tbuckley/cabot-search huggingface dataset:
AB0875 Gut inflammation and inflammatory bowel disease serologies in ankylosing spondylitis and rheumatoid arthritis
Authors: E. Soliman, A. Elgerby, M. Zehairy, O. Ebada
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The association between Seronegative spondyloarthropathies(SpA), especially ankylosing spondylitis (AS), and inflammatory bowel disease (IBD) has been previously reported. Anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA), are serological markers for IBD, but their association with gut inflammation is controversial in AS, and has not been studied in rheumatoid arthritis (RA). <h3>Objectives</h3> To investigate the prevalence of IBD serologies in AS and RA, and their relation to clinical manifestations, ileocolonoscopic and histologic findings. <h3>Methods</h3> We included 40 consecutive AS patients fulfilling the 1984 modified New York criteria, 20 RA in addition to 20 healthy age and sex matched as a second control for the ASCA and ANCA serologies. Ileocolonoscopy and histologic examination of biopsies were performed in all patients. ASCA IgA and IgG (by ELIZA) and ANCA (by indirect immune-florescence) were determined in all patients and controls. <h3>Results</h3> ASCA (IgA and/or IgG) was positive in 37.5% of AS, 20% of RA and 0% of controls. pANCA was positive in 25% of AS, 30% of RA and 0% of controls. Macroscopic gut inflammation was revealed in 90% of AS. Whereas, histologic lesions were present in 95%, with chronic ileocolitis in 40% and crhon's disease (CD) like lesions in 55%. These lesions were more frequent in HLA-B27 negative than B27 positive AS patients. In RA, no macroscopic lesions were detected, while microscopic lesions were detected in all patients, with 70% showing chronic ileocolitis and 30% showing CD-like lesions. All ASCA (IgA and/or IgG) positive AS and RA patients had microscopic gut inflammation, with higher frequency of CD-like lesions than non-specific ileocolitis. Similarly, all pANCA positive AS and RA had microscopic gut lesions. There was no association between these seromarkers and the presence of clinical manifestations suggestive of IBD. <h3>Conclusions</h3> The finding of association between gut inflammation and IBD-specific antibodies (ASCA and pANCA) in both AS and RA, confirms their use independently as markers of underlying subclinical bowel inflammation regardless of the primary disease. The more frequent presence of CD-like lesions in B-27 negative AS supports the assumption that these cases may represent an early stage of IBD. The detection of histologic gut inflammation and CD-like lesions in AS as well as in RA is a further confirmation of the link between the gut and inflammatory rheumatic diseases which may be related to their etiopathogenesis. <h3>Disclosure of Interest</h3> None Declared
The utility of duodenal endosonography examination in the diagnostic work-up of primary sclerosing cholangitis
Authors: Y. Ustundag, M. Eloubeidi
Journal: Endoscopy (2013)

We read with interest the article by Lutz et al. which indicated high accuracy of endosonography (EUS) as a diagnostic tool for extrahepatic involvement of primary sclerosing cholangitis (PSC) [1]. The study included 33 patients with cholestatic hepatopathy and a history of inflammatory bowel disease and/or a positive perinuclear anti-neutrophil cytoplasmic antibodies test (pANCA). Magnetic resonance cholangiography (MRC), endoscopic retrograde cholangiography (ERC), or liver biopsy were also used to complete the diagnostic work-up. The authors set four EUS criteria of PSC with extrahepatic disease, and when two of them were present, sensitivity and specificity of predicting PSC were noted to be 76.4 % and 100 % with positive and negative predictive values of 100 % and 79 %, respectively.
Cervical and Uterine Metastasis From Carcinoma of Breast Diagnosed by PET/CT
Authors: Maria M. D'souza, Rajnish Sharma, Madhavi Tripathi, Sanjiv Kumar Saw, Anuja Anand, Dinesh Singh, Anupam Mondal
Journal: Clinical Nuclear Medicine (2010)

