tbuckley/cabot-search huggingface dataset:
COMPARISON OF SAPIEN 3 AND SAPIEN XT TRANSCATHETER HEART VALVE STENT-FRAME EXPANSION: EVALUATION USING MULTI-SLICE COMPUTED TOMOGRAPHY
Authors: Yoshio Kazuno, Yoshio Maeno, Hiroyuki Kawamori, Nobuyuki Takahashi, Yigal Abramowitz, Mohammad Kashif, Tarun Chakravarty, Hariri Babak, Mamoo Nakamura, Wen Cheng, John Friedman, Daniel Berman, Raj Makkar, Hasan Jilaihawi
Journal: Journal of the American College of Cardiology (2016)
Adequacy of Lymph Node Sampling During Surgical Resection of Lung Cancer at a Regional UK Thoracic Surgical Centre 2011-2013
Authors: M. Evison, S. Britton, H. Al-Najjar, P. Crosbie, M. Jones, P. Bishop, P. Krysiak, K. Rammohan, R. Shah, R. Booton
Journal: Annals of Oncology (2015)
Abstract 1625: Role of EphB4 in esophageal cancer: Expression, amplification, and therapeutic inhibition
Authors: Rifat Hasina, Geetanjali Kanade, Soheil Yala, Nathan Mollberg, Jeffery Muller, Mosmi Surati, Rajani Kanteti, Aliya Husain, Mitchell Posner, Irvine Waxman, Wickii Vigneswaran, Mark Ferguson, Victoria Villaflor, Everette E. Vokes, Parkash Gill, Ravi Salgia
Journal: Cancer Research (2011)

Abstract EphB4 is a member of the largest family of receptor tyrosine kinases (RTKs), classically associated with neural development and vascular patterning in embryonic life. The cellular responses to Eph receptor stimulation by their ephrin ligands are important in mediating a wide range of biological activities, including angiogenesis, cell segregation, cell attachment, shape, and motility. EphB4 has been showed to play an oncogenic role in a number of tumors, and we report the first investigation into its role in esophageal cancer, a disease whose survival has not improved and would benefit from the identification of new targets in its treatment. We have addressed this need by exploring the Eph/ephrin receptor tyrosine kinase pathway. We utilized tissues archived at the University of Chicago as well as commercially purchased TMAs to evaluate the expression of EphB4 by IHC. Approximately 93 squamous cell carcinoma, 100 adenocarcinoma and 25 adjacent normal control samples were utilized. In addition, four adenocarcinoma and nine squamous cell carcinma cell lines were used for in vitro studies. Statistical analysis of IHC data showed a consistently higher expression of EphB4 in both squamous and adenocarcinoma compared to adjacent normal tissue. A statistically significant correlation was established between EphB4 expression and higher grades of squamous cell carcinoma, suggesting that overexpression of EphB4 in squamous cell carcinoma is directly linked to clinically aggressive tumors. The EphB4 gene was found amplified in 8/16 squamous cell carcinoma (30% with a gene copy number ≥ 3, 30% with &amp;gt;8 copies and 10% with a copy number of 20. Of the adenocarcinomas, 3/7 samples were amplified (43% with a gene copy number of ≥4, and 14% &amp;gt;8 copies). Three of 9 squamous cell carcinoma cell lines had a gene copy number ≥4 and rest of them had no significant variation. Only one of four adenocarcinoma cell lines had an increased gene copy number. In vitro experiments with EphB4 specific siRNA inhibited the motility and proliferation of cultured cells and the inhibition of EphB4 specifically abrogated the phosphorylation of functional proteins associated with cell motility and proliferation, especially that of phospho-FAK and phospo-AKT, the expression of which were abrogated completely by the inhibition of EphB4. Our data imply that EphB4 plays a crucial role in esophageal cancer and should be further evaluated as a therapeutic target in this disease. 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 1625. doi:10.1158/1538-7445.AM2011-1625
A Painful Subject
Authors: Claudia P. Rodriguez, Anand Vaidya, Lori W. Tishler, Joji Suzuki
Journal: New England Journal of Medicine (2015)

A 34-year-old single veteran presented to a pain clinic with a report of pain in his lower back that had worsened over the past 6 months and a request for opioid medications. He said that the pain had begun after a motor vehicle accident that occurred 5 years ago. At that time, he had received a prescription for 5 mg of oxycodone every 6 hours as needed for pain. Over the course . . .
