tbuckley/cabot-search huggingface dataset:
SAT0261 Which Conventional DMARD to Select in the Treatment of Psoriatic Arthritis (PSA)? Data From Nor-Dmard on 1351 Treatment Courses with Methotrexate (MTX), Sulfasalazine (SSZ) And Leflunomide (LEF)
Authors: E. Lie, K. M. Fagerli, E. Rødevand, S. Kalstad, K. Mikkelsen, A. Wierød, D. van der Heijde, T. K. Kvien
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> MTX is probably the most commonly used DMARD to treat PsA wordwide and a recommended treatment for patients with active disease (1). In a recent publication of a negative placebo-controlled randomised trial of MTX in PsA, it was suggested that the sequencing of conventional DMARDs before biologics should be re-evaluated (2). <h3>Objectives</h3> To assess the pattern for use of conventional DMARDs in PsA, and to compare the effectiveness of MTX, SSZ and LEF in a longitudinal observational study (LOS). <h3>Methods</h3> Data were extracted from NOR-DMARD, a LOS of arthritis patients starting a new DMARD treatment, with follow-up at 3, 6, 12 months and then yearly. Patients diagnosed with PsA and starting treatment with MTX, SSZ or LEF were identified. We studied baseline characteristics and treatment responses (3 &amp; 6 months) overall, and performed statistical comparisons between treatments including individual patients only. For the latter, the first inclusion per patient was selected. Unadjusted comparisons were done by ANOVA, Kruskall-Wallis or Chi<sup>2</sup> test, as appropriate, and analyses with adjustment for important baseline differences were performed by ANCOVA and logistic regression analysis. <h3>Results</h3> A total of 1351 prescriptions of MTX (n=1000), SSZ (n=212) and LEF (n=139) in 1212 individual patients were identified – 128 patients were registered with ≥2 of the drugs and 11 patients with all 3 drugs. Among MTX/SSZ/LEF patients 71% vs. 61% vs. 6.5% were DMARD naïve, respectively, and 47% of patients on LEF had failed both MTX and SSZ. Patients treated with LEF also had longer disease duration. Mean baseline DAS28 for MTX/SSZ/LEF was 4.2/4.0/4.3, respectively. The baseline characteristics across groups for the first inclusion per patient (MTX n=949, SSZ n=177, LEF n=86) were very similar (baseline DAS28 4.2/3.9/4.3 for MTX/SSZ/LEF, respectively). Selected 6-month outcomes are shown in the table. Responses were numerically similar for the overall group of patients (n=1351). Comparison of 3-month responses yielded similar results. 2-year drug survival was superior for MTX (0.71) vs. SSZ (0.40; HR 1.96; p&lt;0.001) and LEF (0.29; HR 2.47, p&lt;0.001), with no significant difference between SSZ and LEF. <h3>Conclusions</h3> MTX was the most commonly used first-line DMARD while LEF was rarely used as a first-line DMARD. Effectiveness was generally similar, but MTX performed better for some measures, including drug survival. <h3>References</h3> Gossec L et al, Ann Rheum Dis 2012;71:4-12. Kingsley G et al, Rheumatology 2012;51:1368-77. <h3>Disclosure of Interest</h3> None Declared
FRI0362 Contrast-enhanced ultrasound of the sovraortic arteries: the potential role in monitoring disease activity and response to treatment in large vessel vasculitis.
