tbuckley/cabot-search huggingface dataset:
LONG TERM OUTCOMES IN PATIENTS WITH LEFT MAIN CORONARY ARTERY DISEASE TREATED WITH EITHER PERCUTANEOUS CORONARY INTERVENTION OR BYPASS SURGERY-EVIDENCE FROM A META-ANALYSIS
Authors: Partha Sardar, Saurav Chatterjee, Amartya Kundu, Ramez Nairooz, Khaled Tuwairqi, Riyaz Bashir, Brian O’Neill, Brian O’Murchu, Debabrata Mukherjee, Jay Giri, Howard Cohen, Theophilus Owan
Journal: Journal of the American College of Cardiology (2016)
Insulin Resistance and Hyperinsulinemia in Patients with Thalassemia Major Treated by Hypertransfusion
Authors: Peter A. Merkel, Donald C. Simonson, Stephanie A. Amiel, Gerd Plewe, Robert S. Sherwin, Howard A. Pearson, William V. Tamborlane
Journal: New England Journal of Medicine (1988)

Diabetes mellitus in patients receiving hypertransfusion for thalassemia major is usually attributed to damage to β cells. To determine whether iron overload leads to insulin resistance before the development of insulin deficiency, insulin was infused (by euglycemic insulinclamp technique) into 12 children with thalassemia (4 of whom were prepubertal, and 8 pubertal) who had normal or only moderately impaired glucose tolerance and who were receiving chelation therapy. Although insulin-stimulated glucose metabolism in the prepubertal children with thalassemia was similar to that in controls (normal prepubertal children) (319±23 vs. 314±41 mg per square meter of body-surface area per minute, P not significant), the response to insulin was markedly impaired in the pubertal children with thalassemia (155±18 vs. 224±15 mg per square meter per minute in normal pubertal controls, P<0.01). Plasma insulin levels rose excessively after oral glucose administration in the pubertal subjects with thalassemia, but not in the prepubertal patients (P<0.001). Furthermore, in response to a standard hyperglycemic stimulus, insulin levels in the pubertal patients rose to two to three times greater than normal and C-peptide levels became significantly elevated. Our data suggest that insulin resistance and increased insulin secretion develop in older children with thalassemia treated with long-term hypertransfusion therapy before the development of diabetes. (N Engl J Med 1988; 318:809–14.)
SAT0282 Clinical and Laboratory Characteristics Associated with Visual Complications in Patients with Biopsy-Proven GIANT Cell Arteritis
Authors: M. Saleh, C. Turesson, M. Englund, P.A. Merkel, A.J. Mohammad
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Early diagnosis of giant cell arteritis (GCA) and prompt initiation of high-dose glucocorticoid treatment is important to avoid permanent organ damage. One of the most feared outcomes in GCA are ischemic complications, especially visual impairment or irreversible blindness. <h3>Objectives</h3> To compare the clinical and laboratory characteristics of patients with biopsy-proven GCA who develop visual complications to patients with GCA with no visual complications. <h3>Methods</h3> Data from 840 patients with biopsy-proven GCA in Skåne, the southernmost region in Sweden, diagnosed between 1997 and 2010, were used for this analysis. Patients with GCA were identified in the regional register of the Department of Pathology in Skåne using established methods[1].The occurrences of acute visual complications after the onset of GCA were identified by linking the GCA cohort to the Skåne Health care Register as previously described using the ICD-10 codes[2]. A nested case-control study was performed within the GCA cohort in which cases with visual complication were compared to age- and sex-matched patients with GCA without visual complications. In a structured review of all medical records, the presence of ophthalmological disease was validated, and we also recorded the use of selected medications at GCA onset, and histopathology findings (Table). <h3>Results</h3> 100 of the 840 patients (12%) with GCA had an assigned diagnosis code for at least one visual complication. Upon detailed case record review, eight patients with an ophthalmological complication that pre-dated the diagnosis of GCA, and seven cases with either incomplete records or incorrectly assigned ICD codes were excluded. 85 patients were found to have visual complications (10% of patients); 72 patients had unilateral and 13 had bilateral visual impairment. Compared to patients without visual impairment, patients with GCA with new-onset visual impairment were less likely to have headache, fever, palpable abnormal temporal artery, polymyalgia rheumatica, and lower CRP at diagnosis compared with controls. The use of beta-blockers was associated with visual complication (Table). <h3>Conclusions</h3> Patients with GCA with visual complications as a group have lower inflammatory responses compared to patients with GCA and no visual problems, a finding similar to what has been shown in previous studies. Patients with visual complications are more likely to be treated with beta-blockers than patients with GCA without visual changes. The role of beta-blockers in end-organ ischemia related to GCA should be further studied. <h3>References</h3> Mohammad AJ et al. Ann Rheum Dis. 2014 Jan 17. doi: 10.1136/annrheumdis-2013-204652. [Epub ahead of print] Bremander A et al. Arthritis Care Res (Hoboken). 2011 Apr; 63(4):550-556. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3018
