tbuckley/cabot-search huggingface dataset:
AB0298 High level of anti-ccp antibodies is predictive of good response to rituximab in patients with active rheumatoid arthritis.
Authors: A. Gardette, S. Ottaviani, F. Tubach, P. Nicaise-Roland, E. Palazzo, G. Gill, O. Meyer, P. Dieudé
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the current era, where the number of new biologic targets and related therapies for rheumatoid arthritis (RA) is rapidly increasing, identification of factors that predicts the response to biologic therapies is a key issue. Previous studies reported that an anti-CCP positive status is predictive of a good response to Rituximab (RTX) in RA. A quantitative approach could be a good way to better detect subset of individuals that are more likely responders. <h3>Objectives</h3> We investigated whether anti-CCP serum levels were predictive of the response to RTX at M6 in patients having active RA. <h3>Methods</h3> 114 RA patients treated with RTX were retrospectively included. The primary criterion was the decrease of DAS28 &gt;1.2 at M6. Secondary efficacy criteria included the variation of DAS28 (ΔDAS), SJC, TJC, VAS pain, ESR, CRP and use of corticosteroids. Independent predictors of good response were investigated by using multivariate logistic regression analysis. <h3>Results</h3> A total of 114 RA patients (81.6% of female, mean age 53.3 +/- 11.9 years and mean disease duration: 10.9 +/- 8.3 years, 75.2% RF+) were included. Anti-CCP antibodies were present in 81.6% of patients with a median level of 583 [195-1509] U/ml. A decrease of DAS28 &gt;1.2 was observed in 38.6% of patients. In univariate analysis, high anti-CCP level was an independent factor associated with a response to RTX (median 1122 [355-1755] <i>vs.</i> 386 [143-800] U/ml, <i>P</i>=0.0059) at M6. Using the cut-off level of 1000 U/ml, multivariate logistic regression analysis, identified CCP+ patients with anti-CCP levels &gt;1000 U/ml were 5 times more likely to achieve the decrease of DAS28 &gt;1.2 ([OR: 5.10; 95% CI: 1.97-13.2], <i>P</i>=0.0008). High anti-CCP level was also predictive of a higher decrease of i) the DAS28 (<i>P</i>=0.0371) ii) TJC (<i>P</i>=0.0469), at M6. <h3>Conclusions</h3> High anti-CCP level is an independent predictive factor of response to RTX at M6 in RA patients. This factor is easily assessed in clinical practice, can help to a personalised medicine and to select the best candidates for RTX treatment. <h3>Disclosure of Interest</h3> None Declared
P248 Current Copd Disease Burden Associated With Maintenance Monotherapy In The Uk
Authors: S. Edwards, S. Fairbrother, A. Scowcroft, L. White, B. Lipworth
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> National Institute for Health and Care Excellence (NICE) recommends long–acting bronchodilators, including β2-agonists (LABAs) or muscarinic antagonists (LAMAs) as first line maintenance treatment for patients with COPD. The aim of this descriptive study was to characterise a cohort of COPD patients who were on maintenance bronchodilator monotherapy for at least six months to establish their disease burden, measured by healthcare utilisation. <h3>Methods</h3> Data were extracted from the UK Clinical Practice Research Datalink (CPRD) which also linked to Hospital Episode Statistics (HES). The monotherapy period spanned the first prescription of a LABA or LAMA until the end of the study period (31/12/2013) or until step-up to dual/triple therapy; for example the addition of another long acting bronchodilator, an ICS or ICS/LABA. A minimum of four consecutive prescriptions and six months on continuous monotherapy were required for study entry. Patients &lt;50 years old at time of first COPD diagnosis or with another significant respiratory disease prior to the start of monotherapy were excluded. Disease burden was evaluated by measuring patients’ rate of consultations with a healthcare professional (HCP), COPD-related exacerbations, hospitalisations and referrals to key specialities. <h3>Results</h3> A cohort of 8,811 COPD patients (94% GOLD stage A or B) on maintenance monotherapy was identified between 2002 and 2013; 45% (N=3,947) of these patients were still on monotherapy by the end of the study period. The median time from first COPD diagnosis to first monotherapy prescription was 56 days while the median time on maintenance bronchodilator monotherapy was 748 days. The median number of prescriptions during this period was 14. Patients had a median of 19 HCP consultations and a mean of 0.1 (95% CI 0.1, 0.2, N= 8,811) COPD exacerbations and 0.02 (95% CI 0.01, 0.02, N=4,848) COPD hospitalisations per year. <h3>Conclusion</h3> In summary, COPD patients who are on maintenance bronchodilator monotherapy for at least six months appear to remain on this therapy for over two years despite having a disease burden that requires healthcare resources, particularly HCP consultations, at a cost to the NHS.
Differences in Risk of Insulin-Dependent Diabetes in Offspring of Diabetic Mothers and Diabetic Fathers
Authors: James H. Warram, Andrzej S. Krolewski, Marise S. Gottlieb, C. Ronald Kahn
Journal: New England Journal of Medicine (1984)