SP0119 Latest Update on Biosimilars - Chances and Risks
Authors: J. Braun
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Biosimilars also known as follow-on biologics are biologic medical products whose active drug substance is made by a living organism or derived from a living organism by means of recombinant DNA or controlled gene expression methods. These terms are used to describe officially approved subsequent versions of innovator biopharmaceutical products made by a different sponsor following patent and exclusivity expiry on the innovator product. Reference to the innovator product is an integral component of the approval. After expiry of the patent of an approved recombinant drugs such as insulin, human growth hormone, interferons, erythropoietin, TNF blockers and others any other biotech company can copy and market these biologic drugs. However, unlike the more common small-molecule drugs, biologics generally exhibit high molecular complexity, and may be sensitive to changes in manufacturing processes. Nevertheless, it is well known that this also occurs in the original biologics which implies that the final product of these sophisticated processes which are not under a 100% control of the molecular engineers are known to undergo subtle changes over time. Biosimilars are subject to an approval process by the European Medicines Agency and the Federal Drug Administration which requires substantial additional data to that required for chemical generics, although not as comprehensive as for the original biotech medicine, and this includes efficacy and safety data. This has been progressively replaced with a greater dependence on assays, from quality through to clinical, that show assay sensitivity sufficient to detect any significant difference in dose. However, the safe application of biologics depends on an informed and appropriate use by healthcare professionals and patients. Introduction of biosimilars also requires a specifically designed pharmacovigilance plan. It is difficult and costly to recreate biologics. In contrast, small molecule drugs made up of a chemically based compound can be copied identically, they can be easily replicated and are considerably less expensive to reproduce. In order to be released to the public, biosimilars must be shown to be as close to identical to the parent biological product based on data compiled through clinical, animal and analytical studies. The results must demonstrate that they produce the same clinical results. EMA and FDA regulations as well as scientific considerations indicate that biosimilarity does not imply interchangeability. In Rheumatology the first biosimilar has recently been approved in Europe – a biosimilar to infliximab which has passed all tests and examens and that is produced by a Korean company. <h3>Disclosure of Interest</h3> J. Braun Grant/Research support from: Abbvie, MSD, Pfizer, Consultant for: Abbvie, Celltrion, Janssen, MSD, Novartis, Pfizer, UCB, Conflict with: Abbvie, Celltrion, MSD, Novartis, Pfizer, UCB <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6247
Infection with Human T-Cell Leukemia Virus Type I in Patients with Leukemia
Authors: Grace Y. Minamoto, Jonathan W.M. Gold, David A. Scheinberg, William D. Hardy, Nancy Chein, Evelyn Zuckerman, Lilian Reich, Kathleen Dietz, Timothy Gee, Jack Hoffer, Klaus Mayer, Janice Gabrilove, Bayard Clarkson, Donald Armstrong
Journal: New England Journal of Medicine (1988)

Among 211 adults with leukemia who received multiple transfusions, 6 were found to be seropositive for human T-cell leukemia virus Type I (HTLV-I). Before the positive serum specimens were obtained, these patients received a mean of 14 units of red cells and 78 units of platelets. Seroconversion could be documented in three patients. None of the 6 patients seropositive for HTLV-I had a T-cell leukemia, other illnesses attributable to HTLV-I infection, or risk factors for HTLV-I infection other than transfusion: none were seropositive for human immunodeficiency virus. Patients with leukemia who receive multiple transfusions appear to be at risk for HTLV-I infection. (N Engl J Med 1988; 318: 219–22.)
V600E mutations in metastatic melanoma: Case report.
