tbuckley/cabot-search huggingface dataset:
PTH-067 An evaluation study of lactobacillus brevis cd2 in orofacial granuolomatosis
Authors: R Goel, M Ormond, E Hullah, S Nayee, M Escudier, J Sanderson
Journal: Gut (2015)

<h3>Introduction</h3> A small proportion of patients with Crohn's disease develop orofacial granulomatosis (OFG), a rare, chronic disfiguring condition of unknown aetiology affecting the oral mucosa and perioral region. Previous studies have suggested that alterations in the oral microbiota may be involved in the pathogenesis of OFG. CD2 is a novel probiotic containing <i>Lactobacillus brevis</i>which has anti-inflammatory properties, primarily via reduced arginine availability. Previous studies have shown that CD2 reduces oral inflammation in chemotherapy-induced oral mucositis, Behcet's disease and recurrent aphthous stomatitis. Our aim was to evaluate the tolerability and efficacy of CD2 lozenges in reducing oral inflammation in patients with active OFG. <h3>Method</h3> This was a single-centre prospective open-label observational study. Patients were recruited from a specialist OFG clinic between February and August 2014. Patients with active OFG received an eight week course of CD2 lozenges taken four times per day. Patients were reviewed before and after treatment and disease activity assessed by Oral disease activity score (ODAS), Visual analogue scale (VAS) of oral soreness and Global physician assessment (GPA). <h3>Results</h3> 28 patients were recruited with 4 patients withdrawing (3 non-compliance, 1 of which had severe learning difficulties; 1 re-classified as aphthous stomatitis). 7 patients failed follow-up leaving 17 patients (9 males) available for final analysis. The median age was 35 years (range 18–70 years) with 5/17 patients diagnosed with concurrent intestinal Crohn's disease. Before treatment, the median ODAS was 12 (range 2–36), median VAS was 50% (range 0–90%), with 9/17 patients classified as having mild disease, 2/17 moderate and 6/17 severe. Post treatment, the median ODAS was 12 (range 1–34), median VAS was 20% (range 0–70%), with 9/14 patients had mild disease, 7/14 moderate and 1/14 severe. The reduction in the mean ODAS at 2 months was: 15.5–11.9 = 3.6 (p = 0.044). The mean improvement in oral soreness measured by VAS was: 44%–26% = 18% (p–0.003). There were no adverse events, however one patient discontinued treatment due to severe diarrhoea which resolved upon CD2 cessation. <h3>Conclusion</h3> CD2 appears to be safe, well-tolerated and of benefit in reducing oral inflammation and oral soreness in active OFG. Given the marked improvement in oral soreness, CD2 may have a role in symptom relief in other oral inflammatory conditions. Based on these results, a larger double-blind prospective study is recommended. The treatment shows promise as an adjunct to dietary therapy and an alternative to systemic immunosuppression. <h3>Disclosure of interest</h3> None Declared.
False-negative HER2 tests with appropriate positive controls.
Authors: N. Stock, L. Alpert, D. Pilavdzic, M. Brisson, M. Basik, G. Batist, A. Spatz
Journal: Journal of Clinical Oncology (2010)

e11057 Background: Understanding the possible causes of errors in HER2 testing is crucial in breast cancer pathology. We present and discuss cases of false-negative HER2 tests with positive controls on the same slides. Methods: In 490 cases of invasive breast adenocarcinoma, quality control was performed using the standard operating procedure in place at our center. In particular, paraffin blocks were cut onto standard charged glass slides (Superfrost Plus, Thermo Scientific Fisher, NYC, NY) and anti-HER2 4B5 mAb immunohistochemical tests performed on an automated system. External controls were put on each slide made of Tissue Micro-Array punch biopsies with a range of HER2 immunostainings (0 to 3+) validated by FISH. Results: In a first set of 95 cases, two cases were initially negative (0) while the external controls on the same slides were positive with the expected range of positivity. We repeated the procedure with exactly the same preanalytical and analytical conditions, and this time the cases became positive (3+). The FISH showed HER2/neu amplification. We therefore decided to repeat the HER2 test of 395 consecutive “negative” cases (0 or 1+) that had appropriate controls on the same slides (0 to 3+). Three cases became positive (3+). No interpretation error could explain the difference. Conclusions: The most likely cause of results inconsistency in our cases was a slide surface chemistry issue. Charged adhesion slides are manufactured by a process that places a permanent positive charge on the slide. Heterogeneity in slide surface chemistry can cause incomplete reagent spreading on the slide. Charged glass slides should be considered as medical devices and their preparation follows regulations of medical devices. No significant financial relationships to disclose.
