tbuckley/cabot-search huggingface dataset:
PWE-065 Colonoscopy Performance In A District General Hospital. Has The Standardisation Of Training Standardised Performance?
Authors: TM El Menabawey, J O’Donohue, R Srirajaskanthan
Journal: Gut (2014)

<h3>Introduction</h3> Since the introduction of the JAG endoscopy training system (JETS) for trainees in 2003 there have been demonstrable improvements in the key performance indicators (KPIs) of colonoscopy performance. Caecal intubation, polyp detection and polyp retrieval rates are audited KPIs for departments. Terminal ileum (TI) intubation rates are also recorded. The national colonoscopy audit has shown a disparity between medical and surgical performance, but little has been studied to assess if this has improved over time. <h3>Methods</h3> We retrospectively audited these KPIs between 2004 and 2012, analysing for variations in performance for all colonoscopists encompassing both trainees and Consultants. We compared the performance of medics and surgeons for each year, the performance in 2004 with 2012 and the overall performance for 9 years using the Chi-squared test. <h3>Results</h3> 10055 colonoscopies were performed over 9 years: 8938 by medics and 1117 by surgeons. Completion rates improved significantly from 2004 to 2012 for all colonoscopists (80.3 to 92.0%, p &lt; 0.001). A significant improvement in both specialties' completion rates was seen (medics: 84.1 to 93.0%, surgeons: 74.8 to 88.5%, p &lt; 0.001). Over 9 years the overall completion rate for medics was higher (90.2 vs. 86.0%, p &lt; 0.001). Between 2007 and 2011 there was no significant difference in completion rates. Both specialties' TI intubation rate improved between 2004 and 2012 (medics: 46.3 to 64.1%, surgeons: 10.41 to 42.0%, p &lt; 0.001). Overall surgeons were better at polyp detection (28.5 vs. 24.8%, p &lt; 0.001). Surgical performance has not improved since 2004 (29.02 to 23.2% in 2012), whereas medics improved from 14.4 to 29.7% (p &lt; 0.001) to a standard in line with surgical colleagues. Over 9 years there was no significant difference in polyp retrieval rates between specialties (74.9 vs. 76.7% respectively, p = 0.3) and the performance of both improved from 2004 to 2012 (medics: 44.2 to 90.9%, surgeons: 57.6 to 80.2%, p &lt; 0.001). <h3>Conclusion</h3> There has been an overall improvement in colonoscopists' performance in all KPIs between 2004 and 2012. When performance is sub-divided into specialties, one can see that there were significant discrepancies in performance between physicians and surgeons in 2004. With the exception of TI intubation, performance has converged to a similar and higher standard in 2012. This coincides with the introduction of JETS and suggests standardised training may have served to normalise and improve the standard of colonoscopy across both specialties. <h3>References</h3> Gavin DR <i>et al</i>. The national colonoscopy audit: a nationwide assessment of the quality and safety of colonoscopy in the UK. <i>Gut</i> 2012 Kelly NM, <i>et al</i>. Is the 'driving test' a robust quality indicator of colonoscopy performancea<i>World J Gastrointest Endosc</i> 2010 <h3>Disclosure of Interest</h3> None Declared.
TCTAP A-157 Impaired Renal Function Is Associated with Severe Coronary Artery Disease in Chronic Stable Angina Patients
Authors: Jatindra Nath Saha, Abdullah Al Shafi Majumder, Nazir Ahmed Choudhury, Mohammad Ullah, Jafrin Jahan, Kazi Md Zafrul Haq, Md Badiuzzaman, Mohammad Golam Azam
Journal: Journal of the American College of Cardiology (2015)
Book Review
Authors: Susan Holmes
Journal: British Journal of Dermatology (1999)

