tbuckley/cabot-search huggingface dataset:
PTU-071 Impact of body mass index (BMI) upon anti-tnf trough and anti-drug antibody levels
Authors: A Bond, K sager, S Phillips, R Asher, R Jackson, A Kneebone, K Martin, S Subramanian
Journal: Gut (2015)

<h3>Introduction</h3> The anti-tumour necrosis factor (TNF) agents, infliximab and adalimumab, are effective in treating inflammatory bowel diseases (IBD). Response is better in patients with detectable levels of circulating drug prior to the next administration (trough level). Some patients fail to respond to these drugs initially or lose response over time. Factors which influence loss of response are poorly defined but body mass index (BMI), prior surgery and smoking status have been reported to influence outcomes. In particular, BMI adversely affect outcomes with both infliximab and adalimumab, but the relationship of BMI to trough levels has not been reported previously. <h3>Method</h3> We conducted a single centre prospective cross-sectional study. All IBD patients treated with infliximab or adalimumab were eligible. Trough levels and anti-drug antibodies were obtained concurrently with routine clinical data, clinical markers of disease activity, faecal calprotectin (FC), C-reactive protein (CRP) and BMI. Variables including BMI that may predict trough levels and anti-drug antibodies were then assessed. Therapeutic infliximab was defined as trough level &gt;2 mcg/ml (need units and adalimumab as &gt;5.5 microgram/ml. <h3>Results</h3> 87 patients were included in the study; 69 had CD (44 IFX, 25 ADA) and 18 had UC (9 each on IFX and ADA). Of the total cohort, 12 had undetectable trough levels (&lt;0.1) and 22 had supra-therapeutic levels (&gt;8). A higher percentage of patients with undetectable trough levels were on infliximab (92% vs 8%, p &lt; 0.01). Supra-therapeutic levels were noted in 55% and 45% of infliximab and adalimumab patients respectively. In the infliximab group, the median BMI was 24.9 (range 17.23–42.28), and 26 had aBMI &gt;25 (49%). For adalimumab the median BMI was 22.92 (range 16.14–37.64), and 13 had a BMI &gt;25 (38%). Those with sub-therapeutic trough levels had a higher BMI, which is most prominent in the adalimumab group. Patients with sub-therapeutic levels of infliximab had a median BMI of 25.3 (IQR: 22.6–30.5) compared to those with therapeutic levels 23.8 (IQR: 19.9–29.6). For adalimumab the median BMI was 22.8 (IQR: 20.5–25.6) in therapeutic and 27.4 (IQR: 21.9–32.9) in the sub-therapeutic group but this did not reach statistical significance. <h3>Conclusion</h3> There does appear to be a correlation between BMI and trough levels, particularly in patients receiving adalimumab. Therefore trough level measurement and dose adjustment, particularly in those taking adalimumab with a BMI &gt;25, should be considered to optimise therapy and clinical outcomes. <h3>Disclosure of interest</h3> None Declared.
Abstract 5427: EGCG prevents hepatocellular carcinoma development in a diethylnitrosamine-induced rat model
Authors: Suguru Yamada, Tsutomu Fujii, Lan Wei, Yujin Hoshida, Gregory Y. Lauwers, Anthony D. Schmitt, Michael Lanuti, Kenneth K. Tanabe, Bryan C. Fuchs
Journal: Cancer Research (2012)