Authors: Momcilo Inic, Zorka Momcilo Inic, Milan Zegarac, Gordana Pupic, Ivana Inic
Journal: Journal of Clinical Oncology (2013)

e20002 Background: Vemurafenib, a selective BRAF kinase inhibitor, is a new medicine against carcinoma.This work will discuss new approaches to the treatment of patients with metastatic melanoma, who have been proved to have BRAF V600 mutation. Methods: The 62-year-old patient was initially diagnosed in 2002 when the excision of melanoma of the left calf was performed. HP was Melanoma invasivum nodular, Breslow III, Clark IV, p T3, without angioinvasion. The stadium of illness was M1a (AJCC). Afterwards, she was operated four times. Chemyotherapy was performed with DTIC and in the further treatment secundary HT VLB-BLM-CDDP. In June 2012 the examination of the control ultrasound of the abdomen and pelvis registered the progression of illness. The liver indicated multiple changes of seundary deposit type, the largest of which was 24mm parailiac left lgl 53mm, inguinal left 23mm. It was confirmed that the patient had the mutation on the BRAF gene and she was included in the clinical study in the illness stadium M1c (AJCC). Subsequently the therapy with vemurafenib 960 mg twice a day was introduced, after which side effects were registered: rash gr. 2, arthralgia gr. 1 (pain in the hand joints) and the swelling of ankle joints gr. 1. The patient continued the vemurafenib therapy. At the latest examination in October 2012, the control CT screening registered the regression of secundary deposit by 40%. Results: Identifying the significance of BRAF has led to the development of numerous new medicines against carcinoma. One of them is vemurafenib (PLKS4032), a medicine inhibiting particularly BRAF V600 mutation. Stage I of studying this medicine showed a complete or partial tumor regression in 81% patients with V600 BRAF mutation, while stage showed a relative reduction of death risk in 63% patients, as well as a relative reduction of tumor progression risk in 74% patients in comparison to dakarbazin. Still, patients who take vemurafenib develop resistance to this medicine within 7 months on average. Conclusions: The development of vemurafenib and the role of BRAF targeted therapy in the treatment of metastatic melanoma ensure a new basis for the clinical research. Further clinical studies will research complex molecular mechanisms underlying resistance and toxicity to vemurafenib.
A Renal Factor in Hypertension Due to Coarctation of the Aorta
Authors: Gerald C. Timmis, Seymour Gordon
Journal: New England Journal of Medicine (1964)

RENAL disease is instrumental in the generation or maintenance of some forms of systemic arterial hypertension. The experimental production of systolic hypertension by renal artery constriction, by suprarenal coarctation of the aorta, or by establishment of fibrocollagenous perinephritis in animals suggests a renal factor in such hypertension involving an alteration of renal blood flow or renal ischemia per se.1 2 3 4 The clinical counterpart of this assumption stems from the recorded success of reconstructive procedures reversing hypertension in patients with renal-artery stenosis.5 , 6 The correction of hypertension by removal of an ischemic kidney, the physiochemical function of which is measurably altered, further fosters . . .
RAPID IDH1 GENE MUTATION ANALYSIS FOR INTRAOPERATIVE PATHOLOGICAL DIAGNOSIS
Authors: J.-i. Adachi, K. Mishima, T. Suzuki, T. Fujimaki, R. Nishikawa
Journal: Neuro-Oncology (2014)

BACKGROUND: (blind field). METHODS: DNA extracted in 15 min from glioma tissue collected during surgery was used to test for R132 point mutations of the IDH1 gene by using real-time PCR/high resolution melting analysis method (LightCycler 480 system). Normally, detecting IDH1 mutations requires about 80 min from the start of the PCR cycle. For rapid diagnosis, however, DNA extension and annealing times in the PCR cycle were reduced by half. Our results were compared with those obtained using the regular method. RESULTS: Regular analysis and rapid diagnosis analysis were used to detect IDH1 mutations in 6 glioma cases (diffuse astrocytoma, 2 cases; oligodendroglioma, 2 cases; anaplastic astrocytoma, 1 case; glioblastoma, 1 case). Both methods produced the same results in all cases. CONCLUSIONS: Direct DNA sequencing and immunostaining can be used to identify IDH1 mutations. However, because analyses by using the former method require several hours, it cannot be used in rapid diagnosis. The latter method could not identify all R132 mutations, because the current commercially available antibodies can only detect R132H mutant proteins. This method can detect IDH1 mutation in even 1% of tumor purity, and determine all IDH1 R132 mutation-positive gliomas during surgery in 50–60 min after the tissue is collected. Further, this method could aid in intraoperative pathological diagnoses to differentiate IDH1 mutation-positive low-malignancy gliomas from gliosis and other non-neoplastic tissues. SECONDARY CATEGORY: Clinical Neuro-Oncology.