Journal Article Book Review: A Pocketbook of Hair and Scalp Disorders: An Illustrated Guide John Gray and Rodney Dawber (1998). Oxford: Blackwell Science. ISBN 0‐632‐05189‐2, 112 pp. Price £14.95. Get access Susan Holmes Susan Holmes Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 3, 1 September 1999, Pages 610–611, https://doi.org/10.1046/j.1365-2133.1999.3093d.x Published: 01 September 1999
Abstract 5598: Interaction between BRAF inhibitor PLX-4720 and CDK inhibitors can sensitize melanoma cells with BRAF V600E mutation
Authors: Tharcísio Citrângulo Tortelli, Roger Chammas, Srikumar Chellappan
Journal: Cancer Research (2012)

Abstract BRAF V600E mutation happens in 60% of all melanomas cases and this mutation is responsible to poor prognosis of the disease. BRAF is part of the MAPK signaling pathway and the V600E mutation of BRAF confers full activation of this survival pathway. Several clinical trials are being conducted using mutated BRAF as a target but so far, all this trials works during a certain moment but soon, melanoma cells becomes resistant to treatment by activating some survival pathways that can continues the signal initialized in the MAPK pathway. Our objective is to evaluate if the combination of BRAF inhibitors and CDKs inhibitors can suppress the acquired resistance of V600E melanoma cells to BRAF inhibitors. Two melanoma cell lines were used in this study. The SKMel 28 cell line, which has BRAF V600E mutation, and the SKMel 02, which is wild type to BRAF. Olomoucine and Roscovitine were the CDKs inhibitors used in this study, while PLX-4720 was BRAF inhibitor. Western blot and Real time PCR were used to verify some survival pathways, like the MAP3K8 and the PRKD3 pathway, that are overexpressed after BRAF inhibition and MTT assay was used to verify cell viability with both treatments combined. The combination of Olomoucine and PLX-4720 or Roscovitine and PLX-4720 could sensitize the BRAF V600E mutated melanoma cell line SKMel 28, but not the BRAF wild type melanoma cell line SKMel 02. Two survival pathways (MAP3K8 and PRKD3) which are activated after BRAF inhibition by PLX-4720 were downregulated in the presence of the CDKs inhibitors in the SKMel 28 melanoma cell line. Also, the retinoblastoma protein was not phosphorylated when the SKMel28 melanoma cell line was treated with the BRAF inhibitor together with the CDKs. The treatment with the BRAF inhibitor and the CDKs inhibitors can sensitize BRAF V600E melanoma cells by decreasing cell viability, downregulation of survival pathways induced by the BRAF inhibitor and preventing Rb phosphorylation. This strategy may overcome the acquired resistance of BRAF-mutated melanoma after treatment with its 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 5598. doi:1538-7445.AM2012-5598
Two cases of laboratory-confirmed leptospirosis in travellers returning to Spain from Thailand, September 2013
Authors: A Calvo-Cano, E Aldasoro, M F Ramírez, M J Martínez, A Requena-Méndez, J Gascón
Journal: Eurosurveillance (2014)

In September 2013, leptospirosis was diagnosed in two Spanish travellers returning from Thailand. The first case walked in floodwater in the Phi Phi Islands in pouring rain: 20 days later he presented with fever and acute hepatitis. The second presented with fever and renal failure 17 days after visiting the islands. These cases remind clinicians to consider leptospirosis in febrile patients with a history of contact with flood or fresh water while travelling to tropical countries.
OC-123 Obesity drives radioresistance and enhances genomic instability in oesophageal adenocarcinoma
Authors: A M Mongan, N Lynam-Lennon, S Maher, G Pidgeon, J O'Sullivan, J Reynolds
Journal: Gut (2012)