Abstract Background: Hepatocellular carcinoma (HCC) is increasing in incidence and treatment is often unsuccessful. Thus, prevention in high-risk patients with established cirrhosis has been proposed as an alternative strategy. It has been suggested that the increased inflammation and fibrogenesis observed during cirrhosis predisposes the liver to future malignant transformation to HCC through a “field effect”. A growing body of evidence indicates that the green tea polyphenol, (-)-epigallocatechin gallate (EGCG), can reduce inflammation and fibrogenesis during chronic liver injury. Here, we test the hypothesis that physiological concentrations of EGCG administered in the setting of cirrhosis can prevent future HCC development. Methods: A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the efficacy of EGCG for inhibition of HCC formation in these cirrhotic livers. DEN (50 mg/kg) was administered weekly throughout the study while 0.02% EGCG was given in drinking water beginning at the onset of cirrhosis. At the end of the study, rats were sacrificed, livers were sectioned and stained to analyze disease progression and tumor nodules were counted. Liver function tests were performed to determine liver injury and overall liver function. Finally, genome-wide gene expression profiling on the surrounding, non-tumoral liver tissue was used to monitor the “field effect” in response to EGCG. Results: EGCG significantly (p &amp;lt; 0.01) prevented the development of HCC tumor nodules from on average 18.8 in vehicle controls to on average 9.1 in EGCG-treated animals. EGCG also reduced liver injury and improved liver function as assessed by serum chemistry tests. Finally, a gene expression signature predictive of poor survival and HCC development in human cirrhosis patients was reversed in response to EGCG. Conclusions: Our data are consistent with the growing body of evidence suggesting that EGCG has protective effects in liver disease. Further, our results suggest that EGCG is a potentially effective HCC prevention strategy that can be monitored using gene expression signatures. 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 5427. doi:1538-7445.AM2012-5427
A4.07 IL-22 impact on human bone marrow mesenchymal stem cells functions; a unique pathway that may contribute to aberrant new bone formation in human SPA
Authors: YM El-Sherbiny, A El-Zayadi, R Cuthbert, T Baboolal, A Fragkakis, E Jones, D McGonagle
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> The human spondyloarthropathies (SpA) are associated with single nucleotide polymorphisms (SNPs) in the IL-23 pathway and IL-23/17 axis therapy is effective in SpA. The SpAs are also associated with new bone formation that is to a degree independent of TNF blockade. Given that IL-23R receptor signalling in lymphoid cells is associated with IL-22 production and since IL-22 is a pivotal cytokine that maintains gut and skin stem cell function,<sup>1,2</sup> we hypothesised that IL-22 might also drive skeletal stem cells and hence contribute to the SpA bone phenotype. Therefore we explored the effect of IL-22 on bone marrow mesenchymal stem cells (MSCs). <h3>Materials and methods</h3> Human Bone marrow MSCs were expanded and tested by flow cytometry for IL-22R expression. MSC proliferation and migration were tested by colorimetric XTT assay and chamber migration assays. MSC osteogenic functional differentiation was performed with and without cytokines. <h3>Results</h3> MSCs expressed low level IL22RA1 which was significantly up-regulated (1.8 ± 0.12 fold) in combination with IFNG and TNFa. MSCs proliferation and migration dramatically increased following IL-22 exposure after IFNG and TNFa combined priming compared to IL-22 alone or no cytokine. MSCs migration function was enhanced by IL-22 after priming with IFNG and TNFa compared to no cytokine. Osteogenic differentiation was significantly higher in MSCs exposed to IL-22 alone, but decreased when IL-22 combined with IFNG and TNFa. <h3>Conclusion</h3> IL-22 is exclusively produced by immune cells and acts on non-immune cells including stem cells; our findings confirm that IL-22 can drive bone marrow MSC osteogenesis. Furthermore, IL-22 boosted MSCs proliferation and migration after priming with IFNG &amp;&nbsp;TNFa <i>in vitro</i> and had variable effects depending on the inflammatory milieu. Given that the IL-23 axis association with SpA this work opens up a novel pathway for exploring new bone formation in SpA related disease. <h3>References</h3> Eyerich <i>et al. </i>J Clin Invest. 2009;119(12):3573–3585 Serafini <i>et al</i>. J Exp Med. 2014;211(2):199–208
Aspirin-Induced Depression of Renal Function
Authors: Robert P. Kimberly, Paul H. Plotz
Journal: New England Journal of Medicine (1977)

