tbuckley/cabot-search huggingface dataset:
P279 Evaluation of treatment with fixed dose combinations in asthma patients in primary care in Sweden by using mannitol challenge test
Authors: K Romberg, A-C Berggren
Journal: Thorax (2012)

<h3>Background</h3> The mannitol challenge test is an indirect bronchial challenge test suitable for use in a primary-care setting. The test is most often used to diagnose asthma. In this pilot study the test was used to evaluate the effectiveness of ongoing treatment with ICS/LABA combination therapy in patients with asthma. <h3>Objectives</h3> To explore the prevalence of optimal treated asthma patients in primary care in Sweden. The hypothesis was that not all patients are optimal treated. <h3>Methods</h3> Male and female subjects, age 18–65 years with asthma, who were treated with a fixed dose combination (budesonide/formoterol or fluticasone/salmeterol) were included in the study. The subjects performed a mannitol challenge test (direct fall) followed by an inhalation of a β<sub>2</sub>-agonist. A new spirometry (reversibility test) was performed 15 minutes later. The main explorative end-point was positive or negative response of mannitol challenge test and/or a reversibility of ≥15%. <h3>Results</h3> The preliminary result of this pilot study (100 subjects) shows that an unexpected, surprisingly high proportion of the asthma patients had a positive response, either as a direct fall of FEV1 ≥15% in the mannitol challenge test and/or a reversibility of ≥15%. <h3>Conclusion</h3> The result of this study indicates that a large proportion of asthma patients in primary care, who are currently treated with fixed dose combination therapy, may not be optimally treated. Further research is needed to support these findings and to understand the reasons.
NHS can't be expected to continue plugging gaps in social care funding, says NHS Confederation
Authors: M. Limb
Journal: BMJ (2012)

Health service leaders have warned ministers that the NHS in England cannot continue to bear the strain of supporting a social care system that needs urgent reconfiguration and better long term funding.

The NHS Confederation said that there was a £2bn (€2.5bn; $3.2bn) funding shortfall in social care and that temporary transfers of funds from the NHS to plug the gap were “unsustainable.”

In a report published on Monday 24 September, the confederation, the membership body for all organisations that commission and provide NHS services, said that NHS organisations were already struggling to find efficiency savings of £4bn to £5bn a year and could not find a further £2bn a year “without severely affecting patient care.”1

Its policy director, Jo Webber, said, “The health service cannot …
Abstract 2963: ALK is a MYCN target gene and contributes to cell growth, migration and invasion in neuroblastoma
Authors: Md. Kamrul Hasan, Atsushi Takatori, Satoshi Kishida, Miki Ohira, Md. Shamim Hossain, Jesmin Akter, Atsushi Ogura, Yohko Nakamura, Kenji Kadomatsu, Akira Nakagawara
Journal: Cancer Research (2012)

Abstract Neuroblastoma (NBL), the most common solid tumor of childhood, is an embryonal malignancy of the developing sympathetic nervous system. Human Anaplastic lymphoma kinase (ALK) has been identified as an oncogene mutated or amplified in NBLs. However, the role of wild-type ALK in NBL is still largely unknown. For better understanding a molecular event associated with ALK in the pathogenesis of NBL, it is necessary to clarify how ALK gene contributes to NBL progression. Previously in the analysis of NBL clinical samples, we have found that ALK expression is significantly high in MYCN amplified group. Consistent with this evidence, the developing tumors with NBL characteristics in MYCN-transgenic mice possess a high expression of ALK. In the present study, we have found that overexpression of MYCN induced ALK expression and siRNA-mediated knockdown of MYCN resulted in the downregulation of ALK expression in NBL and non-NBL cell lines. We have identified the promoter region of ALK, to which MYCN binds, in the upstream of the first exon from +30 to −350 bp and Luciferase reporter assay showed that MYCN overexpression enhanced the promoter activity of ALK. The site-specific deletion at MYCN binding site of ALK promoter region downregulated its promoter activity and chromatin immunoprecipitation (ChIP) assay indicated that MYCN can be recruited to the ALK promoter region, suggesting that ALK is directly regulated by MYCN. In general, high expression of MYCN is a well-known prognostic marker for aggressive progression and increases growth rate of NBL cells. However, the role of MYCN in enhancing cell migration and invasion has not yet been fully understood. We have further examined an effect of ALK expression in MYCN-induced cell migration. Functional assay revealed that overexpression of ALK enhanced NBL cell growth, migration as well as invasion. Moreover, these activities were suppressed by siRNA-mediated knockdown of ALK, indicating that ALK might be involved in the metastatic phenotype of NBLs. On the other hand, the forced expression of MYCN enhanced cell migration in MYCN-single copy cell line, SK-N-AS cells. Of interest, the increased migration by MYCN expression was suppressed by siRNA-mediated knockdown of ALK, suggesting that the cell migration induced by MYCN is at least partly regulated by ALK expression. Our present findings explore the fundamental understanding of ALK and help a future development of novel therapeutic tools by targeting ALK for aggressive NBLs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2963. doi:1538-7445.AM2012-2963
PTU-087 Management of pyogenic liver abscess: an 11-year retrospective study of practice at a metropolitan hospital and development of local guidelines
Authors: M E B Fitzpatrick, S Pomfret, M Foxton, S Portsmore
Journal: Gut (2012)