Cytogenetic Evolution Associated With Disease Progression in Hematopoietic Neoplasms With t(8;22)(p11;q11)/<i>BCR-FGFR1</i>Rearrangement
Authors: Wei Wang, Guilin Tang, Tapan Kadia, Xinyan Lu, Yan Li, Lanshan Huang, Ximena Montenegro-Garreaud, Roberto N Miranda, Sa A Wang
Journal: Journal of the National Comprehensive Cancer Network (2016)

Hematopoietic neoplasms with FGFR1 rearrangements are rare. Clinically, patients often present with a chronic myeloproliferative neoplasm with eosinophilia and an increased risk of transformation to acute leukemia. We report a patient who initially presented with B-cell acute lymphoblastic leukemia (B-ALL) with t(8;22)(p11.2;q11.2) and an additional derivative chromosome 22 [der(22)t(8;22)]. After induction chemotherapy, B-ALL blasts were eradicated; however, a chronic myeloproliferative process emerged showing persistent t(8;22) (p11.2;q11.2) but not der(22)t(8;22). Combined morphologic and fluorescence in situ hybridization revealed that both lymphoblasts and myeloid cells harbored t(8;22)(p11.2;q11.2); but only lymphoblasts carried the additional der(22)t(8;22). This case provides direct evidence to illustrate the clonal relationship of chronic phase and blast phase in myeloid neoplasms with FGFR1 rearrangement, and demonstrates that clonal cytogenetic evolution plays an important role in disease progression.
SAT0525 Tocilizumab Compared with Anakinra in Refractory Adult-Onset Still's Disease. Multicenter Study of 75 Patients
Authors: N. Palmou, V. Calvo-Río, R. Blanco, J.L. Hernández, F. Ortiz-Sanjuan, A. Olivé, A. Riveros, S. Castañeda, F.J. Narváez, M.L. Velloso-Feijoo, M.V. Hernández, W.A. Sifuentes Giraldo, O. Maiz Alonso, E. Rubio Romero, C. Mata, A. Gallego Flores, J. del Blanco-Barnusell, C. Gόmez-Arango, M.D.C. Ordόñez, M.A. Caracuel, M.L. Velloso Feijoo, I. Jiménez-Moleόn, J.A. Bernal, M.A. González-Gay
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Interleukin (IL)-1 and IL-6 are pivotal cytokines in the pathogenesis of adult-onset Still9s disease (AOSD). <h3>Objectives</h3> Compare the efficacy and safety of tocilizumab (TCZ) versus anakinra (ANK) given for at least 1 year to AODS patients refractory to conventional treatment. <h3>Methods</h3> Multicenter study (31 hospitals) of 75 patients (TCZ; n=34 and ANK; n 41) with AODS refractory to conventional immunosuppressive drugs and in many cases also to other biological agents. <h3>Results</h3> Comparisons of the group of patients with TCZ and ANK were: a) Average age: 39±16 vs. 34±14 years (p=0.2) b) Percentage of women: 76.5% vs. 63.4% (p=0.2) c) Median disease duration 4.2 [1-9] vs. 2.2 [0.3 to 4.9] years (p=0.14) d) Average dose of prednisone 15±9.9 mg/day vs. 28.3±22 mg/day (p=0.013) e) Median of conventional immunosuppressants (2 [1-3] vs 1 [1-2] (p=0.05) f) Median of other biological therapies: 1 [0-2] vs. 0 [0-1] (p=0.04). The initial dose of i.v. TCZ were: 8 mg/kg/4 weeks (n=22), 8 mg/kg/2 weeks (n=10) and 4 mg/kg/4 weeks (n=2). ANK dose was 100 mg/day s.c. Both biologic agents were often combined with a conventional immunosuppressive drug (55.9% vs 70.7%; p=0.2). Both biologic agents yielded a quick