<h3>Introduction</h3> Obesity is strongly associated with oesophageal adenocarcinoma (OAC). However, its role in regulating radiosensitivity and genomic instability is unknown. We developed an isogenic model of radioresistance in OAC called OE33R. We assessed levels of anaphase bridges, a functional genomic instability event, in OE33R compared to an age and passage matched control (OE33P). Spindle assembly checkpoint (SAC) control genes involved in regulating genomic instability were analysed in both cell lines following exposure to adipose conditioned media (ACM). Radiosensitivity following ACM treatment was investigated in OE33R and OE33P cell lines. The aim of this study was to characterise the isogenic radioresistant OAC cell model in terms of genomic instability, SAC gene expression and survival in response to adipose conditioned media (ACM) cultured from obese and nonobese OAC patients. <h3>Methods</h3> OE33R and OE33P cell lines were cultured with ACM from obese and nonobese patients. We assessed anaphase bridges in both lines and quantified the number of bridges present over the total cell number. Expression of five SAC genes (MAD2L2, BUB1B, CDC20, CENPE, and ESPL1) was assessed using qPCR. Survival was determined in both cells lines following ACM treatment using a clonogenic assay. <h3>Results</h3> OE33P and OE33P showed a significant increase in anaphase bridges in response to ACM (p&lt;0.05, p&lt;0.001 respectively). This increase in anaphase bridge formation was three times greater in the resistant line (p&lt;0.05). Levels of anaphase bridge formation correlated with obesity status (BMI and VFA, p&lt;0.05). OE33R cells treated with ACM showed significantly increased expression of the SAC genes MAD2L2 and BUB1B compared to controls (p&lt;0.01). Expression of MAD2L2 and BUB1B correlated with obesity status (p&lt;0.05). OE33P cells treated with ACM showed increased radioresistance (p&lt;0.05). In contrast, in the resistant OE33R cell line, ACM treatment reversed this radioresistance (p&lt;0.001). <h3>Conclusion</h3> Obesity drives genomic instability and alterations in SAC gene expression in radioresistant OAC and alters radiosensitivity in OAC. <h3>Competing interests</h3> None declared.
Abstract 4025: Data-driven computational modeling to identify biomarkers of response to lenvatinib (E7080) in melanoma.
Authors: Tadashi Kadowaki, Yasuhiro Funahashi, Junji Matsui, Kumar Pavan, Pallavi Sachdev, Jim O'Brien, Heming Xing, Paul D. McDonagh, Iya Khalil, Razelle Kurzrock, David S. Hong, John Nemunaitis
Journal: Cancer Research (2013)

Abstract Background: Lenvatinib is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFRβ. Anti-tumor activity has been observed in melanoma patients in Phase I studies. We applied an integrative supercomputer-driven analysis approach to identify biomarkers of lenvatinib treatment response in melanoma patients. Methods: Clinical data sets including tumor response data (RECIST), progression free survival (PFS), pharmacokinetic parameters (PK) and molecular data sets including baseline tumor gene expression (Affymetrix U133Plus2) and BRAF and NRAS mutational status, were collected from 18 patients with metastatic melanoma who received lenvatinib 10 mg orally twice daily in 28-day cycles. These clinical and molecular data sets were used to generate computational models developed using REFS (Reverse Engineering and Forward Simulation) modeling platform, which utilizes Bayesian network inference and simulations. Simulations were performed to identify biomarkers of lenvatinib treatment response. These potential predictive biomarkers were then tested for their ability to predict response to lenvatinib in preclinical models. Results: Using a model comprising gene expression, mutational status and PK data, REFS identified a panel of 18 potential predictive biomarkers of lenvatinib treatment response. Identified biomarkers were able to predict up to 89% of the observed variance in the tumor response data. A total of 32 identified genes including 6 candidate predictive biomarkers (TARBP2, CACNA1, C7ORF, RAP2A, SHMT1, IL22RA2) were further validated in a preclinical melanoma model system (n=12) and tissue bank samples with matched normal adjacent tissue (n=21). Expression of 14 genes correlated with relative tumor volume (r&amp;gt;0.35 or r&amp;lt;-0.35) in the preclinical model and expression levels of 19 genes were found to be higher in tumor compared to normal tissue (FC&amp;gt;2). Conclusions: Potential predictive biomarkers of lenvatinib treatment response in melanoma patients were identified by computational modeling and validated in a preclinical model system and tumor tissue bank samples. The identified biomarkers will be tested for their predictive value in an ongoing Phase 2 trial. Citation Format: Tadashi Kadowaki, Yasuhiro Funahashi, Junji Matsui, Kumar Pavan, Pallavi Sachdev, Jim O'Brien, Heming Xing, Paul D. McDonagh, Iya Khalil, Razelle Kurzrock, David S. Hong, John Nemunaitis. Data-driven computational modeling to identify biomarkers of response to lenvatinib (E7080) in melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4025. doi:10.1158/1538-7445.AM2013-4025
13N-AMMONIA PET-DERIVED VENTRICULAR SYNCHRONY CORRELATES WITH MYOCARDIAL PERFUSION RESERVE BETTER THAN LEFT VENTRICULAR EJECTION FRACTION: A STUDY IN INFARCTED PATIENTS
Authors: Luis Eduardo Juarez-Orozco, Riemer Slart, Rene A. Tio, Fernando Inarra-Talboy, Andrea Monroy, AnaGabriela Ayala-German, Rudi A. Dierckx, Erick Alexanderson Rosas, Erick Alexanderson
Journal: Journal of the American College of Cardiology (2016)
Acute Axillosubclavian Vein Thrombosis (Paget–Schroetter Syndrome) Detected by Tc-99m MAA During Pulmonary Perfusion Scintigraphy
Authors: AKIHIRO UEMURA, IWAO OSAKA, HAJIME FUJIMOTO
Journal: Clinical Nuclear Medicine (2000)

