tbuckley/cabot-search huggingface dataset:
FRI0468 Chronic Nasal Carriage of Staphylococcus Aureus Does not Increase the Risk of Relapse and Severe Infections in Granulomatosis with Polyangiitis Patients When Receiving Rituximab Maintenance Treatment
Authors: E. Besada, W. Koldingsnes, J.C. Nossent
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Chronic nasal carriage of Staphylococcus aureus (SA) has been shown to increase the risk of relapse in patients with Granulomatosis with polyangiitis (GPA). B cell depletion with Rituximab (RTX) is effective in inducing and maintaining remission in GPA. However B cell depletion and hypogammaglobulinemia during RTX could increase the risk of chronic SA nasal carriage. <h3>Objectives</h3> To investigate the effect of long-term RTX treatment on chronic SA nasal carriage, the risk of relapses, severe infections and hypogammaglobulinemia in GPA patients. <h3>Methods</h3> Cohort study with prospectively collected nasal swab data in 29 GPA patients on RTX (median RTX dose of 9 g) treatment for a median period of 49 months. Patients (52% men, median age 50 (19-75) at RTX initiation, 86% PR3-ANCA positive, 3% MPO-ANCA positive and 10% ANCA negative, 66% and 59% with respectively pulmonary and renal involvement) had received a cumulative dose of cyclophosphamide of 17 (0-250) g. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined as the presence of SA in more than 75% of nasal swabs. <h3>Results</h3> The frequency of persistent SA nasal carriage did not change before (20%) and after RTX (28%) (p=0.562). Persistent SA nasal carriage did not increase the risk of relapses (p=0.646), severe infections (p=0.357) or hypogammaglobulinemia (p=1.00), but reduced the risk of chronic infections (p=0.033) during RTX. Patients without nasal SA carriage during RTX maintenance were at increased risk to discontinue RTX due to hypogammaglobulinemia (p=0.048). They had less lung involvement (p=0.032), more disease activity at baseline (p=0.010), lower CD4 cell count after RTX 2 g (p=0.023) and larger decline of total Ig after RTX 2g (p=0.045) and at last visit (p=0.021). <h3>Conclusions</h3> Long-term RTX maintenance therapy in GPA patients did not influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not increase the risk of relapses and infections and was associated with a lower risk of developing hypogammaglobulinemia. Our results suggest that long-term RTX treatment is better tolerated in GPA patients with chronic SA nasal carriage. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5231
PTH-178 Who Calls the Liver Registrar at King’S?
Authors: W Alazawi, K Agarwal, A Suddle, V Aluvihare, M Heneghan
Journal: Gut (2013)

<h3>Introduction</h3> Delivering excellent healthcare in today’s NHS involves multiple agencies and depends on accurate communication between professionals in different locations. King’s College Hospital is a leading Hepatology centre that receives tertiary and quaternary referrals from across the UK and Europe. Frequently, the first point of contact with the Unit is via a telephone call to a Specialist Registrar, for whom no case notes are available in which to record information. Until recently, referrals were recorded on paper and filed in a secure office in the Department. We introduced an electronic database system to record a standardised dataset from each call in order to improve clinical governance and to generate contemporaneous records that could be easily retrieved and audited. We present our five-month pilot data. <h3>Methods</h3> A Caldicott-compliant database was designed and made securely available to Registrars and Consultants. Registrars were encouraged to record all referrals and telephone calls they received. Calls taken by the Liver Intensive Care Unit, consultants, nurses, junior doctors and the out of hours team were excluded. Demographic and clinical data were recorded in real time with information regarding the source of the referral and the outcome of the call. There were no mandatory fields. <h3>Results</h3> Data from 350 calls were entered over five months. The source of the call was recorded in 345 cases. 125 (36%) were from King’s College Hospital and 20 (6%) were from General Practitioners or patients. The remaining 200 calls came from 75 institutions. Of the 220 calls made from outside the Trust, 63 resulted in the patient being transferred (n = 32), reviewed as an out-patient (n = 27) or discussed at a multidisciplinary team meeting (n = 4) at King’s. In 235 cases, discussion with a King’s Consultant was recorded (67%). Of the 115 calls where discussion with a Consultant was not recorded, 41 were from within King’s, 19 were transferred to King’s and in 36 cases there was continuing input by telephone advice from one of the teams at King’s. Only 15 extramural cases (7.5%) were concluded without a documented discussion with a Consultant. <h3>Conclusion</h3> Use of an electronic database to record extramural telephone advice given by senior trainees and Consultants provides clinical governance to this service and forms a contemporaneous record that is kept at the referral centre. The data can be used to estimate workload and to determine the disease burden in this population, thereby tailoring services to the needs of referrers and commissioners. Formal recording of the Consultant input in the advice service also forms an excellent training opportunity for trainees. We recommend the implementation of similar databases in other units that give verbal advice to colleagues outside their own institution. <h3>Disclosure of Interest</h3> None Declared.
Abstract LB-319: A novel cancer-testis antigen, BORIS-based vaccine delivered by dendritic cells is effective against metastatic disease
Authors: Mikayel Mkrtichyan, Anahit Ghochikyan, Dmitry Loukinov, Nina Movsesyan, Hayk Davtyan, Amanda K. Laust, Victor Lobanenkov, Edward L. Nelson, Michael Agadjanyan
Journal: Cancer Research (2010)