A 44-year-old apparently healthy woman presented with a 5-month history of intermittent vaginal bleeding. Clinical examination raised the suspicion of cervical neoplasia which was confirmed to be a metastatic adenocarcinoma on subsequent histopathological evaluation. An F-18 FDG PET/CT scan performed soon after revealed increased uptake in the cervix, extending upwards into the endometrial cavity. Additionally, small FDG avid spiculated soft tissue density masses were visualized in bilateral breast parenchyma, which proved to be lobular carcinoma on sonomammography followed by histopathology. Multiple lytic FDG avid skeletal metastases were also noted. Endometrial biopsy showed infiltrative malignant tumor with cytologic features similar to those observed in the breast biopsy specimen. The entire spectrum of findings pointed to a diagnosis of bilateral lobular carcinoma with uterine, cervical, and skeletal metastasis. Metastasis to the uterus and cervix from a breast primary is extremely rare. Most cases have been diagnosed in the follow-up of known cases of breast carcinoma. Our case is unique in that the patient, who had no prior history of breast carcinoma, was suspected to have a breast primary with cervical and uterine metastasis, based on the PET/CT findings.
Acute pancreatitis induced by vegetable fibers
Authors: Sabrina Testoni, Maria Petrone, Paolo Arcidiacono
Journal: Endoscopy (2015)

Acute pancreatitis induced by ingested foreign bodies is a rare entity [1] [2] [3] [4] [5]. We report an unusual case of acute pancreatitis caused by a foreign body which had migrated into the main pancreatic duct.
Correction of the Permeability Defect in Hereditary Stomatocytosis by Dimethyl Adipimidate
Authors: William C. Mentzer, Bertram H. Lubin, Susan Emmons
Journal: New England Journal of Medicine (1976)

The effect of imidoesters on the extraordinarily increased cation permeability of hereditary stomatocytes was evaluated in erythrocytes from a splenectomized boy with persistent hemolytic anemia. Reaction of stomatocytes with dimethyl adipimidate reduced ouabain-associated potassium loss from 15 to 1.7 and sodium gain from 22 to 2.5 meq per liter of red cells per hours. Red-cell volume, cation concentration, and deformability, previously abnormal, rapidly became normal after stomatocytes were reacted with dimethyl adipimidate. Instead of stomatocytes, normal red cells and target cells were noted. The survival (half-time) of stomatocytes treated with 51Cr-labeled dimethyl adipimidate infused into rats rendered tolerant to human erythorocytes by pretreatment with ethyl palmitate and cobra-venom factor was double that of untreated stomatocytes. Chemical modification of the defect in vitro allowed stomatocytes to regain many properites of normal erythrocytes and favorably influenced the subsequent survival of these cells in vivo.
A1.1 Obesity is a risk factor for worse treatment response in rheumatoid arthritis patients- results from reuma.pt
Authors: A M Rodrigues, J E Reis, C Santos, M P Pereira, C Loureiro, F Martins, J E Fonseca, H Canhão
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> Obesity is a traditional cardiovascular risk factor that affects one third of rheumatoid arthritis (RA) patients. Presently, the importance of obesity in RA activity remains unclear. This study aims to determine the influence of obesity on treatment response to biologic therapy evaluated by DAS28 at six months, in patients with RA, regardless of the targeted cytokine or cell, by analyzing a cohort of patients treated with anti-IL-6, TNFinhibitors (TNFi) or anti-CD20 therapies. <h3>Methods</h3> We conducted a retrospective longitudinal cohort study using the Rheumatic Diseases Portuguese Register (Reuma.pt). RA patients refractory to DMARD therapy, with at least 6 months of follow up after starting their first biologic therapy, with available data on weight and height at baseline were included. A DMARD naïve patients group was used as control Information was obtained on patient demographics, education, body mass index (BMI), present smoking status, disease duration, therapy, baseline disease activity score in 28 joints (DAS28), erosive disease, rheumatoid factor and anti-citrullinated protein antibodies, health assessment questionnaire (HAQ), type of biologic therapy (TNFi vs non-TNFi). BMI was categorised in two classes: non-obese (BMI &lt;30) and obese (BMI &gt; = 30 Kg/m2). Multivariate analysis was performed in order to evaluate the association between obesity and DAS 28 at 6 month and remission state (DAS28 &lt;2.6). <h3>Results</h3> 317 patients treated for the first time with a biologic agent were included in this study. 23% were obese. We found a significant association between obesity and DAS28 at 6 months (β = 0.412 (0.045–0.779); p = 0.028). Other factors also showed a significant association namely baseline DAS28 (β = 0.514 (0.393–0.636); p &lt; 0.001) and the use of a TNFi (β = 1.22 (0.787–1.653; p &lt; 0.001). Considering disease remission the analysis did not show a significant association between obesity and DAS28 remission at 6 months for all biologic agents as a group (OR = 0.391 (0.132–1.161; p = 0.091). Baseline DAS28 (OR = 0.384 (0.264–0.597); p &lt; 0.001) and the use of TNFi as a biologic therapy did show a significant association with achieving remission in these patients (OR = 0.037 (0.012–0.111); p &lt; 0.001). In the 35 DMARD naïve patients evaluated we also found a significantly association of obesity and DAS28 at 6 months (β = 1.048 (0.227–1.829); p-value = 0.009) but not with remission (OR = 0.24 (0.006–1.938); p = 0.24). <h3>Conclusion</h3> Obesity predicts worse treatment response in rheumatoid arthritis. These results suggest that obese RA patients should be encouraged to reduce weight in order to improve disease control.
Abstract LB-138: TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation
Authors: Dong Zhao, Xu Zhi, Zhongmei Zhou, Ceshi Chen
Journal: Cancer Research (2011)

