tbuckley/cabot-search huggingface dataset:
FRI0394 The Proteasome Inhibitor Bortezomib Ameliorates Refractory Systemic Lupus Erythematosus (SLE): A Prospective Multi-Centre Observational Study
Authors: T. Alexander, R. Sarfert, J. Klotsche, A. Rubbert-Roth, H.-M. Lorenz, J. Rech, B. Hoyer, Q. Cheng, A. Waka, A. Taddeo, A.A. Kühl, G. Schett, G.-R. Burmester, A. Radbruch, F. Hiepe, R.E. Voll
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The proteasome inhibitor bortezomib, approved for the therapy of multiple myeloma, depletes plasma cells (PCs) and ameliorates nephritis in mouse models of systemic lupus erythematosus (SLE). Here, we analyzed the efficacy of bortezomib as induction therapy in patients with refractory SLE. <h3>Methods</h3> Twelve patients with active SLE were included in this prospective multicentre cohort study. The patients received one to four cycles of intravenous bortezomib (Velcade®) 1.3mg/m<sup>2</sup> as “off-label” treatment. Disease activity was evaluated using the SELENA-SLEDAI score. We determined serum concentrations of anti–double-stranded DNA (anti-dsDNA) and protective antibodies. Multicolor flow cytometry was performed to analyze peripheral blood B and PC subsets as well as Siglec-1 expression on monocytes as surrogate marker for type I interferon (IFN) activity. <h3>Results</h3> The disease activity significantly decreased upon induction therapy with bortezomib and remained stable for the following 3 months under maintenance therapies. Treatment-related adverse events were mild or moderate. During proteasome inhibition, serum antibody concentrations significantly declined with greater reductions in anti-dsDNA (∼60%) than protective (∼30%) antibodies. Upon bortezomib treatment, numbers of HLA-DR<sup>+</sup> short-lived (p=0.024) and HLA-DR<sup>–</sup> long-lived (p=0.038) peripheral blood PCs were strongly decreased, whereas circulating B cells remained virtually unaffected. Notably, PC numbers significantly increased in-between cycles. Siglec-1 expression on monocytes significantly declined (p&lt;0.001) indicating reduced type 1 IFN activity. <h3>Conclusions</h3> Bortezomib targeting PCs and type I IFN activation may represent an effective treatment option with rather low toxicity in refractory SLE patients. Bortezomib efficiently induces short-term remissions but requires maintenance treatment inhibiting PC regeneration for sustained efficacy. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5884
FRI0032 Increased level of IL-34 in serum and synovial fluid is associated with rheumatoid factor and anti-cyclic citrullinated peptide antibodies titer in patients with rheumatoid arthritis
Authors: S.-J. Moon, J.-K. Min, Y.-S. Hong
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Interleukin-34 (IL-34) is a recently discovered cytokine that binds macrophage colony-stimulating factor (M-CSF). Rheumatoid arthritis (RA) is a representative inflammatory arthritis characterized by increased osteoclastogenesis, which contributes to joint destruction and generalized bone loss. <h3>Objectives</h3> To identify the possible pathophysiological significance of IL-34 in RA, the level of this cytokine was measured in serum and synovial fluid (SF) from patients with RA. <h3>Methods</h3> IL-34 levels were measured in serum from 113 patients with RA, 56 patients with osteoarthritis (OA), and 36 controls, and in SF isolated from patients with RA (<i>n</i> = 36) or OA (<i>n</i> = 24). Correlations between serum IL-34 concentration and clinical and laboratory features, RA disease activity score, and bone mineral density (BMD) were assessed in RA patients. The levels of IL-1β, IL-6, IL-17α, interferon-γ-induced protein 10 (IP-10), receptor activator of nuclear factor kB ligand (RANKL), and dickkopf-1 (DKK-1), which are implicated in osteoclastogenesis, were also measured in serum and SF samples. <h3>Results</h3> RA patients had a significantly higher mean serum level of IL-34 than did OA patients and controls (188.0 ± 550.3, 36.6 ± 38.0, and 49.1 ± 78.5 pg/ml, respectively). Similarly, mean SF IL-34 concentration was also higher in RA than in OA patients. Paired samples isolated from seven RA patients showed similar levels of IL-34 in serum and SF. In serum from RA and OA patients, IL-34 levels were positively associated with IL-6 levels. SF IL-34 concentration correlated significantly with IL-6 (r = 0.482) and RANKL (r = 0.635) levels in RA but not in OA patients. In RA patients, serum IL-34 level did not correlate significantly with variables reflecting inflammation status, joint damage severity, or BMD. However, in RA patients, serum IL-34 level correlated significantly with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody titers (r = 0.282 and 0.491, respectively). <h3>Conclusions</h3> This study shows for the first time increased IL-34 concentrations in serum and SF in RA patients compared with OA patients and controls. Circulating IL-34 level is significantly associated with RF and anti-CCP antibody titers. These observations suggest a link between IL-34 and RA pathogenesis. <h3>References</h3> Lin H et al. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science (New York, NY) 2008; 320:807-811. Chen Z et al. The critical role of IL-34 in osteoclastogenesis. PloS one 2011; 6: e18689. <h3>Acknowledgements</h3> This research was partially supported by grants from Daewoong Pharmaceuticals Corporations. <h3>Disclosure of Interest</h3> None Declared
Heimlich maneuver to relieve choking caused by a duodenal subepithelial tumor that was resected by endoscopic mucosal resection
Authors: W.-H. Liao, C.-S. Chen, P.-F. Liu, W.-H. Lee, I.-L. Lee
Journal: Endoscopy (2012)