Abstract Although broad clinical benefits of anti-tumor immunotherapy have not been demonstrated, the current data suggest such strategies could be beneficial if capable of inducing strong anti-cancer cellular immune responses. We report testing for the first time, the therapeutic efficacy of a dendritic cell (DC)-based immunotherapy strategy targeting a novel cancer testis (CT) antigen, Brother of Regulator of Imprinted Sites (BORIS), which is an epigenetically acting tumor promoting transcription factor expressed in various human and mouse cancer cells. In addition to therapeutic potency, we evaluated the cellular immune responses by assessing BORIS-specific CD4 T cell proliferation, T cell cytokine production both by intracellular cytokine staining and ELISpot analysis, and CTL responses. We evaluated the impact of this therapy on the development of metastatic disease, by analyzing the number of spontaneous clonogenic metastases after a 10-day culture of lung homogenates in presence of 6-thioguanine. The presence of CD4, CD8, Treg and myeloid derived suppressor cells (MDSCs) in the tumor and in the spleen was analyzed by flow cytometry. DC loaded with zink-finger deleted (mutated) BORIS vaccine (DC/mBORIS) was evaluated in the non-immunogenic, very aggressive and highly metastatic mouse model of 4T1 mammary carcinoma. Vaccination of mice after 4T1 tumor implantation inhibited tumor growth (18.75% mice remained tumor-free) and dramatically lowered number of spontaneous clonogenic metastases (50% mice remained metastases-free). Higher numbers of immune-effector CD4 and CD8 T cells infiltrated the tumors of vaccinated mice compared to control animals. Therapeutic vaccination with DC/mBORIS significantly decreased the numbers of MDSC infiltrating the tumor, but not splenic MDSC, likely associated with the effect of the immunotherapy on tumor burden rather than a direct effect on MDSCs. Currently, we are testing the suppressive activity of splenocytes from tumor-bearing mice as well as MDSC isolated from these splenocytes. These data suggest that mBORIS is an attractive target for immunotherapy having substantial efficacy in this highly aggressive tumor model when incorporated into a DC-based immunotherapy, and which may be enhanced even further in combination with agents to attenuate tumor-associated immune suppression. 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 LB-319.
Cigarette Smoking and the Treatment of Angina with Propranolol, Atenolol, and Nifedipine
Authors: John Deanfield, Christine Wright, Shirley Krikler, Paulo Ribeiro, Kim Fox
Journal: New England Journal of Medicine (1984)