To examine the role of heritable factors in insulin-dependent diabetes mellitus (IDDM), we studied the incidence of IDDM in the offspring of patients with the disease who were identified by the medical records of the Joslin Diabetes Center from 1928 to 1939. We found 187 survivors who, after the diagnosis of IDDM, had produced 419 offspring for whom information about diabetes status was available. By the age of 20, 6.1 per cent of the offspring of the 88 men had diabetes; in contrast, only 1.3 per cent of the offspring of the 99 women had the disease by the age of 20 (P<0.05). Daughters and sons of the men with IDDM were affected equally (there were insufficient numbers of affected offspring of diabetic women to permit determination of whether the sexes were equally affected). We conclude that IDDM is transmitted less frequently to the offspring of diabetic women than to those of diabetic men. More study is required to determine whether this difference reflects a genetic mechanism or, instead, selective perinatal loss of the affected offspring of diabetic mothers. (N Engl J Med 1984; 311:149–52.)
Abstract 4197: Mouse xenograft models of human soft tissue sarcomas
Authors: Ewa Sicinska, Samuel Moss, Joseph Brito, Carmen Priolo, Stephen Finn, Andrew Wagner, George Demetri, Massimo Loda
Journal: Cancer Research (2010)

Abstract Sarcoma represents a class of tumors arising from mesenchymal tissue. New approaches that target sarcoma-specific molecular alterations hold a promise of more effective therapies. Currently available sarcoma models do not accurately resemble relevant properties of the human disease and very often are inadequate for predicting the efficacy of investigational drugs in preclinical settings. Thus, in order to test novel targeted therapies, it is essential to develop in vivo models of sarcomas. To this end, we have created a panel of well-characterized xenografts of primary human sarcomas that represent a spectrum of histotypes. Specifically, we transplanted intact human sarcomas under the skin of immunodeficient mice. We then compared the morphologic, phenotypic, and genetic characteristics of the tumor tissues before and after implantation in recipient mice. To date, we have implanted into Nu/Nu recipients tumor tissue fragments from 32 gastrointestinal stromal tumors (GIST) 10 dedifferentiated liposarcomas and 6 leiomyosarcomas. Successful tumor growth was detected in 86% cases of GIST, 44% of liposarcomas and 33% of leiomyosarcomas. Upon serial transplantation, 35% of GISTs, 44% of liposarcomas and 33% of leiomyosarcomas have grown beyond passage F3. Histological analysis of the primary tumors and corresponding xenografts revealed that morphology and immunophenotype (c-Kit status for GISTs, MDM2 for liposarcomas, Smooth Muscle Actin for leiomyosarcomas) was retained throughout all passages. Moreover, all major genetic abnormalities present in the primary tumors were retained in the xenografts, as revealed by genome-wide Single Nucleotide Polymorphism (SNP) array analyses. Our results show that this approach can be used to generate animal models that faithfully reproduce characteristics of human intact tumors. These models can be used for in vivo preclinical drug testing, diagnostic and prognostic molecular markers discovery, and for identification of molecular mechanisms of drug resistance. 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 4197.
Baculoviral IAP Repeat-Containing-4 Protects Optic Nerve Axons in a Rat Glaucoma Model
Authors: Stuart J. McKinnon, Donna M. Lehman, N.Grace Tahzib, Nancy L. Ransom, Herbert A. Reitsamer, Peter Liston, Eric LaCasse, Qiuhong Li, Robert G. Korneluk, William W. Hauswirth
Journal: Molecular Therapy (2002)