<h3>Introduction</h3> Pyogenic liver abscess (PLA) is an uncommon condition associated with considerable morbidity and mortality despite modern treatment. Patients have prolonged lengths of stay, require repeated imaging and procedures, and frequently develop significant complications. We audited the burden of PLA and the outcomes of treatment in Chelsea and Westminster Hospital, London. We used our data to develop local guidelines for PLA, incorporating information from previous case series and a review of the literature. <h3>Methods</h3> Between January 2000 and September 2011, 41 patients had a correctly coded diagnosis of PLA. Electronic or paper medical records were available for 40 patients. We collected anonymised information regarding the medical history, investigations and clinical course. <h3>Results</h3> 40 patients (78% male, mean age 54 years, 70% caucasian) were treated for acute PLA, with no in-hospital deaths. Mean length of stay was 19.3 days (CI 15.1 to 23.4 days). Presentations were non-specific, and the diagnosis rarely considered on admission. Blood results in most patients on admission demonstrated a characteristic pattern of hypoalbuminaemia, high CRP, and non-specific liver dysfunction. 61.1% of patients were septic on admission. In general, appropriate imaging was arranged early in the admission. Diagnosis of PLA was made with CT (54%) or ultrasound (46%). 75% of abscesses were found in the right lobe, with a mean maximum diameter of 6.5 cm (SD 2.4 cm). 48% of patients had multiple abscesses, and 40% had signs of loculation on imaging. 78% of abscesses were larger than 5 cm. 68% of abscesses were aspirated or drained, with three patients requiring repeated intervention, and one referred to a hepatobiliary unit. Length of stay was longer in older patients (p&lt;0.05), those requiring drainage (23.8 vs 11.3 days, p&lt;0.001) and those with complications (28 vs 11.8 days, p&lt;0.001). Abscess size was not related to length of stay or need for drainage. Decisions regarding antibiotics and drainage varied between clinicians. Severe complications developed in 50% of patients and included venous thrombosis (n=4) and need for ITU support (n=4). Resolution was typical, with no in-hospital mortality. Underlying causes for PLA included abdominal malignancy (n=4), appendicitis (n=2) and diabetes mellitus (n=5). Often no cause was found, and screening for causes with MRCP and colonoscopy was not universal. <h3>Conclusion</h3> Our study describes a large UK cohort of patients with PLA, with a lower mortality than described in other case series, and good outcomes without drainage in selected patients with large abscesses. Our cohort showed considerable variation in PLA treatment, and in response we have developed PLA management guidelines. <h3>Competing interests</h3> None declared.
FRI0191 Effectiveness of adalimumab in the treatment of rheumatoid arthritis depends on the dose of methotrexate
Authors: S. Ito, K. Oh, M. Unno, D. Kobayashi, C. Azuma, A. Abe, H. Otani, H. Ishikawa, K. Nakazono, I. Narita, A. Murasawa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In a study on continuation of adalimumab (ADA) therapy in Japan, the concomitant use of MTX with ADA was associated with higher efficacy and treatment retention rate (1). In Western countries, the recommended dose of MTX for patients receiving ADA is 15~20 mg/week on average, while the approved dose of MTX combined with ADA in Japan was 8 mg/week and revised in February 2011 on the basis of the results of analysis of the safety and efficacy of MTX to increase up to 16 mg/week (2). <h3>Objectives</h3> Analyze the efficacy of ADA by the presence/absence of methotrexate (MTX) and its dose in Japanese patients. <h3>Methods</h3> Enrolled were 46 patients who started ADA from Jul 2008 to Feb 2012 and were followed for 24 weeks. Mean dose of MTX was 8.6±2.1 mg/week. Pearson's product-moment correlation coefficient was used to assess the correlations between improvement in DAS28-ESR and MTX dose in patients receiving MTX at &lt;8, 8 and &gt;8 mg/week. <h3>Results</h3> Mean DAS28-ESR at baseline and week 24 were, respectively, 4.7±1.3 and 2.8±1.2 in 38 patients with MTX and 4.5±1.0 and 4.2±1.5 in 8 patients without MTX, and 53% and 25% of them achieved clinical remission by week 24. Patients who continued ADA by week 24 accounted for 84.2% and 50.0% in patients with and without MTX. In 14 patients receiving MTX at &gt;8 mg/week, DAS28-ESR decreased quickly from 4.5±1.1 at baseline to 3.3±1.0 and 2.4±1.0 at weeks 4 and 24. Clinical remission at week 24 with ADA was significantly greater in patients administered high dose MTX (DAS28-ESR&lt;2.6: 71% and 40% of those receiving MTX at &gt;8 and &lt;8 mg/week). A significant correlation was noted between the improvement in DAS-ESR and MTX dose. <h3>Conclusions</h3> Combination with &gt;8 mg/week of MTX maximizes the clinical efficacy of ADA. <h3>References</h3> Takeuchi T <i>et al.</i> Effectiveness and safety of adalimumab in Japanese patients with rheumatoid arthritis: retrospective analyses of data collected during the first year of adalimumab treatment in routine clinical practice (HARMONY study). Mod Rheumatol. 2012;22:327-38. The Japan College of Rheumatology and the Institute for Data Analysis. Study of efficacy and safety of methotrexate at more than 8 mg/week: Evaluation of 3 RA patients cohorts (IORRA, REAL and NinJa) https://www.ryumachi-jp.com/pdf/MTXHighdose.pdf [in Japanese]. <h3>Disclosure of Interest</h3> S. Ito Grant/research support from: S. Ito has received speaking fee from Abbott Japan Co. Ltd; Eisai Co. Ltd; Mitsubishi Tanabe Pharma Co. Ltd; Asahi Kasei Co. Ltd; Chugai Pharmaceutical Co. Ltd., K. Oh: None Declared, M. Unno: None Declared, D. Kobayashi: None Declared, C. Azuma: None Declared, A. Abe: None Declared, H. Otani: None Declared, H. Ishikawa: None Declared, K. Nakazono: None Declared, I. Narita: None Declared, A. Murasawa: None Declared
Case 41-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, H. Shaw Warren, Elizabeth M. Bailey
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 57-year-old man was admitted to the hospital because of evidence of gram-negative bacteremia, with peripheral edema and erythema of the leg with bullae.The patient had been well until six weeks earlier, when edema of the lower extremities developed. Evaluation at another hospital showed ascites in addition to peripheral edema. Serologic studies revealed evidence of chronic hepatitis due to the hepatitis B virus, and a liver biopsy disclosed chronic active hepatitis with postnecrotic cirrhosis. The patient's condition remained stable until six days before admission, when malaise began and the peripheral edema increased, especially in the left . . .
Abstract 556: Cot/Tpl2 is required for neoplastic cell transformation induced by interleukin-22: a possible mechanism in breast carcinogenesis.
Authors: Karam Kim, Hong Seok Choi
Journal: Cancer Research (2013)