To determine whether cigarette smoking affects the results of drug treatment for angina, we studied 10 cigarette smokers with angina who were given placebo, nifedipine (60 mg per day), propranolol (240 mg per day), and atenolol (100 mg per day), each for one week. The four-week double-blind study was repeated with the same randomly determined order of drug sequences, after all 10 subjects had stopped smoking. Before and after the subjects stopped smoking, all three drugs significantly reduced the frequency of angina, as measured with angina diaries, and improved the results of maximal exercise testing and 48-hour ambulatory monitoring of ST segments (P less than 0.01). However, during the nonsmoking phase of the study, there was an overall decline in the frequency of angina and an improvement in performance on exercise testing (P less than 0.05) as compared with the smoking period, although the results of 48-hour ambulatory monitoring remained unchanged. The improvement after patients stopped smoking was greater during treatment with nifedipine than during administration of the other two drugs or placebo. Blood levels of propranolol were increased when patients stopped smoking; levels of nifedipine and atenolol were unchanged. Our data show that smoking had direct and adverse effects on the heart and interfered with the efficacy of all three anti-anginal drugs, but with nifedipine the most.
Esophageal recanalization by combined antegrade/retrograde esophagoscopy for radiotherapy-induced complete esophageal occlusion
Authors: Markus Küper, Dietmar Stüker, Alfred Königsrainer, Thomas Kratt
Journal: Endoscopy (2014)

One side effect of radiochemotherapy of head and neck malignancies is the development of esophageal stenosis [1] [2]. Subsequent therapeutic options include endoscopic balloon dilation or bouginage, with the option to perform combined antegrade/retrograde esophagoscopy in cases of complete esophageal occlusion [3] [4] [5] [6] [7] [8], or major surgery, such as esophageal resection, with its high risk of surgical complications [9]. The limitations of endoscopic therapy for complete esophageal closure have been defined and include long-segmental occlusions over 30 mm in length, in which case it is recommended to achieve patency of the neo-esophagus using stents, although there is a risk of stent-associated complications [5] [6] [7] [8].
Abstract 1956: A novel mouse model of breast cancer metastasis to bone
Authors: Aubie K. Shaw, Rachelle Johnson, Julie Sterling, Greg Mundy, Hal Moses
Journal: Cancer Research (2010)

Abstract Patients with advanced stage breast cancer develop bone metastasis, which leads to hypercalcemia, fractures, nerve compression, paralysis and pain. Breast cancer bone lesions can be osteolytic or osteoblastic, however osteolytic lesions are predominant. Currently, there is no experimental model available to examine osteotropism or trafficking of breast cancer cells to the bone from the primary tumor. TGFβ signaling has been suggested to be responsible for osteotropism. TGFβ stimulates Gli2 and PTHrP expression, which have been shown to be responsible for osteolysis. We have shown that MCF10A, AT-1 and CA1d human breast epithelial cells are responsive to TGFβ and express very high levels of Gli2 and PTHrP. Orthotopic grafting to the cleared fatpad of SCID mice shows that MCF10A and AT-1 cells do not form tumors, even when grafted with normal fibroblasts. CA1d carcinoma cells that are co-grafted with normal fibroblasts show rapid tumor formation with 100% incidence, whereas CA1d cells grafted alone rarely form tumors in the orthotopic site. The tumors can be localized real-time and non-invasively using optical imaging of GFP. X-ray imaging revealed loss of bone density in sacral/caudal vertebrae and hindlimbs. Ca1d grafts generate undifferentiated primary tumors that metastasize to lung and bone. Future studies will determine if CA1d cells stimulate osteolysis. This model may provide a valuable model to examine osteotropism of breast cancer cells. 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 1956.
749 EFFICACY AND SAFETY OF PEGINTERFERON alfa-2a (40KD) IN HBeAg-POSITIVE CHRONIC HEPATITIS B PATIENTS PARTICIPATING IN A RESPONSE-GUIDED THERAPY STUDY: AN INTERIM ANALYSIS AT WEEK 72
Authors: J. Hou, H. Ma, J. Sun, Q. Xie, Y. Xie, Y. Sun, H. Wang, G. Shi, M. Wan, J. Niu, Q. Ning, Y. Yu, Y. Zhao
Journal: Journal of Hepatology (2013)
Abstract 1062: Imaging DNA damage response (DDR) during oncogenesis.
Authors: Bart Cornelissen, Sarah Able, Veerle Kersemans, Katherine A. Vallis
Journal: Cancer Research (2013)