AB0649 Challenges and characteristics of infectious spondylodiscitis of the cervical spine
Authors: L. Dridi, I. Mahmoud, O. Saidane, H. Sahli, R. Tekaya, L. Abdelmoula, L. Chaabouni, R. Zouari
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cervical infectious spondylodiscitis (ISPD) are rare; they represent 3-15% of spinal sites infections. <h3>Objectives</h3> We aim to report epidemiological, clinical and radiological features of cervical (ISPD) and to determine their management and their outcome. <h3>Methods</h3> We retrospectively reviewed records of all patients hospitalized for (ISPD) over a period of 13 years [1999-2012] and then we selected those who had cervical location. <h3>Results</h3> One hundred and three patients were hospitalized for ISPD during the period of 13 years, ten of them (9.7%) had cervical localization. There were six men and four woman with a mean age of 50.4 years [31-79]. Predisposing factor was found in 2 cases: diabetes mellitus. The mean time to diagnosis was 3,3 months and half. All patients complained of inflammatory neck pain. Three patients had radicular pain that was bilateral in 2 cases and unilateral in 1 case. Impaired general condition was reported in four cases and night sweats in 5 cases. On examination, the cervical spine was stiff in all cases. Retro-auricular fistulization was noted in 1 case. Fever was found in 3 patients. Neurological examination found signs of pyramidal irritation in 4 patients. One patient had rapidly developed paraplegia and another patient developed tetraplegia. Elevated inflammation parameters were found in 9 cases. The spinal MRI was performed in all cases, it confirmed the diagnosis of ISPD and showed the presence of paravertebral abscess (5 cases), epiduritis (5 cases), epidural spinal cord compression (2 cases) and intradural extension (1 case). C1-C2 level was involved in 2 cases. Concomitant localization in dorsal level (1 case) and in lumbar level (1 case) were seen. Discovertebral biopsy was necessary and succefully performed in 6 cases. Tuberculosis was the etiology in 7 cases. Diagnosis was made according to histological signs in 3 patients and to presumptive criteria in the 4 remaining cases. Brucellosis was the cause in 1 case. Pyogenic origin was retained in 2 cases, Staphylococcus aureus was isolated in blood cultures in 1 case. All patients received appropriate antibiotic treatment and had spinal immobilization. Three patients required surgical intervention. It was drainage of paravertebral abscess in 2 cases and decompression of the spinal cord by laminectomy in 1 case. One patient died after surgery. The outcome was favorable in all other patients. <h3>Conclusions</h3> Cervical ISPD have a high risk of neurological complications. MRI allows lesions assessment. Quick management is mandatory to provide complications. Because of the location, cervical spondylodiscitis can represent a challenge in diagnostic and even in surgical treatment. <h3>Disclosure of Interest</h3> None Declared
Abstract 5310: Regulation of metastatic breast cancer by E2F transcription factors
Authors: Eran R. Andrechek
Journal: Cancer Research (2012)

Abstract Metastasis is the leading cause of mortality in breast cancer and the purpose of this study was to examine the role of the E2F transcription factors in mediating the dissemination of the primary cancer. E2F transcription factors have previously been demonstrated to play a critical role in regulation of cell cycle progression. However, in prior work we have demonstrated that gene expression signatures for the E2Fs have variable levels of activation in a heterogeneous tumor model. Using predictive bioinformatic methods to assess the probability of gene pathway activation, we have predicted variable roles for the E2Fs in key mouse models of breast cancer, including Myc, PyMT and Neu. We then genetically tested these computational predictions by interbreeding E2F knockout mice to the various transgenic tumor models. These crosses have revealed that the E2Fs have unique roles in tumor initiation and progression depending upon the oncogene driving the initial tumor. There are differential effects on tumor latency with the loss of individual E2F alleles, including decreased latency with E2F2 loss in the PyMT background but increased latency and reduced incidence in the Myc background. Moreover, we have observed key differences in tumor progression, with loss of E2Fs affecting the heterogeneity of the resulting tumors. In addition to tumor initiation, we have observed striking differences in tumor progression with loss of E2Fs increasing metastasis in the Myc model but reducing metastasis in the PyMT model. In order to determine the mechanism of action for these effects, we have undertaken a gene expression analysis from both primary tumors and the metastases. Comparison of tumor models in the various backgrounds has allowed us to generate a list of E2F target genes that have effects on metastasis. Comparison of these genes to human breast cancer has revealed that the key genes also have critical roles in metastatic human breast cancer survival. These E2F targets include genes that have previously been identified as metastasis suppressors and are being validated in this process. Taken together, this work suggests a critical role for the E2F transcription factors, not only as mediators of cell cycle but in regulating the metastatic progression of metastatic breast cancer. These data also illustrate the power of combining various genomic and gene expression analysis techniques with both mouse models and clinical data associated with gene expression analysis in human breast cancer. Using this approach we are able to predict and test for the role of critical pathways, such as the E2Fs, in the progression of breast cancer. 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 5310. doi:1538-7445.AM2012-5310