Authors: G. Germanò, P. Macchioni, N. Possemato, O. Addimanda, C. Salvarani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Promising data has been recently published about the role of contrast-enhanced ultrasound (CEU) in the diagnosis and follow up of Takayasu arteritis (TA) -1,2- <h3>Objectives</h3> To assess the role of CEU examination of the carotid artery in patients with large vessel vasculitis (LVV) compared to Positron Emission Tomography (PET). <h3>Methods</h3> 10 patients (8 TA,2 LVV, mean age 46±19y, mean disease duration 3.9±3.1y ) were contemporary evaluated with total body PET and carotid arteries US gray scale and CEU (Esaote MyLab70, 13-5MH linear probe, contrast agent Sonovue). All the patients underwent complete clinical examination and laboratory determination of acute phase reactants. Imaging results were reported using a semiquantitave score ranging from 0 (no activity) to 3 (high activity). Comparison between the two tests were made using Cohen K test. <h3>Results</h3> At US gray scale examination 8/10 patients have high intima/media thickness (mean 1,5 mm ±0.46). In patients with positive contrast enhanced ultrasound themean carotid intima-media thickness was 2,1mm ±0.48, while patients withnegative contrast enhanced ultrasound presented a mean wall thickness of 0,9mm ±0.47 (P = 0.009). There was no significant differences in clinical, demographic and laboratory data between patients with active and inactive disease. All the 4 patients with high/medium carotid activity at PET examination presented positive (activity score &gt;1) CEU. Five of the 6 patients with low/absent PET signal have negative (activity score &lt;2) CEU (K test = 0.800, good concordance). <h3>Conclusions</h3> CEU have a good concordance with PET. These results outline the potential role of CEU to be used in monitoring disease activity and response to treatment in LVV. <h3>References</h3> Magnoni M. et al.; Assessment of Takayasu arteritis activity by carotid contrast-enhanced ultrasound. Circ Cardiovasc Imaging. 2011 Mar;4(2):e1-2. Giordana P et al.; Contrast-enhanced ultrasound of carotid artery wall in Takayasu disease: first evidence of application in diagnosis and monitoring of response to treatment. Circulation. 2011;124:245-7. <b>Disclosure of Interest</b>: None Declared
Diagnostic Significance of Endoscopic Ultrasonography in Patients with Lower Gastrointestinal Submucosal Tumors
Authors: S Haruki, K Kobayashi, M Kida, K Yokoyama, M Sada, T Katsumata, K Saigenji
Journal: Endoscopy (2006)

Objectives: The aim of this study was to evaluate the diagnostic significance of endoscopic ultrasonography (EUS) in patients with lower gastrointestinal submucosal tumors. Methods: Study subjects were 33 lesions of submucosal tumor in the lower gastrointestinal tract examined by EUS. All lesions were also diagnosed histopathologically by endoscopic biopsy, endoscopic polypectomy, or surgical operation. We examined the internal echo levels and echo patterns, as well as the sites of tumors in the intestinal wall by EUS. Results: 1) Lower gastrointestinal submucosal tumors included 9 malignant lymphomas, 9 lipomas, 5 gastrointestinal stromal tumors or leiomyomas, 5 mucoceles of the appendix, 3 lymphangiomas, and 2 granular cell tumors. 2) Six malignant lymphomas (67%) involved all layers of the intestinal wall. The internal echo was hypoechoic to isoechoic, with a homogeneous pattern. 3) All lipomas were present in the third layer (submucosa). Eight lipomas (89%) had a hyperechoic internal echo, with a homogeneous pattern. 4) As for gastrointestinal stromal tumors or leiomyomas, 4 lesions (80%) were seen mainly in the fourth layer (muscularis propria). The internal echo was hypoechoic in all lesions. Four (80%) of these lesions showed punctual or macular hyperechoic patterns. 5) Most mucoceles of the appendix involved mainly the third layer. The internal echo was hypoechoic to isoechoic. Four (80%) of these lesions showed punctual or macular hyperechoic patterns. 6) All lymphangiomas were situated mainly in the third layer. The internal echo was anechoic, with septums. 7) Granular cell tumors were seen mainly in the third layer. The internal echo was hypoechoic. Conclusions: EUS may be useful for the qualitative assessments of lower gastrointestinal submucosal tumors, as well as the evaluation of tumor location in the intestinal wall.
Treating insomnia
Authors: Anne M Holbrook
Journal: BMJ (2004)

<h3>ABSTRACT</h3> <h3>Background</h3> There is growing awareness that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can include long-term neuropsychological deficits, even in its mild or moderate respiratory forms. <h3>Methods</h3> Standardized neuropsychological, psychiatric, neurological and olfactory tests were administered to 45 patients (categorized according to the severity of their respiratory symptoms during the acute phase) 236.51 ± 22.54 days post-discharge following SARS-CoV-2 infection. <h3>Results</h3> Deficits were found in all the domains of cognition and the prevalence of psychiatric symptoms was also high in the three groups. The severe performed more poorly on long-term episodic memory and exhibited greater anosognosia. The moderate had poorer emotion recognition, which was positively correlated with persistent olfactory dysfunction. The mild were more stressed, anxious and depressed. <h3>Conclusion</h3> The data support the hypothesis that the virus targets the central nervous system (and notably the limbic system), and support the notion of different neuropsychological phenotypes.