Abstract Krüppel-like factor 5 (KLF5) is a PY motif-containing transcription factor promoting breast cell proliferation. The KLF5 protein is rapidly degraded through the proteasome after ubiquitinated by E3 ubiquitin ligases, such as WWP1 and SCFFbw7. In this study, we demonstrate that transcriptional co-activator with PDZ binding motif (TAZ) upregulated KLF5 through antagonizing the WWP1-mediated KLF5 ubiquitination and degradation. TAZ interacted with KLF5 through the WW domain and the PY motif, which is the binding site of WWP1. TAZ inhibited WWP1-mediated KLF5 ubiquitination and degradation. Overexpression of TAZ up-regulated the protein levels of KLF5 and FGF-BP, which is a well established KLF5 target gene. In addition, depletion of TAZ in both 184A1 and HCC1937 breast cells dramatically down-regulated protein levels of KLF5 and FGF-BP and inhibited cell growth. Furthermore, stable depletion of either TAZ or KLF5 significantly suppressed HCC1937 xenograft growth in SCID mice. Knockdown of LATS1, a TAZ upstream inhibitory kinase, up-regulated the protein levels of KLF5 and FGF-BP in 184A1 and promoted cell proliferation through TAZ. Finally, both KLF5 and TAZ are co-expressed in a subset of ER-negative breast cell lines. These results, for the first time, suggest that TAZ promotes breast cell growth partially through protecting KLF5 from WWP1-mediated degradation, and enhancing KLF5's activities. This study is supported by a grant from the American Cancer Society (RSG-08–199–01) and a grant from the Department of Defense (W81XWH-07–1–0191). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-138. doi:10.1158/1538-7445.AM2011-LB-138
Acute HIV Infection among Patients Tested for Mononucleosis
Authors: Eric S. Rosenberg, Angela M. Caliendo, Bruce D. Walker
Journal: New England Journal of Medicine (1999)

To the Editor: Acute infection with human immunodeficiency virus type 1 (HIV-1) is associated with a self-limited, mononucleosis-like illness in the majority of persons. Symptoms may include fever, pharyngitis, lymphadenopathy, rash, oral and genital ulcerations, orthostasis, and gastrointestinal problems. Although many patients seek medical attention during acute HIV-1 infection, the diagnosis is often missed.1 In the early symptomatic stage, the standard enzyme-linked immunosorbent assay (ELISA) is negative for HIV-1, but tests for plasma HIV-1 RNA or plasma p24 antigen are positive. We hypothesized that health care providers are likely to perform testing for heterophil antibodies to Epstein–Barr virus in patients . . .
THU0290 Prognostic Value of Minor Salivary Gland Assessments in Primary SjöGren’s Syndrome
Authors: A. Risselada, A. Kruize, J. van Roon, F. Lafeber, J. Bijlsma
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Salivary gland assessment is important for diagnosing primary Sjögren’s syndrome (pSS), as the lymphocytic focus score (LFS) is part of pSS classification criteria. Quantitative immunohistology (QIH) is another technique used for assessing pSS in which the percentage of immunoglobulin-specific plasma cells is measured, with IgA &lt;70% and/or IgM &gt;10% as positive criteria. <h3>Objectives</h3> To investigate the prognostic value of minor salivary gland assessment (LFS and QIH) for disease severity of pSS. <h3>Methods</h3> Medical charts of 174 pSS patients were retrospectively analyzed, comparing histology results (LFS and percentages of IgA, IgM and IgG plasma cells) with disease outcomes as non-Hodgkin lymphoma (NHL) and clinical scores: cumulative EULAR Sjögren’s Syndrome disease activity index (ESSDAI) and the number of extraglandular manifestations (EGM) during disease course. <h3>Results</h3> Mean age at pSS diagnosis was 47±14 years and median follow-up after biopsy was 105 months (range 10–408). LFS ≥1 were seen in 99%, &lt;70% IgA-positive plasma cells in 90%, and &gt;10% IgM-positive plasma cells in 71% of patients. The number of foci correlated to a decrease in the percentage of IgA-positive plasma cells (R=0.315, p=0.0001). NHL developed in 16 patients (9%). The mean LFS was significantly higher in patients with NHL (3.0±0.9 versus 2.3±1.1; p=0.021). The threshold of ≥3 foci had a positive predictive value of 16% for development of lymphoma, and a negative predictive value of 98% (OR 7.9; p=0,008). QIH results could not predict lymphoma development. Only LFS ≥3 contributed significantly and independently to NHL development in a hierarchical multiple regression model, correcting for presence of anti-SSA/SSB antibodies (beta 0.244; p=0.017). Cumulative ESSDAI and EGM were significantly correlated to LFS, a decreased percentage of IgA-positive and an increased percentage of IgM-positive plasma cells (R range 0.166–0.284; p≤0.04), but not to the percentage of IgG-positive plasma cells. <h3>Conclusions</h3> Routinely performed minor salivary gland assessments have important prognostic value. The number of lymphocyte foci can be used to identify patients with increased lymphoma risk. <h3>Acknowledgements</h3> We would like to thank J.M van Woerkom, R. Goldsmeding and the pathology department of the University Medical Center Utrecht for their work on the minor salivary gland assessments. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-301: Galectin-3 contributes to melanoma metastasis by regulating Autotaxin through NFAT1
Authors: Russell R. Braeuer, Maya Zigler, Takafumi Kamiya, Andrey S. Dobroff, Li Huang, Menashe Bar-Eli
Journal: Cancer Research (2012)

