tbuckley/cabot-search huggingface dataset:
FRI0147 IgG4 antibody response upon long term treatment with adalimumab
Authors: P. van Schouwenburg, C. Krieckaert, M. Nurmohamed, T. Rispens, L. Aarden, D. Wouters, G. Wolbink
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A substantial part of the rheumatoid arthritis (RA) patients is chronically treated with adalimumab. Some of these patients produce antibodies against adalimumab, which correlate with lower serum drug levels and reduced clinical response. Long term exposure to antigens may result in antigen specific IgG4 production as demonstrated in previous studies on prolonged exposure to antigens such as bee venom, factor VIII and IFN-β. <h3>Objectives</h3> Here we investigate whether long term treatment of RA patients with the therapeutic monoclonal antibody adalimumab leads to the production of specific IgG4 antibodies. <h3>Methods</h3> We developed radio immunoassays to detect total IgG or IgG4 against adalimumab and applied these in a cohort of 272 RA patients during three years of adalimumab treatment. <h3>Results</h3> Of the 272 patients 32% developed antibodies against adalimumab. We observed that a fast majority of the patients also produce IgG4 antibodies against adalimumab (29%). The proportion IgG4 of total IgG against adalimumab varies widely between patients (median; 25-75 percentile 38; 21-67%). In some patients the antibody response even seems to be dominated by IgG4. <h3>Conclusions</h3> The role of IgG4 in the immune response against adalimumab is variable in adalimumab treated RA patients. Although IgG4 is often considered to be harmless, because of its lack of effector function, these patients show low adalimumab levels and reduced clinical response. <h3>Disclosure of Interest</h3> None Declared
139 AN UNFAVORABLE INTERACTION BETWEEN DONOR AGE AND LATENT RECIPIENT CYTOMEGALOVIRUS (CMV) INFECTION AFTER LIVER TRANSPLANTATION (LT): INSIGHTS FROM THE LIVER MATCH STUDY
Authors: M. Angelico, T. Marianelli, S. Ginanni Corradini, C. Gavrila, L. Miglioresi, D. Sforza, G.M. Ettorre, G. Gerunda, M. Rossi, G. Tisone, A. Nardi
Journal: Journal of Hepatology (2013)
ROLE OF PERICARDIAL DELAYED HYPERENHANCEMENT IN PREDICTING CLINICAL RESOLUTION AMONG PATIENTS WITH RECURRENT PERICARDITS
Authors: Arnav Kumar, Edlira Yzeiraj, Lin Lin, Kimi Sato, Jorge Betancor, Srikanth Koneru, Steven Assalita, Paul Cremer, Balaji Tamarappoo, Allan Klein
Journal: Journal of the American College of Cardiology (2016)
B-TYPE NATRIURETIC PEPTIDE LEVELS IN PATIENTS WITH PERICARDIAL EFFUSION UNDERGOING PERICARDIOCENTESIS
Authors: Nicola Cosentino, Gianfranco Lauri, Chiara Rossi, Mara Rubino, Valentina Milazzo, Ivana Marana, Marco Moltrasio, Monica De Metrio, Marco Grazi, Jeness Campodonico, Giancarlo Marenzi
Journal: Journal of the American College of Cardiology (2016)
...but "quasirandom allocation" of treatment was reported in 1930
Authors: M. Clarke
Journal: BMJ (1996)

EDITOR,—P D'Arcy Hart rightly points out1 that the history of controlled clinical trials predates the publications in 1948 of the Medical Research Council's trial of streptomycin2 and the Dutch trial of paludrine in malaria.3 In their study Carla van der Wijden and John A Overbeke do not seem to have searched issues of Nederlands Tijdschrift voor Geneeskunde before that year,4 and, if that is so, it is not surprising that they did not find any randomised trials. …
962 HEPATOCELLULAR CARCINOMA DOES NOT SIGNIFICANTLY CONTRIBUTE TO THE RISK OF HEPATOBILIARY MALIGNANCY IN CIRRHOTIC PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS
Authors: R. Zenouzi, T. Weismüller, P. Hübener, K. Schulze, M. Bubenheim, M.P. Manns, A.W. Lohse, C. Schramm
Journal: Journal of Hepatology (2013)
A2.01 The expansion of CD25<sup>high</sup>IL-10<sup>high</sup>FOXP3<sup>high</sup>B regulatory cells is in association with sle disease activity
Authors: E Toubi, Z Vadasz
Journal: Annals of the Rheumatic Diseases (2016)