and sustained improvement of all clinical and laboratory parameters (Table). The improvement in the clinical parameters was similar in both groups. However an earlier improvement of CRP and ESR was observed following TCZ therapy. After a median follow-up of 19 months [12-31] with TCZ and 15.5 months [4.5 to 50] with ANK (p=0.1), the major adverse effects in the TCZ group were: elevation liver enzymes (n=4), mild to moderate leucopenia (4), upper respiratory tract infection (3), pneumonia (1), pyelonephritis and severe enterocolitis (1) and spondylodiscitis (1). In the group of ANK: skin lesions (n=8), mild leucopenia (3), myopathy (1), respiratory infection by P. aeruginosa and gluteal abscess (1), herpes zoster (1), osteomyelitis (1) and infection of urinary tract (2). While none of the TCZ-treated required discontinuation of the drug due to inefficacy, ANK had to be discontinued for this reason in 11 patients (p=0.001). Adverse effects leading to discontinuation of the drug were observed in 2 patients with TCZ and 4 patients with ANK (p=0.54). <h3>Conclusions</h3> TCZ and ANK are associated with a rapid and sustained clinical improvement in most patients with refractory AODS. However, TCZ appears to be more effective than ANK. <h3>Disclosure of Interest</h3> None declared
The emotionally disturbed psychiatric resident
Authors: A T Russell, R O Pasnau, Z C Taintor
Journal: American Journal of Psychiatry (1977)

The authors compared data on 2,860 residents gathered by means of questionnaire responses by residency directors with data on 288 residents found in an earlier similar survey to have emotional difficulties. They found that age, marital status, previous psychiatric treatment, substance abuse, and previous nonpsychiatric medical practice differentiated the "problem" residents from the total residency population surveyed. However, sex, ethnicity, foreigh medical graduation, and transfer from other residency programs did not differentiate the two groups.
PWE-031 Modelling of suspicious and high risk endosonographic morphology, cytopathology and cyst biochemistry highlights the accuracy of endosonography to predict operative histological outcome in pancreatic cystic tumours
Authors: MA Butt, S Papasavvas, A Sangwaiya, J Westaby, D Bansi, D Westaby, C Wadsworth, P Vlavianos
Journal: Gut (2015)

<h3>Introduction</h3> Distinguishing benign from potentially malignant pancreatic cystic lesions has important prognostic and therapeutic implications. Diagnosis is achieved through a combination of history, imaging, biochemical, endoultrasonographic (EUS) and cyst aspirate (CA) analysis. We evaluated the accuracy of suspicious and high risk variables identified at EUS and CA analysis to predict premalignant or malignant histopathology confirmed at surgery. <h3>Method</h3> Patients who underwent EUS prior to surgery were selected. Data on age, sex, cyst location, suspicious (S) or high risk (HR) EUS or CA features, diagnosis (grouped as benign vs premalignant/malignant) at EUS (EUS-D), post CA analysis (CA-D) and combined EUS and CA analysis (EUS&amp;CA-D) were collected. These were compared with final histological diagnosis (H-D) from surgery. High-risk (HR) variables were defined as C4/C5 diagnosis or carcinoma embryonic antigen (CEA) &gt;192 ng/ml on CA, and cyst size &gt;30 mm, PD dilatation &gt;10 mm, mural nodules or mixed solid/cystic components at EUS Suspicious (S) variables included HR features or mucin, C3 diagnosis or amylase &gt;1000 U/L on CA, and pancreatic duct (PD) dilatation or cyst wall thickening on EUS. Variables were assigned a score of 1 when present, and combined with either EUS-D (EUS-D-S or EUS-D-HR) or CA-D (CA-DS or CS-D-HR). A single positive variable defined positivity in groups. EUS and CA outcomes were then evaluated to identify the sensitivity, specificity, area under the ROC curve (AUC) and likelihood ratio (LR) to predict H-D. <h3>Results</h3> 38 patients were identified (mean age 60.4 years, range 19–81; 52.6% female). Histology identified benign (18.5%; retention cysts, accessory spleen, chronic pancreatitis, hydatid, serous cystic neoplasm), premalignant (60.5%; intraductal papillary mucinous neoplasm (IPMN), mucinous cystadenoma, solid pseudopapillary tumour) or malignant disease (21.1%; adenocarcinoma, adenosquamous carcinoma, neuroendocrine tumour). Analysis (AUC and LR) ranked by AUC confirmed EUS-D-S significantly predicted H-D (0.81, p = 0.022; 5.87) with a sensitivity and specificity of 83.7% and 85.7% respectively. This was followed by EUS-D-HR (0.68; 4.29; p = 0.187), CS-D-HR (0.64; 1.83; p = 0.306), EUS&amp;CA-D-HR (0.62; 1.81; p = 0.374) and CS-D-S (0.52; 1.04; p = 0.89). EUS&amp;CA-D-S did not predict H-D (0.5; 1.16; p = 1.0). <h3>Conclusion</h3> EUS can accurately predict final H-D in patients cystic pancreatic lesions with excellent sensitivity and specificity when modelled appropriately. Interestingly, the accuracy of this method diminished when combined with CA variables. <h3>Disclosure of interest</h3> None Declared.
Trends in laboratory‐diagnosed onychomycosis between 2006 and 2014 in the South West of England
Authors: C. Wlodek, A. Trickey, D. Berker, E.M. Johnson
Journal: British Journal of Dermatology (2016)

Onychomycosis is a worldwide health problem.Several factors make it a challenging entity: difficulties confirming the diagnosis, potential side effects of antifungals, treatment duration and relapse.Appreciating local pathogens and identifying changing trends are essential for optimal management.There is no UK data concerning laboratory-diagnosed onychomycosis, therefore we carried out a retrospective analysis in the Southwest of England.Electronic records of all nail specimens received at Public Health England Mycology Reference Laboratory between March 2006 and December 2014 were identified.Data items included age, gender, microscopy/culture results and site of specimen.Statistical analysis was carried out using STATA ® .One-sample t-tests were used to analyse if Candida sp. were split between genders in the same ratio as the rest of the samples.A two-sample t-test was used to examine whether age ranges differed between 2006 and 2014.Comparison of proportions were carried out using Chi squared test.
SP0010 How to Treat Raynaud's Phenomenon &amp; Systemic Sclerosis?