A Prospective Study of Computerized Digital Infrared Image Analysis (NoTouch BreastScanTM) in Biopsy Proven Breast Cancers.
Authors: N. Nair, M. Thakur, R. Hawaldar, M. Nadkarni, V. Parmar, R. Badwe
Journal: Cancer Research (2009)

Abstract Introduction: Early detection of breast cancer is known to have a more favourable outcome. Currently clinical breast examination and imaging modalities, primarily mammography are used for screening purposes. In India, more than 85% of the population is below the age of 50 years, wherein the sensitivity of mammography is at best 64%. Additional drawbacks of the procedure are physical discomfort and ionizing radiation dose to the patient. So newer techniques have been investigated which detect cancer induced neovascularity with digital thermal imaging. The purpose of this clinical study was to determine the efficacy of a software assisted thermal image analysis tool to distinguish between benign and malignant lesions of the breast.Methods: A prospective study was conducted in women who presented to the breast clinic with clinically or mammographically suspicious breast lesions. They also underwent thermal imaging of the breast. All mammographically suspicious lumps were subjected to histopathological confirmation. The mammography and infrared (IR) reports were compared to the histopathology.Results: In 90 women, 180 breasts were independently analyzed by both digital IR software analysis and mammography. Eighty five out of these 180 had suspicious lesions on mammography or clinical examination which were subjected to pathological confirmation. Mammography being the present diagnostic gold standard, all normal mammograms in clinically normal breast were considered as non-malignant. The sensitivity and specificity of digital thermography in detecting malignant lesions was 88.24% and 70.52% respectively with NPV of 87.01% and PPV of 72.82%. While for mammography the sensitivity and specificity were 96.25% and 96.7% with NPV of 96.7% and PPV of 96.25%. In women below 50 years of age (62/90) the sensitivity and specificity of digital thermography was 89.83% and 64.61% with NPV of 87.5% and PPV of 69.74%. Further, in the same subset no statistically significant difference was detected in the sensitivity of digital thermography to that of mammography (p = 0.7263).Conclusion: Our initial experience shows that the detection rate by digital thermal imaging is comparable to mammography in clinically palpable breast tumors. We also note that there is no significant difference in sensitivity of thermal imaging in women on either side of 50 making it a potentially testable tool for screening in younger women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5028.
Abstract SY22-02: Mammalian functional genetic signatures identify efficacy landscapes of combination chemotherapy
Authors: Douglas A. Lauffenburger, Justin R. Pritchard, Michael T. Hemann
Journal: Cancer Research (2012)

Abstract Many current cancer treatments involve the administration of multi-drug regimens. However, no clear consensus exists to explain how drugs interact to create combinatorial effects. Here we will describe recent studies using RNAi-based functional signatures in mammalian cells to test specific hypotheses underlying combination drug mechanisms. We find that while potently synergistic drug combinations reinforce the cytotoxic action of one component in a manner that highlights drug-specific genetic dependencies, clinically used multi-drug regimens minimize the effect of genetic diversity and thus homogenize response across distinct subpopulations. We confirmed this finding in spontaneously arising lymphomas, where standard combination therapy reduced the variation in drug response between different tumors. Thus, we suggest that commonly used chemotherapeutic drug combinations are intrinsically “de-personalized” and function by homogenizing therapeutic response across randomized patient cohorts. 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 SY22-02. doi:1538-7445.AM2012-SY22-02
The AIDS Epidemic — Considerations for the 21st Century
Authors: Anthony S. Fauci
Journal: New England Journal of Medicine (1999)

Humankind has been besieged through-out its evolution by microorganisms that pose a continual challenge to the survival of the species.1 Although such ancient killers as tuberculosis and malaria persistently take a toll of millions of lives per year, occasionally the emergence or reemergence of a microbe results in an unexpected, catastrophic pandemic with global public health consequences. As we prepare to leave the 20th century, it is worth reflecting on the fact that within the framework of an enormous but constant burden of a variety of infectious diseases, as well as a number of mini-epidemics, this century has witnessed two . . .