Gene therapy represents an attractive approach for the treatment of eye diseases such as glaucoma. Ocular administration of viral vectors produces localized retinal gene expression with reduced risks of side effects reported with systemic administration of viral vectors. Recombinant adeno-associated viral (AAV) vectors have proven effective in producing long-term retinal gene expression, due to stable integration of DNA into the genome and lack of host immune response to the virus. Recently developed AAV constructs using the chicken β-actin (CBA) promoter drive highly efficient transgene expression in retinal ganglion cells (RGCs), photoreceptors, and pigment epithelium. Rats were given unilateral intravitreal injections of AAV-CBA vector coding for human baculoviral IAP repeat-containing protein-4 (BIRC4), a potent caspase inhibitor. Ocular hypertension was induced in the same eye by sclerosis of aqueous humor outflow channels. After chronic exposure to elevated intraocular pressure, we performed optic nerve axon counts to determine the neuroprotective effects of retinal BIRC4 expression, and compared axon survival with vector and balanced salt solution control groups. Gene therapy delivering BIRC4 significantly promoted optic nerve axon survival in a chronic ocular hypertensive model of rat glaucoma. Blocking RGC apoptosis with caspase inhibitors represents a promising approach for treatment of human glaucoma.
Unexplained Opportunistic Infections and CD4+ T-Lymphocytopenia without HIV Infection -- An Investigation of Cases in the United States
Authors: D K Smith, J J Neal, S D Holmberg
Journal: New England Journal of Medicine (1993)

The clinical and public health importance of recent reports of patients with CD4+ T-lymphocytopenia without human immunodeficiency virus (HIV) infection is unclear. We conducted investigations to determine the demographic, clinical, and immunologic features of patients with idiopathic CD4+ T-lymphocytopenia; whether the syndrome is epidemic or transmissible; and the possible causes.
EUS-guided anterograde treatment of biliary stones following gastric bypass
Authors: F Weilert, KF Binmoeller, FP Marson, JN Shah
Journal: Endoscopy (2011)

Background: Endoscopic treatment of bile duct stones in gastric bypass patients is a challenge. Current approaches involve attempts at deep enteroscopy with retrograde access or standard ERCP after surgical gastrostomy. However, these techniques can be technically difficult and increase the level of invasiveness. We describe a novel method involving EUS-guided anterograde interventions.
Abstract 5290: MicroRNA-495-3p functions as tumor suppressor by targeting multiple oncogenic epigenetic effector molecules in gastric cancer.
Authors: Min Gyu Kim, Seung Jin Kim, Hyun Jin Bae, Ji Heon Noh, Jeong Kyu Kim, Jung Woo Eun, Kwang Hwa Jung, Young Gyoon Chang, Qingyu Shen, Won Sang Park, Jung Young Lee, Suk Woo Nam
Journal: Cancer Research (2013)