AB0705 Pleuropericardial effusion, a rare presenting feature in patients with sarcoidosis – a case series
Authors: C. Dharmapalaiah, N. Hassan, A. Nandagudi, A. Bharadwaj
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pulmonary involvement is very common and occurs in up to 70% of patients with Sarcoidosis. However, Sarcoidosis presenting with pleural or pericardial effusion is very rare as per published series. Asymptomatic minimal pericardial effusion occurs in up to 20% of biopsy proven Sarcoidosis, while pleural involvement is seen only in about 1-5% of patients. <h3>Objectives</h3> To highlight that pleural or pericardial effusion can be a presenting feature of sarcoidosis. <h3>Methods</h3> We performed a retrospective review of 5 Caucasian patients case notes of with Sarcoidosis seen in one district general hospital, in Essex, UK. Pleuropericardial effusion seen on imaging at presentation was a common feature in all 5 patients. All patients presented with chest pain, shortness of breath and high acute phase response. <h3>Results</h3> All 5 patients were seen by 1 consultant Rheumatologist between September 2010 and September 2011, 3 were admitted to the acute medical unit and 2 were seen in the outpatients. The age range was 34 to 61 years (median 55 years). Four were males and one female. All the patients presented with acute onset of pleuritic chest pain, dyspnoea, polyarthralgia and very high inflammatory markers. Echocardiogram showed pericardial effusion in 4 out of 5 patients, and pleural effusion and lymphadenopathy was present in all 5 patients' CT scans (see table 1). <h3>Conclusions</h3> Pleuropericardial effusion can be a presenting feature of Sarcoidosis as seen in our case-series. It should be considered as an important cause of shortness of breath in patients with Sarcoidosis. <h3>References</h3> Angomachalelis N, Hourzamanis A, Salem N, Vakalis D, Serasli E, et al. Pericardial effusion concomitant with specific heart muscle disease in systemic sarcoidosis. Postgrad Med J. 1994;70:S8–S12 Israel RH, Poe RH. Massive pericardial effusion in sarcoidosis. Respiration. 1994;61:176–180 Cardiac sarcoidosis: a comprehensive review Arch Med Sci. 2011 August; 7(4): 546–554. vSilverman KJ, Hutchins GM, Buckley BH. Cardiac sarcoid a clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation. 1978;58:1204–11. Michael C. Iannuzzi, M.D., Benjamin A. Rybicki, Ph.D., and Alvin S. Teirstein, M.D. N ENGL J MED 2007; 357:2153-2165 Moller DR: Rare manifestations of sarcoidosis. <i>Eur Respir Monograph</i> 2005, 10:233-250. <h3>Disclosure of Interest</h3> None Declared
PTU-155 Progression Of Low Grade Dysplasia To High Grade Dysplasia In Barrett’s Oesophagus In A Single Centre
Authors: L-L Clark, G Richardson, S Paterson
Journal: Gut (2014)

Introduction Barrett’s oesophagus is a common condition found in 4% of patients undergoing upper gastrointestinal endoscopy.(1) The association between Barrett’s oesophagus and oesophageal adenocarcinoma has been well established. Scotland has a particularly high incidence of both Barrett’s and adenocarcinoma of the oesophagus. The risk of progression from high grade dysplasia (HGD) to oesophageal adenocarcinoma (OAC) has been reported at approximately 10% per year.1 However the risk of progression from low grade dysplasia (LGD) is harder to quantify with studies showing progression to OAC from 0.6–1.69% per year, not dissimilar to that of non-dysplasic Barrett’s.2 More recently the SURF trail reported a 25% (17/68) progression from LGD to HGD/OAC in a surveillance group with LGD versus radiofrequency ablation.3 Methods In 2009 a clinical database of Barrett’s patients was developed in Forth Valley Hospital to ensure appropriate surveillance as per BSG guidelines. All patients diagnosed with Barrett’s were cared for by one responsible team, a dedicated Barrett’s endoscopy list was developed, and the use of narrow band imaging was introduced. At the end of 2012 the database was