Abstract Interleukin 22 (IL-22), a member of the IL-10 family of cytokines, is secreted T helper 17 (Th17) cells. Although IL-22 was recently reported to be a novel inflammation mediator through STAT3 signaling activation, the precise mechanisms of IL-22 in neoplastic cellular transformation and breast carcinogenesis are not well explored yet. Here, we report that IL-22 induced neoplastic transformation of JB6 Cl41 cells through activation of Cot/Tpl2. IL-22 dose- and time-dependently increased Cot/Tpl2 phosphorylation in JB6 Cl41 cells through IL-22 receptor. IL-22 phosphorylated MEK1/2, JNK1/2 and STAT3, which were inhibited by a specific inhibitor of Cot/Tpl2 kinase. When small interfering RNA (siRNA) of IL-22 and IL-22 receptor (IL-22R) were transfected into JB6 Cl41 cells, IL-22-induced Cot/Tpl2 phosphorylation was markedly decreased, followed by inhibition of MEK-ERK, JNK-c-Jun and STAT3 signaling pathway. Also, IL-22 activated c-fos and c-jun promoter activity, leading to increased activator protein-1 (AP-1) activity, which was suppressed by Cot/Tpl2 inhibitor. The in vivo chorioallantoic membrane (CAM) assay also showed that IL-22 increased tumor growth of JB6 Cl41 cells, whereas Cot/Tpl2 inhibitor suppressed the tumorigenesis induced by IL-22. In addition, knockdown of IL-22 and/or inhibition of Cot/Tpl2 diminished tumorigenecity of human breast cancer SKBR3 cells. Consistent with these observations, immunohistochemical staining showed that both expressions of IL-22 and Cot/Tpl2 proteins were highly upregulated in human breast cancers. Thus, this suggests that Cot/Tpl2 plays a pivotal role in IL-22-induced neoplastic cell transformation, and that Cot/Tpl2 may be the therapeutic target of breast cancer promoted by IL-22. Citation Format: Karam Kim, Hong Seok Choi. Cot/Tpl2 is required for neoplastic cell transformation induced by interleukin-22: a possible mechanism in breast carcinogenesis. [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 556. doi:10.1158/1538-7445.AM2013-556 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2762: An open-label phase 1 study to evaluate the pharmacokinetics of axitinib (AG-013736) in healthy Chinese volunteers
Authors: Ying Chen, Ji Jiang, Jianyan Zhang, Michael Tortorici, Yazdi K. Pithavala, Lei Lu, Grace Ni, Pei Hu
Journal: Cancer Research (2010)