Abstract Epigenetic effector molecules are involved in many biological processes by regulating post-translational histone modification and DNA methylation. Recent evidence has suggested that several epigenetic effectors are aberrantly over-expressed in gastric cancer (GC). However, underlying regulatory mechanisms of those molecules are not completely understood. In this study, we identified miR-495-3p which regulates multiple epigenetic effectors through a comprehensive miRNA profiling analysis with in silico target prediction in GC. The down-regulation of miR-495-3p was demonstrated in a subset of GC tissue, revealing inverse correlation with expression levels of epigenetic effectors that were predicted to be targeted by miR-495-3p. Ectopic overexpression of miR-495-3p in GC cells suppressed protein expression and 3’-UTR (untranslated region) reporter luciferase activity of multiple epigenetic effectors including histone deacetylase 2 (HDAC2), SET and MYND domain-containing protein 3 (SMYD3), DNA methyltransferase 1 (DNMT1) and metastasis-associated protein1 (MTA1). Moreover, miR-495-3p attenuated cancer cell proliferation accompanied with LC3B-II conversion, PARP cleavage, p16INK4A expression and down-regulation of CDK4/6 and cyclin D1, which were implicated in autophagic cell death, apoptosis and cell cycle regulation, respectively. In addition, ectopically over-expressed miR-495-3p inhibits cell migration via suppressing epithelial-mesenchymal transition (EMT)-related molecules, Snail and SLUG. Taken together, we suggest that a loss or down-regulation of endogenous miR-495-3p triggers aberrant overexpression of multiple oncogenic epigenetic effector molecules, and thereby miR-495-3p functions as a tumor suppressor in gastric tumorigenesis. Citation Format: Min Gyu Kim, Seung Jin Kim, Hyun Jin Bae, Ji Heon Noh, Jeong Kyu Kim, Jung Woo Eun, Kwang Hwa Jung, Young Gyoon Chang, Qingyu Shen, Won Sang Park, Jung Young Lee, Suk Woo Nam. MicroRNA-495-3p functions as tumor suppressor by targeting multiple oncogenic epigenetic effector molecules in gastric cancer. [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 5290. doi:10.1158/1538-7445.AM2013-5290 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
SAT0311 Men and women with psoriatic arthritis express a different genetic profile within the major histocompatibility complex region
Authors: R. Queiro, S. Alonso, P. Tejόn, M. Fernández, M. Alperi, J.L. Riestra, L. Arboleya, J. Ballina
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It has been shown that males with psoriatic arthritis (PsA) tend to suffer from more extended spinal disease while females are more likely to have peripheral joint involvement. It is unclear whether these findings are secondary to differences in occupational physical activity, hormonal changes or other factors (1,2). <h3>Objectives</h3> To investigate whether there are sex-related differences in the genetic profile within the Major Histocompatibility Complex (MHC) among patients with PsA. <h3>Methods</h3> One-hundred ten consecutive patients who fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) criteria were randomly selected from the rheumatology outpatient clinic of a tertiary care hospital. There were 55 men and 55 women with a mean age of 48±12 years. The distribution of the following genes and polymorphisms within the MHC region was analyzed according to sex: HLA-DR, TNFA, MICB, MICA, HLA-B, C1_2_5, HLA-C, C1_4_4, OTF3, HCR, CDSN. This typing was also performed in a control population of 110 (55 men and 55 women) random ethnically and geographically matched blood donors. The odds ratio (OR) was calculated by the cross-product ratio and the 95% confidence intervals by the Cornfield method. The extent of linkage disequilibrium between the two loci is expressed as the observed disequilibrium value (λs), i.e., a proportion of the theoretical maximum disequilibrium value (λ<sub>max</sub>) achievable for this combination of alleles. The λs were calculated using the formula: λs = λ/λ<sub>max</sub> = Pab-(Pa.Pb)/Pa.(1-Pb). <h3>Results</h3> Compared to PsA males, women tended to have more frequently polyarthritis as the main joint pattern (40% vs. 20%, p&lt;0.05), higher HAQ values (1.10±0.73 vs. 0.72±0.62, p&lt;0.01), and higher swelling joint count (5.2±6.6 vs. 3.4±4.2 p&lt;0.05). HLA-C*06 (56.4% vs. 17%, OR 6.18, 95% CI: 3.32-11.5, p&lt;0.00001), B*27 (31.8% vs. 7.3%. OR 5.9, 95% CI: 2.6-13.4, p=0.0001) and MICA*002 (60% vs. 30%, OR 3.5, 95% CI: 2.0-6.12, p&lt;0.0001) were significantly increased in PsA patients. These three markers were also significantly increased in both sexes. However, HLA-C*07 (49% vs. 25%, OR 2.8, 95%CI: 1.3-6.3; p=0.01) and TNF-308A (45.5% vs. 22%, OR 3.0, 95%CI: 1.3-6.9; p=0.009) were only increased among PsA women. <h3>Conclusions</h3> There are gender-related differences in the clinical expression of PsA that might be explained, among other factors, by sex-related differences in the expression of genes and polymorphisms within the MHC region. <h3>References</h3> Gladman DD et al. Psoriatic spondyloarthropathy in men and women: a clinical, radiographic, and HLA study. Clin Invest Med. 1992 Aug;15(4):371-5. Queiro R et al. Comparative analysis of psoriatic spondyloarthropathy between men and women. Rheumatol Int. 2001 Oct;21(2):66-8. <h3>Disclosure of Interest</h3> None Declared
Case 30-2001
Authors: Mahboob U. Rahman, Chieh-Min Fan, Hyon K. Choi
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 22-year-old man was admitted to the hospital because of fever, abdominal pain, diarrhea, and polyarthralgia.The patient had been well until two years before admission, when a tremor developed and a diagnosis of Graves' disease was made. The patient declined radioiodine treatment. The administration of propranolol and methimazole lessened the tremor.Three months before admission, a persistently low thyrotropin level led to an increase in the dose of methimazole. Soon thereafter, migratory arthralgia accompanied by swelling began in the right ankle and spread to the left ankle, knees, small joints of the hands, and both elbows, . . .
Persistent Asymmetric Brain MIBG Activity Related to a Cerebrovascular Infarct
Authors: Xia Bai, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2015)

