tbuckley/cabot-search huggingface dataset:
Metabolic Syndrome Components Are Associated With Symptomatic Polyneuropathy Independent of Glycemic Status
Authors: Brian C. Callaghan, Rong Xia, Mousumi Banerjee, Nathalie de Rekeneire, Tamara B. Harris, Anne B. Newman, Suzanne Satterfield, Ann V. Schwartz, Aaron I. Vinik, Eva L. Feldman, Elsa S. Strotmeyer
Journal: Diabetes Care (2016)

OBJECTIVE Previous studies demonstrate that the metabolic syndrome is associated with distal symmetric polyneuropathy (DSP). We aimed to determine the magnitude of this effect and the precise components involved. RESEARCH DESIGN AND METHODS We determined the symptomatic DSP prevalence in the Health, Aging, and Body Composition (Health ABC) study (prospective cohort study, with subjects aged 70–79 years at baseline), stratified by glycemic status (glucose tolerance test) and the number of additional metabolic syndrome components (updated National Cholesterol Education Program/Adult Treatment Panel III definition). DSP was defined as neuropathic symptoms (questionnaire) plus at least one of three confirmatory tests (heavy monofilament, peroneal conduction velocity, and vibration threshold). Multivariable logistic and linear regression evaluated the association of metabolic syndrome components with DSP in cross-sectional and longitudinal analyses. RESULTS Of 2,382 participants with neuropathy measures (mean age 73.5 ± 2.9 years, 38.2% black, 51.7% women), 21.0% had diabetes, 29.9% prediabetes, 52.8% metabolic syndrome, and 11.1% DSP. Stratified by glycemic status, DSP prevalence increased as the number of metabolic syndrome components increased (P = 0.03). Diabetes (cross-sectional model, odds ratio [OR] 1.65 [95% CI 1.18–2.31]) and baseline hemoglobin A1C (longitudinal model, OR 1.42 [95% CI 1.15–1.75]) were the only metabolic syndrome measures significantly associated with DSP. Waist circumference and HDL were significantly associated with multiple secondary neuropathy outcomes. CONCLUSIONS Independent of glycemic status, symptomatic DSP is more common in those with additional metabolic syndrome components. However, the issue of which metabolic syndrome components drive this association, in addition to hyperglycemia, remains unclear. Larger waist circumference and low HDL may be associated with DSP, but larger studies with more precise metabolic measures are needed.
Abstract 4243: Regulation of H3K9 methylation by the demethyltransferase gene JMJD1C in multiple myeloma.
Authors: Janine LoBello, Danielle DiPerna, Moly Gale, Aprill Watanabe, Galen Hostetter, Rafael Fonseca, Bodour Salhia
Journal: Cancer Research (2013)

Abstract Increasing evidence points towards the importance of epigenetic changes in the pathogenesis of multiple myeloma (MM). The biochemical modifications that govern epigenetics are DNA methylation, and post-translational modifications of histone proteins. Histone methylation is catalyzed by histone methyltransferases (HMT) and histone demethylases (HDMT). The purpose of our study was to interrogate genomics data to identify HMT or HDMT genes that are altered in MM. We mined copy number, gene expression and whole genome sequencing data generated as part of the Multiple Myeloma Research Consortium Genomics Initiative. Collectively, the datasets converged on numerous alterations involving histone methylation of lysine 9 (H3K9). One of these genes, the HDMT JMJD1C, was over-expressed in approximately 15% of MM samples examined. We validated over-expression of JMJD1C expression by RT-PCR in over 50 clinical MM samples and 10 human myeloma cell lines (HMCLs). We also confirmed over-expression of JMJD1C by immunohistochemistry (IHC) in a tissue microarray (TMA) consisting of over 60 MM samples. Next we demonstrated a negative correlation between JMJD1C expression and H3K9 methylation by IHC and western blot in 6/10 HMCL and in over 60% of clinical samples examined on the TMA. This validates the H3K9 demethylase