We observed elevation of serum creatinine and blood urea nitrogen and decrease in creatine clearance in patients taking anti-inflammatory doses of aspirin. In 13 of 23 patients with systemic lupus erythematosus increases in serum creatinine ranged from 27 to 163 per cent, and those in urea nitrogen from 42 to 270 per cent. Sequential creatinine-clearance studies, available in 11 of the 13 patients, demonstrated decreases up to 58 per cent. Patients with aspirin-induced changes in renal function were more likely to have active renal disease (P =0.035) or hypocomplementemia (P =0.030). Four of 22 patients with rheumatoid arthritis and two of three normal volunteers also demonstrated biochemical changes. The rate of aspirin-induced alterations was significantly higher in systemic lupus erythematosus (P =0.007) than in rheumatoid arthritis. Aspirin, and other nonsteroidal anti-inflammatory agents, can have a major reversible effect on renal function that may influence the interpretation of clinical data.
THU0208 Fatigue is an important problem in patients with behcet’s syndrome:
Authors: D. Buyuktas, G. Hatemi, S. Yuksel Findikoglu, K. Tascilar, S. Ugurlu, S. Yurdakul
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fatigue is an important problem in several inflammatory conditions, affecting quality of life. It is a patient reported outcome measure used in the evaluation of disease activity and in drug trials. <h3>Objectives</h3> To evaluate fatigue and its relation to the type of organ involvement in Behçet's syndrome (BS), using diseased and healthy controls. <h3>Methods</h3> We studied 152 BS, 51 RA, 51 SLE, 51 AS patients and 65 healthy controls. We evaluated them using the fatigue severity score, fatigue impact score, fibromyalgia impact score, RAPID3, SF-36 and Behçet's syndrome activity scale (only BS patients). Presence of fibromyalgia was defined as chronic widespread pain together with 11/18 sensitive points. We separately analyzed subgroups of BS patients, 42 with eye involvement, 30 with vascular involvement, 40 with joint involvement and 40 with only mucocutaneous involvement. We also did a separate analysis among women in each group. Groups were compared with stepwise ANOVA and Pearson chi-square tests. <h3>Results</h3> Fatigue severity scores and fatigue impact scores were similar among BS, RA, SLE and AS patients and significantly higher than healthy controls (Table). Fibromyalgia was significantly more frequent among RA patients followed by SLE patients. Fibromyalgia impact score, RAPID3 score and the mental component of SF-36 was significantly higher among RA than all other groups, was similar among BS, SLE and AS patients, and significantly higher than healthy controls. There was no significant difference between the groups in the physical component of SF-36. All BS subgroups had equally high fatigue severity and impact scores, fibromyalgia impact scores, and SF-36 mental and physical scores. Disease activity measured by BSAS was similar among the 4 subgroups (p=0.85). When women were analyzed separately, the results were similar to those of the total group except for the frequency of fibromyalgia and RAPID3 scores which were higher among RA patients compared to the diseased and healthy controls (χ<sup>2</sup> =15.3, p=0.004 and χ<sup>2</sup> =15.3, p=0.004 respectively). <h3>Conclusions</h3> Fatigue is an important problem in BS, as it is in other inflammatory conditions. It is equally severe in subgroups of patients with eye, vascular, joint and only mucocutaneous involvement. Fatigue should be considered as a patient reported outcome measure in BS. <h3>Disclosure of Interest</h3> None Declared
THU0201 Biomechanical and Functional Benefits during GAIT of A New Knee Brace That Combines A Valgus and Tibial External Rotation Effect in Medial Osteoarthritis Patients
Authors: D. Laroche, C. Morisset, C. Fortunet, A. Baudet, J.-F. Maillefert, P. Ornetti
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Non-pharmacological therapies are recommended for the care of knee osteoarthritis patients. Unloader knee braces provide an interesting functional approach, which aims to modulate the mechanical stress on the symptomatic joint compartment. We aimed to confirm the biomechanical effects and evaluate functional benefits of a new knee brace that combines a valgus effect with knee and tibial external rotation during gait in medial osteoarthritis patients. <h3>Methods</h3> 20 patients with unilateral symptomatic medial knee osteoarthritis were included and performed two test sessions of 3D gait analysis with and without the brace at the initial evaluation (W0) and after 5 weeks (W5) of wearing the brace. VAS-Pain, Satisfaction scores, WOMAC scores, spatio-temporal gait parameters (gait speed, stride length, stance and double stance phase, step width), biomechanical data of the ipsilateral lower limb (hip, knee ankle and foot progression angle) were recorded at each session <h3>Results</h3> VAS-pain and WOMAC significantly decreased at W5. Walking speed was not significantly modified by knee bracing at W0, but increased significantly at W5. Knee adduction moments and foot progression angles significantly decreased in the terminal stance and push off, respectively, with bracing at W0 and W5. Lower-limb joint angles, moments and powers were significantly modified by wearing the brace at W0 and W5. <h3>Conclusions</h3> This new knee brace with distraction-rotation effects significantly alters knee adduction moments and foot progression angles during gait, which might lead to significant functional gait improvements and have carry-over effects on pain at the short term in osteoarthritis patients (&lt;2 months). <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1930
A7.18 Pathways Induced by Etanercept and Adalimumab are Specific in RA Patients
Authors: Romain Normand, Celine Derambure, Martine Hiron, Xavier Le Loët, Olivier Vittecoq, Thierry Lequerré
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The development of tumour necrosis factor alpha (TNFα) inhibitors has led to major advances in the management of rheumatoid arthritis (RA). However, the molecular mechanisms of these agents are poorly understood. <h3>Objective</h3> In order to better understand the specifics effects of Adalimumab and Etanercept, we identified and compared the gene expression profiling in peripheral blood mononuclear cells (PBMCs) from responder (R) RA patients treated by methotrexate (MTX)/adalimumab (ADA) or MTX/etanercept (ETA) before and at 3 months after the beginning of the treatment. <h3>Methods</h3> Nineteen RA patients were randomised to receive subcutaneously either ADA (40 mg each other week) or ETA (50 mg per week). Thirteen RA patients [average age: 48.6 ± 14.3 years old (yo), MTX: 13.1 ± 6.3 mg/week (w), initial DAS28: 5.5 ± 0.6] received ADA while six RA patients (age: 52.5 ± 16.1 yo, MTX: 18.3 ± 3 mg/w, initial DAS28: 5.7 ± 1.3) were treated by ETA. The drug efficacy was evaluated with the DAS28 after 3 months of treatment according to the EULAR response criteria in order to discriminate R to NR. A blood sample was carried out before the first injection and after 3 months in order to isolate PBMCs and extract total RNA for hybridisation on whole human genome Agilent 4 × 44 k array. A supervised analysis was performed using t-test (GeneSpring GX software) combined with a fold-change 1.5 in order to identify genes whose expression were altered in PBMCs after 3 months from R to each drug. Next, transcripts sets were analysed to identify potential functional pathways (Human Reactome). Gene expression profiles and functional pathways obtained for R to each anti-TNFα were compared. <h3>Results</h3> Demographic, clinical and biological characteristics of all the patients were comparable before and after treatment administration. From the R (7/13) patients treated with ADA, a combination of 63 transcripts involved in mTORC1-mediated Signalling was identified. Concerning the R (2/6) treated by ETA, a combination of 16 transcripts involved in TNF Signalling, Death Receptor Signalling was observed. Any overlap was found when we compared these transcripts sets. Moreover, any common biological functions and functional pathways were found between R ADA and R ETA. <h3>Conclusions</h3> The absence of overlap of transcripts sets and the absence of common pathways leading us to consider that molecular mechanisms of ADA and ETA are specific.
Contributions of the Virus Laboratory to Community Health
Authors: T. F. McNair Scott
Journal: New England Journal of Medicine (1954)

THE choice of this subject was made for two reasons: with the widespread control of bacterial diseases that has now been achieved, there is an increased recognition of the importance of viral and other nonbacterial diseases in the community; and it seems valuable at intervals to review the part that physicians play in the control of the health of the community of which their individual patients are integral parts. With these two points in mind, one may consider how a virus diagnostic laboratory works and enumerate the individual responsibilities of the physician using the laboratory and of the laboratory itself. . . .
S67 Characterisation of the endothelial outgrowth cell
Authors: M. Toshner, M. L. Ormiston, B. Dunmore, J. Waters, E. McKinney, A. Rana, N. Morrell
Journal: Thorax (2011)

The existence of cells circulating in the peripheral blood with the capacity of an endothelial progenitor cell (EPC) remains controversial. This is best exemplified by the original cell posited by Asahara and colleagues to be an EPC in 1997,1 which has now been clearly phenotyped as a monocyte with dendritic features.2 There remains a viable candidate known as the endothelial colony-forming cell (ECFC) or endothelial outgrowth cell (OEC), named because it cannot be seen in ex vivo culture for at least 10 days. These cells proliferate in culture, form a cobblestone monocellular layer, and form networks in ex vivo assays. Given the lack of understanding of previous candidate cells we sought to better characterise the EOC. Here we present data from electron microscopy studies, immunohistochemistry, ligand stimulation studies, and mRNA microarrays that demonstrate the EOC is a true endothelial cell. Furthermore we demonstrate that these cells can potentially be used as endothelial surrogates in patients with pulmonary hypertension due to a mutation in the bone morphogenetic protein type II receptor (BMPRII). Cells taken from the peripheral blood of patients have a deficiency in intracellular signalling in the BMPRII pathway on stimulation with BMP9. This can be demonstrated by reduced phosphoSmad 1/5 protein on western blotting, and downstream with reduced Id1 gene induction by qPCR. Therefore regardless of its origin and biologically intended function, the EOC is an endothelial cell, and has the capacity to act as an easily derivable endothelial surrogate from patients in whom vascular tissue is not normally obtainable.
The Fish-Eye Sign Revisited
Authors: BRIAN GOLDSTEIN, DARLENE FINK-BENNETT, CRAIG MAGNES
Journal: Clinical Nuclear Medicine (1999)