Abstract 4068: Reciprocal regulation of RNase-L and tristetraproline modulates the induction of proinflammatory cytokines
Authors: Bret A. Hassel, Xiao-Ling Li
Journal: Cancer Research (2010)

Abstract The endoribonuclease RNase-L is the terminal component of an interferon-regulated RNA decay pathway that functions in antiviral and antiproliferative/tumor suppressor activities. We recently identified a novel role for RNase-L in the induction of tumor necrosis factor-a (TNFa). The induction of TNFa is an important mediator of inflammation, therefore the RNase-L-dependent regulation of TNFa may contribute to its tumor suppressor activity. In the current study, we sought to investigate the mechanism of this regulation. The induction of TNFa mRNA was diminished in the absence of RNase-L suggesting that RNase-L targeted a negative regulator of TNFa expression. The RNA binding protein tristetraproline (TTP) is a critical regulator of TNFa that enhances the degradation of its mRNA; thus TTP represented a viable target mRNA by which RNase-L may indirectly modulate TNFa expression. Consistent with this model, inhibition of RNase-L expression using knockdown or knockout strategies enhanced TTP induction by interferon and Toll-Like Receptor agonists and reduced levels of TTP target mRNAs (e.g. TNFa). In contrast, ectopic RNase-L expression diminished TTP expression. Importantly, the stability of TTP mRNA inversely correlated with RNase-L expression, suggesting that the TTP transcript is a direct target of RNase-L. Interestingly, analysis of RNase-L expression in lipopolysaccharide-stimulated macrophages demonstrated a downregulation of RNase-L that corresponded with TTP induction, suggesting that TTP may regulate RNase-L. Indeed, TTP overexpression decreased the half-life of RNase-L mRNA, and pharmacologic MAP kinase inhibitors that block TTP activity stabilized RNase-L mRNA. Taken together, these findings suggest that RNase-L and TTP represent reciprocally regulated components of a post-transcriptional network that functions to tightly control the expression of proinflammatory cytokines, and may influence the antitumor immune response. 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 4068.
TCT-450 PREDICTORS OF ANGIOGRAPHIC OUTCOMES FOLLOWING IN-STENT RESTENOSIS TREATMENT WITH PACLITAXEL-ELUTING BALLOONS AND SECOND-GENERATION DRUG-ELUTING STENTS.
Authors: Guillaume Marquis Gravel, François Gobeil, Nicolas Noiseux, Louis-Mathieu Stevens, Samer Mansour
Journal: Journal of the American College of Cardiology (2013)
Progress and Potential for Gene-Based Medicines
Authors: Mark R. Dyer, Paul L. Herrling
Journal: Molecular Therapy (2000)

During the past decade researchers have explored the potential of gene-based medicines to extend current treatments employing chemical entities and proteins. However, progress has been slower than was originally predicted due to our limited knowledge of the genetic components of major diseases, the complexity of developing active biological agents as therapies, and the stringent and time-consuming tests necessary to ensure safety prior to introduction of these novel modalities in the clinic. In spite of the present technology challenges and clinical setbacks in gene therapy it is anticipated that gene-based medicines will find their niche in disease prevention and management strategies in the coming decade, extending the repertoire of medicines available to satisfy key unmet medical needs. Additionally, progress in xenotransplantation research is creating the opportunity to use gene-modified porcine organs for human transplantation. This innovative approach aims to address the current insufficiency of human donor organs for clinical transplantation.