Abstract Introduction: Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. It is mainly metabolized by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP1A2, CYP2C19, and uridine glucuronyltransferase (UGT1A1). Axitinib currently is in Phase 3 development for renal cell carcinoma. As part of the global clinical development program for axitinib, studies are ongoing in cancer patients in China. A clinical assessment of axitinib pharmacokinetics in healthy Chinese subjects, including dose-proportionality, was conducted to support the regulatory submission in China. Methods: This was an open-label, fixed-sequence study conducted in mainland China in 14 healthy volunteers. All subjects received a single axitinib dose of 5 mg, 7 mg, and 10 mg under fed conditions in study periods 1, 2, and 3, respectively, followed by safety and pharmacokinetic monitoring. Each study period was separated by a washout period of at least 7 days between successive axitinib doses. Serial blood sampling for axitinib pharmacokinetics was performed up to 32 hours postdose in each period. Plasma concentrations of axitinib were measured using a validated LC/MS/MS (liquid chromatography coupled with mass spectrometry) method. Axitinib plasma pharmacokinetic parameters were estimated using standard noncompartmental methods. Results: Axitinib AUC0-∞ (area under the curve from time zero to infinity) and Cmax (maximal plasma concentration) estimates in healthy Chinese volunteers in this study are reported here. The geometric mean estimate of AUC0-∞ was 150, 251, and 321 ng[[Unable to Display Character: &amp;#8729;]]h/mL for doses of 5 mg, 7 mg, and 10 mg, respectively. This represented AUC0-∞ increments of 1:1.7:2.1 for dose increments of 1:1.4:2, respectively (ie, a proportional increase in AUC0-∞ per dose increment). Similarly, the geometric mean estimate of Cmax was 33.5, 51.1, and 69.4 ng/mL for 5 mg, 7 mg, and 10 mg, respectively, representing Cmax increments of 1:1.5:2.1 for dose increments of 1:1.4:2, respectively (a proportional increase in Cmax per dose increment). Axitinib was well tolerated with no serious adverse events (AEs) or discontinuations; the only observed AE was mild abdominal distension in 1 subject. Conclusions:. Dose-proportional linear pharmacokinetics for axitinib were observed for the 5 mg to 10 mg dose range in this study. 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 2762.
Successful drainage of recurrent pancreatic pseudocyst via a transpapillary and transpancreatic approach, using a conventional cystotome
Authors: M. Kraft, P. Simon, C. Nitsche, S. Runge, N. Hahn, R. Puls, M. Lerch
Journal: Endoscopy (2012)

