissue plasminogen activator (t-PA) are low when the occlusion involves a large intracranial artery, with rates of 14% for internal carotid arteries and 55% for middle cerebral arteries.3 These low rates have prompted . . .