<h3></h3> B regulatory cells (Bregs) belong to a subgroup of activated B cells tasked with maintaining self-tolerance and preventing autoimmunity. While sharing similar regulatory mechanisms such as IL-10 dependency, they also defer in exhibiting their suppressive effects by expressing Fas-Ligand, TGF-beta and PDL-1. In this study we show, for the first time, the expansion of CD25<sup>high</sup>FoxP3<sup>high</sup> Bregs in systemic lupus erythematosus (SLE) patients compared to healthy individuals (18.5 ± 3.052% vs 11.0 ± 1.654%, p &lt; 0.001, respectively). This expansion was also shown to correlate with SLE disease activity (r = 0.75). In addition, CD25<sup>high</sup>FoxP3<sup>high </sup>Bregs were also IL-10<sup>high</sup> expressing, and further expanded when stimulated with semaphorin3A. In sum we show that CD25<sup>high</sup>FoxP3<sup>high</sup> are an additional subtype of Bregs, involved in regulating SLE disease activity. Being IL-10 expressing, we may assume that they are one of the sources of increased serum IL-10 in SLE patients. Further studies are required in order to assess the relation between high serum IL-10 and CD25<sup>high</sup>Foxp3<sup>high</sup> Breg cells.
P17.61 * ANTI-TUMOR EFFECTS OF S14161 IN GLIOBLASTOMA CELLS
Authors: H. Nakabayashi, R. Fushitani
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma is the most common and aggressive form of malignant glioma and is very difficult to treat. Controlling glioblastoma cell invasion and angiogenesis is essential to improve the prognosis of glioblastoma patients. It has been reported that the phosphoinositide 3-kinase (PI3K) inhibitor exhibits potent antiumor effects to malignant tumors. The small chemical compound 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene (S14161) was recently identified as an inhibitor of PI3K. Our study aimed to evaluate the antitumor effects of S14167 on two human glioblastoma cell lines (U87MG, T98G) and the molecular mechanisms underlying these effects. METHODS: The anti-invasive effect of S14161 was analysed by an in vitro invasion assay. An in vitro angiogenesis assay was also performed. In vitro growth inhibition of glioblastoma cells by S14161 was determined by the WST-1 assay. The anti-angiogenic effect of S14161 was analysed by an in vitro angiogenesis assay. RESULTS: S14161 suppressed the proliferation of glioblastoma cells. S14161 also suppressed both the invasion of glioblastoma cells and tumor-induced angiogenesis. Molecular-based studies demonstrated that S14161 suppressed gene and protein expression of angiogenic factors. CONCLUSIONS: The results of the present study suggest that S14161 may be a new therapeutic agent for glioblastomas.
Abstract AACR1-1: Synthetic Lethal Approaches to Cancer Therapy
Authors: A Ashworth
Journal: Cancer Research (2010)

Abstract A critical link exists between genomic instability and cancer development. This instability can manifest as small changes at the nucleotide level or as gross chromosomal alterations. Mutations in the genes that encode DNA damage response proteins are responsible for a variety of genomic instability syndromes including Hereditary Non-Polyposis Colorectal Carcinoma, Bloom syndrome, Ataxia-telangiectasia, BRCA1 and BRCA2 mutated breast and ovarian cancers and Fanconi anaemia. Similarly epigenetic silencing of genes associated with the maintenance of genomic stability have also been implicated in the pathogenesis of cancer. Here, I discuss how different tumours may be classified not only by tumour site but also by the type of underlying genetic instability. This type of classification may assist in the optimization of treatment regimens as well as informing the development of new therapeutic approaches in particular based on “synthetic lethality”. I will illustrate these principles by demonstrating potential “synthetic lethal” treatments for mismatch repair deficient cancers. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr AACR1-1.
ASSOCIATION OF SMOKING STATUS WITH HEALTH-RELATED OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTION
Authors: Jae-Sik Jang, Donna Buchanan, Kensey Gosch, Philip Jones, Praneet Sharma, Ali Shafiq, Anna Grodzinsky, Timothy Fendler, Garth Graham, John Spertus
Journal: Journal of the American College of Cardiology (2015)
Transient Memory Impairment and Hallucinations Associated with Tolterodine Use
Authors: Jack W. Tsao, Kenneth M. Heilman
Journal: New England Journal of Medicine (2003)