We present a rare case of choking caused by a duodenal subepithelial tumor resected by endoscopic mucosal resection (EMR). The Heimlich maneuver was performed successfully to relieve the patient's choking.
Disseminated Intravascular Coagulation
Authors: Marcel Levi, Hugo ten Cate
Journal: New England Journal of Medicine (1999)

Disseminated intravascular coagulation is characterized by the widespread activation of coagulation, which results in the intravascular formation of fibrin and ultimately thrombotic occlusion of small and midsize vessels.13 Intravascular coagulation can also compromise the blood supply to organs and, in conjunction with hemodynamic and metabolic derangements, may contribute to the failure of multiple organs. At the same time, the use and subsequent depletion of platelets and coagulation proteins resulting from the ongoing coagulation may induce severe bleeding (Figure 1). Bleeding may be the presenting symptom in a patient with disseminated intravascular coagulation, a factor that can complicate decisions about . . .
PWE-263 Liver to abdominal area ratio: a novel radiology test for prognostication in liver cirrhosis
Authors: M Joseph, T J S Cross
Journal: Gut (2012)

<h3>Introduction</h3> Prognostication in cirrhotic liver disease is difficult. There are several validated indices which are employed including: Child-Pugh score, MELD and UKELD. There is anecdotal data that liver size is important in determining patient survival and likelihood of re-compensation. <h3>Aims</h3> To assess a ratio of liver area and abdominal area on cross-sectional imaging using CT to predict the likelihood of death or need for liver transplantation (LT) in patients with liver cirrhosis. <h3>Methods</h3> A retrospective analysis of 280 patients referred to the South West Liver Unit. All patients with cirrhosis were included who had liver CT available. Patients with acute liver failure or hepatoma were excluded from the analysis. Using a webpacs system patient imaging were retrieved and the cross sectional image with the largest area of liver was identified. The liver to abdomen area ration (LAAR) was estimated from the hypothesised ellipses represented by the liver and abdomen using the formula Πab (where ‘a’ being half of the long axis and ‘b’ being half of the short axis). These values were compared against patient survival vs patient death/LT. Accuracy of LAAR in predicting the outcome was assessed using Mann–Whitney U test. <h3>Results</h3> 280 patients were identified. Sex was available in 200 patients (61% male). Aetiology was available in 266 patients: ALD=103, HCV=32, NASH=10, PBC=10, PSC=13, HCC=31, ALF=12, Others=51. HCC and ALF patients were excluded from analysis. The median age 54.2 (46.6–61.1). Ascites was present in 79 of 127 patients (62%). Not all patients had a CT. LAAR was calculated in 108 patients, median 0.37 (0.3–0.43) and was shown to be predictive of death/LT (p=0.035). The presence of ascites did not predict survival (χ<sup>2</sup> 2.5, p=0.12, OR 1.9 (95% CI 0.86 to 4.01)). <h3>Conclusion</h3> LAAR is a simple, novel imaging based technique to assess prognosis in patients with cirrhosis. It confirms anecdotal data that liver size is important in assessing survival. It is more accurate in determining survival than the presence of ascites. LAAR could be incorporated into existing algorithms for patient selection for LT and in determining patient survival with cirrhosis. Its accuracy should be compared against Childs-Pugh, MELD and UKELD alone or in combination to evaluate its utility in clinical practice. <h3>Competing interests</h3> None declared.
RIGHT VENTRICULAR GLOBAL AND REGIONAL FUNCTION AS ASSESSED BY TWO-DIMENSIONAL STRAIN IMAGING IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY
Authors: Alexandros Briasoulis, Fayez Siddiqui, Issa Alesh, Anupama Kottam, Sabeeh Siddiqui, Nitin Mahajan, Luis Afonso
Journal: Journal of the American College of Cardiology (2015)
Scintigraphic Evaluation of Mild to Moderate Dysphagia in Motor Neuron Disease
Authors: Katarzyna Szacka, Anna Potulska-Chromik, Katarzyna Fronczewska-Wieniawska, Andrzej Spychała, Leszek Kròlicki, Magdalena Kuźma-Kozakiewicz
Journal: Clinical Nuclear Medicine (2016)