interrogated to assess the progress of all patients who had been diagnosed with LGD within the previous three years. Results There were 915 patients with Barrett’s on the database, of which 829 were under follow up. 85 (10%) had LGD and of this patient cohort 19 had progressed to HGD. The progression rate from LGD to HGD was 22% (19/85). The median follow up of patients with LGD was 29 months (range 12–34 months). All patients who progressed from LGD to HGD had endoscopic therapy with endoscopic mucosal resection and /or ablative therapies. There are no recorded cases of progression of LGD to OAC. Conclusion The progression rate from LGD to HGD is similar to reported rates found in the SURF trial. This suggests that LGD carries a greater risk of progression, and therefore worse prognosis than previously reported. This is a potential group of patients in whom to consider early intervention rather than adopt the standard surveillance strategy. Further studies to evaluate the effectiveness of treatment rather than surveillance in this group should be considered. References 1. Consensus Statements for Management of Barrett’s Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process. Gastroenterology 2012;143 (2):336–346 2. Sachin W, Sharad M. How to manage a Barrett’s Esophagus patient with low grade dysplasia. Clin Gastroenterol Hepatol . 2009;7(1):27–32 3. Phoa K, von Vilstern, F. Radiofrequency Ablation in Barrett’s esophagus with confirmed low-Grade dysplaisa: interm results of a European multipcentre randomized controlled trial (SURF). Gastroenterology 2013: 5 Supplement1 S187 Disclosure of Interest None Declared.
OP0078 The TNFRSF1A and MEFV Gene Mutations in the Secondary Amyloidosis Without FMF and HPFS Symptoms
Authors: F. Cosan, Z. Emrence, S.V. Pişkinpaşa, A.R. Odabas, D. Ustek, A. Cefle
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is an autoinflammatory disease with recurrent attacks of fever, serositis and arthritis. The most frequently complication of FMF is amyloidosis, which causes frequently mortality and morbidity. The pathogenesis of amyloidosis is unknown. In the other hand other chronic inflammatory disorders may cause secondary amyloidoses. Except SAA, it was not found a common genetic susceptibility for the secondary amyloidoses associated with different inflammatory disorders. <h3>Objectives</h3> We aimed in this study to investigate the role of MEFV gene and TNFRSF1A gene in the pathogenesis of amyloidosis which is not associated with FMF or other hereditary periodic fever syndromes (HPFS). <h3>Methods</h3> The study group is consisted of 47 FMF patients without amyloidosis, 42 FMF patients with amyloidosis, 37 patients with AA amyloidosis without FMF or other HPFS and 45 healthy controls. We analyzed the TNFRSF1A gene exon 2-5 and MEFV gene exon 10 mutations with sequencing in all patients. <h3>Results</h3> We found increased frequency of rs116336305 SNP in TNFRSF1A gene in the FMF without amyloidosis group. An interesting finding was that this SNP was not found in amyloidosis group (p=0.003, OR:0.809, %95 CI:0, 708-0929). No other mutation was found in the TNFRSF1A gene. The M694V mutation carrier rate is increased in the AA amyloidosis group without any FMF symptoms in comparison with healthy controls (p=0,042, OO:8,52, %95 CI: 0,98-74,3, %16,2 vs %2.2). There was no difference in the carrier rate of other MEFV mutations between these groups. <h3>Conclusions</h3> This study reveals that rs116336305 mutation rate is increased in AAA and there is no amyloidosis in patients with this mutation. This data should be verified with larger patients groups. In the other hand we found increased M694V carrier rate in secondary amyloidosis group without FMF symptomes. These results suggest that M694V mutation should be investigated in the patients with proteinuria and without FMF symptomes, especially in those populations with high carrier MEFV mutation carrier rate. <h3>Disclosure of Interest</h3> None Declared