tbuckley/cabot-search huggingface dataset:
SP0029 Adult neuropsychiatric lupus
Authors: C. Gordon
Journal: Annals of the Rheumatic Diseases (2013)

Neuropsychiatric manifestations in adult lupus patients are common but not always serious. They may occur early or late in the course of lupus, may be the presenting feature of lupus and can be a challenge to manage. The most common manifestations early in the disease are headache, mood disorders and anxiety, seizures, cerebrovascular disease, cognitive dysfunction, and acute confusional state. Other neuropsychiatric manifestations that may occur include movement disorders such as chorea, transverse myelitis, cranial nerve and peripheral neuropathies and myasthenia gravis. Neuropsychiatric features may be due to inflammatory mechanisms related to lupus, thrombosis usually due to antiphospholipid antibodies, atherosclerosis or co-morbid conditions, of which infection is the most important not to misdiagnose. Being aware of the risk factors and underlying mechanisms for different neuropsychiatric manifestations will ensure prompt and appropriate investigations and treatment. Investigations may include MRI and in selected cases other forms of imaging, CSF examination, neurophysiology and cognitive function testing. Therapy may include immunosuppressants, anticoagulation, antiplatelet agents and treatment specific to the clinical presentation. Most headaches in lupus patients are not due to lupus but the possibility of aseptic meningitis, benign intracranial hypertension, cerebral haemorrhage and venous thrombosis should be considered. Seizures may be part of the initial presentation of lupus and unless recurrent or associated with abnormalities on imaging do not require long term therapy with anticonvulsants. Cerebrovascular disease presenting as stroke is more common later in the disease, and is more often due to atherosclerosis, thrombosis or emboli than haemorrhage or vasculitis. Chorea is usually associated with anti-phospholipid antibody syndrome. Transverse myelitis may be due to inflammatory or thrombotic mechanisms and is not always associated with abnormalities on MRI scan at the time of the acute event. Prompt diagnosis and treatment is essential to reduce the risk of permanent disability. <h3>Disclosure of Interest</h3> None Declared
Abstract 3079: Loss of β2-spectrin may lead to the activation of telomerase reverse transcriptase (TERT) and hepatocellular cancer formation
Authors: Zhongxian Jiao, Sanjeev Shukla, Gyanendra Kumar, Wenguo Yao, Hong Cao, Wilma SR Jogunoori, Zhixing Yao, Lopa Mishra, Bibhuti Mishra
Journal: Cancer Research (2010)

Abstract Background and Aims: Telomerase is a specialized reverse transcriptase (TERT) that synthesizes repeat DNA sequences at telomeres- the specialized ends of chromosomes is suppressed in normal cells by multiple proteins that include TGF-β and Smad3 resulting in the progressive shortening of telomeres with each cell division, ultimately leading to chromosomal instability and cellular replicative senescence or growth arrest. Emerging evidence indicates that β2-spectrin (β2SP), a Smad3/Smad4 adaptor protein required for TGF-β signaling, is a powerful tumor suppressor. β2SP+/−, β2SP+/−/Smad3+/− and β2SP+/−/Smad4+/− mice dramatically develop Hepatic cancers. Because TERT is markedly activated in β2SP+/−/Smad3+/− hepatocellular cancer tissues compared to Smad3−/− tissues, we hypothesized that β2SP interaction could be involved in the interaction with Smad3 to suppress TERT expression in normal tissues, and the loss of β2SP may lead to telomerase gene activation resulting in HCC. Results: We tested human TERT (hTERT) expression levels in several HCC cell lines that have different levels of β2SP. hTERT expression levels negatively correlate with β2SP by Western Blot analysis. Loss of β2SP in β2SP+/− and β2SP−/− mouse embryonic fibroblasts (MEFs) significantly activated mTERT expression. Co-transfection of a β2SP expression plasmid and hTERT promoter-luciferase construct significantly inhibited the hTERT promoter in β2SP-deficient SNU-398 cells. Depletion of Smad3 by in vitro RNAi and the expression of hTERT-luciferase in Smad3 depleted cells upon co-transfection with Smad3 and/or β2SP expression plasmids suggest that both Smad3 and β2SP are required for the suppression of hTERT. Furthermore, chromatin immunoprecipitation (ChIP) assay suggests binding of Smad3/β2SP protein to hTERT promoter. Conclusions: Taken together our data suggest that divergent pathways converge on β2SP and Smad3 for the regulation of TERT. Activation of the TGF-β signaling pathway with suppression of TERT provides a strong strategy for generating targeted therapeutics to these lethal human cancers. 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 3079.
FRI0593-HPR Factors Influencing the Occupational Trajectory of Patients with Systemic Sclerosis: A Qualitative Study
Authors: S. Decuman, V. Smith, M. Grypdonck, S. Verhaeghe, F. De Keyser
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Performing a paid job is one of the elements of participation possibly limited by having Systemic Sclerosis (SSc). Nearly all studies done so far have focused on prevalence rates of work participation and related factors. For development of interventions, we need a more comprehensive view on this topic with focus on the experiences and perceptions of patients. We need to know from a patient9 s point of view which factors influence their occupational trajectory. <h3>Objectives</h3> To describe, from a patients point of view, the factors and their related meaning, influencing the occupational trajectory of patients with SSc. <h3>Methods</h3> Data were collected through semi-structured interviews with fourteen patients who fulfilled the ACR and/or Leroy/Medsger criteria for SSc. <h3>Results</h3> The occupational trajectory of patients with SSc is influenced by the continuous interplay between four groups of factors. The first group concerns values patients attribute to work (identity, normality, financial value, social contact and structure). The meaning of those values and how they relate to each other steers the willingness to work. A second group of factors concerns aspects influencing the match between daily life, work participation and medical condition (job content; organizational flexibility and willingness to ask for adaptations; management of daily life; work-related micro-environment; medical treatment and treatment expectations). The occupational trajectory is also influenced by a third group of factors, comprising external factors (availability of support; knowledge of the disease; pressure to work; contact with medical professionals; existing regulations and the patient9s knowledge about it). Lastly, personal factors are important (socio-demographics, psychological assets and disease-related/work-related personal factors). <h3>Conclusions</h3> The decisions patients take concerning work depend on an interplay of factors and especially on the personal interpretation a patient gives to them. It is important that these insights are taken into account when guiding patients in their occupational trajectory. <h3>Disclosure of Interest</h3> S. Decuman Grant/research support: This work is supported by a grant from the "Rotary-National Association to support Disabled People (NVSG)" and "Belgium Fund for Scientific Research in Rheumatology" to DS., V. Smith: None declared, M. Grypdonck: None declared, S. Verhaeghe: None declared, F. De Keyser: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3081
Address on the Modern Treatment of Syphilis
Authors: J. R. Lane
Journal: BMJ (1874)

Mvlexcuse for bringing forward a paper on such a familiar and every- day subject as the treatment of syphilis is, that after twenty-three years' experience at the Lock Hospital, I have niecessarily been led to some definite conclusions-to form, in fact, a sort of creed of my own on the subject, which it may be worth wvhile briefly to put forward, even although it may comprise little that is novel, and may be in most essen- tial particulars confirmatory of the views entertained by the majority of miy contemporaries.Fortunately, in the matter of treatment there is not quite the same divergence of opiniioIn which prevails with respect to the pathology of this obscure anid puzzling disease.To such pathological initricacies I am anxious at preseiit to avoid all reference, except so far as the con- sideration of the practical side of the question may render absolutely necessary.
Endoscopists can sustain high performance for the optical diagnosis of colorectal polyps following standardized and continued training
Authors: Sarah McGill, Roy Soetikno, Amit Rastogi, Robert Rouse, Tohru Sato, Ajay Bansal, Kenneth McQuaid, Tonya Kaltenbach
Journal: Endoscopy (2014)

The learning curve for optical diagnosis of colorectal polyps with the narrow-band imaging (NBI) is unknown. To forego histological analysis of diminutive polyps diagnosed optically with high confidence, guidelines recommend ≥ 90 % negative predictive value (NPV) and concordance of ≥ 90 % for surveillance intervals predicted optically and histologically. We aimed to study the learning of optical diagnosis for colorectal polyps.We studied five endoscopists as part of a randomized multisite trial comparing near-focus and standard-focus views for optical diagnosis. They trained using a computer-based module, followed by 10 real-time colonoscopies with pathology correlation. Endoscopists then optically diagnosed and resected all the polyps found during 558 consecutive colonoscopies, and diagnoses were compared with pathology. Endoscopists repeated the training module at the study midpoint. NPV and concordance of surveillance intervals for diminutive polyps diagnosed optically with high confidence were measured over time.Endoscopists showed high diagnostic performance, with a nonsignificant trend toward higher NPV in the second half of the study. For the 445 polyps in the standard-view arm, the NPV was 88.0 % (95 %CI 75.7 % - 95.5 %) in the first half and 95.8 % (88.3 % - 99.1 %) in the second; P = 0.7. Three endoscopists in the first half and four in the second achieved > 90 % NPV. Concordance of surveillance intervals was identical in the first and second halves at 98.1 % (95 %CI 93.3 % - 99.8 %).High NPV for the prediction of non-neoplasms with NBI was achieved and maintained in this group of endoscopists who participated in standardized and continued training. Both NPV and surveillance interval agreement indicated high performance in the optical diagnosis of colorectal polyps and exceeded thresholds.
FRI0087 Tocilizumab Makes Negative Slope of Inverse-Creatinine Gentle and Prevents Hemodialysis Induction in AA Amyloidosis Patients with Rheumatoid Arthritis of Severe Renal Insufficiency
Authors: O. Saiki, T. Harada, K. Shigematsu, A. Matsumoto, A. Mizimoto, T. Takama, H. Uda
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> It is generally accepted that in AA amyloidosis patients with rheumatoid arthritis the renal function deteriorates gradually and finally most of the patients will receive hemodialysis in five years, even the disease activity is in good control. In recent years, several biologics including tocilizumab were found effective for rheumatoid arthritis. However, the effect of biologics therapy on renal insufficiency is not clarified. The main focus of the present study is to compare the effect of tocilizumab and oral medicines on clinical course of the renal function of AA amyloidosis patients with severe renal insufficiency. <h3>Objectives</h3> At present, the effective therapy for preventing introducing hemodialysis in AA amyloidosis with severe renal insufficiency is quite uncertain. In the present study, we examined the effects of tocilizumab on renal function and preventing introducing hemodialysis in these patients. <h3>Methods</h3> RA patients with amyloidosis who had high disease activity and renal dysfunction (creatinine &gt;2mg/dl) were enrolled. The patients were separated into two groups: group 1, treated with prednisolone and low dose of methotrexate, group 2, tocilizumab alone. The patients of group 2 received only tocilizumab in every 4 weeks and did not have prednisolone nor methotrexate. We followed up for more than three years prospectively. In those patients who had obtained DAS28 remission, we compared the clinical course of renal function and the disease activity between two groups. We stopped the following-up when the patients were introduced hemodialysis. <h3>Results</h3> Total of 14 patients was enrolled in the present study. The mean creatinine levels of the group 1 patients and the group 2 patients were 3.1 and 3.3 mg/dl respectively at the entry. The mean CRP levels of the group 1 patients and the group 2 patients were 3.2 and 3.5 mg/dl respectively at the entry. After treated with either oral medicine or tocilizumab, the levels of CRP were decreased to normal levels in less than one year and DAS28 were improved significantly in both groups. The renal functions of group 1 patients were deteriorated rapidly and were introduced hemodialysis in 2.5 years. However, the patients of group 2 did not progress renal insufficiency rapidly and were not introduced hemodialysis for more than three years. The mean negative slope of inverse-creatinine became gentle by tocilizumab therapy as shown in figure. <h3>Conclusions</h3> Tocilizumab makes negative slope of inverse-creatinine gentle and preventing introducing hemodialysis in AA patients with severe renal insufficiency, suggesting that we should use tocilizumab in these patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5043
PWE-226 Are IBD services up to standard?—results from 1st round of the UK inflammatory bowel disease quality improvement project (IBD QIP): Abstract PWE-226 Table 1
Authors: I Shaw, E Fernandez
Journal: Gut (2012)

<h3>Introduction</h3> IBD is a common cause of gastrointestinal morbidity with an estimated 240 000 people affected in the UK. Successive rounds of the UK IBD Audit have shown variation in care and there is a recognised need to implement the National Standards for IBD Care that were published in 2009. The IBD QIP was established as a pilot project to explore the potential of a web based self assessment tool to assist services benchmark themselves against the standards and develop action plans to improve. <h3>Methods</h3> The IBD QIP assessment tool was developed through a series of meetings consisting of representatives of key stakeholder groups, including patients. Statements relating to aspects of IBD care were identified from analysis of the Standards and UK audit results. These were then included in a web based tool, similar to the "GRS" used in UK endoscopy. All IBD services in the UK were invited to volunteer for the pilot and after a series of regional meetings, participating sites were provided with access to the tool and asked to complete their assessment and provide feedback on the process. Results were collated centrally and fed back to sites locally. The QIP web site, also included tools for formulating an action plan and a "Shared Document Store" for sites to submit examples of good practice that could be shared with others. Re-assessment is planned for March 2012. <h3>Results</h3> 73 sites enrolled for the pilot (64 adult &amp; 9 paediatric services), 62 (85%) of whom submitted data. 52/62 (90%) of sites met to complete the assessment as a multidisciplinary group with at least 2 disciplines represented. 93% of sites took &lt;4 h to complete the rating process. Overall results for all domains showed similar scores for adult and paediatric sites with 18, 17, 23 and 43% of adult and 14, 12, 26 and 48% of paediatric sites scoring A, B, C and D respectively. Representative scores for selected items from adult sites are shown in the following Abstract PWE-226 table 1 (n=56). <h3>Conclusion</h3> We have demonstrated that it is feasibile for services to use a web based self assessment tool to benchmark themselves against nationally agreed standards for IBD care. First round results show that the majority of services are currently failing to meet the UK IBD Standards, with two thirds of sites scoring at level C or D. Feedback from the pilot round is currently being used to refine the tool and re-assessment in March 2012 will give sites an indication of their progress. <h3>Competing interests</h3> None declared.
Abstract 1332: Functional killer-immunoglobulin-like receptor variation and risk of non-melanoma skin cancer.
Authors: Karin A. Vineretsky, Margaret R. Karagas, Michael Pawlita, Heather H. Nelson
Journal: Cancer Research (2013)

Abstract Natural killer (NK) cells of the immune system are the first line of defense against transformed and infected cells. NK cell action is determined through binding of killer immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands on target cells. The KIR gene family is diverse and highly polymorphic, is poorly covered on GWAS platforms, and exhibits significant functional copy number variation. The KIR locus has been primarily studied in the context of HCV, HIV, and transplant outcomes. Here, we have tested the hypothesis that KIR genotypes are associated with Non-Melanoma Skin Cancer (NMSC) etiology. These are among the most prevalent malignancies worldwide with rising incidence. In addition, they are highly antigenic tumors, with a possible viral etiology, making NMSC an ideal model to test KIR as a cancer susceptibility trait. A random subset of a population-based case-control study in New Hampshire was selected for the study: 422 basal cell carcinomas (BCC) (1 BCC=243, 2 BCC=131, ≥3 BCC=48), 132 squamous cell carcinomas (SCC), and 222 controls. KIR genotyping was performed with Lifecodes KIR-SSO typing kit on Luminex using buffy coat derived genomic DNA, capturing KIR loci: 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 3DL1, 3DS1, and 3DL2. Cutaneous HPV status was assessed using serum samples and established Luminex detection assays covering 16 genus beta HPV types. The KIR2DL2/3 locus was associated with a significantly increased risk of BCC (OR=2.65, 95% CI: 1.08-6.48), which was particularly strong for cases with 3 or more tumors (OR=5.77, 95% CI: 1.30-25.66). For SCC, the KIR3DL1 gene was associated with a significantly increased risk of malignancy (OR=3.73, 95% CI: 1.51-9.22). Next we investigated the association of KIR and SCC within HPV strata. The KIR3DL1-SCC association was strongest among those with no evidence of HPV infection (OR=6.81, 95% CI: 1.78-26.12). In contrast, the non-functional KIR2DS4 variant related to an increased risk and the KIR2DL2 gene related to reduced risk of SCC among those with multiple β-HPV infections. Our results implicate a strong role for KIR in the etiology of NMSC. KIR2DL2/3 may be particularly important in the development of multiple BCC, and KIR3DL1 in the pathogenesis of SCC. Finally, we identified a pattern of KIR-SCC associations that supports a potential etiologic role of cutaneous HPV in SCC occurrence. Citation Format: Karin A. Vineretsky, Margaret R. Karagas, Michael Pawlita, Heather H. Nelson. Functional killer-immunoglobulin-like receptor variation and risk of non-melanoma skin 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 1332. doi:10.1158/1538-7445.AM2013-1332
TCT-591 Safety and Efficacy of the biodegradable polymer Biolimus-eluting stent versus the durable polymer Everolimus-eluting stent in all-comers undergoing PCI: Pooled analysis of the COMPARE II and NEXT trials at 1 year
Authors: Pieter C. Smits, Georgios J. Vlachojannis, Ken Kozuma, Masahiro Natsuaki, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2014)
Association of Salmonella Enteritis with Operations on the Stomach
Authors: William R. Waddell, Lawrence J. Kunz
Journal: New England Journal of Medicine (1956)

IN the past, diarrhea occurring in patients who have had definitive surgery for gastric or duodenal ulcer has usually been attributed to the nature of the operation, especially if a vagotomy was included in the procedure. That this is frequently not so is shown by the results of recent studies on some of these cases. During the past two years, 9 cases of enteric infection have been observed in patients who previously had been subjected to operations on the stomach. These operations included 3 subtotal gastrectomies, 1 posterior gastroenterostomy with vagotomy, 4 antral exclusions with vagotomy§ and 1 subtotal gastrectomy . . .
P108 Omalizumab for severe allergic asthma: cost-effective or priceless?
Authors: J. Miles, D. Green
Journal: Thorax (2011)

<h3>Background</h3> Omalizumab is licensed for the treatment of severe allergic asthma to help reduce severe exacerbations. However the decision as to whether to consider Omalizumab therapy is based on a 16 week assessment period with no reference to the licensed indication at all! We were therefore keen to examine omalizumab efficacy in terms of exacerbation reduction in our severe asthma clinic. <h3>Methods</h3> 40 patients had received omalizumab treatment for at least 12 months, on the basis of a successful 16 week assessment period. Hospital and GP records were scrutinised to assess exacerbation frequency and unscheduled hospital attendance before and after treatment. Costs for asthma admissions, attendance for clinic and price per omalizumab vial were analysed. In addition a repeat patient survey was undertaken to assess satisfaction with therapy and our service using a previously validated tool.1 <h3>Results</h3> Complete data was available for 20 patients. A sequential eduction in unscheduled hospital; contacts was seen throughout the first year following commencement of omalizumab. Average cost savings on unscheduled hospital attendances were £2500 per annum. Average costs of attendance for injections were £2080 per annum. Treatment costs varied between £3250 and £26 000 per patient per annum. We did not have data on the absenteeism rates from those patients currently in full or part time employment. Patient satisfaction with both Omalizumab and the clinic set up remained high as in keeping with our previous assessment. <h3>Conclusions</h3> Omalizumab does reduce exacerbation frequency in patients with severe allergic asthma. Patients are extremely satisfied with the efficacy of therapy. The costs of reduced unscheduled care offset the costs of extra planned attendances for injections. Although an expensive treatment, there may be many potentially hidden physical, social and economic benefits of omalizumab therapy. Sophisticated health economic analysis is required to pursue this hypothesis.