The authors describe a 24-year-old man who reported the sudden onset of dyspnea and swelling of his left upper arm. An area of increased activity in the left axillosubclavian region evident on pulmonary perfusion scintigraphy with Tc-99m MAA suggested Paget–Schroetter syndrome (primary deep venous thrombosis of the upper extremity).
Prolonged Correction of Hyperlipidemia in Mice with Familial Hypercholesterolemia Using an Adeno-Associated Viral Vector Expressing Very-Low-Density Lipoprotein Receptor
Authors: Shu Jen Chen, Daniel J. Rader, John Tazelaar, Masa-aki Kawashiri, Guang-ping Gao, James M. Wilson
Journal: Molecular Therapy (2000)

Adeno-associated viral vectors were used to deliver the gene for very-low-density lipoprotein (VLDL) receptor (VLDLR) to liver of a murine model of familial hypercholesterolemia (FH). Infusion of adeno-associated virus-VLDLR into the portal circulation of FH mice resulted in a 40% reduction in serum cholesterol and triglyceride that was stable for the duration of the study (30 weeks). Fractionation of serum lipids revealed a reduction of both VLDL and low-density lipoprotein. Expression of transgene-derived VLDLR was confirmed in livers of recipient animals by Western blot analysis and immunohistochemistry; vector DNA was present at 1 copy/cell. Vector-treated animals had significantly less lipid accumulation in liver and reduced atherosclerosis in the aorta. Adeno-associated viral vectors were used to deliver the gene for very-low-density lipoprotein (VLDL) receptor (VLDLR) to liver of a murine model of familial hypercholesterolemia (FH). Infusion of adeno-associated virus-VLDLR into the portal circulation of FH mice resulted in a 40% reduction in serum cholesterol and triglyceride that was stable for the duration of the study (30 weeks). Fractionation of serum lipids revealed a reduction of both VLDL and low-density lipoprotein. Expression of transgene-derived VLDLR was confirmed in livers of recipient animals by Western blot analysis and immunohistochemistry; vector DNA was present at 1 copy/cell. Vector-treated animals had significantly less lipid accumulation in liver and reduced atherosclerosis in the aorta.
Springing a Leak
Authors: Alexander S. Rabin, Ole-Petter R. Hamnvik, Emily S. Robinson, Amy Leigh Miller, Joseph Loscalzo
Journal: New England Journal of Medicine (2015)

A 52-year-old man presented to the emergency department with general weakness and swelling in his legs. Symmetric swelling had begun 4 weeks earlier and had progressed to the point that it was difficult for him to wear shoes.
COMPLICATIONS OF ACUTE CATATONIC EXCITEMENT
Authors: MORTON J. ARONSON, SAMUEL V. THOMPSON
Journal: American Journal of Psychiatry (1950)