To the Editor: Although anticholinergic medications are widely used to treat urinary incontinence in the elderly, the fact that their use may be associated with memory loss and visual hallucinations has not been well recognized, and these complications may therefore be incorrectly attributed to a degenerative dementia (e.g., Lewy body dementia).1 We report the case of a 73-year-old woman who presented with a two-year history of decreased short-term memory and vivid hallucinations of deceased relatives that occurred only during nighttime sleep; she awoke regularly to converse with these relatives. The symptoms began several weeks after she began to take tolterodine . . .
Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance
Authors: Hisamichi Naito, Taku Wakabayashi, Hiroyasu Kidoya, Fumitaka Muramatsu, Kazuhiro Takara, Daisuke Eino, Keitaro Yamane, Tomohiro Iba, Nobuyuki Takakura
Journal: Cancer Research (2016)

Abstract Angiogenesis plays a crucial role in tumor growth, with an undisputed contribution of resident endothelial cells (EC) to new blood vessels in the tumor. Here, we report the definition of a small population of vascular-resident stem/progenitor–like EC that contributes predominantly to new blood vessel formation in the tumor. Although the surface markers of this population are similar to other ECs, those from the lung vasculature possess colony-forming ability in vitro and contribute to angiogenesis in vivo. These specific ECs actively proliferate in lung tumors, and the percentage of this population significantly increases in the tumor vasculature relative to normal lung tissue. Using genetic recombination and bone marrow transplant models, we show that these cells are phenotypically true ECs and do not originate from hematopoietic cells. After treatment of tumors with antiangiogenic drugs, these specific ECs selectively survived and remained in the tumor. Together, our results established that ECs in the peripheral vasculature are heterogeneous and that stem/progenitor–like ECs play an indispensable role in tumor angiogenesis as EC-supplying cells. The lack of susceptibility of these ECs to antiangiogenic drugs may account for resistance of the tumor to this drug type. Thus, inhibiting these ECs might provide a promising strategy to overcome antiangiogenic drug resistance. Cancer Res; 76(11); 3200–10. ©2016 AACR.
Crossed Cerebellar Diaschisis Demonstrated by Brain SPECT With Tc-99m MAA in a Child With an Intracardiac Right-to-Left Shunt
Authors: KAZUYOSHI SUGA, NORIHIKO KUME, AYAMI HIRABAYASHI, KEIKO KISHIMOTO, AKIKO HARA, NAOFUMI MATSUNAGA
Journal: Clinical Nuclear Medicine (1999)

A 12-year-old girl with an intracardiac right-to-left shunt associated with asplenia cardiac syndrome had multiple cerebral infarctions caused by thromboembolism in the right internal carotid artery. Tc-99m MAA whole-body imaging and a brain SPECT scan showed reduced radioactivity in the right cerebrum and in the contralateral cerebellum, suggesting the phenomenon of crossed cerebellar diaschisis. Brain SPECT with Tc-99m hexamethylpropylene amineoxime (HMPAO) confirmed this phenomenon, showing a distribution pattern nearly matching that of Tc-99m MAA.
MULTICENTER VALIDATION OF TECHNICAL PERFORMANCE SCORE AS A QUALITY ASSESSMENT TOOL IN CONGENITAL CARDIAC SURGERY
Authors: Meena Nathan, Hua Liu, Steven Colan, Lazaros Kochilas, Geetha Raghuveer, David Overman, Emile Bacha, O Brien James, James St Louis, David Kalfa, Brett Anderson, Marko Vezmar, Kimberlee Gauvreau, Kathy Jenkins, Pedro del Nido
Journal: Journal of the American College of Cardiology (2015)
Abstract 987: XCE853: A novel anticancer candidate preferentially killing drug-resistant human tumor cells.
Authors: Matthieu Gutmann, Jean-François Briand, Gregoire Pierre Prevost, Denis Carniato, Marc-Henry Pitty
Journal: Cancer Research (2013)