HEALTH CARE RESOURCE UTILIZATION IN PATIENTS REQUIRING URGENT SURGICAL/INTERVENTIONAL MANAGEMENT WHILE TAKING DABIGATRAN: INTERIM RESULTS FROM THE RE-VERSE AD STUDY
Authors: Charles V. Pollack, Fredrik Gruenenfelder, Jerrold H. Levy, Paul Reilly, Anastasia Ustyugova, Eva Kleine, Richard Bernstein, Menno Huisman, Elaine Hylek, Frank Sellke, Jeffrey I. Weitz
Journal: Journal of the American College of Cardiology (2016)
P1 A Novel Capsaicin Cough Challenge In Healthy Adults; Beyond The C5
Authors: K. Holt, C. Gibbard, K. Ahern, J. Smith
Journal: Thorax (2014)

<h3>Introduction</h3> We have developed a novel cough challenge methodology and previously showed that evoked maximal cough responses, defined as E<sub>max</sub>, better discriminate health from disease than traditional endpoints.<sup>1</sup> It is unclear how other factors influence E<sub>max</sub> or how it relates to the low cough rates observed in health. We therefore aimed to investigate the variability, repeatability and influences on E<sub>max</sub> in a larger group of healthy volunteers. <h3>Objective</h3> To assess maximum cough responses to capsaicin in a group of healthy adults representing a wide range of ages. <h3>Method</h3> Doubling doses of capsaicin 0.49 to 1000[micro]M) were inhaled sequentially up to the maximum tolerated dose. Four inhalations of each dose were administered 30 seconds apart and the number of coughs evoked within 15 seconds was recorded. The maximum number of coughs evoked by any dose of capsaicin (E<sub>max</sub>) and the dose that elicited half of the E<sub>max</sub>, defined as ED<sub>50</sub>, were calculated. General linear models were used to assess the influence of subject demographics on these endpoints. <h3>Results</h3> Forty seven healthy volunteers performed the capsaicin challenge; median age 38 years (range 20–74), 17 males, median FEV<sub>1</sub> 103% predicted (97–115), median BMI 25.0 (22.2–28.6), and median total cough rate 0.2 c/h (0.0–0.1). The median E<sub>max</sub> was 11 coughs (IQR, 8–19) with an ED<sub>50</sub> of 15.6[micro]M (7.8–109.4). The intraclass correlation coefficients for E<sub>max</sub> and ED<sub>50</sub> were 0.89 and 0.96 respectively which were highly significant (p &lt; 0.001). Age, gender, FEV<sub>1 </sub>and BMI had no significant influence on E<sub>max</sub>. In contrast, gender (p &lt; 0.001) and BMI (p = 0.029) both significantly influenced ED<sub>50</sub> explaining 41.7% of the variation. Those subjects with a higher BMI and females tended to have a lower ED<sub>50</sub>. Objective 24 h cough frequency did not correlate with either E<sub>max</sub> or ED<sub>50</sub>. <h3>Conclusion</h3> Data collected to date has demonstrated that in healthy volunteers, E<sub>max</sub> and ED<sub>50</sub> are stable measures over time however E<sub>max</sub> has the advantage of being independent of patient factors. Intere stingly, objective cough frequency in healthy volunteers seems to be unrelated to capsaicin evoked coughing. <h3>References</h3> <i>J Allergy Clin Immunol</i>. 2013 Oct;132(4):847–55
The German competence network ‘Acute and chronic leukemias’
Authors: R Hehlmann, U Berger, C Aul, Th Büchner, H Döhner, G Ehninger, A Ganser, N Gökbuget, D Hoelzer, K Überla, W Gassmann, W D Ludwig, H Rieder, M Kneba, A Hochhaus, A Reiter, W Hiddemann, O G Ottmann, U Germing, K Adelhard, M Dugas, P Dirschedl, D Messerer, A Böhme, E Harrison-Neu, M Griesshammer, J Kienast, H J Kolb, A D Ho, M Hallek, A Neubauer, B Schlegelberger, D Niederwieser, G Heil, T Müller, J Hasford
Journal: Leukemia (2004)
VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION AS A BRIDGE TO RIGHT VENTRICULAR RECOVERY FOLLOWING FAILURE OF RIGHT VENTRICULAR ASSIST DEVICE IN RIGHT VENTRICULAR FAILURE ACCOMPANYING PULMONARY EMBOLECTOMY
Authors: Poojita Shivamurthy, David Underhill, Daniel Fusco, Jeffrey Walden, Jason Gluck, Joseph Radojevic
Journal: Journal of the American College of Cardiology (2015)