1. Two cases of acute catatonic excitement with unusual complications are presented. 2. The first case survived a stormy course of peripheral vascular collapse, acidosis, and hyperthermia to 106°. Recovery was complicated by the development of lower nephron nephrosis. 3. The second case died in the course of voluntary apnea. This is the first such case to be reported. 4. It is suggested that suicide may be accomplished at a physiological level.
P1049 RISK FACTORS FOR HEPATOCELLULAR CARCINOMA AMONG PATIENTS WITH CHRONIC HEPATITIS B TREATED WITH ENTECAVIR
Authors: R. Yamada, N. Hiramatsu, N. Morishita, N. Harada, T. Oze, T. Yakushijin, T. Miyagi, Y. Yoshida, T. Tatsumi, K. Ohkawa, A. Kasahara, E. Mita, H. Hagiwara, M. Oshita, T. Itoh, T. Hijioka, H. Yoshihara, Y. Imai, N. Hayashi, T. Takehara
Journal: Journal of Hepatology (2014)
THU0441 Potential Fatality Predictors Caused by Pneumocystis Pneumonia (PCP) in Rheumatic Disease
Authors: R. Yanai, S. Isojima, H. Tsukamoto, T. Tokunaga, M. Umemura, H. Furuya, K. Otsuka, R. Takahashi, K. Wakabayashi, N. Yajima, Y. Miwa, T. Kasama
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Complications of pneumocystis pneumonia (PCP) are one of the predictors of fatality in rheumatic disease. Although clinical characteristics and risk factors for PCP in rheumatic diseases have been studied, there have been no reports of poor prognosis factor of the PCP. <h3>Objectives</h3> We examined the poor prognosis factors caused by PCP in rheumatic disease at admission. <h3>Methods</h3> From 2010 to 2012, 28 patients with rheumatic diseases and coexisting PCP were examined retrospectively (rheumatoid arthritis, 19 patients; systemic lupus erythematosus, 2 patients; systemic sclerosis, 2 patients; microscopic polyangiitis, 2 patients; relapsing polychondritis, 1 patient; pseudogout, 1 patient; autoimmune hepatitis, 1 patient). We divided the patients into two groups: surviving patients (group A; n=23) and deceased patients (group B; n=5). Age, sex, smoking history, past history of pulmonary disease, hospitalization and prednisolone dosage were examined. The following were also recorded at admission: white blood cell count, lymphocyte count, arterial blood gas PaO<sub>2</sub>/F<sub>I</sub>O<sub>2</sub> ratio, serum creatinine level with estimated glomerular filtration rate (eGFR), and the levels of hemoglobin, lactase dehydrogenase(LDH), albumin, C-reactive protein (CRP), β-D-glucan, Krebs von den Lungen-6 (KL-6), pulmonary surfactant-D (SP-D), IgG, and IgA. <h3>Results</h3> The results were as follows: <h3>Conclusions</h3> Either higher age, high serum creatinine levels and CRP or low serum albumin levels, IgA and PaO<sub>2</sub>/F<sub>I</sub>O<sub>2</sub> ratio are potential fatality predictors following admission caused by PCP in patients with rheumatic disease. <h3>Disclosure of Interest</h3> None Declared
Lume trial: searching for survival prognostic factors in malignant pleural mesothelioma
Authors: C. Proto, G. Lo Russo, M. Macerelli, M. Vitali, F. Agustoni, M. Platania, N. Zilembo, M. Ganzinelli, M. Tiseo, G. Pasello, R. Gallucci, M.S. Cona, L. Botta, A. Trama, F. de Braud, M.C. Garassino, D. Signorelli
Journal: Annals of Oncology (2015)
Abstract 4190: miR-30 as a tumor suppressor connects EGF/Src signal to EMT and ERG.
Authors: Chiao-Jung Kao, Anthony Martiniez, Xu-Bao Shi, Albert Dobi, Ralph W. de Vere White, Hsing-Jien Kung
Journal: Cancer Research (2013)