Abstract Introduction: DNA damage repair (DDR) signalling is upregulated during tumorigenesis and acts as a p53-mediated block on proliferation. Expression of the DNA double strand break (DSB) repair protein, γH2AX, is induced by the activated kinases pATM or pATR during oncogenesis. Previously, we showed that γH2AX presents an abundant epitope for non-invasive in vivo imaging of DSBs. We used 111In-labelled anti-γH2AX antibodies, conjugated to the cell penetrating peptide, TAT, to non-invasively image DDR during oncogenesis in a genetically engineered mouse model of HER2/neu-overexpression driven breast cancer. Methods: Balb/neuT mice, genetically modified to express mutated rat neuT under MMTV promotor control, form multiple palpable carcinomas in mammary fat pads when animals are 130 days old. SPECT images were acquired weekly from balb/neuT mice (age 40-140 days; n=23) 24 h after i.v. injection of 111In-labelled anti-γH2AX-Tat or the non-selective agent, 111In-rIgG-Tat using a small animal SPECT/CT scanner. 111In uptake in fat pads was determined using volume of interest analysis. 111In uptake of &amp;gt;5%ID/g was deemed positive. Anatomical and histological changes were assessed at different ages using DCE-MRI imaging and immunohistochemistry. Results: Balb/neuT mice that were 80 days old developed multiple hyperplastic and dysplastic lesions in mammary fat pads. γH2AX foci were observed in these regions in balb/neuT mice that were 80-100 days old (10-15 foci/cell), but were less numerous in overt tumor tissue in 130-day-old mice (4-5 foci/cell). γH2AX foci were not observed in normal tissues in older mice (0 foci/cell), in mammary fat pads in younger mice (0 foci/cell), or in wild type mice (0 foci/cell). Serial SPECT imaging revealed a 7-fold increase in 111In-anti-γH2AX-Tat accumulation in mammary fat pads in mice 80-110 days old (up to 8.5 %ID/g), compared to non-specific control (P=0.0007), but not in younger or older mice (P&amp;gt;0.05). Repeated SPECT imaging itself did not influence tumor occurrence (P&amp;gt;0.05). The median time to detection of positive tissue was 96 days, much sooner than detection of lesions &amp;gt;150 μm by DCE-MRI (117 days), or palpation (130 days) (P&amp;lt;0.0001). Conclusion: Using a γH2AX-targeted radiopharmaceutical, we were able to image the DNA damage response during neuT-mediated oncogenesis in balb/neuT mice. DDR imaging identified neoplastic tissue significantly earlier than anatomical imaging. These results suggest that γH2AX imaging has potential as a screening tool for cancer-prone individuals. Citation Format: Bart Cornelissen, Sarah Able, Veerle Kersemans, Katherine A. Vallis. Imaging DNA damage response (DDR) during oncogenesis. [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 1062. doi:10.1158/1538-7445.AM2013-1062
ANÁLISIS RETROSPECTIVO DE 52 CASOS DE DRENAJE ENDOSCÓPICO GUIADO POR USE DE PSEUDOQUISTES Y ABSCESOS PANCREÁTICOS.
Authors: M Medina Cruz, R Romero Castro, F Argüelles Arias, FJ Romero Vázquez, M Jiménez Sáenz, FJ Pellicer Bautista, A Caunedo Álvarez, JM Herrerías Gutiérrez
Journal: Endoscopy (2012)