Synchronous Second Primary Neoplasms Detected by Initial Staging F-18 FDG PET/CT Examination in Patients With Non-Hodgkin Lymphoma
Authors: Tomáš Papajík, Miroslav Mysliveček, Zuzana Šedová, Eva Buriánková, Vít Procházka, Luděk Raida, Zuzana Kubová, Čestmír Neoral, David Starostka, Petr Mikula, Bohuslav Melichar, Ladislava Kučerová, Martin Tichý, Karel Indrák
Journal: Clinical Nuclear Medicine (2011)

Cases of synchronous non-Hodgkin lymphoma (NHL) and second primary carcinoma in previously untreated immunocompetent patients are relatively rare. The aim of this part of our prospective study was to a revealed 2-F-18 fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission tomography (PET)-positive lesion in an extranodal organ suggestive of second primary neoplasm in newly diagnosed NHL patients.A total of 209 patients with NHL underwent initial staging F-18 FDG PET/computed tomography (CT). The finding was assessed by a radiologist, nuclear medicine physician, and hematologist. In 6 suspicious cases (2.9%) of second neoplasm, the decision was made to perform further investigations before lymphoma therapy.Two patients were diagnosed with colorectal carcinoma, 1 with esophageal adenocarcinoma, 1 with invasive ductal breast carcinoma, 1 with medullary thyroid carcinoma, and 1 with squamous cell lung carcinoma. In 5 of the 6 patients, the second solid tumor was completely asymptomatic and revealed only by F-18 FDG PET/CT examination.We conclude that in patients with NHL, appropriate imaging, clinical, and histologic analysis of organ lesions detected by F-18 FDG PET/CT will occasionally demonstrate significant synchronous neoplasms.
Abstract 1391: Cellular and molecular bases of susceptibility to estrogen-induced mammary cancer in the rat.
Authors: Lina Ding, Yang Zhao, Christopher Warren, James Shull
Journal: Cancer Research (2013)

Abstract Known breast cancer risk factors include a family history of breast cancer, cumulative exposure to endogenous and exogenous estrogens and breast mammographic density. Although several genes have been identified that significantly impact risk when mutated or aberrantly expressed, the genetic determinants of responsiveness to estrogens and mammographic density remain poorly defined. We are using the ACI rat model of 17β-estradiol (E2)-induced mammary cancer to identify genetic and environmental determinants of susceptibility to mammary cancer. When treated continuously with physiologic levels of E2, female ACI rats develop mammary carcinoma at an incidence approaching 100%. The mammary cancers that develop in E2 treated ACI rats express estrogen receptor-α (ERα) and progesterone receptor (PgR) and are dependent upon E2 for continued growth. By contrast, Brown Norway (BN) rats are highly resistant to E2-induced mammary cancer. The purpose of this study was to compare the impact of E2 treatment on mammary gland biology in susceptible ACI and resistant BN rats. Dramatic differences in numerous cellular and molecular responses to E2 were observed when these two inbred rat strains were compared. Whereas the mammary epithelium of susceptible ACI rats exhibited a marked proliferative response to E2, the epithelium of resistant BN rats exhibited responses associated with differentiation to secretory epithelium. Strain differences in expression of multiple genes associated with mammary epithelial cell proliferation and differentiation were observed. Specifically, Areg, Pgr, Wnt4 and Tnfsf11 were highly expressed in mammary glands of E2 treated ACI rats, relative to treated BN rats, whereas Lcn2, Spp1, Cd44, Mmp7 and Mmp9 were highly expressed in mammary glands of BN rats, relative to ACI rats. This study provides novel insight into the molecular bases of inherited susceptibility to E2-induced mammary cancer. We further propose that the observed strain differences in mammary gland responsiveness to E2 represent phenotypes that underlie variation in mammographic density in humans and may have the potential to serve as biomarkers that predict breast cancer risk. Citation Format: Lina Ding, Yang Zhao, Christopher Warren, James Shull. Cellular and molecular bases of susceptibility to estrogen-induced mammary cancer in the rat. [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 1391. doi:10.1158/1538-7445.AM2013-1391
Cutaneous and Gastrointestinal Purpura
Authors: Genki Naruse, Kota Shimada
Journal: New England Journal of Medicine (2013)

A 38-year-old previously healthy man presented with progressive rash, abdominal pain, arthralgia, and low-grade fever of 2-weeks' duration despite treatment with oral prednisolone. Physical examination showed diffuse abdominal tenderness and palpable purpura distal to the knees.