Abstract Src tyrosine kinase (Src) is implicated in the development of bone metastasis and castration-resistance of prostate cancer. Src inhibitors are currently being tested in clinical trials for such diseases. Understanding the molecular and cellular actions of Src inhibitors holds the key to future improvement of this line of therapy. Here we describe the microRNA expression profiles modulated by two Src inhibitors and demonstrate that the miR-30 family members are the most prominently induced species. Consistent with its tumor suppressor role, miR-30 is downmodulated by oncogenic signals such as epidermal growth factor (EGF) and hepatocyte growth factor (HGF), and is generally underexpressed in prostate cancer specimens. A number of epithelial to mesenchymal transition (EMT)-associated genes are predicted targets of miR-30. Among these genes the Ets Related Gene (ERG) is the most frequently overexpressed-oncogene in prostate cancer activated by genomic fusion events between promoter upstream sequences of the TMPRSS2 and coding sequences of ERG. We showed by ERG 3’UTR-reporter and mutagenesis assays that ERG is a direct target of miR-30. Overexpression of miR-30 in prostate cancer cells suppresses EMT phenotypes and inhibits cell migration and invasion. It also inhibits the in vitro and in vivo growth of VCaP cells, which depends on TMPRSS2-ERG for proliferation. TMPRSS2-ERG is generally regulated by androgen at the transcriptional level. Our finding reveals a new post-transcriptional mechanism of TMPRSS2-ERG regulation by Src and growth signals via miR-30 providing a rationale for targeting ERG positive castration resistant tumors with Src inhibitors. Citation Format: Chiao-Jung Kao, Anthony Martiniez, Xu-Bao Shi, Albert Dobi, Ralph W. deVere White, Hsing-Jien Kung. miR-30 as a tumor suppressor connects EGF/Src signal to EMT and ERG. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4190. doi:10.1158/1538-7445.AM2013-4190
AB1252 Subclinical left ventricular systolic dysfunction in patients with takayasu’s arteritis. A velocity vector imaging-based study
Authors: F. Alibaz-Oner, S. Yurdakul, Y. Tayyareci, H. Direskeneli, S. Aytekin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Takayasu’s arteritis (TA) is a chronic, granulomatous vasculitis of the aorta and its major branches. Impairment in left ventricular (LV) systolic function might be a major concern in TA due to chronic inflammation. <h3>Objectives</h3> We aimed to evaluate subclinical LV systolic dysfunction in patients with TA, without any cardiovascular disease and to compare them with patients with systemic lupus erythematosus (SLE), by using a novel strain imaging method, “velocity vector imaging” (VVI). <h3>Methods</h3> We studied 31 patients with TA (F/M, 29/2; mean age: 31,4), 18 patients with SLE (F/M, 17/1; mean age:32,3) and 20 20 age and sex-matched controls, without any cardiac disease and with preserved LV ejection fraction (EF). Conventional echocardiography and VVI- based strain imaging were performed to analyze subclinical LV systolic function. <h3>Results</h3> Conventional echocardiographic measurements (LV end diastolic diameter, LV end systolic diameter and LV EF) were similar between the groups. Longitudinal peak systolic strain (13.20±3.5% to 20.97±4.5%, p=0.0001) and strain rate (0.23±0.18 1/s to 4.92±0.55 1/s, p=0.0001) of the LV were significantly impaired in patients with TA, compared to controls, demonstrating subclinical ventricular systolic dysfunction. Supporting these results, we revealed impaired subclinical LV systolic function in patients with SLE, when compared to the control group (14±4.53% to 20.97±4.5%, p=0.0001 for strain; 0.23±0.12 1/s to 4.92±0.55 1/s, p=0.0001 for strain rate). The mean disease duration of the patient was 5.6 years in patients with TA. The LV systolic dysfunction was negatively correlated with disease duration, but this correlation couldn’t reach the statistical significance(r=-0,085, p=0,648.) <h3>Conclusions</h3> Ventricular long axis functions are important markers of myocardial contractility. Novel echocardiographic techniques may provide additional data for detecting early deterioration in ventricular systolic function in patients with systemic inflammatory diseases like TA and SLE. <h3>Disclosure of Interest</h3> None Declared