The fish-eye sign originally described a scintigraphic pattern representing a benign thyroid adenoma. Two patients with clinically palpable nodules had a focus of functioning tissue within an area of decreased activity, or a fish-eye sign. The cytologic diagnosis for each was degenerating colloid nodule with a focus of thyroid follicular cells. Although this sign is not pathognomonic of a benign process, it has not yet been described in a malignant one. It may, therefore, prove helpful in minimizing a patient's concern that a nodule is malignant before it is aspirated.
Incarcerated giant hiatal hernia
Authors: Ana Ponte, Rolando Pinho, Fernando Viveiros, Joana Ferreira, Amélia Tavares, Carlos Fernandes, João Carvalho
Journal: Endoscopy (2014)

An 89-year-old man with valvular heart disease and third-degree atrioventricular block with a permanent pacemaker presented with a 1-day history of nausea, coffee ground emesis, and dyspnea. Physical examination revealed hyperthermia of 37.8 °C, oxygen saturation measured by pulse oximetry of 94 %, and hemodynamic stability. Laboratory tests showed a hemoglobin level of 13.9 g/dL, leucocytosis of 13 640/mm3 with neutrophilia, and a C-reactive protein level of 3.8 mg/L. A chest radiograph showed a giant hiatal hernia with migration of the entire stomach with an air-fluid level inside ([Fig. 1]). After orotracheal intubation, upper gastrointestinal endoscopy was performed which revealed signs of mucosal ischemia of the proximal gastric body with a 5-cm-long ulcer just distal to the esophagogastric junction ([Fig. 2]). The patient was referred to surgery which revealed total gastric herniation ([Fig. 3]) with incarceration and signs of ischemia ([Fig. 4]) that reversed spontaneously after reduction of the hernia sac. A laparoscopic hernia repair ([Fig. 5]) was performed followed by a fundoplication ([Fig. 6]).
P225 Routes of Domiciliary Non-Invasive Ventilation (NIV) Set-Up
Authors: S Agarwal, M Vaughan, C Wharton, S Ejiofor, B Chakraborty, E Gallagher, R Mukherjee
Journal: Thorax (2012)

<h3>Introduction</h3> Domiciliary NIV is being increasingly used to treat chronic ventilatory failure, particularly due to obesity and neuromuscular conditions. In the course of evolution of an NIV unit within an acute hospital, most domiciliary NIVs are set up at the end of an acute episode of admission with hypercapnic acidotic respiratory failure to start with, but overtime, as more at-risk patients come under surveillance for respiratory failure, we hypothesized that a unit supervising domiciliary NIV/Home Mechanical Ventilation is expected to do more elective set-ups. <h3>Methods</h3> Comparison of the volume of new domiciliary NIV set-ups and the elective NIV set-up rate over two 12-month periods: Apr 2005-Mar 2006 (period 1) and Apr 2011-Mar 2012 (period 2) in a dedicated 11-bedded ward-based NIV unit (established: Aug 2004) in a 1000-bedded central England teaching hospital trust, providing domiciliary NIV support to over 200 patients with over 350 under surveillance for respiratory failure. <h3>Results</h3> The volume more than doubled from 19 new domiciliary NIV set-ups in period 1 to 39 new domiciliary NIV set-ups in period 2; the elective domiciliary NIV set-up rate increased from 7/19 (36.8%) to 19/39 (48.7%) between periods 1 and 2. <h3>Discussion</h3> Over time, both the volume and the elective set-uprate for new domiciliary NIV have gone up. This probably indicates that a larger proportion of people at risk of respiratory failure treatable with NIV are coming under the unit’s surveillance and has clearly been associated with the expansion and maturation of the NIV service in our experience. The ‘elective domiciliary NIV set-up rate’ can therefore be tested as a metric for comparison of centres supervising domiciliary NIV/Home Mechanical Ventilation in this rapidly evolving field.
Case 26-2002
Authors: David L. Berger, Maryam Mohammadkhani
Journal: New England Journal of Medicine (2002)

Presentation of CaseAn 87-year-old woman was admitted to the hospital because of abdominal pain, vomiting, bloody diarrhea, and an abdominal mass.The patient had been in stable health until two days before admission, when crampy, increasingly severe lower abdominal pain developed, accompanied by nausea, vomiting, and diarrhea, with the intermittent passage of fresh blood. She had eaten little food since the onset of symptoms. She was admitted to the hospital.There was a remote history of pemphigus vulgaris, which had resolved, and a six-year history of atrial fibrillation, for which she took digoxin, warfarin, hydrochlorothiazide, and metoprolol, with control . . .