Objetivo: Evaluar a corto y largo plazo los resultados obtenidos con esta técnica en nuestro Centro. Pacientes: Todos los pacientes intervenidos endoscópicamente para el drenaje de estas colecciones en nuestro hospital entre octubre de 2005 y a julio de 2012 se incluyeron en este estudio. Se excluyeron lesiones quísticas primarias del páncreas y la necrosis sin pared en el contexto de pancreatitis aguda grave. Técnica endoscópica: Realizamos un drenaje guiado por eco-endoscopia, utilizando una aguja de 19 G o un cistostomo, asociado a una corriente de corte de 100–120 W para crear la comunicación entre la colección y la luz intestinal, con limpieza de la colección y colocación posterior de prótesis plásticas. Resultados: Se trataron 52 pacientes con pseudoquistes (n=31) y abscesos pancreáticos (n=21), según la clasificación de Atlanta. El 69,23% eran varones y el 30,76%, con una media de edad de 56 años. El diámetro medio de las colecciones drenadas fue de 9,415cm. Respecto a las prótesis utilizadas, la más frecuente es la doble pigtail de 10 Fr 4cm para pseudoquistes y de 3cm para absceso, siendo el número medio de prótesis por procedimiento de 1,8. El porcentaje de resolución de la colección fue del 87,09% para los pseudoquistes (27/31) y del 76,19% (16/21) ara los abscesos. La tasa de fracaso de la terapéutica endoscópica fue del 15,38% (9/52), recurriendo a la cirugía de forma electiva dentro de 7días posteriores a la misma. Las complicaciones más frecuentes fueron la hemorragia, la perforación y la pérdida de las prótesis (11,53%, 7,69% y 5,76%, respectivamente), controlándose la mayoría de las mismas de forma conservadora. El 82% de los pacientes se encontraban asintomáticos al tercer mes del tratamiento, con reducción o desaparición de la colección en la TAC de control. Este porcentaje de pacientes se mantuvo asintomático durante todo su seguimiento. Conclusiones: El drenaje endoscópico de las colecciones pancreáticas es una técnica segura y eficaz para el tratamiento de dichas colecciones, con una tasa aceptable de complicaciones.
FRI0388 Us lung examination in ssc patients: could we simplify it?
Authors: A. Delle Sedie, P. Pepe, C. Lodato, E. Cioffi, L. Carli, S. Bombardieri, L. Riente
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic sclerosis (SSc) is a disease characterized by a progressive fibrosis of the skin and internal organs, which can lead to death. Lung involvement includes a wide range of disorders and interstitial lung disease (ILD) is the most common manifestation, being clinically significant in about 40% of patient. Recently, the role of US in the assessment of ILD (counting the B-lines, generated by the reflection of the US beam from thickened sub-pleural interlobar septa) has been confirmed after comparison with high-resolution computed tomography (HRCT) and a few scoring systems proposed. The comprehensive examination of lung intercostal spaces (LIS) is time consuming (54 LIS in each patient) and a previous attempt to give a simplified US B-line scoring system has been done in connective tissue diseases patient (1). <h3>Objectives</h3> To investigate which LIS are more frequently involved in SSc patients, with and without ILD, in order to find a reduced number of LIS to scan using US. <h3>Methods</h3> Seventy-nine SSc patients were enrolled independently of the presence of any dispnoea. Each patient underwent a lung US with comprehensive US B-line assessments by an experienced rheumatologist. A cut-off of &gt;12 B-lines was decided based on the correlation between US and HRCT in 76 patients, then US was performed alone in the rest of the SSc patients. The presence/absence of B-lines was registered in each LIS. <h3>Results</h3> A highly significant correlation between US assessment and HRCT was found (ICC=0.576; sensitivity and specificity were 81 and 73%, respectively). Single LIS significantly correlates to the diagnosis of ILD + in 41/54. In a multivariate analysis, even examining only 2 LIS, sensitivity and specificity of the US, with respect to the comprehensive scan, remains high (93.5 and 81.4%, respectively). <h3>Conclusions</h3> Most of single LIS significantly correlate to the presence of ILD. Even scanning only the 5<sup>th</sup> right emiclavear and the 3<sup>rd</sup> left parasternal LIS, sensitivity and specificity of US examination remains high. <b>References:</b> Gutierrez M, Salaffi F, Carotti M et al. Arthritis Res Ther 2011;13(4):R134. <b>Disclosure of Interest</b>: None Declared
NHS agency takes out private prosecution against mentally ill patient who hit healthcare assistant
Authors: C. Dyer
Journal: BMJ (2013)

A psychiatric inpatient who knocked unconscious a healthcare assistant at an NHS hospital has been given a section 37 hospital order and ordered to pay £75 (€90; $120) compensation to the victim, whose jaw was dislocated. 

Prosecutions of psychiatric inpatients are rare because of the problem of establishing that someone who is mentally ill enough to be in hospital is responsible for his or her actions.

Ronald Ashworth, 35, pleaded guilty to causing actual …
1169 HEALTH-RELATED QUALITY-OF-LIFE AMONG GENOTYPE 1 TREATMENT-NAIVE CHRONIC HEPATITIS C PATIENTS RECEIVING TELAPREVIR COMBINATION TREATMENT: POST-HOC ANALYSES OF DATA FROM THE ADVANCE TRIAL
Authors: Z. Younossi, J. Aggarwal, M. Martin, N. Hernandez, M. Donepudi, M. Bayliss, T. Goss, M. Vera-Llonch
Journal: Journal of Hepatology (2012)