Abstract Melanoma is the deadliest form of skin cancer in which patients with metastatic disease have a five year survival-rate of less than 10%. Recently the over expression of a beta galactoside binding protein, Galectin-3, has been correlated with metastatic melanoma. Yet its role in melanoma progression is not completely understood. We have previously demonstrated that silencing Galectin-3 in melanoma cell lines leads to decreased melanoma cell invasion and migration in vitro and inhibits tumor growth and metastasis in vivo via the regulation of VE-cadherin and IL-8. To determine whether Galectin-3 can enhance the expression of other genes involved in the metastatic phenotype, a cDNA microarray analysis was performed after silencing Galectin-3 in melanoma cell lines. One of the many genes down regulated after silencing Galectin-3 is the lysophospholipase D enzyme Autotaxin. Autotaxin expression enhances melanoma migration and invasion by converting Lysophosphatidylcholine (LPC) to Lysophosphatidic acid (LPA) within the tumor microenvironment. LPA binds to EDG family G-protein coupled receptors to initiate downstream signaling which drives invasion and metastasis. Here we show that Galectin-3 regulates Autotaxin expression at the transcriptional level. Moreover, silencing Galectin-3 decreases total protein expression of the transcription factor NFAT1 which reduces its binding to the Autotaxin promoter. This in turn decreases Autotaxin promoter activity and protein expression. Therefore, Galectin-3 is required to maintain NFAT1 protein expression which enhances Autotaxin transcription and induces angiogenesis, tumor growth, and metastasis of melanoma cells. This is the first report to connect Galectin-3 with Autotaxin and LPA synthesis along with assigning an important role for NFAT1 in melanoma metastasis. 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 LB-301. doi:1538-7445.AM2012-LB-301
AN UPDATED COMPREHENSIVE META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS COMPARING RADIAL VERSUS FEMORAL ACCESS FOR PERCUTANEOUS INTERVENTIONS IN PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Sajjad A. Khan, Yenal Harper, Teresa Slomka, Leah A. John, Beatrix Ramos Bondy, Rahman Shah
Journal: Journal of the American College of Cardiology (2016)
Abstract LB-42: PDK1 knockdown selectively inhibits growth of cancer cells harboring activating mutations involved in MAPK signaling
Authors: M. Phillip DeYoung, Christine M. Gardiner, Antony R. Chadderton, Jesus R. Medina, Jeffrey M. Axten, Sridhar K. Rabindran
Journal: Cancer Research (2010)