P7 Are we screening survivors of pulmonary embolism (PE) for chronic thromboembolic pulmonary hypertension (CTEPH)?
Authors: M. Wilczynska, K. Taylor
Journal: Thorax (2011)

<h3>Background</h3> Incidence of CTEPH following idiopathic PE has been reported as 4%. The British Thoracic Society recommends that patients with massive or submassive PE should undergo echocardiography 6–12 weeks following the index event. <h3>Aim</h3> To investigate local practice in the follow-up of patients with acute PE to devise management guidelines. <h3>Methods</h3> A retrospective study of 110 patients diagnosed with acute PE at our hospital between 2007 and 2008 was conducted. Mean age was 68.6 years (range 27–100), 40 (36%) were male and 18 (16%) had previous venous thromboembolism. In 51 (46%) patients PE was idiopathic. <h3>Results</h3> All patients diagnosed with PE were normotensive and 27 (25%) had in-patient echocardiography (ECHO). In 5 (18%) patients scan confirmed RV dilatation and 2 of them had repeated ECHO within 2 months. Subsequently one patient was diagnosed with CTEPH and underwent pulmonary endarterectomy. In the group of patients with acute PE but without in-patient echocardiography 40 of 83 (48%) received a follow-up appointment (mean 4 months) and 10 (25%) had follow-up ECHO. Two more patients were diagnosed with CTEPH during this period (mean 34 months) with an overall incidence of 2.9%. <h3>Conclusion</h3> Recorded outcome, literature review and the BTS/ERS guidelines resulted in the development of local protocol for the screening acute PE survivors for CTEPH. [Abstract P7 figure 1].
Abstract C29: Periostin, a regulator of adhesion, is a novel effector of tumor invasion
Authors: Gabrielle Wong, Carmen Z. Michaylira, Charles G. Miller, Christie M. Gutierrez, Douglas B. Stairs, Jiri Kalabis, Hiroshi Nakagawa, Alan J. Diehl, Meenhard Herlyn, Anil K. Rustgi
Journal: Cancer Research (2009)

Abstract Squamous cell cancers in aggregate comprise the most common forms of epithelial cancers, arising from the skin, head/neck, oral cavity, esophagus, lung and anogenital tract, and they share a number of environmental exposures and genomic alterations. A prototype of this cancer is esophageal squamous cell carcinoma (ESCC), which is associated with a high mortality rate worldwide. Local invasion and metastasis are important factors which influence patient survival. Amongst the frequent oncogene alterations are EGFR and cyclin D1 overexpression, and that in tumor suppressor genes are p53 mutation and p120-catenin loss or mislocalization. However, the functional interplay between these genetic alterations contributing to cancer progression remains unclear. Our previous studies have addressed this by presenting a tumor microenvironment model for tumor cell invasion using a 3D organotypic culture system and transformed human esophageal cells overexpressing EGFR and mutant p53 (Genes and Development 2007). From this, we have now utilized laser capture microdissection (LCM) and microarray analysis to identify novel targets of EGFR overexpression and mutant p53 by comparing gene expression of invading versus non-invading transformed cells. Results from these studies reveal a marked upregulation of periostin, a gene involved in cell adhesion, whose expression is restricted to invading tumor cells, as validated by qPCR, immunohistochemistry and Western blot. Furthermore, its expression was found to be upregulated in human esophageal cancer compared to normal esophagus. Using genetic approaches, gain-of-function of periostin fosters tumor cell invasion, whereas silencing of periostin markedly attenuates tumor cell invasion. Bioinformatic analyses reveal that periostin is upregulated in other human squamous cell cancers as well. Promoter studies assessing the transcriptional regulation of periostin upon EGFR overexpression and p53 mutation have been done. Our novel findings indicate periostin induction upon convergence of EGFR signaling and p53 mutation provides a cue for tumor cell invasion in the tumor microenvironment, and that it may be part of tumor invasion signature in squamous cell cancers in general. This work was supported by P01-CA098101, NIH/NRSA F32-DK075230 and T32 CA115299. Citation Information: Cancer Res 2009;69(23 Suppl):C29.
Abstract 1616: Survivin regulates endothelial cell proliferation, survival and angiogenesis.