A 54-year-old patient was previously admitted to our hospital in 2010 with a history of biliary necrotizing pancreatitis and pancreatic fluid collection with necrotic debris projecting into the tail of the pancreas. We carried out endoscopic ultrasound-guided (EUS) transgastric drainage of the superinfected necrotic area. The patient was discharged and 6 months later the pigtails were removed after complete resolution of the fluid collection. After another 6 months, transabdominal ultrasound showed a large pseudocyst at the same site without any signs of inflammation. The diagnosis was confirmed by computed tomography (CT) ([Fig. 1]). EUS revealed a large stenosis in the pancreatic duct and there was suspicion of a fistula in relation to the pseudocyst. Transgastric access for pseudocyst drainage was impeded by the presence of multiple varices because of splenic vein thrombosis. We therefore chose a transpapillary approach for draining the pseudocyst (diameter 10 cm).
AB0703 Prevalence and Risk Factors of Spondyloarthritis Associated with Inflammatory Bowel Disease in Japanese Patients: A Single Center, Cross Sectional Study
Authors: K. Kamo, H. Suekane, T. Shuto, A. Haraguchi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Spondyloarthritis (SpA) is one of the most common extraintestinal manifestations in those patients<sup>1</sup>. In Japanese multicenter study, the musculoskeletal complication of IBD was reported to be 5.8%<sup>2</sup>, which is much lower than the global average. On the other hand, many Japanese physicians feel that musculoskeletal symptoms are more frequently present in patients with IBD. In Japan, the prevalence of SpA-IBD is not clear. One reason is that many patients have not been evaluated by rheumatologists. It is possible that a substantial number of patients with IBD have not been recognized to have SpA. <h3>Objectives</h3> We aimed to clarify the prevalence and risk factors of IBD associated SpA in Japanese IBD patients. <h3>Methods</h3> We performed questionnaire survey about SpA symptoms in 51 patients with Crohn9s disease and 93 patients with ulcerative colitis (UC) on their office visit. A consultant rheumatologist (KK) examined the patients who were suspected to have SpA, and classified them based on the Assessment of SpondyloArthritis international Society classification (ASAS) criteria<sup>3</sup>. <h3>Results</h3> After the survey by the questionnaire, 46 (33.6%) patients were suspected to have SpA. Twenty (13.9%) patients have SpA: 2 (1.4%) patients were diagnosed as axial SpA and 18 (12.5%) patients were diagnosed as peripheral SpA. The mean disease duration were 12.3 years in the patients with SpA (SpA group) and 9.2 years those without SpA (non-SpA group) (p&lt;0.05). However the age of onset, sex and type of IBD were not significantly different between the groups. The stratified analysis showed in the male patients UC was independently associated with SpA (OR 0.06, 95% CI 0.003 to 0.917, p=0.043) and longer disease duration in the patients with UC was associated with SpA (OR 1.24, 95% CI 1.02 to 1.5, p=0.031). <h3>Conclusions</h3> The prevalence of IBD-SpA in Japanese patients (13.9%) may be higher than previously estimated. The correct recognition of SpA will lead to appropriate treatments and further to improvement in ADL and QOL in patients with IBD-SpA. <h3>References</h3> Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol hepatol. 7(4): 235-41, 2011 Sakurai T, Matsui T, K Aoyagi, et al. Extraintestinal complication of inflammatory bowel disease. Stomach and Intestine. 48(5): 591-600, 2013 Rudwaleit, M., Van Der Heijde, D., Landewé, R., Akkoc, N., Brandt, J., Chou, C. T., Dougados, M., et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Annals of the Rheumatic Diseases, 70(1), 25–31, 2011 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1050
Unusual Presentations of Uncommon Tumors
Authors: R. V. Datta, T. Daskalakis, H. Adler, H. Lehman
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.9.2405 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11981016 Unusual Presentations of Uncommon Tumors Case 3. Giant Cell Plasmacytoma Presenting as an Intraperitoneal Mass R. V. DattaxR. V. DattaSearch for articles by this author , T. DaskalakisxT. DaskalakisSearch for articles by this author , H. AdlerxH. AdlerSearch for articles by this author , H. LehmanxH. LehmanSearch for articles by this author Show More South Nassau Communities Hospital, Oceanside, and Maimonides Medical Center, Brooklyn, NY https://doi.org/10.1200/JCO.2002.20.9.2405 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology