tbuckley/cabot-search huggingface dataset:
Genetic and Phenotypic Correlates of Colorectal Cancer in Young Patients
Authors: Rajiv V. Datta, Michael P. LaQuaglia, Philip B. Paty
Journal: New England Journal of Medicine (2000)

Spironolactone in Patients with Heart FailureTo the Editor: The study by Pitt and colleagues (Sept. 2 issue) 1 of the effect of spironolactone on morbidity and mortality in patients with severe heart failure addresses a very important issue.Spironolactone, a relatively inexpensive and safe agent, has not previously been shown to increase the value of triple therapy with an angiotensin-convertingenzyme (ACE) inhibitor, furosemide, and digoxin.We have not used it because of concern that it may precipitate serious hyperkalemia.We are concerned, however, that the practical message of this study -that is, that spironolactone can decrease morbidity and mortality in patients with severe heart failure who are already receiving triple therapy -is undercut by the failure of the investigators to maximize the effect of triple therapy.For example, at base line, the mean daily doses of ACE inhibitors in the placebo and spironolactone groups were 62.1 and 63.4 mg of captopril, 16.5 and 13.5 mg of enalapril, and 13.1 and 15.5 mg of lisinopril, respectively.These doses are considerably lower than the target doses used in other studies and suggested by the American College of Cardiology and American Heart Association. 2 Pitt et al. do not report the mean doses of digoxin or furosemide.They state that "the investigator was encouraged first to adjust the doses" of ACE inhibitors, digoxin, and diuretics before changing the dose of spironolactone.If so, what effect did this approach have?Could the favorable outcome with respect to morbidity and mortality be the result of maximizing the effects of these medications rather than adding spironolactone?
SAT0146 Dissecting the Impact of Comorbidities on Disease Activity in Rheumatoid Arthritis: Ancillary Analysis from the COMORA Study: Table 1.
Authors: G. Crepaldi, C.A. Scirè, G. Carrara, G. Sakellariou, R. Caporali, I. Hmamouchi, M. Dougados, C. Montecucco
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Suppression of disease activity is the goal of the treatment of rheumatoid arthritis (RA). Therefore the use of validated composite measures of disease activity is needed in order to treat RA to target<sup>1</sup>. <h3>Objectives</h3> To evaluate which comorbidities may influence each component of the clinical composite measures used to assess disease activity in RA. <h3>Methods</h3> All RA patients enrolled in the international, cross-sectional study COMORA were eligible for the analyses. Collected data included demographics, disease characteristics and comorbidities (hypertension, diabetes, dyslipidemia, renal deficiency, ischemic heart disease, stroke, cancer, gastro-intestinal ulcers, hepatitis, depression, chronic pulmonary disease, obesity). Linear regression models explored the relationship between each comorbidity and the following disease activity measures: 28-swollen joint count (SJC), 28-tender joint count (TJC), erythrocyte sedimentation rate (ESR), patient9s and physician9s global assessment of disease (PtGA, PhGA), patient reported fatigue, functional disability (HAQ), DAS28 and CDAI. Results are presented as mean difference (MD). <h3>Results</h3> A total of 3920 patients were included. Age (mean ± SD) 56.27±13.03 yrs, female 81.65%; disease duration median 7.08 yrs (IQR 2.97-13.27), DAS28 (mean ± SD) 3.74±1.55. Variations of the clinimetric indexes, in patients affected by considered comorbidities, are summarized in Table 1. <h3>Conclusions</h3> Diabetes and dyslipidemia seem to be associated with higher and lower disease activity respectively affecting almost all the variables considered. Other comorbidities influence single items suggesting a relationship with measure tools rather than with disease activity. Comorbidity specificities should be taken into account in the management of RA. <h3>References</h3> Smolen JS et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69(4):631–7. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4388
Endoscopic resection with the cap technique of a carcinoid tumor in the duodenal bulb
Authors: S. Karagiannis, K. Eshagzaiy, C. Duecker, B. Feyerabend, E. Mozdzanowski, S. Faiss
Journal: Endoscopy (2009)

Well-differentiated neuroendocrine tumors, also called carcinoid tumors, in the duodenum are rare. The therapeutic approach is highly dependent on both tumor size and depth of invasion; for tumors smaller than 1.0 cm and without penetration of the muscularis propria, endoscopic resection is considered as the method of choice [1].
Abstract 453: Myeloid regulatory cells in cancer patients
Authors: Samuel J. Pirruccello, Holly Samson, Alicia Dafferner, Sarah Maas, Howard Julius, Dennis Weisenburger, Phyllis Warkentin, James E. Talmadge
Journal: Cancer Research (2011)

Abstract Adaptive immunotherapy can augment host immunity, although the outcomes to date in cancer patients have been limited, due in part, to increased numbers of myeloid derived suppressor cells (MDSCs) in the peripheral blood. MDSCs are key cellular regulators that can limit T-cell and dendritic cell (DC) number and function. They are believed to be myeloid precursors that are increased as part of the hematopoietic response to myelosuppression, stress, chemotherapy, and tumor growth. Recently, we found that mononuclear cell apheresis of some cancer patients (melanoma, leukemia and lymphoma), but not normal donors were enriched for hypodense myeloid cells as confirmed by elutriation and Ficoll-Hypaque gradients. These cells are also found in the peripheral blood, although their frequency is enriched by mononuclear cell apheresis. Despite their low density, cytologically they appear as granulocytes containing &amp;lt; 1% bands or metamyelocytes. Phenotypic analysis by flow cytometry revealed that &amp;gt;98% of the granulocytes (FSxSS), were MDSCs, defined as linage−(CD3, CD19 and CD56)DR−CD14dullCD13dull CD11b+CD33+. Consistent with an immature granulocyte phenotype &amp;gt; 50% of the granulocytes were CD16dull/− as compared to &amp;lt;3% of the granulocytes in the PB or apheresis products of normal donors. The frequency of these cells in an apheresis product or the peripheral blood from cancer patients can be as high as 60% of total nucleated cells and following mononuclear cell elutriation &amp;gt;95% of nucleated cells. It is emphasized that this is not observed in all patients and in our limited experience occurs in 20% or less of patients with advanced disease. Enrichment of hypodense MDSCs by Miltenyi magnetic bead selection of CD11b+ cells following subtractive depletion of DR+ cells provided a 60-85% pure population of MDSCs that can suppress an allogeneic T-cell response and by quantitative TaqMan analysis have significantly increased levels of NOS2, IL10, LTB4R1, MPO, MMP9 and VEGFα. We conclude that the majority of MDSCs in cancer patients are immature granulocytes; rather than myeloid precursors, as evidenced by their CD16dull phenotype, a lack of CD34 expression and segmented granulocyte morphology. Further, the presence of hypodense MDSCs has a significant impact on monocyte enrichment (apheresis, elutriation and Ficoll Hypaque separation) for maturation of monocytes into dendritic cells and use as a vaccine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 453. doi:10.1158/1538-7445.AM2011-453
SAT0415 Diagnostic and predictive value of novel method for analyzing IGG galactosylation in rheumatoid arthritis
Authors: S. Ohshima, T. Nakagawa, A. Taguchi, T. Taguchi, A. Kitatobe, E. Kudo-Tanaka, S. Tsuji, Y. Maeda, M. Yoshimura, A. Watanabe, M. Katayama, Y. Harada, Y. Katada, J. Hashimoto, M. Matsushita, A. Kondo, Y. Saeki
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> While the emphasis in rheumatoid arthritis (RA) treatment is on early diagnosis and intervention, we cannot provide the certain strategies for diagnosis. It is well known that serum immunoglobulin G (IgG) from RA patient exhibit decreased galactosylation of conservative N-glycans in CH2 domains of the heavy chains. Kondo et al. developed novel high-performance liquid chromatography (HPLC) method for precise analysis of oligosaccharides of IgG<sup>1)</sup>. <h3>Objectives</h3> To evaluate both diagnostic and predictive value of agalactosyl IgG in RA, we analyze serum IgG oligosaccharide structures using HPLC both in established RA, and in early undifferentiated arthritis as a diagnostic marker for future development ofRA. <h3>Methods</h3> Firstly, serum samples were collected from 94 patients with RA fulfilled the 1987-ACR-criteria, 16 with OA, 18 with SLE, and 24 with healthy subjects (HS). The percentage agalactosyl IgG oligosaccharides (%G0) were analyzed in serum samples by high performance HPLC method. Secondly, we analyzed %G0 in 144 patients with recent-onset undifferentiated arthritis (UA) defined as not fulfilling existing classification criteria. They were studied for whether UA progressed to RA after 2 year. <h3>Results</h3> In the first study, serum levels of %G0 were significantly higher in established RA (41.5±9.1) than in HS (21.1±4.4; p&lt;0.01), OA (26.2±7.1; p&lt;0.05), and SLE (28.7±10.4; p&lt;0.05). The second study comprised 144 patients (35 males; 109 females) with early UA. The following parameters were assessed at baseline: %G0, rheumatoid factor (RF), autoantibody to galactose deficient IgG (CARF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 144 patients with early UA, 58 (40.3%) developed RA, 9 (6.2%) developed collagen disease, 33 (22.9%) diagnosed as OA, 21 (14.6%) were UA as ever, and 23 (16.0%) were healthy (transient arthropathy) within two years after registration. %G0 predicted progression of UA to RA with high accuracy (AUC=0.807) at a highest sensitivity of 79.3% among 4 diagnostic markers (Table 1). Moreover, combination of %G0 and ACPA predicted progression of UA to RA with highest accuracy (AUC=0.905; 95% CI, 0.835-0.962). <h3>Conclusions</h3> In conclusion, this novel method for analyzing agalactosyl IgG revealed excellent diagnostic value inRA. %G0 as well as ACPA would contribute to prediction of RA, allowing early therapeutic decisions. Furthermore, agalactosyl IgG may be involved in pathogenesis of RA. <h3>References</h3> Kondo A, et al. Separation of pyridylamino oligosaccharides by high-performance liquid chromatography on an amine-bearing silica column. Anal Biochem 1994, 219, (1), 21-5. <h3>Disclosure of Interest</h3> None Declared
Endoscopic resection of a giant pedunculated polyp using scissor-type forceps
Authors: Keiichiro Kume, Shintaro Takahashi, Keiichiro Kumamoto, Tatsuyuki Watanabe, Ichiro Yoshikawa, Masaru Harada
Journal: Endoscopy (2014)

An 83-year-old man presented with a feeling of abdominal fullness and underwent colonoscopy. Two pedunculated polyps were identified in the sigmoid colon: the one on the oral side was about 20 mm, while that on the anal side was a giant lesion nearly as large as the diameter of the bowel lumen ([Fig. 1 a]). It was judged to be difficult to perform polypectomy by snaring the latter polyp. Both polyps were therefore resected employing the following procedure. The end hood was placed on the scope, and multiple clips were placed around the base of the stalk to block blood flow ([Fig. 1 b]). Next, we pulled forward the stalk of the polyp by grasping the head of the polyp with the SB knife Jr (MD-47703; Sumitomo Bakelite, Akita, Japan) ([Fig. 1 c]), pulling it into the end hood ([Fig. 1 d]), and performing electric incision until the polyp could be resected ([Fig. 1 e]). Stalk excision was performed with endocut mode 120 W. Hemostatic treatment was performed with soft coagulation mode 80 W.
THU0186 Anti-Drug Antibodies, Drug Levels and Clinical Efficacy of the Anti-TNF Biologics in Rheumatic Diseases
Authors: C. C. Mok, D. van der Kleij, G. Wolbink
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the effect of drug levels and anti-drug antibodies on the clinical efficacy and withdrawal of the anti-TNFa biologics in Chinese patients with rheumatic diseases. <h3>Methods</h3> A cross-sectional study was performed in patients with various rheumatic disorders who were newly started on anti-TNFa treatment in the preceding 24 months. Serum samples were collected for the assay of drug levels and antibody titers against the corresponding agents. Comparison of the clinical efficacy and drug retention rate was performed between patients with and without the presence of anti-drug antibodies. <h3>Results</h3> 58 Chinese patients were recruited (64% women). The underlying diseases that require anti-TNFa treatment were rheumatoid arthritis (RA) (60%), spondyloarthritis (SpA) (21%), psoriatic arthritis (PSA) (17%) and others (2%). The mean age was 47.8±12.9 years and the mean duration of the underlying diseases was 6.7±6.4 years. The proportion of patients treated with infliximab (IFX), adalimumab (ADA) and etanercept (ETN) was 41%, 28% and 31%, respectively. Antibodies against IFX, ADA and ETN were demonstrated in 12 (50%), 5 (31%) and 0 (0%) patients, respectively (p=0.002). Patients who developed anti-drug antibodies had significantly lower levels of the corresponding drugs (IFX level: 0.004±0.01 vs 3.81±3.49 ug/ml; p=0.002; ADA level: 0.0 vs 7.6±8.3 ug/ml; p=0.008). Compared to those without anti-drug antibodies, patients with antibodies had a significantly higher cumulative drug withdrawal rate due to inefficacy (64.7% and 71.8% vs 10.3% and 10.3% at month 12 and month 24, respectively; p&lt;0.001). In patients with RA and PSA, the proportion of non-responders (according to the EULAR RA response criteria) was significantly higher in patients with anti-drug antibodies than those without (54% vs 11%; p=0.01). In patients with SpA, the mean improvement in ankylosing spondylitis disease activity score (ASDAS) score was significant in patients without antibodies (3.89±0.82 to 2.22±0.86; p=0.01) but not in those with anti-drug antibodies (3.40±1.67 to 3.23±1.40; p=0.73). <h3>Conclusions: Conclusion</h3> The presence of neutralizing antibodies to the anti-TNFa biologics leads to lower serum levels of the corresponding drugs, which is associated with lower clinical efficacy and higher withdrawal rate. <h3>Disclosure of Interest</h3> None Declared
Andrew Murray
Authors: Johann Windt
Journal: British Journal of Sports Medicine (2016)

![Graphic][1]</img> I worked at the North Pole one year when William Tan completed a marathon, in a wheelchair in the North Pole. I must admit I didn't think he could do it—which taught me to be as resilient as hell, and find a way to get 'it' done—whatever the task in front of you. Also Commonwealth Games and Ryder Cup both at home in Scotland 2014. Listen more, don't be in such a rush. Also, your mullet with the dyed blonde bit at the back is ridiculous and all your friends are right. Cut it off! Resilience. Find a way to get it done. I broke both my arms. That made visits to the bathroom a lot harder. By accident—I once ran 4300 km from far north Scotland to the Sahara desert. It was just to raise a bit of cash for charity, and to see the sights. But half way there I remember reading the 'Fat and fit' editorial in BJSM and started promoting physical activity as part of the run. Both the relevant minister and our Chief Medical Officer watched a TV programme that … [1]: /embed/inline-graphic-1.gif
AB0571 Efficacy of tocilizumab prescribed as first line biologic: A 48-week post marketing observational study in romanian rheumatoid arthritis patients (stone) - interim analysis:
Authors: R. Ionescu, C. Codreanu, I. Ancuta, A. Balanescu, M. Parvu, D. Opris
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Optimal care of patients with Rheumatoid Arthritis (RA) requires an integrated approach of pharmacologic therapies which usually includes conventional DMARD's and biological DMARD's such as Tocilizumab (TCZ). In Romania, official guidelines recommend start of a biologic compound only after failure of 2 consecutive cDMARD's administered at a maximum tolerated dose (MTX is mandatory). TCZ is used as first line biological therapy according to SPC and local therapeutic guidelines approved by Romanian Ministry of Health. <h3>Objectives</h3> The purpose of this interim analysis is to evaluate the efficacy of TCZ therapy in patients with RA who have had intolerance or inadequate response prior to cDMARD's therapies in Romania. <h3>Methods</h3> In this open-label, multicenter, prospective, non-comparative, non-interventional study, target population was represented by adult patients with active RA, DMARD-IR and biologics naïve, administrated according to real life practice. They were treated for 48 weeks with TCZ, prescribed according to the current Romanian standard of care (8 mg/kg every 4 weeks). The primary objective was the median change in DAS28 at W24 and 48. Secondary objectives included: remission (DAS28 &lt;2.6), low disease activity rates and EULAR response rates. We analyzed 62 patients (87.1% women, 12.9% men, average age of 50) who reached W48 of treatment at 1st September 2011. <h3>Results</h3> At baseline, median DAS28 was 6.66, with 91.84% of patients in HDA and 8.06% in MDA. At W24, DAS28 decreased to 2.59, with 51.61% of patients achieving remission and 22.58% in LDA. At W48, DAS28 was 2.30 and 60.38% patients reached remission and only 16.98% were in LDA. For analyzed patients median change in DAS28 was - 4.07 at W24. This response is consolidated by results obtained at W48 (ΔDAS28=4.36). <h3>Conclusions</h3> In our study, significantly improved DAS remission rates were achieved suggesting that Tocilizumab therapy can be successful used, in real life settings, in order to meet Treat-to-Target principles, for patients with active RA, DMARD-IR and Biologics naive. <h3>Disclosure of Interest</h3> None Declared
Case 11-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Lee S. Simon, Alan H. Gorn
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 38-year-old woman was admitted to the hospital because of abdominal pain, fever, and a rash.She was well until two months earlier, when she experienced the onset of intermittent weakness, nausea, and vomiting that continued for six weeks. Two weeks before admission fever developed, with pruritic skin lesions on the arms, hands, and legs. She used aspirin and experienced recurrent sweats. Five days before entry she was seen at another hospital, complaining of a stiff neck, chilliness, weakness, and myalgia. The temperature was 38.3°C. The hematocrit was 36.9 percent; the white-cell count was 8100, with 62 . . .
Comparison of molecular and pathologic features of stage II and stage III colon cancer in four large studies conducted for development of the 12-gene colon cancer recurrence score.
Authors: M. J. O'Connell, I. C. Lavery, R. G. Gray, P. Quirke, D. J. Kerr, M. Lopatin, G. A. Yothers, M. Lee, K. Clark-Langone, N. Wolmark
Journal: Journal of Clinical Oncology (2010)

3503 Background: An understanding of biologic similarities and differences between st II and III colon cancer is needed to inform clinical practice and trial design. We compare pathologic markers and gene expression by stage in 4 colon cancer studies conducted to develop the 12-gene recurrence score (RS): NSABP C01/C02, C04, C06, and CCF. Methods: Gene expression was quantitated by RT-PCR from 30 μ m manually microdissected FPE colon cancer tissue. St II colon cancer with < 12 LN examined was excluded to minimize under-staging. Pathologic markers and expression of 375 genes were compared b/w 634 st II and 844 st III pts, and stage-specific associations with recurrence were evaluated using Cox models. Results: As expected, nodal status was a strong predictor of recurrence. St II pts were more likely to be MMR deficient (17 vs. 12%, p = 0.04) and have mucinous histology (19 vs. 14%, p = 0.007) while proportions of high grade and T4 were similar by stage (p > 0.5). Interaction of grade and stage was significant (p = 0.005) with HR for grade = 0.58 for st II and 1.27 for st III. Interactions of stage with T stage, MMR and mucinous histology as predictors of recurrence were borderline (p = 0.07-0.11), with indication of prognostic effects in st II but not st III. Absolute differences b/w st II and III in mean expression of 375 genes were small: median 0.09 CT. 5 genes had significant (p < 0.05) differences in expression by stage in all 4 studies. 45 genes showed evidence of expression by stage interaction (p < 0.1), with 37 of these expected to be false discoveries. RS showed no interaction with stage (p = 0.87). Unsupervised cluster analysis revealed similar patterns of gene expression by stage. In st II colon cancer pts w/ ≥ 12 LN examined from the QUASAR validation study (n = 506), gene expression patterns paralleled those observed in the 4 studies. Conclusions: Quantitative analysis by RT-PCR identified very similar expression in st II and III disease for the vast majority of genes tested. Future studies should examine the clinical significance of differences identified between st II and III, including MMR, grade, and a small number of individual genes. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genomic Health Genomic Health Genomic Health