Authors: G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2015)

Systemic sclerosis is characterized by autoimmunity, vasculopathy and different degrees of inflammatory fibrosis. The link between these three features is still not fully elucidated as well as the heterogeneity of the disease. Mortality and morbidity are high. For the treatment of Raynaud9s phenomenon and its complications vasoactive therapies such as ACE inhibitors, prostanoids, endothelin receptor blockers, or PDE-V inhibitors are used in patients with vascular complications. The role of calcium channel blockers to prevent disease complications is still a matter of debate. However; manifestations such as digital ulcers or PAH represent already existing structural changes and therefore, these therapies are prescribed at a late stage and, at least for PAH, despite existing knowledge about best therapeutic effects in early disease processes. Therefore, predictors are needed to identify those patients with high risk of vascular complications. Several observational studies have elucidated risk factors for vascular complications such as decreases in lung function, high concentrations of anti-angiotensin, anti-endothelin receptor antibodies, and high NT-proBNP values to predict PAH. Initiatives are ongoing to treat early PAH with lower mean pulmonary arterial pressure and hopefully, more drugs are available based on pathophysiologic concepts. Compared to Systemic Lupus Erythematodes (SLE) or Mixed Connective Tissue Disease (MCTD), systemic sclerosis is more resistant to immunosuppressive therapies. On the other hand, primary Sjoegren9s syndrome and primary antiphospholipid antibody syndrome are other related autoimmune diseases with poor response to immunosuppressant. Recent studies on autologous stem cell transplantation serve as proof of concept for immunosuppressive effects. In addition, several immunosuppressants, combination therapies, and biologic agents have shown efficacy mostly in small observational studies. In comparison to SLE, more intensive therapies are needed. However; they can reduce signs of fibrosis and can improve skin sclerosis, lung function parameters and HR-CT findings. There are several novel therapeutic concepts with promising results in pilot studies. Nevertheless, some disease manifestations such as arthritis, contractures, severe gastrointestinal involvement, or calcinoses remain therapeutic problems. Systemic sclerosis has still a need for effective therapies with impact on morbidity and mortality. Therefore, centres of excellence, registries, multidisciplinary cooperations, and clinical trials are needed. Initiatives such as the European Scleroderma Trial and Research Network (EUSTAR) or DeSscipher are important to understand the disease and the natural course. <h3>Disclosure of Interest</h3> None declared
Alteration of Serum Proteins in Chickens With a Lymphoid Tumor&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Oscar J. Fletcher, Jr., Carl Olson
Journal: JNCI Journal of the National Cancer Institute (1969)

A progressive increase in the β -2 globulin fraction of serum was found in birds with a rapidly growing transplantable lymphoid tumor. Birds with tumor also had a progressive decrease in albumin and a terminal decline in total protein. The nature of the increased fraction was investigated by sucrose density gradient ultracentrifugation, diethylaminoethyl cellulose and Sephadex G-200 chromatography, horizontal starch gel, and microimmunoelectrophoresis. Results of these studies indicated that the β-2 globulin fraction was not γ-G or γ-M. An increase in the total iron-binding capacity which paralleled the increase in β-2 indicated that this material was transferrin. The increased transferrin in birds with tumor may be produced by the tumor cells themselves or may be a secondary response of the birds to progressive tumor growth.
AB1177 Validation of Rheumatoid Arthritis Diagnosis in the Korean National Health Insurance Claims Database
Authors: S.-K. Cho, D. Kim, S.-Y. Won, M. Han, J. Lee, E.J. Jang, S.-C. Bae, Y.-K. Sung
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Healthcare claims database is one of powerful sources of epidemiologic study for RA patients. It is crucial, however, to assess the validity of using diagnosis codes contained in this healthcare claims database to identify RA cases prior to utilizing them for epidemiological studies. Prior studies have examined the validity of RA diagnostic code and insisted that the addition of disease modifying anti-rheumatic drugs (DMARDs) with RA diagnostic code increase the PPV and accuracy for identifying RA patients in the claims database. However, this algorithm tends to identify only patients in use of DMARDs. <h3>Objectives</h3> To validate various algorithms using information of medication and health utilization for identifying RA patients in the healthcare claims database in Korea. <h3>Methods</h3> A total of 134,930 patients≥19 years old with seropositive RA code (M05) covering the period of January 2009 to June 2011 were included in this validation study. We regarded patients registered in the "individual copayment beneficiaries program for rare and intractable diseases (ICBP)" in Korea as gold standard RA. This registration requires an official report by doctors documenting that the patients fulfilled the 1987 ACR criteria for RA. We constructed algorithms using RA diagnostic code and incorporated claims of (1) RA treatment: DMARDs, NSAIDs, or corticosteroid, (2) Laboratory tests: ESR, CRP, or rheumatoid factor, and (3) Health utilization: outpatient visit or hospitalization. We calculated the sensitivity, positive predictive value (PPV), and accuracy of each algorithm and PPV and accuracy were mainly compared between them. <h3>Results</h3> PPV for identification of RA with RA diagnostic code and any DMARDs or biologics use was 82% and it was higher than those of combination with NSAIDs (52%), corticosteroid (63%), outpatients visits≥3 (74%) or hospitalization (63%). PPV of algorithm for identifying RA with diagnostic code and any DMARDs or biologics or hospitalization was not increased (80%) but the sensitivity (94.9%) was higher than that of RA diagnostic code and any DMARDs or biologics (94.6%). <h3>Conclusions</h3> We suggest that RA patients can be identified with the algorithm of RA diagnostic code of any DMARDs or biologics with high level of PPV in claims database. Addition of hospitalization increased the sensitivity of algorithm in identifying RA patients. <h3>References</h3> Cho SK, Sung YK, Choi CB, et al. Development of an algorithm for identifying rheumatoid arthritis in the Korean National Health Insurance claims database. Rheumatol Int. 2013;33:2985-92. Kim SY, Servi A, Polinski JM, et al. Validation of rheumatoid arthritis diagnoses in health care utilization data. Arthritis Res Ther 2011;13:R32. <h3>Disclosure of Interest</h3> None declared
Preclinical activity of ENMD-981693, an inhibitor of Aurora A kinase and multiple receptor tyrosine kinases, against multiple myeloma (MM) cells
Authors: X. Wang, S. Zhang, L. Chen, J. Liang, A. Suvannasankha, R. Abonour, M. R. Bray, S. S. Farag
Journal: Journal of Clinical Oncology (2008)

8609 Background: ENMD-981693 is a novel, orally-active molecule that has been shown to have significant activity against Aurora A kinase as well as multiple receptor tyrosine kinases (RTKs). We investigated the activity of ENMD-981693 against MM cells. Methods: Human MM cells (IM-9, ARH-77, RPMI-8226, U266, MM.1S, MM.1R, H929) were treated with ENMD-981693 for 6–72h. Cytotoxicity was assessed using MTT assay and annexin V/PI staining, and intracellular signaling by Western blotting. Results: ENMD- 981693 showed significant cytotoxicity against MM cells with mean LC50 of 7.15±2.97 μM and 3.84±0.86 μM at 24 and 48 hours, respectively. Cytotoxicity was associated with cleavage of caspases 3, 8, 9 and PARP, and loss of mitochondrial membrane potential as early as 6 hours. Inhibition of caspase 9, but not of caspase 8, protected against cell death at 6 and 24 hours indicating that apoptosis was predominantly mediated via a mitochondrial pathway. ENMD-981693 also downregulated survivin and X-linked inhibitor of apoptosis at 6 hours, although Bcl-2, Bcl-xL, and Bax remained unchanged. At the earliest time point evaluated (6h), inhibition of VEGFR-1 and 2, c-kit, and FGFR-1 and 3 was also observed following treatment. Consistent with activity against RTKs, inhibition of the PI3K/AKT pathway was observed at 6 hours with downregulation of downstream targets including phosphorylated (p)-AKT, p-p70s6k, p-4EBP1, p-BAD, p-Foxo1a, p- GSK-3β. Although downregulation of JAK-2 was also observed, there was minimal effect on p-Stat-3(Tyr 705) and cyclin D1. With longer treatment (24–48h), ENMD-981693 also inhibited Aurora A kinase, with downregulation of p-Aurora A, G2 cell cycle arrest, and reduction in cyclins A and B. Conclusions: ENMD-981693 shows significant activity against MM cells. Cell death appears to follow a biphasic response, with apoptosis mediated early by a caspase 9-dependent mitochondrial pathway and RTK inhibition with consequent effects predominantly on the PI3K/AKT pathway. Later, G2 cell cycle arrest occurs due to Aurora kinase A inhibition. These results provide pre-clinical rationale for clinical investigation of ENMD-981693 in MM. No significant financial relationships to disclose.