activity of JMJD1C. Furthermore, we demonstrated that, in general, H3K9 methylation, a repressive mark associated with heterochromatin, is low in a large percentage of samples. To study the functional significance, we generated a double knockout isogenic cell line pair in U266 cells using zinc finger nuclease technology. We performed ChIP-seq and RNA-seq analyses to identify genes affected by JMJD1C binding to H3K9. Our data indicate that loss of JMJD1C expression alleviates the repression conferred by H3K9 methylation in MM. Studies are ongoing to realize JMJD1C as a potential and novel therapeutic target in MM. Citation Format: Janine LoBello, Danielle DiPerna, Moly Gale, Aprill Watanabe, Galen Hostetter, Rafael Fonseca, Bodour Salhia. Regulation of H3K9 methylation by the demethyltransferase gene JMJD1C in multiple myeloma. [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 4243. doi:10.1158/1538-7445.AM2013-4243
AB0874 Assessment of spinal mobility improvement in an education and home excercise program for ankylosing spondylitis patients using a motion capture system:
Authors: E. Collantes, J.L. Garrido-Castro, R. Medina, A.M. Galisteo, C. Gonzalez, D. Ruiz, P. Font, E.M. Gomariz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A study on 622 patients diagnosed with ankylosing spondylitis were realized by researchers of GRESSER Group [1]. They were randomized to an education intervention or standard care. The intervention included an informative session and a physical activity program at home. Education group diminished activity of the disease with significant reductions in VAS, BASDAI, BASFI and ASQoL. 30 participated at the Reina Sofia University Hospital where more exhaustive metrology were applied using a motion capture system. <h3>Objectives</h3> To assess spinal mobility improvements on patients included in an education program using a motion capture system. <h3>Methods</h3> On 30 patients with AS, we used a motion capture system (UCOTrack) to assess spinal mobility. 15 were included in the education group and 15 in control group. Two measurements were made at the beginning and at the end of the activity (6 months) in both groups. Some 3D new measures were defined, including UCOASMI (an index based on 5 measurements), although conventional measurements were obtained using the system. VAS, BASDAI, BASFI, ASQoL and BASMI were also evaluated. <h3>Results</h3> Mean values and standard deviations of different parameters are shown in table.To analyze response, mean difference and coefficient of variation of both groups are shown with statistically significant differences (*P&lt;0.05). <h3>Conclusions</h3> Our results confirm a significant decrease in activity indicators of education group, like previous mentioned studies. But there isn’t significant improvement in mobility, in contrast to other more active interventions as physiotherapy, hydrotherapy, biological therapies, etc. However, in some measurements, there have been significant differences, specially in UCOASMI. Motion capture has proven to be more sensitive in assessing mobility and can be a useful tool to analyze change in patient’s physical condition. <h3>References</h3> Rodriguez-Lozano et al. Outcome of an Education and Home Exercise Program for Ankylosing Spondylitis Patients: A Nationwide Randomized Study. Arthritis Rheum 2010, 62 Suppl 10, 2268. <h3>Disclosure of Interest</h3> None Declared
HIGH SERUM IMMUNOGLOBULIN G AND M LEVELS IMPROVE CARDIOVASCULAR RISK DISCRIMINATION IN HYPERTENSION: A NESTED CASE-CONTROL SUBSTUDY OF THE ANGLO-SCANDINAVIAN CARDIAC OUTCOMES TRIAL
Authors: Ramzi Yousef Khamis, Alun Hughes, Mikhail Caga-Anan, Choon-Lan Chang, Joseph Boyle, Chiari Kojima, Paul P. Welsh, Naveed Sattar, Michael Johns, Peter Sever, Jamil Mayet, Dorian Haskard
Journal: Journal of the American College of Cardiology (2016)
P2-08-03: Quantitative MRI for Noninvasive Prediction of Prognostic Markers in Breast Cancer.