Abstract Phosphoinositide-dependent protein kinase-1 (PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway which is the most commonly deregulated signaling pathway across all cancers. Increased PDK1 activity confers chemoresistance in tumor cell lines, and reduced PDK1 expression prevents the onset of tumorigenesis in mouse models. To demonstrate that PDK1 is a promising target for cancer therapy, we used a siRNA-based approach to determine the effects of PDK1 knockdown in cancer cells and primary early-passage normal cells. Loss of PDK1 protein caused a significant reduction in phosphorylation of two PDK1 substrates, AKT (T308) and RSK1 (S221). Interestingly, knockdown of PDK1 protein had preferential growth inhibitory effects in cancer cells containing activating mutations of KRAS or BRAF, compared to cells with wild-type KRAS or BRAF. In KRAS/BRAF-mutant cells, apoptosis was evidenced by PARP-1 cleavage and an increase in the number of sub-G1 DNA content. Overexpression of mouse PDK1 rescued these cells from apoptosis, confirming the specificity of the siRNA-mediated effects. Consistent with these observations, stable expression of mutant KRAS (G12V) in NL-20 immortalized normal lung epithelial cells sensitized these cells to apoptosis upon knockdown of the PDK1 protein. Importantly, overexpression of a kinase-dead mouse PDK1 mutant did not rescue cells from apoptosis, suggesting that the kinase activity is required for these PDK1 functions. Based on these results, we sought to identify inhibitors of the kinase activity of PDK1 for development as anticancer agents. GSK2334470 was identified as a potent inhibitor of PDK1 kinase (IC50 0.5 nmol/l) that demonstrated a high level of specificity to PDK1 in an in vitro kinase panel. In cell-based mechanistic assays, GSK2334470 effectively inhibited phosphorylation of the PDK1-dependent phosphorylation sites [AKT T308 (IC50: 100 nmol/L) and RSK S221 (IC50: 291 nmol/L)], but not the PDK1-independent phosphorylation site on AKT, S473 (IC50: &amp;gt;30 umol/L). Antiproliferative effects were seen in several cell lines using low micromolar concentrations of inhibitor; however, no correlation between growth inhibition and KRAS/BRAF mutations was observed. Further optimization may be necessary for improved potency and KRAS/BRAF selectivity. Currently, efforts are underway to better understand the disconnect between siRNA data and compound data in several experimental cancer models, particularly in those where KRAS or BRAF mutations predominate. 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-42.
1-YEAR SAFETY AND EFFICACY OF PATIROMER FOR HYPERKALEMIA IN HEART FAILURE PATIENTS WITH CHRONIC KIDNEY DISEASE ON RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS
Authors: Bertram Pitt, David Bushinsky, Dahlia Garza, Yuri Stasiv, Charles Du Mond, Lance Berman, George Bakris
Journal: Journal of the American College of Cardiology (2015)
Comparative effectiveness of radioembolization and the standard of care for hepatocellular carcinoma: Is a randomized survival study feasible?
Authors: R. Salem, A. Riaz, R. Lewandowski, L. Kulik, M. Abecassis, M. F. Mulcahy
Journal: Journal of Clinical Oncology (2010)

4045 Background: Chemoembolization is one standard of care treatment for hepatocellular carcinoma (HCC). Alternatively, yttrium-90 radioembolization (90Y) represents a novel brachytherapy treatment concept. We performed a comparative effectiveness analysis of chemoembolization and 90Y for the treatment of HCC. Methods: 463 patients were treated with either chemoembolization or 90Y at our institution over a 9-year period. 245 patients were identified specifically (chemoembolization n = 122, 90Y n = 123) in order to directly compare the two interventions while minimizing the effect of confounding variables. Patients were followed for toxicities; all had baseline and follow-up imaging. Time-to-progression (TTP) and survival were determined. Uni/multivariate analyses were performed. Results: Fatigue and fever were more common following 90Y (p < 0.05); abdominal pain, diarrhea and transaminase elevations were more frequent following chemoembolization (p < 0.05). 1065 cross-sectional imaging scans were reviewed to assess response and TTP. Response rate trended in favor of 90Y over chemoembolization (49% vs. 36%, p = 0.052). Overall, although 90Y TTP outperformed chemoembolization (90Y: 13.3 months, chemoembolization: 8.4 months, p=0.0232), median survival was not different (chemoembolization:17.4 months, 90Y:20.5 months, p = 0.2316). For intermediate HCC, survival was similar (chemoembolization: 17.5 months, 90Y: 17.2 months, p = 0.42). Post hoc sample size analyses based on these findings suggest that > 1,000 patients would be required to confirm statistical equivalence between these treatments. Conclusions: 90Y appears to provide better disease control with less toxicity than chemoembolization, with equivalent survival. Our data suggest that a randomized survival study demonstrating equivalence may not be feasible due to the prohibitively large enrollment that would be required. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MDS Nordion MDS Nordion