Abstract Cancer drug pan-resistance is associated with patients having a disease progression despite receiving new treatments. Often resistance arises in two steps, initially, the tumor responds to the drug, but not all tumor cells are killed leading to a selection of tumor cells that do not respond to any current drug. The nature of the residual disease is linked to different conditions such the efflux pumps, the quiescent cells, the stem cells, the DNA repair deficiency or the EMT. Here, we have identified a family of synthetic compounds displaying a preferential antiproliferative activity on drug resistant human cancer cells. The lead compound XCE853 is 5 to 94 more potent on drug resistant cancer cell lines compared to their parental tumor cell lines (HL60/HL60-Doxorubicin; MCF7/MCF7-Doxorubicin; A2780/A2780-Cisplatin and A549/AA549-Taxotere). XCE853 induced a strong and irreversible cytolysis of MCF7-Adriamycin cells after a short exposure in vitro (250nM, 6 hours). The mechanism of action of XCE853 is independent of efflux pumps and involves an early high ROS production leading to cell death by autophagy. The antitumor activity of XCE853 is also observed using in vivo xenograft models of human NSCLC. Altogether, these data support further efforts on this drug candidate to better understand its molecular mechanism of action and the description of the most sensitive tumor types. Citation Format: Matthieu Gutmann, Jean-François Briand, Gregoire Pierre Prevost, Denis Carniato, Marc-Henry Pitty. XCE853: A novel anticancer candidate preferentially killing drug-resistant human tumor cells. [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 987. doi:10.1158/1538-7445.AM2013-987
Intestinal perforation as a complication of balloon-assisted enteroscopy
Authors: T. Kav
Journal: Endoscopy (2010)

In the May issue of Endoscopy, Aktas et. al. [1] reported the complications of single-balloon enteroscopy (SBE). They found that diagnostic SBE is a safe procedure without any significant complication. They had one perforation that occurred after dilation of a benign stricture. I believe the same as the authors: that SBE is a safe procedure.
POLIPECTOMÍA DE PÓLIPOS GÁSTRICOS. ESTUDIO RETROSPECTIVO DE UNA SERIE DE 20 AÑOS
Authors: S Marín Pedrosa, C García Caparrós, A Hervás Molina, C Carmen Galvez, A González Galilea, C González Alayón, A Naranjo Rodríguez, V García Sánchez, M Pleguezuelo Navarro, L Casáis Juanena
Journal: Endoscopy (2013)