Authors: S Parsian, R Sun, BF Kurland, H Rahbar, KH Allison, JM Specht, WB DeMartini, CD Lehman, SC Partridge
Journal: Cancer Research (2011)

Abstract Background: Magnetic resonance imaging (MRI) is a valuable tool for assessing extent of breast cancer and monitoring treatment response. Quantitative measures by diffusion-weighted MRI (DWI) and dynamic contrast-enhanced (DCE) MRI reflect tumor cellularity and vascularity. Tumor grade and some histopathological markers, such as ER, PR, HER-2, Ki67 and P53, are prognostic factors that can also be associated with tumor cellularity and vascularity. DWI and DCE measures may therefore provide a noninvasive means for predicting disease prognosis and stratifying patients to appropriate therapies. The purpose of this study was to investigate the correlation between quantitative MRI features and prognostic pathological factors in patients with invasive breast cancer. Methods: This IRB-approved retrospective study included patients with biopsy-proven invasive cancer who underwent 1.5T breast MRI (including DCE and DWI) from October 2005 to May 2006 prior to treatment. Pathology data was obtained from pre-treatment biopsy and intrinsic subtype classification was approximated by standard immunohistochemistry characteristics. After excluding cases with missing MRI or pathology data, the final study cohort included 41 invasive cancers (36 ductal and 5 lobular carcinomas) in 36 patients. MRI measures included lesion DCE kinetic features: peak initial enhancement (PE), percent rapid enhancement (RE), and percent washout (WO), and DWI normalized apparent diffusion coefficient values (nADC). Associations between imaging features and pathology markers, cancer grades and intrinsic subtypes were evaluated by Mann-Whitney U test and multivariate logistic regression. Results: Results of univariate comparisons are summarized in Table 1. One or more DCE-MRI kinetic parameters were significantly predictive (p&amp;lt;0.05) of each of the histopathological markers with the exception of ER, which was marginally associated with WO (p=0.05). Each of the DCE kinetics parameters significantly discriminated grade III tumors from grades I and II and luminal A from luminal B and basal-like intrinsic subtypes. In multivariate regression, both PE and WO were significant independent predictors of tumor grade (p=0.0094, p=0.0005, respectively). WO and nADC were significant independent predictors of PR status (p=0.0054, p=0.0027), while PE was the only significant independent predictor of both Ki67 (p=0.014) and intrinsic subtype (p=0.015). Conclusion: This preliminary study suggests that quantitative MRI measures are associated with prognostic tumor markers and may provide valuable noninvasive characterization of tumor biology. Larger prospective studies are needed to validate our findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-03.
AB0023 Gene-gene interaction and early rheumatoid arthritis: effects on the response to therapy
Authors: M.C. Totaro, B. Tolusso, F.M. Carpi, A.L. Fedele, V. Napolioni, S. Canestri, F. Di Pietro, D. Frezza, E. Serone, S.L. Bosello, E. Gremese, G. Ferraccioli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the relationship between the response to therapy in early rheumatoid arthritis (ERA) and polymorphisms in the genes of molecules involved in inflammatory processes (TNF-α, TNF-RII, IL6, IL1b, IL1Ra, BAFF) or in the homeostasis of T and B cells (PTPN22, HS1,2 enhancer). <h3>Methods</h3> Two hundreds and eighty six ERA patients were enrolled in the study (females: 75.2%; mean age: 55.1±13.6 years; anti-CCP positive patients: 63.3%; IgA RF positive patients: 34.5%; IgM RF positive patients: 51.0%). All patients were treated with Methotrexate for three months, then with a combination with Tumor Necrosis Factor (TNF) blockers if they had an incomplete response after 3-month treatment period. DNA from patients was genotyped for the TNF-α (-308G&gt;A and -238G&gt;A), TNF-RII +196T&gt;G, IL6 -174G&gt;C, IL1b (-511C&gt;T and +3953C&gt;T), IL1Ra VNTR, BAFF -871C&gt;T, PTPN22 +1858C&gt;T, HS1,2A polymorphisms by polymerase chain reaction restriction fragment length polymorphism method. Clinical and laboratory data were recorded at baseline and every 3 months. The EULAR response criteria based on DAS were used to assess the disease activity after 3 and 6 months of follow-up (good response: DAS &lt;2.4 and a fall in this score from baseline by &gt;1.2; sustained remission: DAS value of &lt;1.6 for at least two consecutive visits 3 months apart). Exact Hardy Weinberg Equilibrium (HWE) tests were performed for each polymorphism independently. Generalized multifactor dimensionality reduction (MDR) was used to verify interaction results. Models were evaluated on the testing balanced accuracy statistic (TBA), the cross-validation consistency (CVC) and the statistical significance of the model. <h3>Results</h3> All the polymorphisms were in Hardy-Weinberg equilibrium. According to the multi-locus GMDR approach, TNF-308G&gt;A, TNFRII+196T&gt;G, IL1RA VNTR, IL1b-511, IL1b+3956, IL6-174G&gt;C and BAFF-871C&gt;T polymorphisms predicted the EULAR good response at 3 months correctly 60.9% of the time (Sign Test <i>p=0.001</i>). The EULAR sustained remission at 6 months was predicted 55.9% of the time by an ensemble of 5 polymorphisms (TNF-α-308, TNF-RII+196, IL1Ra VNTR, IL1β+3953, BAFF-871; Sign Test <i>p=0.055</i>). <h3>Conclusions</h3> The genetic background is a possible predictor of the response to therapy of patients with early rheumatoid arthritis. The analysis of gene-gene interactions, especially in genes of molecules related to the major inflammatory cytokines, will lead to a better understanding of the biological pathways underlying the therapeutic outcome in the earliest phases of the disease. <h3>Disclosure of Interest</h3> None Declared
THE EFFECT OF TICAGRELOR ADMINISTRATED THROUGH A NASOGASTRIC TUBE TO COMATOSE PATIENTS UNDERGOING ACUTE PERCUTANEOUS CORONARY INTERVENTION AFTER CARDIAC ARREST: THE TICOMA TRIAL
Authors: Lene Holmvang, Golnaz Sadjadieh, Hedvig B. Andersson, Martin Frydland, Sebastian C. Wiberg, Jesper Kjaergaard, Hanna Ratcovich
Journal: Journal of the American College of Cardiology (2016)
AB1130 An unusual aspect of bartonellosis mimicking an autoimmune disease
Authors: D. Maritsi, G. Vartzelis, G. Papaioannou, S. Balani, D. Zarganis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although previously considered a rare cause of pyrexia of unknown origin(PUO), with the aid of new diagnostic tools the clinical spectrum of bartonella henselae infection has expanded[1]. <h3>Methods</h3> We present a case of a seven year old immunocompetent female patient who developed systemic symptoms mimicking an autoimmune rather than an infectious disease. <h3>Results</h3> The patient, offspring of an unrelated Caucasian couple with uneventful past medical history, presented with erythematous papular rash, biquotidian fever, night sweats and arthralgias. There was no antecedent history of foreign travel or contact with animals. Investigations showed increased inflammatory markers (ESR 86,CRP 80 [range 0-10mg/dl)], thrombocytosis, hypercalcemia and raised ALP and angiotensin converting enzyme(ACE). Quantiferon test was negative. Abdominal imaging (USS followed by MRI) showed multifocal calcified granulomas of the liver and spleen, chest radiograph showed enlarged hilar lymph nodes; ophthalmology review showed low grade panuveitis. Diffrentials included systemic JIA, small vessel vasulitides and sarcoidosis. Clinical, laboratory and imaging features pointed towards sarcoidosis. However, subsequent raised titers (IgM 1:32, IgG 1:256) against bartonella confirmed the diagnosis of B. henselae infection. She tested negative for HIV1+2 and lymphocyte subset analysis did not reveal an underlying primary immunodeficiency. She was treated with intravenous gentamycin followed by oral ciprofloxacin.Pyrexia and rash subsided with 24 hours; repeat investigations showed complete resolution of findings. <h3>Conclusions</h3> Conclusion: The presence of hepatic and splenic lesions in children with bartonellosis is well documented[2]. Our case however, exhibited certain unusual findings such as the co-existence of ocular and solid organ involvement as well as the presence of calcifications during the acute phase. Serological testing is an inexpensive and effective way to diagnose bartonellosis in immunocompetent patients; we suggest that bartonella serology is included in the baseline tests performed in immunocompetent children with PUO even in the absence of contact with cats. <h3>References</h3> Florin TA, Zaoutis TE, Zaoutis LB Beyond cat scratch disease: widening spectrum of Bartonella henselae infection. Pediatrics. 2008 May;121(5):e1413-25. Ventura A, Massei F, Not T, Massimetti M, Bussani R, Maggiore G Systemic Bartonella henselae infection with hepatosplenic involvement. J Pediatr Gastroenterol Nutr. 1999 Jul;29(1):52-6. <h3>Disclosure of Interest</h3> None Declared
THU0128 The Utility of Clinical Disease Activity Index for Tight Control of Disease Activity in South African Rheumatoid Arthritis Patients
Authors: B. Hodkinson, N. Monyai, M. Tikly
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Better outcomes are achieved by using a "tight" control strategy to treat rheumatoid arthritis (RA), but this approach has not yet been explored in resource-contrained sub-Saharan Africa. Utilizing the Clinical Disease Activity Index (CDAI) score, thus obviating the need for acute phase reactant measurement, may be a resource-sparing approach. <h3>Objectives</h3> We prospectively compared the disease control with a tight control strategy utilising either the Simplified Disease Activity Index (SDAI) or the CDAI. <h3>Methods</h3> In a 26-week study, 97 DMARD-naïve RA patients attending Chris Hani Baragwanath Hospital in 2011-12, were randomised to either an SDAI or CDAI arm and treated with traditional DMARDs, escalated on a monthly basis according to pre-defined protocol to achieve low disease activity (LDA). The primary outcome was the number of patients achieving at least LDA in both arms as by the DAS28. Additionally, the outcomes of entire cohort were compared to a cohort of 145 early RA patients attending the same hospital between 2005 and 2009 and treated with traditional DMARDs according to routine care<sup>1</sup>. No patients received biologic therapy. <h3>Results</h3> The two arms were well-matched for disease activity and symptom duration at baseline (see table). At 26 weeks, neither the mean DAS28 score nor the proportion of patients achieving LDA was signficantly different beween the CDAI and SDAI groups. All patients received low dose prednisone (7.5mg daily) and at 26 weeks the mean methotrexate (MTX) dose was 20.8mg/week. Compared to the historical cohort treated with routine care, patients in the present study achieved a significantly lower mean DAS28, despite a signficantly longer symptom duration before commencement of DMARDs. Remission was achieved in 29% of patients treated by tight control, compared to 8% in the routine care group (p&lt;0.0001, OR=4.6;SD 2.2-9.4). The historical cohort had significantly less exposure to low dose prednisone (52%, p&lt;0.0001) and the majority (91%) received MTX, with a mean dose of 17.1mg/week at 26 weeks, significantly less than prescribed in the tight control group. <h3>Conclusions</h3> In a resource-constrained setting, the less costly CDAI is an acceptable alternative to the SDAI in measuring disease activity. A tight control strategy improves disease control in the short-term. Further follow-up is necessary to see whether the better outcome is sustained in the longer term. <h3>References</h3> Hodkinson B et al. Clin Rheumatol (2012) 31:613–619 <h3>Acknowledgements</h3> This study was funded by the Carnegie Corporation and the University of the Witwatersrand Connective Tissue Diseases Research Fund <h3>Disclosure of Interest</h3> None Declared
Effect of Omeprazole and Ranitidine on Ulcer Healing and Relapse Rates in Patients with Benign Gastric Ulcer
Authors: A Walan, J P Bader, M Classen, C B Lamers, D W Piper, K Rutgersson, S Eriksson
Journal: New England Journal of Medicine (1989)

Omeprazole blocks the action of H+,K+-ATPase in the gastric mucosa and thus inhibits the secretion of hydrochloric acid. We conducted a double-blind multicenter study (45 centers in 13 countries) of 602 patients with benign gastric or prepyloric ulcers to compare the effectiveness of omeprazole (20 mg once daily, 203 patients, or 40 mg once daily, 194 patients) and ranitidine, an H2-receptor antagonist (150 mg twice daily, 205 patients) in promoting ulcer healing and to evaluate the pattern of ulcer relapse during a six-month follow-up. Healing occurred at four weeks in 80 percent of the patients receiving 40 mg of omeprazole, 69 percent of those receiving 20 mg of omeprazole, 69 percent of those receiving ranitidine. At eight weeks, the corresponding figures were 96, 89, and 85 percent. A multivariate analysis of ulcer healing showed that at four weeks the ulcers of significantly more patients receiving omeprazole had healed as compared with patients receiving ranitidine (omeprazole, 40 mg, vs. ranitidine, P less than 0.0005; omeprazole, 20 mg, vs. ranitidine, P = 0.01). At eight weeks, the 40-mg dose of omeprazole was significantly more effective than ranitidine (P = 0.001) or the 20-mg dose of omeprazole (P = 0.03). Ulcer symptoms were relieved faster with omeprazole. In 68 patients receiving concurrent nonsteroidal antiinflammatory drugs, the healing rates at four weeks were 81 percent in the group receiving 40 mg of omeprazole, 61 percent in the group receiving 20 mg, and 32 percent in the group receiving ranitidine; at eight weeks, the corresponding figures were 95, 82, and 53 percent. During the six-month follow-up period (without treatment), significantly more patients in the omeprazole groups were free of symptoms and ulcers than in the ranitidine group. We conclude that in the dose used, omeprazole is superior to ranitidine in the treatment of benign gastric ulcers.