Authors: Cath Eberlein, Grace Opoku-Ansah, James Legg, Tim London, Frank Gebhardt, Gareth Davies, Natalie Tigue, Matthew McCourt, Julia White, Darren Cross, Ute Schaeper, Viia E. Valge-Archer
Journal: Cancer Research (2013)

Abstract Background - Survivin is a member of the inhibitor of apoptosis protein (IAP) family, and is reported to be overexpressed in a number of human cancers with high unmet medical need including breast, non-small-cell lung (NSCLC), colorectal, gastric, glioblastoma, and pancreatic cancers. Multiple studies have described survivin as a key regulator of tumour cell proliferation, survival and drug resistance, which has led to the advancement of survivin inhibitors, including antisense and small molecule drugs, and cancer vaccines, into clinical testing. In the tumour micro-environment, survivin overexpression has also been reported in tumour blood vessels and conditional deletion of survivin in endothelial cells results in murine embryonic lethality secondary to haemorrhage and defective vascular development. We therefore hypothesised that inhibition of survivin function in endothelial cells could have anti-angiogenic or vascular disruptive effects. Methods and Results - To better understand the role of survivin in primary endothelial cells we designed siRNAs capable of targeting multiple isoforms of human survivin. Using high content imaging assays we demonstrated that the siRNA were highly selective for survivin, inhibited the expression of multiple survivin splice variants, and had potent in vitro effects on endothelial cells. Survivin knockdown resulted in inhibition of cell cycle progression with the formation of enlarged, multi-nucleated cells, and in reduced endothelial cell survival. Survivin knockdown also impaired the formation of tube-like networks in vitro when co-cultured with human fibroblasts, but did not disrupt more established networks. Conclusion These data show an important role for survivin in primary endothelial cells, and suggest that targeted inhibition of survivin may have anti-angiogenic effects, but may not disrupt more established blood vessels. Citation Format: Cath Eberlein, Grace Opoku-Ansah, James Legg, Tim London, Frank Gebhardt, Gareth Davies, Natalie Tigue, Matthew McCourt, Julia White, Darren Cross, Ute Schaeper, Viia E. Valge-Archer. Survivin regulates endothelial cell proliferation, survival and angiogenesis. [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 1616. doi:10.1158/1538-7445.AM2013-1616
AB1319 Examination of determinants of patient preferences for total knee replacement (TKR) among men and women:
Authors: C.K. Kwoh, Y. Cloonan, R. Boudreau, M. Hannon, E. Vina, S. Ibrahim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Elective TKR is an effective treatment option for end-stage knee osteoarthritis (OA) that is rapidly growing. Although women have as much or greater prevalence of knee OA than men, men undergo TKR more often than women. Patient preference is emerging as an important consideration in TKR gender disparities. However, few studies have examined the determinants of patients' preference in a racially diverse sample of men and women. <h3>Objectives</h3> We sought to identify whether determinants of patients' preference for TKR differ by gender. <h3>Methods</h3> Our sample consisted of 509 women (59% white) and 290 men (73% white) with chronic, frequent knee pain and radiographic evidence of knee OA. We used logistic regression models, stratified by gender, to identify clinical and socio-cultural determinants of patients' preference for TKR. Clinical and socio-cultural factors were entered simultaneously into the stratified models. Stepwise selection methods were used to select socio-cultural items to be included in the final models, using a criterion of p&lt;0.20. All models were adjusted for age, income level, disease severity (using the WOMAC), and study site. <h3>Results</h3> White women had lower preference for TKR compared to white men (adjusted OR=0.56, 95%CI 0.34 to 0.94), whereas African-American (AA) women had higher preference for TKR compared to AA men (adjusted OR=1.24, 95%CI 0.70 to 2.18). Among women, items related to knowledge (p&lt;0.001) and expectations (p=0.007) regarding surgical outcomes, and religiosity (p=0.045) were selected for inclusion in the multivariate model. Among men, items related to knowledge (p=0.46) and expectations regarding surgical outcomes (p=0.027) were selected for inclusion in the multivariate model (see Table 1). <h3>Conclusions</h3> Expectations regarding surgical outcomes are important for both men and women with regard to their preferences for TKR, but the genders differ with regard to which other socio-cultural determinants impact these preferences. Interventions to reduce or eliminate gender disparities in the utilization of TKR should consider and target these factors. <h3>Disclosure of Interest</h3> None Declared