Introducción: Los pólipos gástricos suelen ser un hallazgo incidental, aunque pueden causar anemia crónica o hemorragia digestiva alta. Ante el hallazgo de un pólipo gástrico se recomienda realizar polipectomía o en su defecto toma de biopsias. Objetivos: Conocer las características endoscópicas, anatomopatológicas así como las técnicas de polipectomía en pólipos gástricos. Determinar frecuencia de complicaciones tras polipectomía gástrica endoscópica así como los posibles factores relacionados. Material y Método: Estudio retrospectivo (01 – 1993 a 05 – 2013) de todos los pacientes sometidos a polipectomía gástrica endoscópica. Se recogieron variables demográficas, clínicas y del procedimiento de una base de datos específica para realización y codificación de informes. Análisis con el programa Gstat. Resultados: Se realizaron 312 polipectomías gástricas (0,32% de 96.751 exploraciones). Edad media 64,38 años (rango 14 – 89 años), 58,97% mujeres. 66,35% realizadas en régimen ambulatorio. Tamaño medio de lesiones 9,48 mm. (mediana 6 mm. rango 1 – 80 mm.), localizadas en cuerpo (32,69%), antro (33,33%), siendo 33,97% pediculadas y 36,54% sesiles. Estudio anatomopatológico: pólipos hiperplásicos 58,66%, inflamatorios 5,45% y adenomatosos 5,13% Técnica de polipectomía: asa 57,05%, pinza 31,73%, indeterminado 11,22%. Se realizaron técnicas de profilaxis (inyección solución adrenalina, clips, coagulación argón) en el 30,86%. Hubo 28 (8,97%) complicaciones precoces resueltas mediante endoscopia salvo una y 3 (0,96%) complicaciones tardías, todas hemorragias. No hubo mortalidad. Mayor porcentaje de complicaciones en polipectomías con asa (13,71%, p = 0,001). En análisis univariante: régimen, calidad de exploración, tamaño del pólipo y técnica de polipectomía se correlacionan con complicaciones (OR 3,67 p = 0,0136; 12,21 p = 0,0159; 1,06 p = 0,046 y 0,10 p = 0,0332); en el análisis multivariante la variable relacionada fue tratamiento profiláctico (OR 0,24 p = 0,0397), condicionado por variables confusoras (R2 de Nagelkerke = 0,21 y Curva ROC = 0,791). Conclusiones: La polipectomía gástrica endoscópica es una técnica poco frecuente, con moderada tasa de complicaciones, fundamentalmente hemorragia. El riesgo de éstas disminuye con procedimientos profilácticos.
Evaluation of endoscopic ultrasonography guided fine needle aspiration biopsy of submucosal lesions
Authors: Dong Wenzhu, Yao Ping, Wang Qunying, Song Jian
Journal: Endoscopy (2011)

Objective:To determine the value of endoscopic ultrasonograpy guided fine needle aspiration biopsy for the diagnosis of submucosal tumors in stomach. Methods : We found 42 patients with upper gastrointestinal tract solid submucosal lesions by endoscopies. endoscopic ultrasonograpy was performed to assess the lesions arised from the specific layer of the wall and the lymph node metastasis. After excluding extrinsic normal tissues compressing the gastrointestinal tract, endoscopic ultrasonography guided fine needle aspiration biopsy were carried out. Results: Among these patients four were extrinsic normal tissues compressing the gastrointestinal tract and all other 38 patients were examined by endoscopic ultrasonography guided fine needle aspiration biopsy. endoscopic ultrasonography guided fine needle aspiration biopsy failed in 5 patients. Among the other 33 patients, cytology, pathology and immunohistochemistry demonstrated 4 malignant stromal tumors, 19 benign stromal tumors, 5 ectopic pancreases in stomach, 2 lipomas, 2 cysts in gastric fundus, 1 varice. The results of endoscopic ultrasonography guided fine needle aspiration biopsy were validated by surgery and clinical follow-up. Conclusion: endoscopic ultrasonography guided fine needle aspiration biopsy is a safe and accurate method for diagnosis of submucosal lesions.
THU0413 Magnetic resonance imaging of hands and feet joints of ACPA positive persons without clinical arthritis
Authors: A. Krabben, W. Stomp, L.K.P.M. Brakenhoff, D.M.F.M. van der Heijde, J.L. Bloem, T.W.J. Huizinga, M. Reijnierse, A.H.M. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Until recently, the development of clinical detectable arthritis was considered as the start of Rheumatoid Arthritis (RA). Several studies have revealed that anti-citrullinated peptide antibodies (ACPA) can be present and mature years before arthritis develops and that markers of systemic inflammation and bone degradation are also elevated in the preclinical phase. These data suggest that the process of RA starts earlier than clinical arthritis occurs. It is however unknown whether local subclinical inflammation is present in the preclinical phase. MRI is sensitive in detecting subclinical inflammation. <h3>Objectives</h3> To investigate whether there is subclinical inflammation in painful joints in ACPA-positive arthralgia patients without clinical arthritis. <h3>Methods</h3> Painful hand or feet joints of 15 ACPA positive patients without clinical arthritis were imaged, as well as comparable small joints at a non-painful site. In addition, for further comparisons, small joints of 6 ACPA positive RA patients and 8 persons with inflammatory bowel disease but without arthralgia were evaluated. Imaging was performed on a MSK Extreme 1.5T extremity MRI (GE, Wisconsin, USA). Acquired sequences were coronal T1, coronal T2 fat sat and coronal and axial T1 fat sat after IV Gadolinium-chelate administration. Scoring was performed by two trained readers according to the OMERACT RAMRIS scoring method. The mean scores of the two readers were analyzed. Analyses were performed on joint level (MCP, PIP, wrist or MTP joints). <h3>Results</h3> The mean total RAMRIS score of the MCP/PIP joints in the persons without arthralgia, the painful joints of ACPA-positive arthralgia patients and painful joints of ACPA-positive RA patients were 0.1, 0.8 and 3.7 respectively (Kruskal-Wallis test, p=0.004). The scores of the painful joints and painless joints in ACPA-positive arthralgia patients were strongly correlated (r<sub>s</sub>=0.75) and not different between the groups (mean 1.9 and 2.4, respectively). The mean total RAMRIS scores of the wrist and MTP joints in ACPA-positive arthralgia were 4.2 and 2.1, which was lower than those of RA patients (7.8 and 2.8 respectively). Unfortunately the wrist and MTP joints of the controls were not imaged. <h3>Conclusions</h3> The present data suggest that, when compared to both controls and ACPA-positive RA, patients with arthralgia with ACPA but no clinical arthritis have subclinical inflammation locally at the site of the pain. Furthermore, the non-painful small joints show abnormalities that are comparable in severity to that of the painful joints. <h3>Disclosure of Interest</h3> None Declared
Bacteriobilia and fungibilia are associated with outcome in patients with endoscopic treatment of biliary complications after liver transplantation
Authors: Daniel Gotthardt, Karl Weiss, Christian Rupp, Konrad Bode, Isabella Eckerle, Gerda Rudolph, Janine Bergemann, Petra Kloeters-Plachky, Fadi Chahoud, Markus Büchler, Peter Schemmer, Wolfgang Stremmel, Peter Sauer
Journal: Endoscopy (2013)

<b>Background and study aims:</b> To determine the importance of bacteriobilia and fungibilia in patients with endoscopic treatment of biliary complications after orthotopic liver transplantation (OLT). <b>Patients and methods:</b> In a prospective study at a tertiary center, 213 patients underwent 857 endoscopic retrograde cholangiographies (ERCs) after OLT. Findings at first ERC were: anastomotic stricture in 24.4 %, nonanastomotic stricture in 18.3 %, leakage in 11.3 %, and gallstones in 4.7 %. <b>Results:</b> Bile samples from first ERC showed Gram-positive bacterial isolates in 102/180 (57 %) and Gram-negative in 44/180 (24 %). Main species were <i>Enterococcus </i>spp<i>.</i> (40 %; 72/180) and <i>Escherichia</i> <i>coli</i> (10 %; 18 /180). Enteric bacteria (present in 47 %) and <i>Candida </i>spp<i>. </i>(present in 18 %) were both associated with clinical signs of cholangitis, but not with laboratory signs of inflammation. Multiresistant strains (present in12 % of samples) showed no association with clinical or laboratory parameters. Detection of microbiological isolates was independent of endoscopic findings and treatment. In patients with successful endoscopic intervention, the actuarial survival free of retransplantation was significantly lower in those with detection of enteric bacteria, being 51.8 months (95 % confidence interval [CI] 42.9 – 60.6) vs. 62.9 months (95 %CI 59.1 – 66.7); <i>P</i> = 0.025). Fungibilia was associated with significantly lower actuarial retransplantation-free survival, independently of successful endoscopic treatment (mean 35.1 months [95 %CI 23.5 – 46.7] vs. 53.1 months [(95 %CI 48.0 – 58.2]; <i>P</i> = 0.019). <b>Conclusions:</b> Bacteriobilia and fungibilia can frequently be detected by routine microbiological sampling in patients after OLT. Regular bile sampling is recommended since the presence of difficult-to-treat multiresistant strains is unpredictable. Survival is affected by this altered biliary microbiological environment after OLT.