A 13-year-old woman with a history of left malignant carotid body paraganglioma status postsurgical resection underwent 123I-MIBG scan for staging. The images demonstrated no definite evidence of MIBG-avid disease. However, there was asymmetric activity in the region of the brain with relatively less activity on the left compared with the contralateral right side on the head images, which was related to prior infarct revealed from the patient's history. This asymmetric MIBG activity persisted 8 years later.
Sarcomatoid Hepatocellular Carcinoma Diagnosed by FDG PET/CT
Authors: Baoming Mi, Weixing Wan, Chunjing Yu, Xuyang You, Qiaoling Xu
Journal: Clinical Nuclear Medicine (2011)

Sarcomatoid hepatocellular carcinoma is a rare histologic variant of hepatocellular carcinoma. We present a 72-year-old woman with a hepatic V segment neoplasm, whose tumor markers were all in normal range. Positron emission tomography/computed tomography images show intense uptake of FDG in her hepatic V segment and 2 porta hepatis nodes. Histopathology showed that the neoplasm was a malignant tumor not originating from hepatic cells, and lymph nodes were metastasis, while the neoplasm was revealed sarcomatoid hepatocellular carcinoma through immunohistochemistry.
AB0798 Prevalence, severity, and clinical correlates of pain in patients with systemic sclerosis
Authors: F. Teixeira, D. Peixoto, J. Costa, C. Afonso, D. Araujo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic sclerosis (SSc) is a multisystem disease characterized by immune system activation, fibrosis, and vasculopathy. Because SSc is a complex multisystem disease, pain may have multiple sources, patients with SSc report numerous painful symptoms, including skin breakdown, digital ulcers, Raynaud's phenomenon, musculoskeletal pain, and gastrointestinal symptom <h3>Objectives</h3> To estimated prevalence, severity and associations between SSc clinical variables and pain in all patients with SSc and in limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets. <h3>Methods</h3> A total of 42 patients (36 females, 6 males) with a mean age 53.7±15.3 years, diagnosed according to American Rheumatism Association criteria for SSc completed a standardized clinical assessment and questionnaires about their physical and psychosocial health, including a pain severity numerical rating scale (NRS; range 0–10). Pain prevalence and severity were estimated with descriptive statistics. SSc clinical variables and pain were estimated with linear regression for the entire group and by SSc subtype. <h3>Results</h3> Of the patients, 37 (88%) reported pain. Sixteen (39%) had mild pain [NRS 1–4], 11 (27%) moderate pain [NRS 5–7], and 15 [36%] severe pain [NRS 8–10]). Active ulcers, a high modified Rodnan skin thickness score, worse synovitis andgastrointestinal (GI) symptoms were associated with pain in multivariate analysis adjusting for demographic variables, depressive symptoms, and comorbid conditions. Patients with dcSSc reported higher mean ±SD pain than those with lcSSc (dcSSc 5.1±3.4 versus lcSSc 2.7±2.8. <h3>Conclusions</h3> Pain symptoms were common in the present study of patients with SSc and were independently associated with more active ulcers, worse synovitis, skin thicknessand GI symptoms. Subsetting by extent of skin involvement was related to pain severity variables. <h3>Disclosure of Interest</h3> None Declared
The Cellular Basis of Hepatic Fibrosis -- Mechanisms and Treatment Strategies
Authors: S L Friedman
Journal: New England Journal of Medicine (1993)

Hepatic fibrosis is a common response to chronic liver injury from many causes, including alcohol, persistent viral and helminthic infections, and hereditary metal overload. Emerging evidence suggests that cellular mechanisms of hepatic fibrosis are shared among these different insults and, moreover, that the liver's response is a paradigm for parenchymal wound healing in other tissues.Advances in the isolation and characterization of liver cells, in conjunction with progress in matrix and cytokine biology, have led to important new insights about the cellular basis of hepatic fibrosis. In particular, the hepatic lipocyte (also known as the stellate, fat-storing, perisinusoidal, or Ito . . .