tbuckley/cabot-search huggingface dataset:
PWE-210 Needle-based confocal laser endomicrosocpy for pancreatic cystic lesions: initial results from the UK concyst study
Authors: MG Keane, D Stefanescu, N Cieplik, GK Fusai, D Thorburn, A Metz, SP Pereira
Journal: Gut (2015)

<h3>Introduction</h3> Pancreatic cystic lesions (PCL) are an increasingly common clinical finding, present in up to 2% of patients undergoing CT and 14% of those undergoing MRI for non-pancreatic indications. Cytology from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) often has a low diagnostic yield. Needle-based confocal laser endomicroscopy (nCLE) allows a sub-millimetre AQ-flex 19 miniprobe (Mauna Kea Technologies, Paris, France) to be inserted into the cyst via a 19G FNA needle, enabling real-time imaging of the interior of the cyst. The aim of the study was therefore to evaluate the diagnostic potential, safety and efficacy of nCLE in the management of indeterminate PCL. <h3>Method</h3> The CONCYST study aims to recruit 60 patients prospectively with indeterminate CLP who require EUS-FNA from hepatopancreaticobiliary referral centres with nCLE in the UK; currently Royal Free Hospital, London, and Addenbrooke's Hospital, Cambridge. The study commenced in July 2014; 21 patients have been recruited to date. The procedure was performed under conscious sedation (Midazolam and Fentanyl). Patients received antibiotics immediately prior to the start of the procedure. 2.5mls of 10% fluorescein was injected once the cyst was visualised at EUS. After observation in the recovery room for up to 4 h all patients were discharged home the same day. Following the procedure all patients were followed up by telephone clinic. Ethical approval for the study was granted by the National Research Ethics Service (14/LO/0040). <h3>Results</h3> Of the 21 patients that underwent EUS-nCLE, 12 were male and 9 female. Median age was 70 (range 40–86) years. Confocal images were obtained in all cases. Median nCLE scanning time was 5 min and did not exceed 10 min in any case. EUS-nCLE findings correlated with final diagnosis (based on imaging, cytology and multidisciplinary team review) in 91% (19/21) of cases which was superior to cytology alone which correlated with final diagnosis in 71% (15/21) of cases. One patient experienced mild pruritus immediately following the procedure (possibly related to the fluorescein injection) but this settled promptly with a single dose of chlorphenamine. No complications were reported during follow-up. <h3>Conclusion</h3> These preliminary results are encouraging and suggest that nCLE under conscious sedation in the daycase setting is safe. Our initial findings indicate that EUS-nCLE is more sensitive than standard EUS-FNA for diagnosing indeterminate cystic lesion of the pancreas, but larger numbers will be required to confirm these findings. <h3>Disclosure of interest</h3> None Declared.
Psychiatry's contribution to medical ethics education
Authors: R C Sider, C Clements
Journal: American Journal of Psychiatry (1982)

Two recent trends in medical education, the growth of interest in biomedical ethics and the examination of psychiatry's status in medicine, have important implications for psychiatry. Educators are needed to bring a clinical perspective to bear on ethics instruction, yet psychiatrists risk missing this opportunity. Psychiatrists are uniquely suited to contribute because of their expertise in three areas: an understanding of the affective, nonrational components in ethical thought and behavior, a developmental perspective regarding personal morality, and an appreciation of the rootedness of ethics in the social ethos. Problems with contemporary ethical models of informed consent illustrate the value of psychiatry's contribution.
PTU-028 Peroral cholangioscopy – experience with conscious sedation
Authors: A Sinha, C Beasley, AD Strickland, AJ Portal
Journal: Gut (2015)

<h3>Introduction</h3> Per-oral Cholangioscopy (POC) offers the facility for direct visualisation of bile ducts, targeted biopsy and interventional techniques including Electro Hydro lithotripsy (EHL). Procedure completion time is often longer than conventional Endoscopic Retrograde Cholangio-Pancreatography (ERCP), patients often require high doses of standard sedation or general anaesthesia. We present our data where POC is performed under conscious sedation. <h3>Method</h3> Retrospective analysis was performed for all POC cases between January 2013 –December 2014. Definitions and endpoints were as used by Kalaitzakis <i><i>et al</i></i>.<sup>1</sup>Procedural success was defined as direct visualisation of the lesion enabling tissue sampling. Adequacy of tissue samples were analysed against the final Multidisciplinary meeting (MDM) decision-detailing both benign and malignant diagnosis. <h3>Results</h3> 47 cases of POC were performed in 43 patients. Median age was 63 years (IQR 22–86 years). 31 cases were performed for non stone-related disease (28 for indeterminate lesions 3 for other reasons). 16 patients underwent POC for choledocholithiasis, 9 of which had EHL. All patients had conscious sedation during POC. Median midazolam dose was 7 mg (IQR 5–11 mg), fentanyl 150 mcg (IQR 50–225 mcg). Buscopan was used in 42 cases (range 20–60 mg) and glucagon (1 mg) in 6 cases. Lowest oxygen saturations recorded were 95% (range 95–99%). Where a score of 1 represented maximum discomfort and 5 least, worst comfort score recorded was 3 for a single case. There were 4 failed procedures, 1 due to patient related factors and 3 due to equipment failure. Median procedure time was 86 min (IQR 34–114 min) for non-EHL and 92 min (IQR 76–132 min) for EHL cases. Procedural success was established in in 42 (89%) cases with positive visualisation of the target lesion. For non-stone related disease, 27 were successful (87%). For suspected malignancy, POC performance was again comparable with published data (sensitivity 70%, specificity 93%, positive predictive value 88%, negative predictive value 81%), when compared against the final MDT decision. Overall complication rate was comparable with other published data (6.3%). Over sedation requiring reversal was not encountered in the study. <h3>Conclusion</h3> Diagnostic results and complication rates, in our study, were comparable with published UK outcomes. Our practice demonstrates that POC can be performed under conscious sedation without compromising patient safety, test tolerance or efficacy. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Kalaitzakis E, Webster GJ, Oppong KW, Kallis Y, Vlavianos P, Huggett M, <i>et al</i>. Diagnostic and therapeutic utility of single-operator peroral cholangioscopy for indeterminate biliary lesions and bile duct stones. Eur J Gastroenterol Hepatol. 2012;24(6):656–64
PWE-042 Natural history of compensated cirrhosis due to chronic hepatitis C infection: a systematic review
Authors: W Alazawi, M Cunningham, J Dearden, G R Foster
Journal: Gut (2010)

<h3>Introduction</h3> A significant proportion of patients with chronic hepatitis C (HCV) progress to cirrhosis with its attendant complications. Most studies evaluating the natural history of HCV infection have taken development of cirrhosis as an endpoint. We therefore sought to establish, by means of a systematic review and analysis of the literature, the natural history of compensated HCV cirrhosis. <h3>Methods</h3> A systematic literature review was performed. Where studies compared treated vs untreated patients, or HCV vs hepatitis B infection, only data regarding untreated, HCV monoinfected patients were included. Weighted mean annual percentage rates for death or transplantation, complications of cirrhosis and development of hepatocellular carcinoma (HCC) were calculated from the raw data. <h3>Results</h3> Our search returned 12 papers which met the inclusion criteria. Despite some heterogeneity (inclusion of other causes of cirrhosis or HCV patients who had received antiviral therapy) we extracted data from these studies relating to 2138 patients. In compensated HCV cirrhosis the estimated rate of death or transplantation is 4.75% per annum, of decompensation is 5.61% per annum and of HCC is 3.76% per annum. Five studies reported combined outcomes for both treated and untreated patients. When considered together, these studies reported significantly lower annual percentage rates of HCC than those reporting untreated patients only (mean 2.51%±0.37 vs 5.20%±0.76, p=0.016), but not of decompensation (mean 5.34%±0.79 vs 9.58%±1.14, p=0.057) or death or transplantation (mean 3.84%±0.53 vs 4.76%±0.62, p=0.29). <h3>Conclusion</h3> The estimated annual percentage rates of death or transplantation, decompensation and HCC confirm the relatively slow progress of compensated HCV cirrhosis, but highlight the need for continued vigilance for the occurrence of HCC. Heterogeneity in reporting, particularly the lack of distinction of outcomes according to treatment status or sustained virological response, means that the summary data presented may underestimate rate of disease progression, particularly HCC development. It will be important to ensure a clear distinction is made between treatment responders, partial responders and non-responders in future studies on the outcome of HCV cirrhosis.
AB0662 Tocilizumab in Takayasu Arteritis: A Single Center Experience
Authors: P. Toniati, M.G. Lazzaroni, A. Tincani
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Takayasu arteritis is a rare, chronic-relapsing idiopathic vasculitis affecting large vessels. <h3>Objectives</h3> The objective of this study is evaluating the response and efficacy of Tocilizumab in Takayasu Arteritis (TA) treatment. Tocilizumab was started as a second treatment for resistant cases or as a first steroid sparing association treatment in order to achieve clinical remission as soon as possible. <h3>Methods</h3> The patients (three women and one male) were selected from a our center as affected by active TA. Activity of disease was demonstrating by CT-PET in all patients. Inclusion criteria were resistance to anti-TNF (one patient) or treatment with high doses of prednisone (two patients) or refuse to use steroid (one patient). <h3>Results</h3> The mean age at diagnosis was 32 years (17-45 years). Mean diagnostic delay 3.5 years (range 1-5 years).Three patients were on prednisone &gt;15 mg/die. Three were treated with methotrexate (mean dose 15 mg/w, as tolerated). The other patient was on azathioprine 2 mg/kg. Two patients started remission treatment with prednisone 0.5 mg/kg and 1 mg/kg, methotrexate 15 mg/w and tocilizumab 8 mg/kg/4 w. The CT-PET was positive before Tocilizumab treatment in all patients. After four-six months of Tocilizumab, PET was negative in two patients (one of these patients developed later a positive PET when prednisone was reduced under 10 mg/die). One patient showed a reduced uptake of FDG glucose with a reduced SUV. The remaining patient was awaiting for CT-PET. CRP was elevated before treatment (mean 41.75 mg/dl, range 7-77) and negative after the first infusion of Tocilizumab. During Tocilizumab treatment no patients developed new arterial stenosis or worsening of known stenosis. <h3>Conclusions</h3> Tocilizumab is a good option in anti-TNF resistant TA patients. It is useful as steroid-sparing treatment during remission and manteinance, but do not allow steroid suspension. Tocilizumab was a valid treatment in critically ill patient (severe aortic insufficiency) in order to achieve a rapid remission. <h3>Disclosure of Interest</h3> None declared
A novel method for endoscopic ultrasound-guided pancreatic rendezvous with a microcatheter
Authors: Juan Vila, Carlos Huertas, Bruno Gonçalves, Alba Cebrián, David Ruiz-Clavijo, Belén González de la Higuera, Carlos Prieto
Journal: Endoscopy (2015)

A 69-year-old woman with chronic pancreatitis and recurrent pancreatic-type abdominal pain underwent computed tomography, which showed dilatation of the pancreatic duct. Subsequent endoscopic retrograde cholangiopancreatography revealed a fibrotic papillary stenosis preventing cannulation of the pancreatic duct.
PTH-269 Protein biomarkers in the rectal mucosa: a novel test for colorectal cancer?
Authors: J Lacy-Colson, M Norwood, C Murray, J Booth
Journal: Gut (2015)

<h3>Introduction</h3> Earlier detection of colorectal cancer is a clinical priority. Currently very high numbers of patients are referred for colonoscopy under the 2 week rule system, with a pick up rate for cancer of 1:20 or less putting a major strain on endoscopy units investigating large numbers of the worried well. The aim of this study was to assess the correlation of protein biomarkers captured from the rectal mucosa with the presence or absence of colorectal cancer. <h3>Method</h3> We conducted a case control study of 20 patients with colorectal cancer, and 20 controls. All patients had been referred to colorectal outpatients with potentially worrying symptoms; presence or absence of cancer was determined by colonoscopy or CT virtual colonoscopy. A novel sampling device, OriCol™, was employed to collect samples of rectal mucosa for biomarker analysis. The device incorporates a nitrile membrane which, following insertion into the unprepared rectum via a standard proctoscope, is inflated to make contact with the rectal mucosa for a period of 10 s. Upon deflation and retraction of the membrane, a preservation buffer is added to preserve the sample prior to analysis. Sampling can be performed in an outpatient setting in under 2 min and has been shown to be well tolerated in &gt;2500 patients. The levels of various antibodies, haemoglobin and carcinoembryonic antigen were analysed using conventional ELISA techniques. Statistical analysis of the trial results was performed using the Wilcoxon test for non-parametric comparisons with two sided p values. The area under the receiver operating characteristic (ROC) curve for distinguishing between the two diagnostic groups, together with its confidence interval, was calculated for each biomarker. Logistic regression analyses were used to investigate the performance of different combinations of biomarkers. This study was conducted with appropriate research ethics committee approval. <h3>Results</h3> Univariate analyses identified five candidate predictive biomarkers for colorectal cancer. All combinations of two and three predictors were investigated using logistic regression. The best performing combination of biomarkers was haemoglobin and IgA. The area under the ROC curve for this best linear combination was 0.86. <h3>Conclusion</h3> We suggest that ELISA analysis protein biomarkers collected with the OriCol™ device offers a potentially useful and cost-effective pre-colonoscopy screening tool in patients referred under the 2 week rule criteria. Data from this pilot study suggests that a sensitivity of ≥95% can be achieved while massively reducing the number of patients requiring urgent colonoscopy to exclude a diagnosis of cancer. <h3>Disclosure of interest</h3> J. Lacy-Colson Grant/ Research Support from: Origin Science Ltd, Consultant for: Origin Science Ltd, M. Norwood Grant/ Research Support from: Origin Science Ltd, C. Murray Consultant for: Origin Science Ltd, J. Booth Employee of: Origin Science Ltd.
SP0166 A Synerkine of IL4 and IL10 for Inflammatory Disorders
Authors: C. Hack
Journal: Annals of the Rheumatic Diseases (2015)

Stand-alone cytokines IL4 and IL10 have been succesfully used in preclinical models for inflammatory disease but yielded disappointing results in phase 2 clinical studies. We reasoned that this may have been due to poor bioavailability and lack of synergistic effects with other anti-inflammatory cytokines. To solve these issues we developed a fusion protein of IL4 and IL10, IL4-10 synerkine. The synerkine suppressed proinflammatory cytokine production in multiple in vitro assays, while unaffecting or increasing production of anti-inflammatory mediators, which effects were mediated by both cytokine moieties. Moreover, it improved cartilage metabolism in vitro. In vivo the synerkine normalized hyperalgesia in multiple animal models including carrageenan induced inflammatory pain in mice and osteoarthritis pain in dogs. Therefore, the IL4-10 synerkine seems a promising therapeutic option for inflammatory pain. <h3>Disclosure of Interest</h3> None declared
Proportion of workers who were work-injured and payment by workers' compensation systems - 10 states, 2007.
Authors: D. K. Bonauto, J. Z. Fan, T. W. Largo, K. D. Rosenman, M. K. Green, J. K. Walters, B. L. Materna, J. Flattery, T. St. Louis, L. Yu, S. Fang, L. K. Davis, D. J. Valiente, K. R. Cummings, J. J. Hellsten, S. L. Prosperie
Journal: MMWR Morbidity and Mortality Weekly Report (2010)
SP0148 Immunology of the Fracture Hematoma
Authors: P. Hoff
Journal: Annals of the Rheumatic Diseases (2015)

Patients suffering from autoimmune diseases like rheumatoid arthritis often exhibit delayed or unsuccessful fracture healing. The fracture healing process comprises overlapping stages. The most fundamental steps are inflammation, repair, and remodeling. The inflammatory phase starts with the formation of the fracture hematoma under bioenergetically restricted conditions and is of great importance for the clinical outcome. From an immunological point of view, the fracture hematoma represents the starting point of inflammatory processes, thus initiating the healing cascade. The early inflammatory phase is disturbed in patients with autoimmune disorders and may contribute to delayed-healing or non-unions. The fracture hematoma possesses abilities such as induction of angiogenesis or periosteal cell proliferation and subsequently initiation of intramembranous bone formation underlining the fact, that in a mature fracture hematoma the initial steps of fracture healing have already taken place. The early human fracture hematoma is characterized by maturation of granulocytes and immigration of monocytes/macrophages and hematopoietic stem cells. Both T helper cells and cytotoxic T cells proliferate within the fracture hematoma and/or migrate to the fracture site. High concentration of pro-inflammatory cytokines such as IL-6, IL-8, IFNγ and TNFα are found. Immunologically restricted patients exhibit a pronounced initial inflammation. This specific microenvironment is among the crucial factors that determine fracture healing. In patients with autoimmune diseases the medicinal manipulation of the initial inflammatory milieu could be of therapeutic interest to improve the clinical outcome of fracture healing. <h3>Disclosure of Interest</h3> None declared
Value and Limitations of Testicular Scanning by in vivo Labelling of RBC with 99mTc
Authors: M.M. Rehani, M.S. Rao, B.C. Bapna, R.R. Sharam, L.J. Rajendran, C.L. Subudhi, V.V. Shrilhande, S. Kumar, A.K. Malik, S. Vaidyanathan
Journal: European Urology (1980)
AB0096 PEP-1-FK506BP12 Inhibits Matrix Metalloproteinase Expression in Human Articular Chondrocytes and in a Mouse Carrageenan-Induced Arthritis Model
Authors: I.Y. Park, K.M. Son, H.A. Kim
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Osteoarthritis (OA) is a degenerative disease characterized by the death of chondrocytes and the gradual loss of articular cartilage. Recently, transfer of a therapeutic protein into cells by the use of protein transduction domain (PTD) that targets the lipid bilayer directly has been tested in terms of therapeutic applications. The FK506-binding protein 12 kDa (FK506BP12) binds immunosuppressive drugs such as FK506 and modulates T cell activation via calcineurin inhibition. The anti-inflammatory properties of and immunomodulatory role played by FK506BP12, independent of FK506, have been demonstrated in several disease models <h3>Objectives</h3> In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the PTD PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. <h3>Methods</h3> Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. <h3>Results</h3> In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13; and cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model of carrageenan-induced paw arthritis, PEP-1-FK506BP12 suppressed both carrageenan-induced MMP-13 production and paw inflammation. <h3>Conclusions</h3> Thus, PEP-1-FK506BP12 may have therapeutic potential in the alleviation of OA progression. <h3>References</h3> S.R. Goldring, M.B. Goldring, The role of cytokines in cartilage matrix degeneration in osteoarthritis, Clin. Orthop. Relat. Res. (2004) S27-36. D.W. Kim, S.H. Lee, S.K. Ku, et al., Transduced PEP-1-FK506BP ameliorates corneal injury in Botulinum toxin A-induced dry eye mouse model, BMB Rep. 46 (2013) 124-129. S.Y. Kim, E.J. Sohn, D.W. Kim, et al., Transduced PEP-1-FK506BP ameliorates atopic dermatitis in NC/Nga mice, J. Invest. Dermatol. 131 (2013) 1477-1485. <h3>Acknowledgements</h3> This research was supported by a grant (A120960) from the Korean Health Technology R&amp;D Project, Ministry of Health &amp; Welfare, Republic of Korea, by National Research Foundation of Korea; Mid-career Research program grant (NRF-2009-0084569), and by Hallym University Research Fund. <h3>Disclosure of Interest</h3> None declared
Diagnostic instability and depression
Authors: W Coryell, M Lowry, P Wasek
Journal: American Journal of Psychiatry (1980)

Blind raters applied research criteria to the charts of patients whose discharge diagnosis changed through several hospital admissions from depression to schizophrenia and to the charts of matched control patients. Fewer diagnostically unstable patients than control patients satisfied research criteria for depression despite matching discharge diagnoses. The use of operational criteria, then, can be expected to reduce diagnostic instability in depression and thus improve prognostic accuracy. Some patients satisfied the research criteria for depression when they were initially admitted and for schizophrenia at their final admission. This suggests that diagnostic error may not account for all cases of major diagnostic instability.