Approximately 30% of patients with motor neuron disease (MND) present swallowing difficulties even in early disease stages. The aim of this study was to examine the usefulness of esophageal scintigraphy in detecting early stage of dysphagia in MND.Esophageal scintigraphy (ES) including mean transit time (MTT) estimation was performed in 121 MND patients presenting various levels of upper (UMN) and lower motor neuron (LMN) degeneration.ES detected dysphagia in more than 80% of MND patients who had referenced swallowing difficulties. In MND patients with ES-confirmed dysphagia, the MTT was increased approximately 2-fold without significant differences between the clinical phenotypes. The MTT was significantly longer in patients with bulbar-pseudobulbar syndrome in comparison to patients with isolated pseudobulbar syndrome, which indicates a higher involvement of the LMN deficiency in developing dysphagia in MND. The esophageal passage in MND was not dependent on age, sex, disease duration, or diagnosis delay. Interestingly, ES was also able to detect dysphagia in almost 70% of MND individuals who had no swallowing complaints (subclinical dysphagia). A more benign disease course and a higher percentage of male patients characterized this group.Esophageal scintigraphy is a helpful screening tool in determining early swallowing impairment in a high percent of patients with MND of various clinical phenotypes.
Reversal of Impaired Splenic Function in Patients with Nephritis or Vasculitis (or Both) by Plasma Exchange
Authors: C. M. Lockwood, Sheila Worlledge, Adele Nicholas, Charles Cotton, D. Keith Peters
Journal: New England Journal of Medicine (1979)

By studying the clearance of autologous labeled antibody-coated or heat-damaged erythrocytes, we showed that reversible blockade of the splenic component of reticuloendothelial function existed in 14 of 15 patients referred for treatment of nephritis or vasculitis. In 10 patients treated by plasma exchange — alone in three and combined with steroids and cytotoxic drugs in six — reversal of splenic blockade followed in nine, and in the three patients treated solely by plasma exchange this reversal was demonstrated to occur within 48 hours of the procedure. Only gradual reversal of splenic blockade was found in three of five patients treated by steroids with or without cytotoxic drugs; no change in splenic function was observed in two. When circulating immune complexes were detected by a C1q-binding assay, there was, in serial studies, an approximate inverse correlation between splenic function and the level of C1q-binding material, though hyposplenism was also a feature of patients in whom the C1q-binding assay was negative. (N Engl J Med 300:524–530, 1979)
THU0203 Elevated C-Reactive Protein is Associated with Lower Knee Muscle Strength in Patients with Knee Osteoarthritis: A 2 Year Follow up Study in the AMS-OA Cohort
Authors: D. Sanchez, M. van der Leeden, M. van der Esch, L. Roorda, S. Verschueren, J. van Dieen, J. Dekker, W. Lems
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In patients with knee osteoarthritis (OA) lower muscle strength is associated with disease progression and activity limitations. Lower muscle strength in this group of patients is determined by several factors, including pain, avoidance of activities and aging. More recently evidence from cross-sectional studies has suggested that inflammation is an additional factor influencing muscle strength in patients with knee OA [1]. <h3>Objectives</h3> To examine the associations of elevated serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) with change in muscle strength in patients with established knee OA, over two years. <h3>Methods</h3> Data from 186 patients with knee OA were gathered at baseline and at two-years follow up. CRP (mg/l) and ESR (mm/l) were measured in serum from patients9 blood. Strength of quadriceps and hamstrings muscles was assessed using an isokinetic dynamometer. The association of inflammatory markers with change in knee muscle strength was analysed using uni- and multivariate linear regression models. <h3>Results</h3> Patients with elevated CRP values at both baseline and two-years follow up exhibited a lower increase in knee muscle strength over two years (β= -0.22; p=0.01) compared with the group with not elevated levels at both times of assessment. The association persisted after adjustment for relevant confounders. Elevated ESR values at both times of assessment were not significantly associated with change in knee muscle strength (β=-0.05; p=0.49). <h3>Conclusions</h3> Our results indicate that elevated CRP values are related to a lower gain in muscle strength over time in patients with established knee OA. Although the mechanism to explain this relationship is not fully elucidated, these results suggest inflammation as a relevant factor influencing muscle strength in this group of patients. <h3>References</h3> Sanchez-Ramirez DC, van der LM, van der EM, Gerritsen M, Roorda LD, Verschueren S, van Dieen J, Deker J, Lems WF: Association of serum C-reactive protein and erythrocyte sedimentation rate with muscle strength in patients with knee osteoarthritis. Rheumatology (Oxford) 2013, 52: 727-732. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1362
Calcified thrombosis in the portal system mimicking choledocholithiasis and diagnosed by endoscopic ultrasound
Authors: Augusto Carbonari, Flavio Amaro, Frank Nakao, Osvaldo Araki, Mauricio Assef, Lucio Rossini
Journal: Endoscopy (2014)

A 67-year-old woman with abdominal pain and jaundice for the preceding 6 months was referred for endoscopic ultrasound (EUS) to evaluate the presence of choledocholithiasis. The patient had a history of diabetes, schistosomal infection, and chronic hepatitis C (cirrhotic portal hypertension). A computed tomography (CT) scan showed cholelithiasis, calcified thrombosis in the portal system, and possible choledocholithiasis ([Figs. 1, 2]). EUS showed cholelithiasis and calcified thrombosis in the portal and splenic veins. Evidence of choledocholithiasis was not observed ([Figs. 3 – 6]).
A8.02 Methyl cap binding protein 2 (MECP2) in systemic sclerosis
Authors: S O’Reilly
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objective</h3> Systemic sclerosis (SSc) is an autoimmune connective tissue disease with a high all cause mortality. Although there is a small genetic component it is likely that the majority of variation in the disease is due to epigenetic events. Methylation is important in regulating gene expression and methylated DNA can bind to MeCP2 aiding repression. MeCP2 is more commonly associated with the neurological disease Rett syndrome where this is enriched, but MeCP2 is expressed ubiquitously. It is known that MeCP2/Rett mice are protected from experimentally induced liver fibrosis. The aim of this study was to examine the role of MeCP2 in systemic sclerosis. <h3>Materials and methods</h3> Dermal fibroblasts were isolated from patients or controls from skin punch biopsies n = 5. MeCP2 was quantitated by real time PCR and normalised to 18S housekeeping gene. MeCP2 was silenced with MeCP2 siRNA or scramble control siRNA using HiPerfect transfection. Collagen was measured using qPCR and alpha smooth muscle actin was quantitated using western blotting method. PPAR-γ was also measured. Mice were treated with bleomycin to induce fibrosis. Skin sections from the mice treated or control was measured for MeCP2 and collagen levels by qPCR. <h3>Results</h3> SSc dermal fibroblasts have significantly elevated MeCP2 levels compared to controls. Silencing of MeCP2 levels attenuates the expression of collagen transcripts and alpha-Sma expression. Also reduction of MeCP2 leads to elevated PPAR-γ. Mice treated with bleomycin have elevated levels of MeCP2 and collagen levels within the fibrotic skin. <h3>Conclusion</h3> MeCP2 is important in SSc and is elevated. MeCP2 appears to regulate ECM markers. PPAR-γ is a master regulator of fibrosis and this may be altered by MeCP2 levels leading to derepression of ECM genes.
[Comparison of 17 Methods of Predicting the Carcinogenicity of 30 Chemicals]: Response
Authors: Douglas W. Bristol, Joseph T. Wachsman, Arnold Greenwell
Journal: Environmental Health Perspectives (1997)

20 of 30 chemicals will be carcinogenic (66%).Third, some methods have a high proportion of unresolved predictions, for example, 13 of 17 for the CSWG method and 11 of 17 for the FALS method.Fourth, the carcinogenicity of inorganic chemicals seems to be particularly difficult to predict (e.g., 11/17 unresolved pre- dictions for molybdenum trioxide and 7/17 for both gallium arsenide and vanadium pentoxide).Finally, Lewis et al. (2) list a full set of Ames test results for these 30 chemicals, 8 of which are reported to be mutagenic.It would be useful if those data could be endorsed and made part of the overall study, the Ames test being the most generally used carcinogenicity prediction technique.Broad analyses, such as that undertaken above, can be done in the absence of the final carcinogenicity data, and they are to be encour- aged subsequent to a reformulation of the sum- mary table.With the wide range of performance characteristics evident, it is inevitable that some of the predictive methods will be found to be of no general value when the final cancer data are avilable.Whether any of the assays that perform well can be generally adopted for routine use will then become the leading question.The hope must be that such decisions will be faced and that some methods will disappear while others will be generally endorsed and developed.What is certain is that a major shake-out of predictive methodologies lies ahead of us, as illustrated by the need to understand why there is only 60% agreement between the predictions made by Tennant and Spalding (4) and those made by Ashby (5)each of whom used the same predictive method (6).
Who are you calling fat?
Authors: T. Delamothe
Journal: BMJ (2012)

As England’s adults and children are plumping up (doi:10.1136/bmj.e2332) doctors are tying themselves up in knots over the right words to use with their podgy patients. It’s a minefield out there. On a ward round Ian Seetho wondered aloud whether a patient was too heavy for the hospital’s CT table—only to see his patient’s demeanour rapidly deteriorate (doi:10.1136/bmj.e1370). Apparently, studies show that patients prefer terms like “body mass index” and “excess weight” to “fat,” “obese,” and “extremely obese.” Seetho’s bottom line: “When describing a diagnosis or talking to patients, it is important to be ever so mindful of our choice of words in relation to how …
Impairment of homologous recombination directed DNA repair in prostate cancer cells exposed to anchorage independence
Authors: K. Reiss, J. Y. Wang, T. Ho, T. Stoklosa, T. Skorski, P. Mencel
Journal: Journal of Clinical Oncology (2004)

9638 Background: The majority of patients with androgen dependant prostate cancer develop a transition to highly invasive metastatic disease, which is refractory to hormonal therapy. This complication relies on the acquisition of new properties, which allow cancer cells to invade other tissues. One mechanism via which rapid genetic changes could occur is a failure of systems controlling stability of the genome, including DNA repair. In parallel, metastatic cells are temporarily exposed to anchorage-independence -a condition in which cellular interactions with extracellular matrix proteins are restricted. The purpose of this study was to evaluate whether and how anchorage-independence could predispose prostate cancer cells to develop genomic instability. Methods: DNA repair mechanisms: non-homologous end joining (NHEJ) and homologous recombination directed DNA repair (HRR) were evaluated in human prostate cancer cell lines: DU145, LNCaP and PC-3. Cell survival was evaluated by trypan blue exclusion, cell cycle distribution by flow-cytometry, and DNA repair proteins by western blotting and immunocytofluorescence. Results: The sensitivity of prostate cancer cells to irradiation, cisplatin and mitomycin increased several fold in anchorage-independence. This enhanced drug sensitivity was associated with a severe impairment of HRR. The mechanism involved Rad51, which is the major enzymatic component of HRR. The protein level of Rad51 and its recruitment to DNA breaks were both attenuated. Rad51 deficiency in anchorage-independence was not associated with Rad51 promoter activity, and was not compensated by a constitutive overexpression of Rad51 cDNA. However, Rad51 protein was efficiently restored in the presence of the proteosom inhibitor epoxomycin, or when cells from suspension cultures were allowed to reattach. Conclusions: Anchorage-independence sensitizes prostate cancer cells to genotoxic agents; however, it also attenuates a faithful component of DNA repair by targeting the stability of Rad51. This may contribute to the development of the metastatic phenotype in cells, which survive genotoxic treatment. No significant financial relationships to disclose.
Keratitis from Misuse of Corneal Anesthetics
Authors: David L. Epstein, David Paton
Journal: New England Journal of Medicine (1968)

Five cases are presented to emphasize the fact that chronic use of topical anesthetics on the eye can lead to severe keratitis and even permanent reduction of visual acuity. These reactions can be evoked in any eye that has been subjected to prolonged topical anesthesia as a means of relieving the discomfort of minor injuries. Loss of corneal epithelium (with resultant increased reliance on the anesthetic), opacification and edema of the corneal stroma and marked inflammatory changes in the anterior segment of the eye is the sequence of events that follow days or weeks of such treatment. Topical anesthetics should only be used for the purpose of obtaining transient loss of corneal sensitivity and never as part of a prolonged medical regimen.